Background: Antiretroviral therapy (ART) is administered to preserve maternal health and prevent perinatal transmission of HIV, however, there are concerns of potential adverse birth outcomes. We have previously shown that protease-inhibitor (PI)-based ART regimens contribute to these adverse events by dysregulating progesterone and altering early placentation events including uterine endometrium decidualization and decidual spiral artery remodeling, which are central to optimal placentation. It is not known whether exposure to INSTI-based ART affects the early gestational events. We hypothesize that decidualization and vascular remodeling is impaired by INSTI exposure.

Methods: Human first-trimester decidua (N=8) were digested and cells were treated with vehicle or various INSTIs at Cmax concentrations alone and in clinically-relevant combinations (Dolutegravir, DTG; Raltegravir, RAL; and Bictegravir; BIC; using the NRTI backbone TDF/FTC). Decidua conditioned media (DCM) was collected after 72h and concentrations of relevant biomarkers were quantified using multiplex assays. Healthy extravillous trophoblast (EVT)-containing villi were dissected from human first-trimester placental tissue and incubated in INSTI-treated or untreated DCM. The degree of EVT outgrowth after 48h was measured by image analysis.

Results: DTG-treated decidual cells had higher levels of secreted matrix metallopeptidase-9 (MMP-9) compared to controls (mean±SD; 22.7 ± 8.1 ng/ml versus 18.6 ± 6.9 ng/ml, p=0.0052) and lower secreted MMP-7 (19.2 ± 7.2 ng/ml versus 38.3 ± 5.1 ng/ml, p<0.0001). Biomarkers of decidualization (angiopoietin-2, prolactin, IGFBP-1) were similar between groups. Placental villi incubated in DCM from DTG- and RAL-treated cells demonstrated a significant reduction in EVT outgrowth as compared to DCM-treated controls.

Conclusions: Our data suggest that DTG and RAL impact decidual soluble factors that affect EVT migration. MMPs are key proteases in the reproductive system and integral to the vascular remodeling process. A reduction in MMP-7 may reflect an impairment of uterine natural killer cell-mediated vascular remodeling. Further studies are necessary to understand the mechanisms involved.

Background
Migrants living with HIV (MLWH) are a growing and diverse population who experience numerous barriers to HIV care engagement. To improve outcomes, rapid and free treatment dispensation upon care linkage are recommended. However, quantitative evidence supporting such an approach to care is lacking. We sought to examine change over time and by sociodemographics in treatment adherence and satisfaction for MLWH enrolled in a program with free and rapid treatment initiation.

Methods
In January 2020, we initiated a 96-week prospective cohort study at a hospital-based clinic in Montreal, Canada. All patients received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for free, on-site, and as soon as possible following care linkage. Three patient-reported measures were administered at weeks 4, 24, 48, and 96 after treatment initiation: (1) Forgetting Treatment (score range: 0-30, higher scores indicate more forgotten days); (2) Perceived Adherence (score range: 1-6, higher scores indicate better adherence); (3) HIV Treatment Satisfaction (score range: 10-70, lower scores indicate greater satisfaction). Descriptive statistics and linear mixed model analyses with bootstrapping for parameter estimates are reported.

Results
As of December 2022, data for 31/37 enrolled MLWH were available for analysis. Many participants are: men-who-have-sex-with-men (n=16, 52%); from Africa (n=14, 45%); <39 years of age (n=17, 55%); unemployed (n=22, 71%). At the four time-points, average scores ranged from: (1) 0.29-0.82 (SD range: 0.66-1.27) for forgetting treatment; (2) 5.09-5.38 (SD range: 0.87-0.98) for perceived adherence; and (3) 15.31-18.31 (SD range: 4.13-6.84) for treatment satisfaction. Those unemployed had a significantly higher estimate of forgetting treatment compared to those with paid employment (p=0.037). No other significant differences were detected by time or between other sub-groups.

Conclusion
Migrants reported few forgotten days of treatment, high perceived adherence, and high satisfaction with B/F/TAF. However, unemployment was linked with forgetting to take treatment by MLWH. Further qualitative research could help understand these results.

Cardiovascular diseases and neurocognitive disorders have a high prevalence in the HIV population (PLWH), impacting quality of life, treatment compliance, and survival. To our knowledge, no study has addressed the link between subclinical coronary artery disease and cognition in the HIV population so far. Our team has set up the Canadian HIV and Aging Cohort Study (CHACS) which prospectively follows > 1000 PLWH and non-HIV participants. Participants in a cardiovascular sub-cohort of CHACS were previously assessed by cardiac computed tomography (CT) for the evaluation of subclinical coronary artery atherosclerosis. In our current study, we select 30 PLWH from the cardiovascular sub-cohort. Based on the results already obtained in CT, these participants will be classified according to the presence or absence of coronary plaque (volume of plaque > 0 mm3 vs = 0 mm3). Each participant will undergo a brain magnetic resonance (MRI), for structural evaluation (measurement of brain volumes), and functional evaluation by diffusion tensor imaging (measurement of fractional anisotropy and mean diffusivity). Neurocognitive testing using the Brief Cognitive Ability Measure (B-CAM) test battery will yield cognitive function scores. The statistical analysis will compare the neuro-structural integrity of white matter, brain volumes, cognitive scores, and coronary plaque in PLWH. We expect lower fractional anisotropy values, higher mean diffusivity values, lower brain volumes, and lower cognitive scores in PLWH with coronary plaque compared to PLWH without coronary plaque. This pilot study is a preliminary step to a larger study, aiming to assess the link between cardiac impairment and neurocognitive decline in the HIV population.

Background:
Side effects associated with antiretroviral (ARV) therapy confer considerable morbidity and healthcare expense. However, little is known about how side effects are experienced by groups historically underrepresented in clinical trials, such as women, particularly on contemporary ARV regimens. Herein, we analyze prevalence and influencing factors of side effects experienced by women.
Methods:
Self-reported survey-based data (Dec 2020-Dec 2022) were obtained from women (trans-inclusive) ≥16 years, living with HIV, currently taking ARVs, and enrolled in the BCC3 cohort. Side effects were defined as any self-reported adverse effect currently experienced at time of survey completion. Self-reported adherence <95% in the previous month was considered suboptimal and polypharmacy was defined as ≥3 non-HIV medications. Univariable and multivariable logistic regression models were used to identify factors associated with side effects.
Results:
Among 170 women aged 49 (mean) ±11 (SD) years, 46% were taking integrase-inhibitors, 15% protease-inhibitors, 9% non-nucleoside-reverse-transcriptase-inhibitors and 18% other/multiple regimens. Sixty-one women (36%) reported having ≥1 side effect; median (range) 3 (1-13). The most common were neuropsychiatric (n=40), gastrointestinal (n=34), pain-related, (n=34), and body weight changes (n=19). Suboptimal adherence was reported by 28% of women, and this proportion increased with greater side effects (no side effects: 20%, 1-2: 38%, ≥3: 50%; p=0.002). In adjusted analyses, suboptimal adherence and polypharmacy remained independently associated with higher odds of side effects (aOR: 3.2 [1.4-7.2]; p=0.005 and aOR: 2.8 [1.1-7.4]; p=0.04). ARV class showed no association with side effects.
Conclusion:
Side effects are frequently experienced by women on contemporary ARVs, regardless of drug class. The observed association between suboptimal adherence and side effects draws into question whether non-adherence may sometimes be intentional, to mitigate adverse effects. The association between polypharmacy and side effects has growing implications as women living with HIV age, experience multimorbidity, and greater polypharmacy. Ongoing efforts are needed to reduce ARV-related morbidity.

Background: While most existing neuro-HIV studies focus on neuropsychological testing, clinicians are usually responding to self-reports on cognition, not to test results. The relationships between self-reported and performance-based cognitive ability, and how these are influenced by mood have not been well-defined, particularly over time. The objective of this study is to estimate, among older PLWH, the extent to which these constructs co-evolve over time.
Methods: Data were collected from 4 visits over 27 months of PLWH over age 35 enrolled in the longitudinal +BHN cohort study. At each visit, cognition was measured with a questionnaire about cognitive difficulties (C3Q) and a brief computerized test of cognitive ability (B-CAM). Mood was measured with the Hospital Anxiety and Depression Scale (HADS). Group Based Trajectory Analysis was used to identify groups with unique longitudinal trajectories on each construct, and the extent to which the trajectories of self-reported cognition were concordant with trajectories of mood and performance-based cognitive ability were estimated.
Results: Complete data were available from 845 participants, 85% male, mean age 52.9 (SD: 8.3). Six trajectories were identified for each of the C3Q, B-CAM and HADS. There was a small but statistically significant improvement in C3Q scores over time among 49.0% of participants, a slight statistically significant improvement over time in all participants on the B-CAM and no change on the HADS. Trajectories of performance-based cognition (B-CAM) were not concordant with trajectories of mood (HADS) or self-reported cognition (C3Q), but trajectories of self-reported cognition were concordant with trajectories of mood.
Conclusions: Overall, self-reported cognition was stable over 3 years among older PLWH. Self-reports provided little information about performance-based cognition but were related to mood. To establish the direction of causality, it would be helpful to test the effect of improving anxiety and depression on self-reported cognitive difficulties among older PLWH .

Background: Women living with HIV (WLWH) disproportionately experience comorbidities and psychosocial stressors. Chronic stress, which can result in dysregulated cortisol levels, negatively impacts health. We compared cortisol levels in WLWH and HIV-negative women and assessed whether they relate to number of comorbidities.

Methods: Cortisol levels were assayed by ELISA from extracted hair specimens (3cm). Demographics and select comorbidities (depression, cognitive dysfunction, kidney/liver disease, diabetes, hypertension, cardiovascular/peripheral vascular disease, dyslipidemia, and osteoporosis) were ascertained via survey. Demographics were compared by Chi-square or Mann-Whitney test. Multivariable Poisson and median regression models assessed factors independently associated with number of comorbidities and cortisol levels, respectively, adjusting for confounders (Table 1).

Results: Participants (n=245) are described in Table 1. In adjusted analyses, age (Prevalence Ratio, PR [95% CI]=1.02 [1.01 to 1.03] or 2.0 [1.0 to 3.0]% per year; p<0.0001) and past substance use (PR=1.35 [1.05 to 1.75] or 35.0 [5.0 to 75.0]%; p=0.02) were independently associated with greater number of comorbidities, while HIV and cortisol levels were not. Older age (β=0.45 [0.14 to 0.81] per year; p=0.01) and current substance use (26.5 [4.11 to 49.0]; p=0.02) were independently associated with higher cortisol levels, whereas HIV was associated with lower cortisol levels (-13.1 [-22.5 to 3.72]; p=0.01).

Conclusions: After considering potential clinical and psychosocial confounders, we report lower cortisol levels among BCC3 WLWH than HIV-negative women. Further, we observed no association between number of comorbidities and cortisol levels. Substance use was the most important modifiable risk factor for higher cortisol levels and increased number of comorbidities.

OBJECTIVES: Our aim was to examine wireless physical activity monitor (WPAM) use and its associations with contextual factors (age, highest education level, social support, mental health) among adults living with HIV engaged in a community-based exercise (CBE) intervention.

METHODS: We conducted a quantitative longitudinal observational study using data from a community-based exercise (CBE) intervention study with adults living with HIV in Toronto, Canada. Participants received a WPAM to track physical activity during a 25-week CBE intervention involving thrice-weekly exercise, supervised weekly (Phase 1) then a 32-week follow-up phase of independent exercise (Phase 2). Uptake was measured as participants who consented to WPAM use at initiation of the intervention. Usage was defined as the median proportion of days participants had greater than 0 steps out of the total number of days in the study. We measured contextual factors using a baseline demographic questionnaire (age, highest education level) and median scores from the Medical Outcomes Study Social Support Scale and Patient Health Questionnaire (mental health), where higher scores indicated greater social support and mental health concerns, respectively. We calculated Spearman correlations between WPAM usage and contextual factors defined as weak (ρ≥0.2), moderate (ρ≥0.4), strong (ρ≥0.6), or very strong (ρ≥0.8).

RESULTS: Seventy-six of 80 participants (95%) consented to WPAM use. In Phase 1, 66% of participants (n=76) used the WPAM at least one day. Median WPAM usage was 50% (25th, 75th percentile: 0%, 87%; n=76) of days enrolled in Phase 1 and 23% (0%, 76%; n=64) of days during Phase 2. Correlation coefficients ranged from weak for age (ρ=0.26) and mental health scores (ρ= -0.25) to no correlation (highest education level, social support).

CONCLUSIONS: The majority of participants consented to WPAM use, however, usage declined over time. Future implementation of WPAMs should consider factors to promote sustained usage with adults living with HIV.

Background: The prevalence of mental health concerns among women living with HIV in Canada was previously reported to be 57.4%, highlighting the need for accessible mental health care for this population. We aimed to: 1) describe the availability and use of services among women living with HIV with unmet mental health needs and 2) identify characteristics associated with these unmet needs.

Methods: Baseline data from the Canadian HIV Women’s Sexual and Reproductive Health Cohort Study were analyzed. Unmet mental health need was defined by participant-reported shortage of mental health support. Self-reported availability and use of mental health services were examined using descriptive statistics. Logistic regression models were constructed to determine associations between sociodemographic, clinical, and psychosocial characteristics and unmet need.

Results: Of 1422 participants, 38% (n=541) perceived unmet mental health needs. Among this subset, 22.1% (n=119) accessed services at HIV clinics, 26.5% (n=143) reported available services at clinics but did not access them, and 51.4% (n=277) indicated these services were unavailable, did not know if services were available, or were not engaged in HIV care. Factors associated with unmet needs included rural residence [adjusted odds ratio (aOR): 1.69, 95% confidence interval (CI): 1.03-2.77], higher educational level (aOR: 1.43, 95% CI: 1.02-2.02), and higher stigma scores (aOR: 1.03, 95% CI: 1.02-1.03). Conversely, African/Caribbean/Black identity (aOR: 0.37, 95% CI: 0.26-0.54), history of recreational drug use (aOR: 0.56, 95% CI: 0.39-0.81), and Quebec residence (aOR: 0.69, 95% CI: 0.50-0.96) were associated with lower odds of unmet needs.

Conclusion: Our findings indicate existing services may not be sufficient to reach all participants or may need to be adapted to respond to specific needs as some participants reported unmet needs despite accessing care. Characteristics associated with unmet needs also reflect geographic and socioeconomic disparities that must be accounted for in future service design.

Background: Co-infection HIV and syphilis rates in Saskatchewan have spiked at epidemic proportions. These overlapping infections lead to poor clinical outcome and additional complications, particularly among women of child baring years.
Objective: To better understand the shifting landscape of HIV in relation to an emergence of syphilis infections and other STBBIs through an analysis of the epidemiologic characteristics of newly diagnosed HIV infections.
Methods: A retrospective chart review was conducted with data from the Wellness Wheel Medical Outreach Clinic, which serves on-reserve First Nation communities across Saskatchewan. The data range included diagnosed HIV cases between 2018 and 2021, and was stratified by date of diagnosis into those diagnosed prior to the COVID-19 pandemic (01/01/2018- 12/31/2019) and those diagnosed during the pandemic (01/01/2020-12/31/2021). Differences in socio-demographics, clinical characteristics, treatment outcomes, and pregnancy status between the groups were analyzed.
Results: There were 47 new HIV diagnoses across both time points: 21 prior to the pandemic and 26 during the year following the onset of the pandemic. The proportion of female clients increased from 33% to 69% (p=0.014). The gender discrepancy is more significant for those <40 years of age (p=0.005). Self-reported heterosexual exposure with no injection drug use increased from 10% to 67% (p=0.021). The incidence of pregnancy among female clients diagnosed with HIV increased by 300% across the two periods. During COVID-19, 75% of pregnant clients were diagnosed during prenatal care, and 50% of those were in their third trimester.
Conclusions: Epidemiological characteristics of new HIV diagnosis differed across the two time point periods, with an increase in younger females and in heterosexual transmission risk factors. Further, the high prevalence of pregnancy among new diagnoses demonstrates a need for targeted preventative strategies directed to meet the changing context for HIV infection risk in a post-pandemic context.

Introduction: This study aims to establish a risk stratification model for classifying emotional health and belief-related barriers to antiretroviral therapy (ART) adherence based on sociodemographic variables to address barriers to ART adherence in specific PWH sub-populations.

Methods: A cross-sectional survey was self-administered online and in-person between January to November 2022 to PWH in Montreal, at the McGill University Health Centre and HIV community organizations using convenience sampling. It examined sociodemographic factors and seven domains of barriers to ART adherence, identified from prior literature. We focused on the emotional health and beliefs domain (11 items), which includes affect, beliefs about HIV/ART, and motivation. To assess multivariable associations, linear regression models examined the association of barriers with age, sex, education level, sexual orientation, and immigration status as independent variables. Random forest analyses with 1000 classification and regression trees were conducted to explore sociodemographic variables that classify their association with barriers.

Results: A total of 232 PWH were included. Their average age was 51.1 years (SD=12.5). Two-thirds were men (n=153; 66%). Multivariable regression models showed a statistically significant association (p<0.05; t-test for regression coefficients) between age and barriers to adherence related to feeling sad or depressed, discouraged, and viewing medications as reminders of HIV. Random forest analyses, with a global type I error rate <5%, indicated younger PWH (about <50 years) more often reported feeling sad or depressed as a barrier; while PWH of other ages, sex, and education levels rarely reported this barrier. Immigration status and age were key classifiers of the barrier for feeling unsure regarding how to take ART (overall classification accuracy (OCA)=89.5%), and that of feeling not informed about ART (OCA=86%).

Conclusion: Recognizing the roles of PWH’s age, sex, and immigration status relative to their emotional health and belief-related barriers to ART adherence may help tailor HIV care.

Background: People with HIV (PWH) are at risk of hepatic steatosis (HS) due to a complex pathogenesis, including HIV-related inflammation, frequent metabolic comorbidities and lifelong exposure to antiretroviral therapy. There are limited data whether HIV-associated HS differs in clinical presentation from metabolic dysfunction-associated fatty liver disease (MAFLD). We aimed to compare severity of metabolic and hepatic dysfunction between PWH with HS and MAFLD patients.

Methods: In this international case-control study, 212 consecutive HIV mono-infected patients with HS at McGill University in Montreal were compared to a sex and age matched MAFLD control group at Policlinico Hospital in Milan. Fibroscan with controlled attenuation paremeter (CAP) was used to define HS (CAP≥248 dB/m), severe HS (CAP>280 dB/m), and significant liver fibrosis (liver stiffness measurement>7.0 kPa). Serum fibrosis biomarkers APRI, FIB-4 and Fibroscan-AST (FAST) score were also computed.

Results: PWH presented lower median BMI (28[25-31] vs 29[27-32] Kg/m2, p=0.002) and lower prevalence of obesity (26% vs 44%, p<0.001) compared to MAFLD patients, along with a lower prevalence of hypertension (21% vs 38%, p<0.001). The prevalence of dyslipidemia (41% vs 26%, p<0.001) and statin prescription (23% vs 11%, p=0.003), as well as of high triglycerides (26% vs 9%, p<0.001) and low HDL cholesterol (34% vs 15%, p<0.001), was higher among PWH compared to MAFLD patients. No difference in cardiovascular events and diabetes prevalence was observed between the two groups. As for liver disease, PWH had a lower prevalence of severe HS (54% vs 74% p<0.001) but higher prevalence of significant liver fibrosis (15 vs 7%, p=0.03) by Fibroscan, as well as higher serum fibrosis biomarkers APRI, FIB-4 and FAST score, compared to MAFLD patients.

Conclusions: Despite having lower BMI, PWH seem to have a more severe hepatic and atherogenic presentation of HS than MAFLD patients. Screening and follow-up for HS in PWH is recommended.

Many people living with HIV (PLWH) use cannabis for medicinal reasons. Patients’ knowledge of the tetrahydrocannabinol (THC) and cannabidiol (CBD) concentration of the cannabis products they use may be important for guarding against potential risks of cannabis use. Knowledge of cannabinoid (THC, CBD) concentration among people who use cannabis is generally low, but no studies have examined knowledge among PLWH. This study characterized PLWH’s knowledge of the cannabinoid concentration of the various products they used each day for 2 weeks. We hypothesized that knowledge of cannabinoid concentration would be greater for cannabis that is being used for medicinal (versus nonmedicinal) reasons, and that greater knowledge of cannabinoid concentration would predict reduced likelihood of negative cannabis-related consequences. PLWH (N=29, 76% men, mean age 47 years) who reported using cannabis for both medicinal and nonmedicinal reasons completed daily surveys over 14 days assessing cannabis use, knowledge of cannabinoid concentration of cannabis products used, reasons for cannabis use (medicinal, nonmedicinal, both), and positive and negative cannabis-related consequences. A total of 361 daily surveys were completed across all participants. Participants reported having at least some knowledge of cannabinoid concentration on an average of 44.9% (THC) and 27.4% (CBD) of the days they used cannabis. Generalized linear mixed models revealed that reporting a greater proportion of medicinal (relative to exclusively nonmedicinal) cannabis use days was linked with greater knowledge of cannabinoid concentration, on average, across days. Further, participants who reported knowledge of cannabinoid concentration on a greater proportion of daily surveys were less likely to report cannabis-related consequences. Findings suggest that PLWH report relatively low knowledge of the cannabinoid concentrations in the cannabis products they use, although knowledge may be higher among those reporting a greater proportion of medicinal use occasions. Moreover, knowledge of cannabinoid concentration may be associated with protection against negative cannabis-related consequences.

Islatravir (ISL) is a nucleoside reverse transcriptase translocation inhibitor being studied for HIV-1 treatment and prevention. Exposure-related decreases in total lymphocyte and CD4+ T-cell counts were observed across ISL trials, especially at higher doses. Pharmacokinetic/pharmacodynamic modeling and simulation predict ISL 0.25mg will increase lymphocyte and CD4+ T-cell counts similar to standard ART. Post hoc analyses of changes in total lymphocyte and lymphocyte subset counts were conducted in a dose-ranging phase 2b study (P011; NCT03272347) of ISL+doravirine (DOR)±lamivudine (3TC). Randomized participants received ISL (0.25mg, 0.75mg, or 2.25mg)+DOR+3TC (100mg/300mg) or fixed-dose combination DOR/3TC/tenofovir disoproxil fumarate (TDF) once daily (part 1). Participants receiving ISL who achieved HIV-1 RNA <50 copies/mL at ≥week 20 (W20) stopped 3TC and continued ISL+DOR (blinded; part 2). Participants randomized to ISL switched to 0.75mg between W60-W84 and continued through W144; participants in the comparator arm continued DOR/3TC/TDF through W144. Post hoc analyses evaluated ISL effects on lymphocytes in parts 1-2 through W72 (predose conversion). Participants who switched to ISL 0.75mg before W72 were censored from the W72 analysis but included in preswitch time points. Incidence of infection and hematology parameters were examined. Percentage changes in total lymphocytes were comparable for ISL 0.25mg and DOR/3TC/TDF and more favorable than ISL 0.75mg and 2.25mg (Table). Increases in CD4+ T-cell counts were similar for ISL 0.25mg and DOR/3TC/TDF. Incidence of infection was comparable across groups through W72. No changes were observed for other hematology parameters. Results support further evaluation of ISL 0.25mg+DOR in treatment-naive and virologically suppressed people living with HIV.

Background
Improved efficacy of antiretroviral therapy (ART) over the last 20 years has led to improved health among people with HIV, resulting in a reduced need for frequent laboratory monitoring using CD4 count, HIV viral load (VL), and genotypic antiretroviral testing (GART). Reduced laboratory surveillance has been promoted as one approach to decrease growing program budgets. We examine the changing use and costs of HIV-specific laboratory tests within a clinic cohort over a 20-year timespan within context of improved care.

Methods
Among PWH active patients in care at Southern Alberta Clinic (SAC), aged 18 years and older, we evaluated the use and cost of CD4 count, VL, and GART testing between 1/1/2000-12/31/2020. Annual number of tests per patient and per population are reported along with associated costs, which were obtained from SAC database. The impact of reduced testing on the program costs are evaluated.

Results
Between 2000-2020, with improved care options, median CD4 and viral suppression rates increased. Overall, annual CD4 testing increased by 147% from 2000 to 2014 and decreased by 42% in 2020, despite a 172% increase in the cohort population. Concurrently, VL increased by 104% then decreased by 13%, respectively. GART testing decreased from 270 in 2008 to 125 in 2020. However, annual tests per PWH decreased 47% for CD4, 35% for VL and 16% for GART from 2000 to 2020. Annual program costs for HIV-specific lab testing increased from $186,500 Cdn$ in 2000 to $535,611 in 2014 then decreased to $364,925 in 2020.

Discussion
The frequency of laboratory surveillance of CD4 count, VL, and GART per patient has decreased over time. This has been achievable due to increased rates of viral suppression and improved CD4. Reducing frequency of laboratory investigations among HIV care programs may be a safe approach to help offset other growing budgetary needs.

Introduction: Treatment of HIV using antiretrovirals (ARVs) has been pivotal in reducing perinatal transmission of the disease. While most children who are HIV-exposed but uninfected remain in good health, previous studies showed that these children are at higher risk for growth impairments, lower IQ levels, language and cognitive delays, and other neurological deficits. We have developed mice models of in-utero ARV exposure to understand the effects of ARVs on the fetal brain and subsequent neurodevelopmental and behavioral outcomes.

Methods: Plugged C57BL/6 female mice were randomly assigned to one of the two treatment arms and administered therapeutic doses of either abacavir/lamivudine+ritonavir-boosted atazanavir (ABC/3TC+ATV/r) or tenofovir/emtricitabine+ATV/r (TDF/FTC+ATV/r) by oral gavage. Control mice received an equal volume of water. Offspring (males and females) were used for behavioral tests (rotarod, open field maze, contextual fear conditioning, and Barnes maze). The hippocampus and striatum were extracted from the brain and used to study gene expression analysis by real-time quantitative PCR.

Results: Compared to the controls, mice exposed to TDF/FTC+ATV/r showed increased hyperactivity through rotarod tests. Additionally, in the open field maze, we found increased rearing and distance traveled in both TDF/FTC+ATV/r and ABC/3TC+ATV/r groups. Further, we observed sex-based differences in hippocampal-dependent behavioral tests, where males in both treatment groups showed deficits in spatial navigation and contextual fear memory. Lastly, gene expression analysis revealed changes in the expression of the neurotrophic factor BDNF and its receptor TrkB, and the glutamate receptors NMDAR and AMPAR in the striatum and hippocampus for both treatment groups.

Conclusion: In-utero exposure to protease inhibitor-based antiretroviral regimens lead to deficits in memory and spatial navigation of exposed mice as well as hyperactivity reminiscent of autism spectrum disorders. This phenotype was supported by our gene expression analysis that showed molecular changes in neurons affecting subsequent behavior associated with specific brain regions.

Objective: In Canada, exclusive formula feeding is recommended among persons living with human immunodeficiency virus (PLWH). Cabergoline can be used to suppress physiologic lactation in this population. On December 23, 2020, cabergoline was added to the electronic postpartum medication order-set in our institution. The primary objective of this study was to determine whether this intervention increased the timely ordering and administration of cabergoline.

Methods: A retrospective chart review was performed to assess cabergoline administration among PLWH pre- and post-intervention, between November 2018 and December 2020, and December 2020 and August 2022, respectively. Deliveries among those who chose to breastfeed were excluded.

Results: Seventy-two deliveries among PLWH were included, with 48 occurring in the pre-intervention period and 24 occurring post-intervention. Cabergoline was administered in 62/72 (86%) of eligible patients. Prior to cabergoline being added to the electronic order set (pre-intervention), it was given in 40/48 (83%) of eligible patients, compared with 22/24 (92%) post-intervention. In 7/48 (15%) pre-intervention deliveries, cabergoline was not ordered nor offered to eligible patients, whereas cabergoline was always ordered and/or offered in the post-intervention group. The average time between delivery and cabergoline administration was 382 minutes for the pre-intervention group versus 194 minutes for the post-intervention group.

Conclusions: Cabergoline was administered in a large majority of deliveries among PLWH, both in pre- and post-intervention groups. In both groups, administration was timely. Once cabergoline was added to the order set, time between administration and delivery was approximately halved. Over 1/10th of patients who chose not to breastfeed did not get offered cabergoline prior to our order-set, compared to none after. In this population, preset order-sets appear to improve overall access and timely administration.

Objective: While the World Health Organization currently recommends breastfeeding among persons living with human immunodeficiency virus (PLWH) where formula feeding is not safe or available, exclusive formula feeding is recommended in Canada and other high-resource countries. Still, some PLWH choose to breastfeed. Our study reviewed feeding choices in this population in an effort to improve culturally competent counselling surrounding these risk-benefit conversations.

Methods: A retrospective chart review was performed to assess demographic details and infant feeding choices among PLWH between November 2018 and August 2022. Data was analyzed in Microsoft Excel.

Results: Eighty-four deliveries among PLWH took place during the study period. On average, individuals were 34 years of age and the majority had previously had at least one child. Eighteen per cent (15/84) chose to breastfeed. Of those, 11/15 (73%) were born in low and low-middle income countries. Conversely, among those who formula fed, 43/69 (62%) were born in low and low-middle income countries (p=0.56, NS). All individuals who chose to breastfeed were on antiretrovirals during their pregnancy and all had undetectable viral loads at the time of delivery.

Conclusions: Despite current guidelines recommending formula feeding in PLWH in Canada, nearly one fifth of our cohort chose to breastfeed. Nearly all of these individuals were born outside of Canada and the vast majority were born in low or low-middle income countries, where infant feeding guidelines may recommend exclusive breastfeeding. Culturally competent risk-benefit conversations surrounding infant feeding choices should acknowledge the differences between recommendations in patients’ home country and place of delivery to ensure parents can make informed decisions.

Background: Mindfulness is increasingly popular across Canada and beyond, and there is growing evidence that it can improve the physical and mental wellbeing of people living with HIV (PLWH). However, little is known about the experience of and adverse effects from mindfulness in this population. Cross-sectional and population-based studies show that meditation-related adverse effects can be common in the general population, yet they are underreported in clinical trials of mindfulness-based interventions.
Aim: To explore the experiences of PLWH who participated in an 8-week mindfulness-based stress reduction course (MBSR) as part of a larger feasibility trial
Method: Positively Mindful was the first UK-based research on mindfulness for PLWH, randomising participants to MBSR (n=16) or a waiting list (n=6). Semi-structured interviews were conducted (n=5) with participants allocated to MBSR – three study completers and two dropouts. Transcripts were analysed thematically.
Findings: An unmet need for interventions like mindfulness was identified and emergent themes characterising participant experience included Seeing Anew, Using Course Techniques and Materials, and how the group dynamic and facilitator influenced intervention effect. Interactions with existing mental health conditions necessitated two participants’ withdrawal; this did not lead to a negative perception of MBSR or the study in either case. Their data highlight the tension between motivation to engage and capacity to engage in particular mindfulness practices.
Conclusion: Qualitative evidence and adverse effects data on mindfulness is limited but could inform PLWH, researchers and service providers, when assessing its safety and therapeutic potential for specific populations. Our results suggest that, like all health interventions, mindfulness has the potential to improve wellbeing while also having the capacity to elicit unwanted side-effects. This should be factored in when risk assessing its appropriateness for every individual.

Background: Dolutegravir (DTG) is associated with weight gain, hyperglycemia, and adipocyte changes. We evaluated the impact of DTG on glucose homeostasis and metabolic health using a mouse model.

Methods: Healthy female C57BL/6 mice were randomly assigned to daily treatment with either control (water, N=15), 1xDTG (2.5mg/kg DTG+33.3/50mg/kg emtricitabine (E)/tenofovir disoproxil fumarate (T), N=13), yielding therapeutic levels of DTG, or 5xDTG (12.5mg/kg+33.3/50mg/kg E/T, N=15) for 9 weeks. Overnight fasted glucose, body weight, and oral glucose tolerance test (OGTT) were measured at 2, 4, 6 and 8 weeks. Fasting hyperglycemia was defined as fasting glucose >10.4 mmol/L and OGTT glucose concentrations were quantified by area under the curve (AUC). Mice were sacrificed at 9 weeks, and tissues and plasma were collected for gene and plasma factor expression of factors in glucose homeostasis pathways. ANOVA and Kruskal-Wallis tests were used for statistical comparisons at various time points.

Results: No differences were observed in weight gain between groups. By week 6, 1xDTG animals displayed a significant increase in overnight fasted glucose. 13 of 28 animals treated with DTG (8 in 1x-DTG, 5 in 5x-DTG) had fasting hyperglycemia at least once, compared to only 1 in the control, and 12 of the DTG mice were euglycemic by week 8. Mice developing fasting hyperglycemia also showed higher OGTT AUC compared to controls. After 9 weeks of treatment, we observed lower plasma leptin and higher plasma corticosterone in DTG-treated mice compared to controls. A negative correlation between leptin and corticosterone levels was observed in the DTG-treated mice. Plasma glucose at 9 weeks positively correlated with plasma corticosterone in DTG-treated mice.

Conclusions: DTG was associated with transient glucose dysregulation in some, but not all, animals. DTG-treated animals also exhibited changes in plasma hormones after 9 weeks of treatment, which may be linked to compensatory mechanisms in energy homeostasis.

Pregnant individuals with HIV on protease inhibitor (PI)–based antiretroviral therapy (ART) have a greater risk for adverse birth outcomes including small for gestational age (SGA) births. This study assessed levels of the angiogenic factors angiopoietin (ANG)-1 and ANG-2 and their receptor Tie-2 in maternal plasma of pregnant individuals with HIV on PI-based ART and assessed their utility as potential biomarkers of placental pathology.

Maternal plasma samples were collected longitudinally throughout pregnancy from a cohort of Canadian pregnant people with and without HIV. Birth outcomes were recorded. Levels of ANG-1, ANG-2 and soluble Tie-2 (sTie-2) were quantified by enzyme-linked immunosorbent assay. Factors were ln transformed and plotted against gestational age. Mixed effects modeling was used to examine differences between factors and their ratios across gestation by HIV status. Associations with SGA births were examined in the HIV-positive group.

109 pregnant individuals (64 with HIV and 45 controls) were included. All with HIV were on a PI-based ART regimen. Each participant contributed an average of 3 samples across gestation. Maternal plasma levels of ANG-1 and sTie2 remained constant across gestation and did not differ by HIV status. Levels of the ANG-1 antagonist, ANG-2, were significantly higher in the individuals with HIV compared to controls at all time points past 28 weeks gestation. Correspondingly the ratio of ANG-2:sTie-2 was also elevated at these later time points. There were 16 SGA births, all in the HIV-positive group. We did not observe any significant associations between any of the factors or their ratios with SGA births.

It is known that ANG-2 counteracts ANG-1‘s maturation effect on placental blood vessels in the 3rd trimester. We suggest that the increase in ANG-2 in HIV-positive/PI-exposed group may contribute to the increased branching angiogenesis that we have previously observed in placentas from individuals with HIV on PI-based ART.

Cognitive impairment is a common comorbidity among people aging with HIV, and a significant source of stress and anxiety. Psychosocial interventions have the potential to alleviate symptoms associated with cognitive impairment and help improve the quality of life of people living with HIV as they continue to age. These interventions are in the infancy of development. Dementia directly related to HIV replication in the brain is most commonly diagnosed as HIV-Associated Neurocognitive Disorder. Cognitive impairment is thought to result from HIV penetrating the blood–brain barrier and causing structural damage to fronto-striatial-thalamatory circuits in the brain. The slow development of interventions may be partially attributed to a common trend of requiring a formal HAND diagnosis to qualify for psychosocial intervention programs. HAND is a diagnosis of exclusion concluded via intensive, time-consuming tests, and many cases of HAND remain undiagnosed, misdiagnosed, or misclassified due to the limitations of the assessment process. HAND screening has been well-recognized as a burden by people aging with HIV and has poor test–retest reliability. Psychosocial trials for dementia in the general population frequently employ a low-barrier entry condition for cognitive impairment, such as the Mini-Mental State Examination or the Montreal Cognitive Assessment. For people aging with HIV, a similarly brief cognitive assessment could partly determine participants’ cognitive strengths and deficits. This presentation will suggest alternate methods of screening for cognitive impairments through the use of brief, low-barrier assessments alongside strategies to validate these briefer screens. Such alternate screening considerations have the potential to ease the burden of extensive testing that is commonly associated with a HAND diagnosis, while still providing valuable insight into individuals’ cognitive functioning, and making psychosocial support more accessible. Screening considerations are critical to consider for closing the research-to-practice gap by trialing interventions that may be efficacious and implementable.

Background. People with HIV (PWH) face high rates of metabolic dysfunction and nonalcoholic fatty liver disease (NAFLD). Visceral adipose tissue (VAT) is a hormonally active tissue associated with ectopic fat accumulation in the liver. We investigated NAFLD diagnosed by controlled attenuation parameter (CAP) associated to Fibroscan as a marker of visceral adiposity in PWH.

Methods. We conducted a pilot study of HIV mono-infected patients undergoing metabolic characterization and paired CAP with dual-energy X-ray absorptiometry (DEXA) scan. NAFLD was defined as CAP ≥285 dB/m, in absence of alcohol abuse. Excess visceral adiposity was defined as VAT>1.32 Kg. Pairwise correlation, area under the curve (AUC) and logistic regression analysis were employed to study the association between VAT and CAP.

Results. 30 patients (90% male, mean age 48.5, mean BMI 29.9, mean waist circumference 100.9, 50% with NAFLD) were included. CAP was higher in PWH with excess VAT (319+52 vs. 213+52 dB/m, p<0.001). CAP positively correlated with all measurements of visceral fat by DEXA, including VAT (r=0.650, p<0.001), VAT/body weight ratio (r=0.565, p=0.001) and fat mass (r=0.390, p=0.033). After adjusting for duration of HIV infection (aOR 1.01 per year, 95% CI 0.91-1.12), BMI (aOR 1.77, 95% CI 0.74-4.23) and waist circumference (aOR 0.91 per cm, 95% 0.68-1.21), CAP remained the only factor associated with excess VAT (aOR 1.05 per dB/m, 95% CI 1.01-1.10; p=0.036). The AUC analysis determined CAP had excellent performance to diagnose excess VAT (AUC 0.92, 95% CI 0.81-1.00), higher than BMI (AUC 0.83, 95% CI 0.68-0.99) and waist circumference (AUC 0.81, 95% CI 0.65-0.97). The optimized CAP cut-off to diagnose excess VAT was 266 dB/m, with a sensitivity of 88.3% and a specificity of 84.6%.

Conclusions.
NAFLD diagnosed by CAP is associated with VAT in PWH independent of anthropometric measurments. CAP could be utilized to diagnose visceral obesity in PWH.

There is international consensus on the utility of patient-reported outcome measures (PROMs) to inform HIV care; however little is known on the scope of related PROM initiatives to date. Our team conducted a rapid scoping review of literature published from 2005 on efforts to collect PROM data to inform individual patient care within HIV clinical practice. Medline, Embase, PsychINFO, and CINAHL databases were searched on May 4, 2022, using a search strategy designed with an academic librarian. Projects involving symptom screens for tuberculosis case-finding were excluded. Here, findings are presented on the country of origin of retained PROM initiatives and on the patient-reported outcomes (health issues) they measured to inform HIV care. Of 13,062 records generated from the database search, we retained a final sample of 107 documents, referring to 70 distinct initiatives. All except one were led in a single country. Represented were the United States of America (n=30; 43% of initiatives), seven European countries (n=20; 29%), nine African countries (n=12; 17%), two Southeast Asian countries (n=3; 4%), Australia (n=3), Canada (n=2), and Korea (n=1). The most frequently measured patient-reported outcomes were: symptoms of depression (n=40; 57% of initiatives), alcohol use (n=21; 30%), drug use (n=20; 29%), symptoms of anxiety (n=17; 4%), adherence to antiretroviral therapy (n=14; 20%), smoking (n=11; 16%), interpersonal violence or abuse (n=8; 11%), cognitive problems (n=7; 10%), (health-related) quality of life (n=7; 10%), side effects (n=6; 9%), sexual risk behaviors (n=5; 7%), symptoms of post-traumatic stress disorder (n=5; 7%), material deprivation (e.g., housing/financial issues) (n=4; 6%), sexual satisfaction/problems (n=4; 6%), and HIV disclosure (n=4; 6%). All other outcome categories occurred in 3 or fewer initiatives. PROMs initiatives within HIV care have spanned the globe and assessed a wide range of outcomes. However, they have mostly targeted mental health, substance use, and adherence.

Introduction: Since 2015, the incidence of congenital syphilis (CS) in Canada has increased significantly. The current epidemics of syphilis and other sexually transmitted and blood-borne infections have been described as a syndemic. Canadian studies have reported the prevalence of syphilis among HIV-positive individuals to be around 8% to 11%. The objectives of the study are to describe sociobehavioral risk factors, including coinfections, screening, and treatment of mothers with infants affected by syphilis; and the presentation and management of affected infants.
Methods: Cases of CS were elicited from paediatricians through the Canadian Paediatric Surveillance Program between June 2021 and October 2022. Survey responses were analyzed using descriptive statistics.
Results: In total, 143 cases were reported. The median maternal age was 27 years (range 17-39) and 63% (n=90) resided in urban areas. Substance use was the most reported risk factors for 66% (n=94) of the mothers. 29% (n=41) were not screened for syphilis during pregnancy. The most frequent co-infections were chlamydia (27%, n=38), gonorrhea (15%, n=22), hepatitis C (14%, n=20) and HIV (5%, n=7). Most affected infants had no physical exam findings of CS (58%, n=83). 24% (n=34) reported intensive care unit (ICU) hospitalization. Most cases began antibiotic treatment within one week of life (89%, n=127). Of the seven mothers with HIV coinfection, six used substances and were screened for syphilis during pregnancy. Six out of the seven affected infant of an HIV coinfected mother did not require ICU hospitalization. All infants of a coinfected mother began treatment for syphilis within one week of life.
Conclusions: Syphilis increases the risk of acquisition and transmission of HIV and HIV can enhance the progression of syphilis. It is essential to better understand the clinical and epidemiological interactions between HIV and syphilis in pregnant individuals to reduce vertical transmission to their infants.

Background: Historical drug resistance results are not always available when considering treatment options. In the phase 3 TANGO and SALSA trials evaluating switch to dolutegravir/lamivudine (DTG/3TC), absence of historical resistance results or presence of archived M184V/I mutations did not impact efficacy. This meta-analysis describes virologic failure (VF) using real-world data from people with HIV-1 (PWH) receiving DTG+3TC in suppressed-switch settings, with historical RNA- or archived proviral DNA-detected M184V/I.

Methods: Embase®, Ovid MEDLINE®, MEDLINE® In-Process, and Cochrane library (January 2013-March 2022) and relevant conference archives (2016-2021) were searched for real-world studies reporting virologic outcomes for PWH receiving DTG+3TC (systematic review) and randomized controlled trials (RCTs) assessing M184V/I impact on DTG+3TC efficacy (targeted review). Studies were screened for populations reporting pre-switch M184V/I. Common- and random-effects model analyses were conducted from real-world studies (primary objective) and RCTs (sensitivity analysis; secondary objective).

Results: Of 3492 publications and 198 abstracts, 5 real-world studies and 5 RCTs met search criteria. Few VFs and no treatment-emergent resistance mutations were reported at each time point (Table). Random-effects model–estimated proportions (95% CI) of PWH with historical M184V/I with VF at Weeks 24, 48, and 96 were low in real-world studies (0.01 [0.00-0.14], 0.03 [0.01-0.08], and 0.04 [0.01-0.17], respectively) and RCTs at Week 48 (0.01 [0.00-0.04]); common-effects model estimates for RCTs reporting zero VF events at Weeks 24 and 96 were 0.00 (0.00-0.02) and 0.00 (0.00-0.03), respectively.

Conclusion: This meta-analysis provides reassuring data on outcomes with DTG+3TC in PWH with incomplete history or where M184V/I was inadvertently missed.

Background: The social brain hypothesis suggests that primates developed a larger brain to meet the social complexities of living in a group. Social group size has been shown to correlate with volumetric changes in several brain regions among both macaques and healthy humans. Here, we tested for a relationship between grey matter volume and social network size in a sample of older people living with HIV in Canada.
Methods: Fifty-eight HIV-positive participants drawn from the Positive Brain Health Now cohort underwent structural brain MRI as part of a pilot neuroimaging study. Social network size was measured using Dunbar’s Social Network Questionnaire. Grey matter volumes were assessed with Voxel Based Morphometry, focusing on 7 regions of interest based on a prior study in our group using the same social network size questionnaire in healthy older people.
Results: We observed a correlation between social network size and grey matter volume in the regions of interest, with statistically significant effects in left anterior cingulate cortex and left anterior temporal cortex, controlling for gender, age, and education. However, the direction of the correlation was in the opposite direction to that predicted: those with larger social networks had smaller grey matter volumes. We sought to explain this effect by considering additional variables, including chronic stress, and current and nadir CD4 counts. The negative correlation was more striking in those with CD4 counts < 500, whereas current self-reported stress was not related to grey matter volumes in these regions.
Conclusion: This preliminary study found a negative relationship between social network size and grey matter volume among older people with chronic HIV infection, most striking in those with low CD4 cell counts. Further work is needed to replicate this effect and explore the underlying mechanisms.
Supported by HIV Clinical Trials Network(CTNPT 026; CTN 273)and CIHR Team Grant(TCO-125272)

Background: Community-based sexual health counselling can complement biomedical approaches by offering attitudinal change and sexual health promotion. Gay-Positive Sex, or GPS, is a peer-administered sexual health counselling program. In a previous RCT, GPS, using a group counselling format, reduced serodiscordant condomless anal sex (CAS) and self-reported sexual compulsivity among Canadian GBQM living with HIV. GPS has not been examined for HIV-negative GBQM nor in individual counselling.

Methods: The present study examines outcomes of a 4-session (four 1 hour-long weekly sessions) peer-delivered individual, in-person counselling version of GPS. GPS was delivered to a mixed-serostatus sample of GBQM who had engaged in CAS in the past 3 months. Sessions were held on-site at 3 community-based organizations in Vancouver, Toronto, and Ottawa. The primary outcome was serodiscordant CAS. Secondary outcomes were loneliness, self-reported sexual compulsivity, and condom use self-efficacy. Multivariable generalized estimating equations (GEE) models examined changes from baseline to post-intervention and 3-month follow-up.

Results: The sample included 39 GBQM and was 82% gay-identified, 69.2% white, 61.5% single, and 66.7% HIV-negative (34.6% of whom used PrEP); all GBQM living with HIV (n=13/39) reported an undetectable viral load. At post-intervention, there were significant reductions in number of casual partners in the past 3 months (IRR=0.44, 95%CI=0.23-0.82, p=0.01), but not 3-month follow-up. Reductions in serodiscordant CAS or any CAS were statistically significant at post-intervention (IRR=0.03, 95%CI=0.02-0.04, p<0.001) but not at 3-month follow-up. There were significant decreases at post-intervention and 3-month follow-up in loneliness and sexual compulsivity and an increase in condom use self-efficacy.

Discussion: The individual format of GPS appears to be effective in promoting the sexual health of GBQM by reducing loneliness, self-reported sexual compulsivity, and increasing condom use self-efficacy among sexually active GBQM. Community-based counselling may be a helpful complementary strategy to promote sexual health of GBQM.

Background: The use of antiretroviral therapy (ART) during pregnancy, particularly protease-inhibitor-based regimens (PI), has been linked to adverse outcomes including preterm birth. As this outcome may be related to systemic inflammation, we sought to characterize the inflammatory profile of pregnant people living with HIV (PPLWH) by comparing their levels of inflammatory mediators in the second and third trimesters according to their HIV status and, within PPLWH, their class of ART.
Methods: Samples from 146 PPLWH treated with ART and 24 controls without HIV were retrieved from the CARMA-PREG cohort. Second and third trimester plasma was analyzed via Luminex for 12 markers linked to HIV status and/or pregnancy outcomes: HMGB1, GM-CSF, IFNα, IFNβ, IFNγ, IL-10, IL-17, IL-1β, IL-6, TNFα, AGP, and CRP. Inflammatory mediator levels were further compared between PPLWH treated with integrase strand transfer inhibitors (InSTI) or PI-based regimens and controls.
Results: In bivariate analyses, second and third trimester levels of AGP (alpha(1)-acid glycoprotein) were significantly higher among PPLWH compared to controls. No significant differences between PPLWH and controls were detected for the other markers. There were significantly higher levels of IFNβ, IL-6 and IL-10 in the PI subgroup compared to the InSTI subgroup in the third trimester but not in the second trimester.
Conclusion: HIV infection during pregnancy while treated with ART is associated with increased levels of AGP, a marker of inflammation and infection, at both time points studied. Treatment with PI-based regimens is associated with increased IFNβ, an immunomodulatory marker of inhibition of HIV viral replication; IL-10, a potent anti-inflammatory cytokine, and IL-6, a pro-inflammatory cytokine, specifically in the third trimester. This could point to an immunological response explaining the association between PI-based regimens and preterm birth. Further investigations into the trends of these markers during pregnancy and pregnancy outcomes would be important in the future.

Background:
Composition of the gut microbiota in people living with HIV (PLWH) receiving ART has been associated with risks to develop cardiovascular, non-alcoholic fatty liver and metabolic diseases. Camu Camu (CC), an Amazonian fruit, was shown to modify the gut microbiota and decrease inflammation in animal models and in smokers. In this pilot study, we assessed whether daily intake of capsules of CC extracts could reduce inflammation and modify gut microbiota and liver markers in ART-treated PLWH.

Methods
22 ART-treated PLWH with a CD4/CD8 ratio below 1 were recruited in a single arm trial. Participants took CC capsules daily for 12 weeks in addition to their ART. Blood and stools were collected at 2 baselines before CC intake, after 4 and 12 weeks of CC and 8 weeks after stopping CC. Serum chemistries were performed by clinical labs. Biomarkers were quantified in plasma by ELISA. Microbiota was characterized in stools by 16S rDNA sequencing.
Results
Median age of participant was 53.5, and 21 were male. CD4 and CD8 counts as well as viral load were not influenced by CC during all study visits. After 4 weeks of CC intake, serum levels of AST and ALT liver enzymes decreased (median 23.5 vs 20.5 and 18 vs 16 IU/mL respectively, p<0.001 for both comparisons) compared to baseline. Similarly, levels of FGF21, a biomarker of non-alcoholic fatty liver disease, decreased at 4 weeks (63.5 vs 60 pg/mL, p<0.05). A trend toward lower levels of AST, ALT and FGF21 was also detected at week 12. Levels of gut damage markers I-FABP and REG3α, as well microbial translocation marker LPS tended to decrease at week 12. Modification of the gut microbiota was more prominent at week 12.

Conclusions
CC intake was safe and reduced liver transaminases and FGF-21 levels over 12 weeks in ART-treated PLWH.

Background: Concern of negative drug-drug interactions between feminizing hormone therapy (FHT) and ART can be a barrier to taking ART for trans women with HIV. We measured serum estradiol concentrations in trans women with HIV taking FHT and INSTI-based ART versus trans women without HIV taking FHT.

Methods: This was a parallel-group study of trans women with HIV (on suppressive ART) and without HIV, ≥18 years, taking ≥2 mg/day of oral estradiol plus a form of anti-androgen therapy, with no changes for ≥1 month. Blood was collected prior to ART and estradiol dosing and then at 2, 4, 6, and 8 hours post-dose and serum estradiol concentrations were measured using CMIA. Estradiol concentrations geometric means (GMs) at each time-point, estradiol Cmax, area-under-the-curve (AUC) and GM ratios (GMRs) were calculated and compared using Wilcoxon rank-sum tests.

Results: Participants (n=15) (enrolled from March to August 2022) had a median age of 32 (IQR: 28-39). Among trans women with HIV (, the median duration of HIV was 9.5 years (IQR: 5.0-23.0); 6 were on bictegravir/emtricitabine/tenofovir alafenamide and 2 on dolutegravir/abacavir/lamivudine. Participants took a median oral estradiol dose of 4 mg (range 2-6 mg) for a median of 4 years (IQR: 2-8). Anti-androgen therapy included spironolactone (n=8), orchidectomy (n=6), central hypogonadism (n=1), and cyproterone (n=1). Table 1 summarizes estradiol GMs and GMRs by HIV status. No statistically significant differences were identified by HIV status.

Conclusions: In trans women on FHT, estradiol concentrations were similar between trans women on ART and trans women without HIV.

Objective: Intersections between mental health, food security, and access and use of health services have been established among women living with HIV (WLWH). However, limited research identifies how these factors shape access to health services among WLWH during COVID-19. This study, therefore, examined: (1) the prevalence and social-structural correlates of changes to food insecurity, mental health, and social isolation during COVID-19; and (2) how changes to these factors were associated with increased difficulty accessing routine healthcare during COVID-19.

Methods: Data were drawn from the Sexual Health & HIV/AIDS: Longitudinal Women’s Needs Assessment (SHAWNA) study. WLWH who completed a pre-COVID questionnaire (03/01/2019-03/01-2020) were included. Bivariate and multivariable logistic regression using generalized estimation equations were used to examine associations between social-structural factors experienced pre-COVID-19 and experiencing (a) heightened negative psychological outcomes; (b) heightened social isolation; (c) negative changes to food insecurity, all measured since COVID-19 restrictions started in BC (COVID-19 study period: 03/15/2020-08/31/2021). We then examined relationships between these variables and (d) increased difficulty accessing routine healthcare during the COVID-19 period. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) are reported.

Results: Among the study sample of 151 WLWH, 54.3% were Indigenous, 36.4% were White, and 9.3% identified as other racialized/women of colour, and 10.6% reported transgender identity. Everyday discrimination (AOR:1.08, CI:1.01-1.15) was associated with negative psychological outcomes. Everyday discrimination (AOR:1.07, CI:1.01-1.14) and gender minority identity (AOR:3.63, CI:0.89-14.88) were associated with heightened social isolation. HIV-related stigma (AOR:1.08, CI:1.01-1.16) and sexual minority identity (AOR:2.60, CI:1.13-5.99), were associated with negative changes to food insecurity. Heightened social isolation (AOR:3.49, CI:1.58-7.75) and negative changes to food insecurity (AOR:2.19, CI:0.96-5.00), were associated with difficulty accessing routine healthcare.

Conclusion: Policies and interventions to address intersecting discrimination and stigma, food insecurity, mental health, and social isolation are urgently needed, alongside and to help improve access to health services.

Background:
HIV Pre-exposure prophylaxis (PrEP) is highly effective, but many PrEP-eligible individuals do not perceive their risk of contracting HIV as high.

Methods:
Non-PrEP-using gay, bisexual, and other men who have sex with men in Ontario and British Columbia answered the cross-sectional PRIMP survey, using REDCap. The HIV Incidence Risk Index (HIRI) and HIV prevalence data were used to estimate individualized risk of contracting HIV. Using a randomization sequence created in STATA, participants received their personalized HIV risk expressed either in ‘absolute’ (“your risk of acquiring HIV is X%”) or ‘relative’ (“your risk of acquiring HIV is X% higher than other GBM”) terms. The survey then asked how this individualized HIV risk a) compared with self-perceived risk, and b) influenced interest in using PrEP; we compared outcomes by study arm among participants with a HIRI score >11.

Results:
We analyzed 289 responses (147 absolute, 142 relative). Mean age was 33.9 (SD=10.2) years. Mean HIRI score was 20.1 (SD=7.4). Participants in the ‘absolute’ arm appeared more likely to perceive the individualized risk as lower than expected, and less likely to report not knowing how to interpret the information; impact on intention to use PrEP was similar between arms (Table 1). Some participants described the strategy as reductive and anxiety-provoking.

Conclusions:
Communicating personalized HIV risk using absolute or relative wording was effective in increasing interest in PrEP, though both methods could be anxiety-provoking and reductive. Randomized approaches to survey administration can inform strategies for communicating health information, while allowing for community feedback.

Contexte :
Analyse rétrospective des mesures mises en place pour assurer l’accès à la PrEP pour des personnes utilisatrices de drogues par injection (PUDI) dans le cadre d’un projet de recherche intégré en milieux communautaires. La fermeture et les restrictions des milieux cliniques entre mars et novembre 2020 ont créé une situation critique pour les personnes à risque d’une infection du VIH. Les études sur les évènements majeurs ont démontré que les risques d’exposition aux infections transmises par le sang augmentent dans ces contextes pour les PUDI.
Méthodes :
Identification des défis : 1) suivi virtuel n’était pas possible avec moins de 35 % des participants qui ont accès à un téléphone et une majorité en logement précaire 2) une infirmière de recherche en retrait préventif COVID-19, 3) les risques de déviation aux protocoles de traitement clinique 4) éviter les risques d’infection au VIH pour les personnes sous la PrEP.
Mesures d’adaptation : 1) Inscription des activités de recherche auprès des PUDI reconnues comme essentielles 2) Mise en place d’un protocole d’accès au traitement plus simplifié en pharmacie de recherche 3) intégration d’un protocole de prévention dans unité de soins hospitaliers spécialisée dans la prise en charge clinique des maladies transmises par le sang.
Résultats : 17 PUDI participants de recherche ont été suivi en milieu hospitalier pour le dépistage régulier, accès à la PrEP par la pharmacie de recherche, et suivi clinique de la PrEP (analyse des niveaux de créatinine….). Parmi les 5 PUDI qui ont poursuivi leur traitement, aucune séroconversion n’a été documentée.
Discussion : L’accès à la PrEP est à considérer dans les milieux cliniques d’intervention pour les PUDI. Au-delà des mesures exceptionnelles, l’approche test and treat et test and prevent est efficace pour la prévention auprès des groupes vulnérables et à risque de l’infection du VIH.

Introduction: Research demonstrates that youth living with HIV (YLHIV) are particularly susceptible to attrition from the HIV care cascade. In addition to the normative developmental tasks of adolescence, YLHIV bear the added responsibilities of managing their HIV, which may include transitioning to adult care, navigating healthcare systems, accessing and adhering to medications, and addressing experiences of HIV-related stigma. Strength-based practice is an integrative approach to care that aims to cultivate resilience and empowerment among participants. Among adults living with HIV, strength-based frameworks have demonstrated significant improvements in outcomes across the care cascade. This review synthesizes available literature on strength-based strategies in improving clinical engagement among YLHIV in North America.

Methodology: A scoping literature review was conducted using OVID Medline, EMBASE, and PsycInfo. 185 articles were identified, from which 6 studies were selected for inclusion. Inclusion criteria comprised a) implementation of a strength-based initiative for people living with HIV, b) inclusion of participants between 10-25 years of age, and c) reporting on at least one clinical outcome (appointment frequency, appointment attendance, medication adherence, CD4 count, or viral load). Studies were excluded if the intervention was performed outside North America or if the analysis failed to stratify results by age demographics.

Results: Across a variety of geographical settings and diverse populations, all studies showed statistically significant improvements in appointment frequency and attendance, medication adherence, and longitudinal retention in care. Two studies reported significant improvements in CD4 count and viral load compared to youth receiving standard-of-care. Strength-based care also improved participants’ resilience and facilitated the development of intrapersonal and intrapersonal assets that contributed to positive long-term personal, economic, social, and clinical outcomes.

Conclusion: Strength-based approaches appear to have promising benefits in supporting engagement of YLHIV through the HIV care cascade. However, further study is needed, particularly among populations facing intersecting marginalizations.

Background/Purpose: Advances in HIV treatment have reduced mortality rates and consequently increased the number of individuals that are 50 years of age or older living with HIV, who are considered older adults living with HIV (OALWH). Despite this, there have been significant gaps in HIV treatment and prevention campaigns for OALWH. Moreover, a gold-standard model of care for the OALWH population has not yet been defined. Developing evidence-based Geriatric-HIV models of care can support an accessible, equitable, and sustainable HIV health care system that supports healthy aging in the OALWH population.

Methods: Guided by Arksey & O’Malley (2005), a scoping review was conducted to explore existing geriatric models of care of OALWH and to determine the key components, identification of gaps in the literature and provide recommendations for future research. Five databases and the grey literature were systematically searched. Titles, abstracts and full texts of the search results were screened independently by two reviewers. Data were analyzed using a qualitative case study and key component analysis approach to identify necessary model components.

Results: 5702 studies underwent title and abstract screening, with 154 entering full-text review. 15 peer-reviewed and 6 grey literature sources were included. Almost all articles were from We identified three main models of care components that may improve the successful delivery of geriatric care to HIV populations: Collaboration and Integration; Organization of Geriatric Care; and Pillars of Care. Most articles included some aspects of all three components.

Conclusions: To provide effective geriatric care to OALWH, health services and systems are encouraged to use an evidence-based framework and should consider incorporating distinct models of care characteristics that have been identified in the literature. Future directions include further study into Geriatric-HIV models of care in different settings as well as their impact on healthy aging in the OALWH population.

Background
Women Living with HIV experience earlier menopause than HIV-negative women. We explored timing of menopause, quality of life, and connection to menopause/gynecological care among participants of the Ontario HIV Treatment Network Cohort Study (OCS).
Methods
OCS is a cohort of people in HIV care with clinical and questionnaire data from 15 clinics in Ontario, Canada. From 2021-2022, 450 women aged 30+ completed interviews including reproductive health questions. Women are described as having experienced menopause if they reported menopausal/perimenopausal status or reported no period for more than one year due to natural menopause. 184 experienced menopause at ages that were premature(30-39years)/early(40-45years)/normal(>45years). We examined quality of life using the Short-Form 12 Health Survey (SF-12). Descriptive statistics, t-test, and one-way ANOVA were used for statistical analysis.
Results
Mean age(STD) in years was 47(9.38), 26.6% were white, 63.1% Black, 4.0% Indigenous, 6.3% of other races. For 184 menopausal women mean(STD) age was 54(8.64), 33.5% were white, 55.1% Black, 3.8% Indigenous, 7.6% other. Mean age(STD) of menopause start in premature group was 35(4.41), early 43(1.38), and normal 53.1(3.77). The mean (STD) scores of the SF-12 for physical (PCS-12) and mental health (MCS-12) for the 3 groups of menopausal women were PCS_12 49.8(9.76), 44.2(13.17), 46.6(10.36), and MCS-12 39.7(12.31), 48.0(10.58), 47.6(11.51); lower scores indicating less quality of life, which was significant for those with premature menopause (p=0.05). Of 450 women, 15.8% normally discussed gynecological issues with an HIV specialist, 17.8% with a gynecologist, and 54.8% with a general practitioner. Among menopausal women, 51.4% had never discussed menopause with a provider, and 30.8% think that their menopausal needs and concerns are not met.
Conclusions
Early menopause may have downstream health impacts on women, and we lack knowledge of what causes earlier menopause in HIV+ women. Women living with HIV should have improved access to menopause care.

Background: Previous reports suggest that women living with HIV (WLWH) have a high prevalence of post-traumatic stress disorder (PTSD), however, the prevalence of PTSD has not been compared among WLWH and HIV-negative women in Canada. Additionally, there are mixed reports as to whether cortisol levels are elevated among people with PTSD. We compared the prevalence of PTSD in WLWH and HIV-negative women and investigated possible associations between cortisol levels and PTSD.

Methods: Cortisol levels were assayed by ELISA from 3cm extracted hair specimens. Demographic and PTSD data were collected through questionnaires and compared by Chi-square or Mann-Whitney tests. PTSD was defined as self-report of current/past diagnosis by a healthcare provider or meeting criteria on the Post-Traumatic Checklist–6-item Civilian Version. Associations between odds of PTSD symptoms and cortisol levels were investigated through multivariable regression models, adjusting for possible cofounders (Table 1).

Results: Participants (n=251) are described in Table 1 . Current and past substance use (Adjusted Odds Ratio, AOR [95% CI] 3.32 [1.12 to 10.70];p<0.04 and 3.11 [1.23 to 8.15];p<0.02), lower income (AOR=2.20 [1.05 to 4.69];p<0.04) and fewer hours of sleep (AOR=0.76 [0.62 to 0.93] per hour;p<0.01) were independently associated with PTSD, while HIV status (p=0.47) and cortisol levels (p=0.77) were not.

Conclusions: We observed no independent association between PTSD and either HIV status or cortisol levels, although there was a high prevalence of PTSD in both groups. Furthermore, substance use, sleep, and income may be potential markers of trauma and important factors to address to improve PTSD care for women.

Background: Chronic HIV infection is characterized by persistent inflammation despite successful antiretroviral therapy (ART). With anti-inflammatory properties, cannabinoids may represent a potential strategy to reduce systemic inflammation in people with HIV (PWH).
Methods: Ten PWH (median age: 57.5 years, 8 males) on ART were randomized (n=5/group) to increasing doses of oral Δ9-tetrahydrocannabinol (THC): cannabidiol (CBD) combination (THC/CBD: 2.5/2.5 to 15/15mg daily) capsules or CBD-only (200 to 800mg daily) capsules, for 12 weeks. Blood was prospectively analyzed as part of the clinical trial before starting and after completing cannabinoid treatment. Hematology and biochemistry profiles were used to assess the safety of cannabinoids. Plasma levels of inflammatory markers interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, and IFN-γ-induced protein (IP)-10, and anti-inflammatory IL-10 were determined using a Luminex assay, and Lipopolysaccharide (LPS), sCD14, sCD27, gut damage markers regenerating family member (REG)-3α and intestinal fatty-acid binding protein (I-FABP) were quantified by ELISA. Total HIV DNA and cell-associated RNA were measured in blood CD4+ T-cells and in cell pellets from semen by ultra-sensitive qPCR, and cell-free viral RNA was measured in blood and semen supernatant. Non-parametric Wilcoxon signed rank test was used for statistical analyses.
Results: Eight individuals completed the study. Cannabinoids did not alter participants’ hematology/biochemistry profiles. CD4 count and CD4/CD8 ratio were stable and viral load remained suppressed throughout the study. Cannabinoids significantly reduced mean plasma levels of the following inflammatory markers from the initiation time-point versus the end of the intervention: IFN-γ (10.98-8.54 pg/ml; P=0.03), TNF-α (2.61-2.12 pg/ml; P=0.02), IL-1β (0.62-0.39 pg/ml; P=0.02), and REG-3α (5621-4950 pg/ml; P=0.04). Cannabinoids had no significant effect on HIV DNA and RNA levels in blood or semen, nor other plasma inflammatory markers.
Conclusions: Cannabinoids reduced some inflammatory markers and gut microbial translocation markers in PWH, providing rationale for a larger clinical trial.

People living with HIV (PLWH) are living longer. However, there has been an increase in the early development of aging-related syndromes such as frailty. Drugs with anticholinergic effects are widely used to treat various conditions. However, anticholinergics have been associated with adverse outcomes such as frailty. This study aimed to know the extent to which anticholinergic exposure, measured using different anticholinergic burden scales, is associated with physical frailty in people aging with HIV.

This study used cross-sectional data from 824 middle-aged and older adults living with HIV recruited from five clinics in Canada from the first visit of the Positive Brain Health Now cohort. The anticholinergic burden was estimated using the Anticholinergic Cognitive Burden (ACB) scale, Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale, and anticholinergic list of the Anticholinergic and Sedative Burden Catalog (ACSBC-Ach). Anticholinergic exposure was characterized by total anticholinergic burden score, use of any anticholinergic, and the number of anticholinergics. The primary outcome was physical frailty determined using a modified frailty phenotype criteria based on self-report items. A multivariable logistic regression model adjusted for confounders was used to estimate the association between anticholinergic burden and physical frailty.

128 (15.53%) were identified as frail. Compared to no use, the use of any anticholinergic as defined using the ACSBC-Ach (1.82[1.07-3.08]) and ADS (1.72[1.04-2.83]) were associated with physical frailty. Anticholinergic burden score and number of anticholinergics estimated using the ACSBC-Ach were also associated with frailty (1.32[1.10-1.57] and 1.44[1.12-1.85], respectively). Using the ACB, only the number of definite anticholinergics was associated with frailty (1.76[1.00-3.05]).

Our results suggest that the anticholinergic burden may increase the risk of frailty in PLWH. The strength of this association may differ depending on how exposure is characterized and the burden scale used. The prevention and management of frailty may benefit from reducing the anticholinergic burden through deprescribing.

Integrase strand transfer inhibitor (INSTI) drugs can improve maternal health and prevent vertical HIV transmission. Dolutegravir (DTG) has been linked to neural tube defects and other congenital anomalies. Limited data are available in pregnancy for newer INSTIs. Here we compare outcomes in a mouse pregnancy model for INSTI-based regimens.

C57BL/6 female mice were mated and randomly allocated to treatment arms: Control (water; n=91 litters), DTG (n=103 litters), DTG+TDF/FTC (n=143 litters), raltegravir (RAL)+TDF/FTC (n=113 litters), bictegravir (BIC)+TDF/FTC (n=76 litters), cabotegravir (CAB)+TDF/FTC (n=86 litters), DTG+3TC (n=96 litters). Dosing for all INSTIs was optimized to yield plasma drug levels equivalent to those reported clinically. NRTIs were administered at 10x the human-equivalent dose. Drugs were administered once daily by oral gavage from day of plug detection to sacrificed on GD15.5. Fetal and placenta weight, and number of resorptions (early fetal loss) were assessed.

Resorption rate was highest in the DTG+TDF/FTC group (9.7%), followed by RAL+TDF/FTC (8.4%), DTG alone (7.2%), DTG+3TC (7.4%), BIC+TDF/FTC (6.9%), control (6.3%), and CAB+TDF/FTC (5.3%). None of the INSTIs were significantly different from control, although resorption rates were significantly higher in the DTG+TDF/FTC vs. CAB+TDF/FTC group. Total viability was also significantly lower in the DTG+TDF/FTC vs. CAB+TDF/FTC group. Compared to controls (0.38g) litter average fetal weight was significantly lower in the DTG+TDF/FTC (0.34g), DTG+3TC (0.35g), BIC+TDF/FTC (0.34g), and CAB+TDF/FTC (0.33g) groups, but not in the DTG (0.37g) and RAL+TDF/FTC (0.37g) groups. Litter average placenta weight was significantly lower in the DTG+TDF/FTC and CAB+TDF/FTC compared to control. Fetal to placenta weight ratio was significantly lower in the BIC+TDF/FTC and CAB+TDF/FTC groups compared to control. A lower percent increase in maternal weight was observed in the DTG, DTG+3TC, RAL+TDF/FTC, BIC+TDF/FTC and CAB+TDF/FTC groups compared to control, but not in the DTG+TDF/FTC group. These results suggest that the birth outcomes may differ between INSTIs.

Background : ICW-NA Approach ;The International Community Of Women Living With HIV - North America 's strategic plan for 2020-2024 provides the background and the rationale for the trauma -informed approaches which address the needs and experiences of women living with HIV. As stated in the plan of comorbidity, aging women living with HIV in the world in 2019 . The factors that place women at risk of HIV are rooted not only in biology but in patriarchal social norms ,through which too many often compromising their own health in exchange .Intersecting ,vulnerabilty ,stigmazation and systematic injustice intervention .

Method : Healing Together(HT) is an integrated HIV trauma -informed , stigma- reduction intervention that enchances the ability of BWLWH to powerfully share their lived experiences with each other and others of their choice. The purpose of the healing togetheris to enlighten participants to the commonality of certain aspect of the humain experience . The interconnectedness of specific lived experiences , and how these experiences may or may not have increased vulnerability to HIV . Phase one of the healing together intervention consists of training compromised of six sessions . Training content focuses on the intersectinality of various forms of stigma and trauma resulting

Result : To participate , individual eligibility includes (1) a verifiable diagnosis of HIV , (2) a willingness to learn storytelling techniques on how and when to disclose one's HIV status and lived experiences , (3) receipt of HIV care from a verifiable HIV medical provider ; (4) engagement in case management service .

Conclusion : Healing Together is an approach to reduce trauma ,stigma , share the story of life is a strong education for make change in all community ,( language, age , color of skin ,culture , religion , gender , sex orientation ).

Background: Isolation due to infectious disease can have negative impacts on psychological wellbeing, particularly when there is stigma associated with the disease. We describe the psychological distress experienced by a cohort of Mpox patients, and explore how HIV status, race, and financial hardship may influence these experiences.

Methods: Mpox patients seen at St. Michael’s Hospital from May-November 2022 self-administered questions from The Kessler Psychological Distress Scale (K10) and questions regarding financial hardship experienced during isolation, at the end of their isolation period. We compared psychological distress scores among HIV+ and HIV- participants, white and racialized participants, and participants who experienced financial hardship versus those who did not, using the Wilcoxon test.

Results: Of 21 respondents, all self-identified as gay/queer/bisexual, 11 (52.4%) were HIV+, 7 (33.3%) were white, 14 (66.7%) were racialized, and median (IQR) age was 38 (33, 43) years. Median (IQR) psychological distress score was 23 (20, 29) out of 45, and 12 respondents (57.1%) reported experiencing financial hardship during isolation. Median (IQR) psychological distress scores were similar among HIV+ and HIV- respondents at 24 (20, 31) and 21 (20, 28) respectively (p=0.50); among white and racialized participants at 28 (22, 31) and 21 (20, 25) respectively (p=0.43); and among those who did and did not experience financial hardship at 22 (14, 28) and 24 (20, 32.5) respectively (p=0.24). Of those who scored in the upper quartile of psychological distress scores, a majority (66.7%) were HIV+.

Conclusions: Patients with Mpox may experience varying degrees of psychological distress. Clinicians should bear in mind the effects of infection and isolation on the psychological wellbeing of Mpox patients. Due to the limited sample size, further research on severity and type of psychological distress in the context of HIV and other comorbid infectious diseases is warranted.

Background: Frailty affects older adults with HIV more so than the general population who is not infected. Because HIV has been understood as a chronic condition in the past few decades, the affected individuals are now living longer than before. This creates a community of older adults with HIV who are also experiencing comorbidities along with aging. Frailty amongst PWH needs to be assessed in a timely manner so the individuals can lead a healthy life.

Design: A quality improvement study has been ongoing since 2017 where adults with HIV in the Southern Alberta Clinic (SAC) are assessed using the Clinical Frailty Scale. The participants who score 4+ are contacted for consent from the research team to conduct a questionnaire which inquires for additional factors such as loneliness, falls, impaired gait and balance, polypharmacy, unintentional weight loss, food insecurity, and subjective cognitive concerns

Setting: The Southern Alberta Clinic (SAC) in Calgary, Alberta

Participants: Frail adults with HIV who are 50 years or older in Southern Alberta

Results: There has been 1122 patients at SAC who are 50 and older since December 2022. The median age of the total SAC patient population(n=2094) is 54 years (in tables attached). 43 older adults were new since January 2021. 15 patients who had the frailty questionnaire conducted reported major issues with gait and balance; memory; and social connections since Covid-19. Older adults will have the frailty questionnaire conducted continuously to be referred to appropriate clinicians such as geriatrician, social workers or pharmacy.

Background
The UNAIDS 95-95-95 targets encompass testing and treatment outcomes for people living with HIV (PLWH). These targets do not include quality of life (QoL) for people living with HIV, leading to calls for a fourth 95. The PozQol tool which measures quality of life was developed specifically for PLWH.

Methods
The OHTN Cohort Study (OCS) follows PLWH at 15 clinics in Ontario. In 2022, 1842 PLWH completed the PozQol in the annual interview. The PozQol has four sub-scales: health concerns, psychology, sociology, and functionality; and contains 13 questions with answer options ranging from 1 to 5 (not at all to extremely). Its overall mean and sub-group means were calculated using SAS 9.4.

Results
In the health concerns domain, 47% worry about their health and 55% about the impact of HIV on their health. 49% fear the health effects of HIV as they age. For the psychology domain, 82-89% moderately/ very/ extremely enjoy and feel in control of their life, are optimistic about their future and feel good about themselves. In the sociology domain, 63% feel HIV does not/slightly limits personal relationships and 68% feel a sense of belonging. However, 53% of participants fear being rejected because they have HIV. For the functionality domain, 73% responded that HIV does not/slightly prevents them from doing as much as they’d like and 70% said that having HIV does not/slightly limits opportunities. 20% of respondents said managing HIV wears them out. The overall PozQol mean score was 3.72, health concerns 3.4, psychology and sociology 3.7, and functionality 4.1.

Conclusion
QoL is an important indicator for HIV treatment care and support. PLWH in the OCS show high scores for QoL, but more support is necessary to ensure that PLWH feel confident about their health and free of stigma.

PURPOSE:The Episodic Disability Questionnaire (EDQ) is a patient-reported outcome measure that assesses the presence, severity and episodic nature of disability across six domains: physical, cognitive, mental-emotional health challenges, difficulties with day-to-day activities, uncertainty about future health, and challenges to social inclusion. We assessed the measurement properties of the EDQ among adults living with HIV.

METHODS:We conducted a measurement study with adults living with HIV in five clinical sites in Canada, United Kingdom, Ireland, and United States. We electronically administered the EDQ followed by three reference measures (World Health Organization Disability Assessment Schedule, Patient Health Questionnaire-8; Social Support Scale) and a demographic questionnaire. We administered the EDQ again 1 week later. We assessed internal consistency reliability (Cronbach’s alpha;>0.8 acceptable) and test-retest reliability (Intra Class Correlation Coefficient (ICC)>0.8 acceptable). We estimated required change in EDQ domain scores to be 95% certain that a change was not due to measurement error (Minimum Detectable Change (MDC95%)). We evaluated construct validity by assessing 80 hypotheses of relationships between EDQ scores and scores on the reference measures (>75% hypotheses confirmed indicated validity).

RESULTS:Of the 359 participants who completed time point 1 questionnaires; 321(89%) completed the second EDQ. Median age of participants was 51 years (25,75th percentile:42,59), 83% were men, with a median of 4 concurrent health conditions. Cronbach’s alpha ranged from 0.84-0.91 (severity scale domains); 0.72-0.88 (presence scale domains); and 0.87-0.89 (episodic scale domains). ICCs ranged from 0.80-0.89 (severity scale domains) and 0.70-0.85 (presence scale domains). MDC95% ranged from 18-24 (out of 100) in the severity scale domains and 35-52 in the presence scale domains. Sixty-five of 80(81%) construct validity hypotheses were confirmed.

CONCLUSION:The EDQ possessed internal consistency reliability, construct validity, and test-retest reliability for severity scale domains, with limited precision when administered electronically with adults living with HIV across five clinical settings in four countries.

Minimal weight gain was observed with doravirine (DOR)–based regimens in first-line and switch clinical trials. Factors associated with weight loss/stable weight were examined in phase 3 trials for participants continuing or switching to DOR. In the initial 96-week double-blind base studies, adults were randomized to receive first-line treatment with DOR+2 NRTIs or DRV/r+2 NRTIs in DRIVE-FORWARD (P018; NCT02275780) and DOR/3TC/TDF or EFV/FTC/TDF in DRIVE-AHEAD (P021; NCT02403674). Participants could continue or switch to DOR in 96-week open-label extensions (P018+P021 continued or switch groups). In DRIVE-SHIFT (P024; NCT02397096), virologically suppressed adults on stable ART were randomized to switch to DOR/3TC/TDF at day 1 or week 24 and continue through week 144. Weight loss was defined as ≤−5%, stable weight >−5% to <5%, and weight gain ≥5%. Generalized logistic models were used to analyze factors associated with weight change. Most participants who continued or switched to DOR had weight loss/stable weight versus weight gain (Table). No clinical or demographic factors were associated with weight change during the extension for the P018+P021 continued group. Non-Black participants, particularly non-Black women, showed weight loss/stable weight after switching to DOR. Participants switching from PIs had weight loss in P024 and stable weight in P018+P021 versus those switching from NNRTIs. Switching to DOR resulted in weight loss/stable weight in most participants in these trials, although weight change may differ by race, sex, and prior regimen. Further research will characterize the participant profile and mechanism for weight loss/stable weight with DOR.

Neuropsychiatric adverse events (NPAEs) occur with multiple antiretrovirals. Doravirine (DOR) does not significantly interact in vitro with known neurotransmitter receptors. In phase 3 studies, NPAE rates with DOR/lamivudine/tenofovir (DOR/3TC/TDF) as first-line therapy were significantly lower than with efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF) and were similar for DOR+2NRTIs and darunavir/ritonavir (DRV/r)+2NRTIs. We examined NPAEs in participants who switched to DOR-regimens in the open-label extensions of two phase 3 trials.

In DRIVE-AHEAD (NCT02403674) and DRIVE-FORWARD (NCT02275780), participants were randomized to a DOR-regimen (DOR/3TC/TDF or DOR+2NRTIs) or comparator (EFV/FTC/TDF or DRV/r+2NRTIs) for the 96-week double-blind phases. Eligible participants could continue or switch to a DOR-regimen in the 96-week open-label extensions.

In DRIVE-AHEAD week 96 (W96), 155/269 participants (57.6%) who switched from EFV/FTC/TDF to DOR/3TC/TDF reported NPAEs versus 96/364 participants (26.4%) originally randomized to DOR/3TC/TDF. By week 192 (W192), 19/26 participants (73.1%) receiving EFV/FTC/TDF with ongoing NPAEs at W96 had resolved/resolving NPAEs after switching to DOR/3TC/TDF. In DRIVE-FORWARD (W96), 41/233 participants (17.6%) receiving DRV/r reported NPAEs versus 60/383 participants (15.7%) receiving DOR+2NRTIs. By W192, 6/15 participants (40%) with ongoing NPAEs receiving DRV/r (W96) had resolved/resolving NPAEs after switching to DOR+2NRTIs. In the open-label extensions, new-onset NPAEs (most commonly sleep disorders and depression) were reported by 25/269 participants (9.3%) and 18/233 participants (7.7%) who switched in DRIVE-AHEAD and DRIVE-FORWARD, respectively; by W192, these NPAEs were resolved/resolving in ∼60.0% of participants.

Among participants with ongoing NPAEs while receiving EFV/FTC/TDF, most experienced resolution after switching to DOR/3TC/TDF. Similar rates of NPAEs with DOR- and DRV/r-based regimens may represent background incidence.

Background: Chronic pain (CP) is the most common cause of disability worldwide, and has been associated with HIV, antiretrovirals, trauma, and adverse socio-structural factors. We compared CP among women living with HIV (WLWH) and controls (≥16y) in BCC3.
Methods: We used the Brief Chronic Pain Questionnaire (BCPQ) to screen for CP, and validated surveys to describe CP, psychological distress, and social support (Table 1). Additional questions examined mental health/stigma/sleep. Groups were compared using t-, Chi-Squared, Mann-Whitney tests and logistic regression. Associations with CP were investigated using Spearman’s correlation.
Results: Age-adjusted prevalence of CP was not different between WLWH (58/151;38%) and controls (73/230;32%), p=0.4, nor was the age of women living with CP in both groups (Table 1). Similar proportions of WLWH and controls reported moderate to extreme stigma (39%vs46%, p=0.4), mental health diagnoses (54%vs60%, p=0.5), and sleep disturbances (82%vs83%, p=0.9) related to CP. While women in both groups shared many pain characteristics and experiences, WLWH reported higher social support. In both groups, CP intensity was high but showed no association with psychological distress. However, higher social support was associated with lower CP intensity among controls (rho=-0.3, p=0.02) but not WLWH (p=0.9).
Conclusions: In this study of WLWH and well-matched controls, 1/3 of women reported chronic pain in both groups but few differences were observed between groups with respect to CP or pain-related experiences. However, CP intensity and psychological distress were high in both groups, as were CP-related stigma/sleep disturbances/mental health diagnoses, warranting further research and clinical attention to support healthy aging.

Background: Chronic pain (CP) is prevalent among women living with HIV (WLWH), and has been associated with biological (antiretrovirals, HIV, diabetes) and social (trauma, stress, violence) factors. CP management in WLWH is a research priority affecting quality of life, adherence to care, and wellbeing. We describe and compare medication and substance use in the context of CP among WLWH and well-matched controls in BCC3.
Methods: BCC3 is a community-based study of healthy aging enrolling WLWH and controls ≥16y. We used the Brief Chronic Pain Questionnaire (BCPQ) to screen for CP. Current pain-related prescriptions, over-the-counter (OTC) medication, and substance use were self-reported. Groups were compared (WLWH with CP vs WLWH without CP and controls with CP) using Chi-Square/Fisher’s and Mann-Whitney tests.
Results: WLWH with CP were of similar age as controls with CP but older than WLWH without CP (Table 1). There were no differences in medication/cannabinoid/substance use between WLWH and controls with CP, and less than half of women with CP reported using prescription pain medications. Compared to WLWH without CP, WLWH with CP were more likely to use prescribed medications and opioids for pain/cannabinoids/substances, but not OTC medications. Overdose history was high among women with CP, but there were no differences in overdose experiences within the last 6 months.
Conclusions: WLWH and controls with CP shared similar medication/substance use patterns. These data further suggest that CP is a prevalent comorbidity associated with cannabinoid/substance use, stressing the need for access to safe CP management as a health priority for women aging with or without HIV.

Background
Goal Management Training (GMT) is a promising cognitive rehabilitation intervention that could improve adherence to lifestyle interventions.
Objective
To identify, for the first wave of participants in a novel virtual lifestyle intervention for older people living the HIV in Canada, feasibility and uptake considerations to inform the rest of the trial.
Methods
Data from participants contacted, enrolled, and persisting in the 52-week trial are reported. Participants were recruited from the Positive Brain Health Now study, a multi-site Canadian cohort of 800+ people with HIV (≥ 35 years). Enrolled participants performed the 30-second chair stand test (30CST) and set goals using a mobile application. Participants are sent weekly visual analogue scale (VAS) questionnaires and wear a Garmin Vivofit4 activity tracker to monitor step counts. Downstream outcomes include health-related quality of life (SF-36) and cognitive ability. We created a word cloud using Voyant software to describe the healthy lifestyle goals.
Results
Sixty-one participants were contacted (mean age=58.4, 75.4% male), 13 were enrolled (mean age=57.7, 61.5% male), and 11 are persisting (mean age=57.2, 63.6% male) in the trial. In comparison with participants who did not enrol or dropped out, persisting participants had better physical functioning (mean diff=15.2) and worse role-emotional (mean diff=25.7) SF-36 scores (0-100), as well as a lower proportion of male (63.6% vs 78.0%) and working participants (72.3% vs 92.0%). All enrolled participants were below age- and sex-stratified normative values for the 30CST. The most frequent words in the goal-setting word cloud included sleep (n=23), weight (n=17), fatigue (n=12), and energy (n=12). Of the 130 person measures of persisting participants, we had data on 110 of the VAS questions and step counts. GMT participants (n=7) attended an average of 5.5 of 9 sessions.
Implications
Attention needs to be paid to recruit and maintain those most in need of intervention.

People living with HIV (PLWH) have a higher risk of developing cardiovascular diseases (CVD) compared to controls. We and others have described that composition of the coronary artery atherosclerotic plaques in PLWH exhibits less calcium deposition, a feature that renders these plaques prone to rupture. However, mechanisms involved in this vulnerability are yet to be identified. Here, we investigated the impact of the multi-isoform proinflammatory cytokine IL-32 that we recently showed to be chronically upregulated and associated with CVD in PLWH, on the differentiation of monocytes to osteoblasts and osteoclasts (cells involved in calcium deposition/resorption, a mechanism involved in plaque formation/destabilization, respectively).
Primary CD14+CD16- monocytes were isolated by negative selection from HIVneg donors. IL-32 isoforms (α, β and γ) were used with/without RANKL (a typical inducer of osteoclasts) and M-CSF to stimulate monocytes for 21 days. Immunofluorescence imaging was used to analyze the differentiated cells to osteoclasts with the phenotype TRAcP+F-Actin ring+ with multiple nuclei (identified by DAPI) and osteoblasts (F-Actin ringneg osteocalcin+ with single nucleus).
In the absence of co-stimulations, IL-32γ and IL-32β alone, compared to negative controls, induced the differentiation of monocytes to osteoblasts (P=0.005). Interestingly, when either IL-32γ or IL-32β were combined with RANKL, these IL-32 isoforms counteracted the effect of RANKL and maintained their function by inducing osteoblast differentiation (p=0.028 for both), further suggesting their dominant role in osteoblastogenesis. In contrast, IL-32α significantly induced the differentiation of monocytes to osteoclasts in a similar magnitude to the positive control RANKL (P=0.02).
Our data suggest that, depending on the dominant IL-32 isoforms upregulated in the site of inflammation in PLWH, a subset of monocytes may either differentiate into osteoblasts or osteoclasts. This may potentially interfere with the calcification or decalcification/destabilization of the atherosclerotic plaques, explaining the increase in non-calcified (high-risk) atherosclerotic plaques observed in PLWH compared to controls.

Background: Non-AIDS comorbidities in people living with HIV (PLWH) on ART are associated with persisting inflammation and modification of the gut microbiota. Fecal microbiota transplantation (FMT) is used for the treatment of recurrent Clostridium difficile infections. This process consists of transferring fecal microbes from a healthy individual into another individual. FMT can be performed using colonoscopy, nasopharyngeal tubes or capsules, the latter being easier to implement and leading to a higher engraftment. Previous FMT studies in PLWH with coloscopy or capsules prepared in other countries showed transient effect on inflammation markers.

Methodology: We developed a randomized, single blind, placebo-controlled FMT study to assess the influence of microbiota modification on the leaky gut and inflammation in ART-treated PLWH with a CD4/CD8 ratio below 1 to select people with dysbiosis and higher risk of non-AIDS comorbidities. 10 participants will be recruited in each arm. All will receive a bowel cleanse to make room for the new microbiota colonization, then two rounds of FMT or placebo capsules (around 35 capsules) 3 weeks apart. Comparisons of the outcomes will be performed at two baselines to assess intraparticipant variability, and up to 12 weeks after the first treatment. In an optional substudy, gut biopsies will be collected by colonoscopy at baseline and week 12.

Hypothesis and challenges: We hypothesized that the bowel cleanse and two rounds of large FMT will increase gut beneficial microbe colonization and reduced leaky gut marker more than in the placebo group. During the implementation of the study, the donor selection process had to be updated to exclude COVID-19 and mPox positive donors with validated diagnosis tests. The study is expected to recruit in April 2023.

Conclusion: the Gutsy study will be the first study using bowel cleanse and FMT in capsules aiming at repairing gut epithelium in ART-treated PLWH.

Background
Autophagy allow production of IL21 by CD4 T-cell through degradation of cytosolic structures and energy production, allowing efficient cytolytic function of CD8. Autophagy is in part regulated by acyl-CoA-binding protein (ACBP) which has two functions depending on its localization: intracellular ACBP favors autophagy, whereas secreted extracellular ACBP inhibits autophagy. Herein, we assessed whether autophagy and the ACBP pathway were associated with COVID-19 severity.
Methods
Through the BQC-19 Quebec biobank, somalogic proteomic analysis was performed on 5200 proteins in plasma samples collected between March 2020 and December 2021. Plasma from 903 patients (all data available) during the acute phase of COVID-19 were assessed. COVID-19 severity was stratified using WHO criteria. Plasma levels of anti-SARS-CoV-2 (full spike protein or Receptor binding domain) IgG were assessed by ELISA.
Results
Median age of the cohort was 62 yo, 48% were female, 55% had comorbidities. Increasing plasma levels of ACBP were found with severity (mild, moderate, severe and fatal groups having 5.3, 7.3, 9.5 and 10.6 RFU/50µL of plasma, respectively, p<0.001 for all comparisons). Patients with comorbidities had higher plasma ACBP levels (7.4 vs 6.4 RFU/50µL, p<0.001). Plasma ACBP levels were higher during the delta and omicron-variant periods (8.4 vs 6.8 RFU/50µL; p<0.001). Plasma ACBP levels correlated with LC3II levels (r=0.51, P<0.001) and IL6 (r=0.41, p<0.001), but neither with markers IL1β nor IL8. ACBP levels negatively correlated with IL21 levels (r=-0.27, p<0.001), independently of age, sex, and severity. ACBP levels were not associated with levels of anti-SARS-CoV-2 IgG levels.
Conclusions
Plasma ACBP levels were inversely linked with IL21 levels, suggesting that autophagy and IL21 allow control of SARS-CoV-2 infection, independently of the level of SARS-CoV-2 antibody secretion. ACBP is a targetable autophagy checkpoint and its extracellular inhibition may improve SARS-CoV-2 immune control.

Background
Reemergence of HHV-8-induced Kaposi sarcoma (KS) in people living with HIV (PLWH) on antiretroviral therapy (ART) has been described. We aimed to explore immunological and virological factors involved in KS development in ART-treated PLWH compared to HIV-uninfected people with classic KS.

Method
4 groups of 11 participants were compared: 1. ART-treated PLWH with KS (KS HIV+), 2. Age-matched ART-treated PLWH without KS (HIV+), 3. HIV-uninfected patients with classic KS (KS HIV-), 4. Age-matched HIV-uninfected people without KS. We assessed circulating cytokines, anti-HHV-8 IgG levels, anti-HHV-8 specific T-cells, and circulating/skin T-cells phenotypes. HHV-8 viral loads (VL) were quantified and next-generation sequencing was performed.

Results
KS ART HIV+ were younger than KS HIV- (p<0.001). In KS HIV+, anti-HHV-8 IgG levels were higher compared to KS HIV- (p=0.02) and frequency of specific T-cells was low but similar. Circulating and tissular CD4 T-cells of both KS HIV+ and KS HIV- expressed high frequency of senescence markers (CD57+/CD28-) and PD1, higher than in controls. Among cytokines, IL-10 levels were higher only in KS HIV- (p=0.02). HHV-8 VL were lower in KS HIV+ than in KS HIV- in plasma (p=0.02) and PBMCs (p=0.04), but similar in skin biopsies. HHV-8 genetic subtypes A and C were similarly isolated in both KS groups, and a newly identified variant was found in two KS HIV- Inuit participants.

Conclusion
ART-treated PLWH with KS exhibited features of early immune senescence compared to those without KS. Despite the younger age, senescent T-cells frequency was similar among KS HIV+ compared to KS HIV-. However, anti-HHV8 IgG levels were higher in KS HIV+ compared to KS HIV-, which was associated with lower circulating HHV-8 DNA and IL-10 levels. A new HHV-8 variant was isolated in Inuit participants. Altogether, early immune senescence/exhaustion seems involved in the development of KS in ART-treated PLWH.

Background: BICSTaR is an ongoing, multinational, observational, cohort study evaluating the effectiveness and safety of B/F/TAF in antiretroviral treatment‐naïve (TN) and treatment‐experienced (TE) PLWH.

Methods: After 2 years, participants from Germany, France and Canada could remain in the study for an additional 3 years (extension phase). Pooled data through 36M, were analyzed for effectiveness (HIV-1 RNA <50 copies/mL, missing=excluded [M=E] /discontinuation=failure [D=F]), safety, SF-36v2 mental component score (MCS), and HIV Symptom Index (HIV-SI).

Results: Of 781 participants, 449 (57%) entered the extension phase (391, 177, 213 from Germany, Canada, France). Most (659) were TE. Pooled effectiveness at 36M was 97% /97% (M=E) and 76%/78% (D=F) in TN and TE, respectively. Persistence on B/F/TAF was 82% (TN) and 81% (TE). Median change in CD4 cell count/μL was +232 (TN) and +44 (TE). Canadian specific data in Table1.

Drug-related adverse events (DRAEs) and serious DRAEs occurred in 16%/0% in TN and 14%/0.3% in TE. Median weight change (Q1, Q3) was +4.3 kg (-0.5, 7.3) and +1.7 kg (-1.0, 4.3) for TN and TE. DRAEs leading to discontinuation of B/F/TAF were low, weight increase (2%), depression (1%), and fatigue (1%).

Overall bothersome symptom counts improved (median change [Q1, Q3]) in TN (-2 [-5, 0.5], p < 0.05), remaining stable in TE (0.0 [-2, 1]). SF-36 MCS improved for TN (median change [Q1, Q3]: 2.4 [-1.8, 11.1], p=0.026) and TE (1.4 [-4.0, 6.7], p=0.008).

Conclusion: B/F/TAF continued to demonstrate effectiveness and was well-tolerated through 36M follow-up with improvements in HIV-related symptom burden and MCS.

Background
People with HIV (PWH) are at high risk for metabolic dysfunction-associated fatty liver disease (MAFLD). In the general population, sex differences exist in MAFLD spectrum, with higher prevalence of MAFLD in men, but higher incidence of liver fibrosis in women. Less is known about sex differences in MAFLD in PWH.

Method
This was an international collaborative cohort including consecutive PWH. MAFLD was defined as hepatic steatosis, diagnosed by controlled attenuation parameter >270 dB/m, plus any among type 2 diabetes, BMI>25 Kg/m2 or two other metabolic abnormalities. Liver fibrosis was diagnosed as liver stiffness measurement >8 kPa. Incidence of MAFLD and liver fibrosis was assessed through survival analysis.

Results
1359 PWH (25% females, 30% HCV coinfected) were included. Prevalence of MAFLD at baseline was lower in women than in men (17.7% vs. 24.3%, p=0.013). Compared to men, women with MAFLD were more frequently of black ethnicity (48% vs. 14%; p<0.001), had lower ALT (26.4+20.4 vs. 33.4+22.5; p=0.035), higher HDL cholesterol (1.46+0.57 vs. 1.11+0.33; p<0.001), lower triglycerides (1.69+0.96 vs. 2.47+2.63; p=0.035). 485 of PWH were followed for a median of 3.5 years. Incidence of MAFLD was similar between women and men with HIV. However, incidence of liver fibrosis was higher in women compared to men (7.0 vs. 5.9 per 100 persons-year; p=0.035), particularly after 50 years of age. On multivariable Cox regression and after adjusting for age, MAFLD (adjusted hazard ratio [aHR] 3.3, 95% CI 2.0-5.6) and female sex (aHR 2.2, 95% CI 1.3-3.5) were associated with liver fibrosis while CD4 cell count was protective (aHR 0.99, 95% CI 0.99-0.99).

Conclusion
MAFLD seems a sexual dimorphic disease in PWH. Despite having lower rates of MAFLD, women have higher incidence of liver fibrosis compared to men, especially after 50 years of age. Studies should adequately consider sex differences for MAFLD in PWH.

Background
People with HIV (PWH) are at risk for metabolic dysfunction-associated fatty liver disease (MAFLD), a new definition of fatty liver not requiring the exclusion of viral hepatitis. We aimed to investigate the effect of MAFLD on liver fibrosis progression in PWH with and without viral hepatitis.

Methods
Patients with serial liver stiffness measurement (LSM) were recruited from three international cohorts. Fibrosis progression was defined as development of liver fibrosis (LSM >8kPa), or transition to cirrhosis (LSM >13kPa for those with LSM >8 but <13kPa at baseline). MAFLD was defined as hepatic steatosis (controlled attenuation parameter >248dB/m), plus any among type 2 diabetes, overweigh or two other metabolic abnormalities. A continuous-time multi-state Markov model was used to describe the process in which PWH moved through the next fibrosis state. Cox regression model was used to identify predictors of fibrosis progression.

Results
1183 PWH were included (25% with HCV, 4% with HBV). Prevalence of MAFLD and liver fibrosis was 46.8% and 14.3%, respectively. Patients were followed for a median 3.5 years. Weight gain was associated with both progression and regression of fibrosis in Markov model: odds ratio (OR)=3.11 (95% CI, 1.59-6.08) and OR=0.30 (95% CI, 0.04-2.51). The incidence rate of fibrosis progression was 3.4 per 100 persons-year, resulting in 9.6% fibrosis progressors. On multivariable analysis, predictors of fibrosis progression were MAFLD and weight gain (see Table).

Conclusion
Liver fibrosis progression occurs in a significant proportion of PWH, independently of HCV coinfection and antiretroviral exposure. Its main drivers include metabolic health variables.

Introduction: A syndemic is the clustering of social and health problems at a population level. A syndemic model aims to incorporate social and economic factors, as well as the overlap of other diseases, in understanding and describing a specific disease. Although Canada has met the 90-90-90 HIV targets, Manitoba is reporting increasing HIV cases, suggesting Manitoba’s HIV population is distinct. A syndemic model approach is needed to better understand people living with HIV (PLHIV) in Manitoba.
Objective: To describe the Manitoba HIV syndemic with a focus on substance use, houselessness, and previously diagnosed comorbidities in PLHIV in Manitoba.
Methods: A retrospective cohort study was completed. Clinical charts of all people newly diagnosed with HIV in Manitoba, Canada between January 1st, 2018 and December 31st, 2021 were reviewed.
Results: The main self-reported modes of transmission were heterosexual sex and injection drug use. Greater than 60% of women and 40% of men reported injection drug use, with methamphetamine as the primary substance. Of the new diagnoses, 42.4% were female sex. The reported sexual orientation of new diagnoses was: 75.6% heterosexual, 18.8% gay, 5.1% bisexual, 0.5% lesbian. Pre-existing medical conditions was reported by 81.7%, with mental health and sexually transmitted infections the most common. Houselessness was reported by 31%. The average CD4 count at time of diagnosis was 425.5.
Conclusions: Manitoba’s HIV population represents a new group of PLHIV, distinct from the typical HIV population of men who have sex with men. The data demonstrates an overlap of injection drug use, houselessness, and mental health comorbidities in new HIV cases, as well as increasing cases amongst females. This is Manitoba’s syndemic. A multipronged approach addressing substance use disorder, housing, and mental health supports is needed to help Manitoba’s growing, unique HIV population.

Background: The province of Saskatchewan (SK) has had the highest rates of HIV in Canada since 2009. Current rates are 16.9 per 100,000 – over 4x the national average. Cases in Saskatchewan have gone from 26 in 2002, to a total estimate of 3500 cases as of 2022. Current data reports that Saskatoon has the highest rates of HIV in the province at 28 cases per 100,000 – equating to 13x the national average. Social determinants of HIV infection in SK indicate higher rates of new infections among women, younger individuals, and Indigenous populations. Poor health outcomes are also amplified by malnutrition, unsafe housing, and barriers to accessing support services and care. Despite efforts to reach patients, numbers of those engaged along the cascade are falling, with infection rates increase and fewer patients retained in care and/or achieving viral suppression.

Objective: To provide an overview of the patient population who have not achieved HIV viral suppression to better understand barriers for the population and to inform appropriate intervention approaches.

Methods: We conducted a retrospective data analysis of active patient electronic medical records having at least one HIV-related visit between May 1, 2019 and April 30, 2022. We defined viral suppression as <200 copies/ml.

Results: The number of patients that are not retained in care, not on antiretroviral medication, and not virally suppressed between 2019-2020, 2020-2021, and 2021-2022, increased from: 20-26%, 35-38%, 42-44%, respectively. Overall men, or those identifying as male, had higher rates of non-suppression than their female counterparts. However, women aged 20-34 had the highest rates of non-suppression across the cohort.

Conclusion: This analysis offers important insights into risk factors, clinical outcomes, and demographic characteristics of the patient population who are persistently unsuppressed. Predictive factors that exacerbate the viral non-suppression require exploration as barriers to accessing care.

Background: In Saskatoon, Saskatchewan (SK), HIV care is primarily accessed at two clinical sites: (1) the Positive Living Program (PLP) located in the Royal University Hospital – an infectious disease clinic providing specialized acute care; and (2) the Westside Community Clinic (WSCC) providing inner-city primary health care and addictions support. A third model, the Wellness Wheel (WW) offers mobile medical and community-led healthcare services to on-reserve First Nation communities across SK. WW provides culturally responsive care in clinical, remote and on-reserve community settings. These models represent three unique care delivery approaches: (1) facility-based care (PLP); (2) community-based care (WSCC); and (3) rural-remote care with Indigenous communities (WW). Collectively, they care for over 2500 persons living with HIV (PLWH).

Objective: To identify the gaps in the HIV care cascade across three different clinical settings, highlighting care model effectiveness in SK.

Methods: We analyzed retrospective active patient electronic medical records from May 1, 2019 to April 30, 2022 who attended at least one HIV-related visit during that period. We defined viral suppression as <200 copies/ml.

Results: HIV rates were found to be increasing across SK, with decreasing suppression rates. The PLP cascade outcomes were lowest, with consistent 50% engagement rates. Total clients at the WSCC and WW also increased across the timepoints. Overall, WSCC had the highest patient numbers with better outcomes along the cascade, despite increases in infection rates. By comparison, the WW community-led care had the highest viral suppression rates.

Conclusions: The care gaps found in the care models offers insight into the limitations in providing HIV care to clients in SK. As rates remain well below the global targets for engagement, treatment and suppression rates, governmental support is required to ensure care capacity and approaches responds to transmission rates and the needs of the patient population.

Background: In phase 3 randomized controlled trials, dolutegravir/lamivudine (DTG/3TC) demonstrated durable efficacy in treatment-naive (GEMINI-1/-2) and suppressed-switch (TANGO, SALSA) settings. Trial eligibility criteria included no history of virologic failure (VF) or major NRTI- or INSTI-associated mutations, no hepatitis B virus (HBV) or hepatitis C virus therapy, and viral load (VL) <500,000 c/mL at screening (GEMINI) or <50 c/mL for >6 months (TANGO, SALSA). We analyzed real-world evidence (RWE) for DTG + 3TC use in people with HIV (PWH) with baseline characteristics not consistent with these inclusion criteria.

Methods: We conducted a systematic literature review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RWE studies reporting DTG + 3TC use were retrieved from Ovid MEDLINE®, Embase®, PubMed, Cochrane library, and relevant conference proceedings from January 2013 to February 2022.

Results: This review includes 122 publications from 103 studies of 44 unique cohorts (N=8034 PWH; Table). In PWH with previous VF, probability of VF at 1 year was low (0.4% or 1.2%, depending on VF criteria). In PWH with baseline resistance, VF was low (range, 0%-5.4% at ~1 year), and the difference in VF between those with or without M184V/I was not significant in 3/4 (75%) cohorts. None of the 35 PWH with HBV experienced VF, and 16/18 (89%) treatment-naive PWH with baseline VL >500,000 c/mL achieved virologic suppression at Week 24.

Conclusion: Published RWE outcomes support clinical data demonstrating the high effectiveness and barrier to resistance of DTG + 3TC in PWH with various baseline characteristics.

Background: Testosterone is an important hormone for women’s health, with abnormal levels potentially contributing to morbidity. However, current research comparing testosterone levels in women living with and without HIV is lacking. Here, we compare total testosterone levels and their association with number of comorbidities in women living with and without HIV.
Methods: Cis-gender women aged ≥16y were included. Number of select age-related comorbidities (depression/cognitive dysfunction, kidney/liver disease, diabetes, hypertension, cardiovascular/peripheral vascular disease, dyslipidemia, and osteoporosis) were assessed by self-report, validated scales, and medication usage. Plasma total testosterone levels were assayed by ELISA and normalized by log-transformation. Groups were compared by Mann-Whitney or Chi-square tests. Multivariable Poisson and linear regression models assessed variables associated with number of comorbidities and log-transformed testosterone levels, respectively (Table 1).
Results: Participants (n=223) are described in Table 1. Women living with HIV had lower testosterone levels than HIV-negative women. Older age (Prevalence Ratio, PR [95% CI]=1.02 [1.01 to 1.03]; p<0.0001) and past substance use (PR=1.31 [1.03 to 1.65]; p=0.03) were associated with greater number of comorbidities, while HIV and testosterone levels were not. HIV (-11.1 (-18.7 to -2.83)%) and older age (-0.75 (-1.06 to -0.43)%) were independently associated with lower testosterone, whereas ever having hepatitis C virus was associated with higher levels (16.8 (3.31 to 31.0)%).
Conclusion: We observed lower testosterone levels in women living with HIV than HIV-negative women, independent of confounders. Lower testosterone was not associated with having more comorbidities. These findings emphasize the need to investigate the impacts of testosterone on women’s health.

Background: Integrase strand transfer inhibitor-based regimens have become the standard of care for HIV post-exposure prophylaxis (PEP), but no such single tablet regimens are recommended in current Canadian guidelines.
Methods: We analyzed the tolerability of and adherence to bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) as HIV PEP in an ongoing clinical trial of text-messaging support for PEP patients. Adults initiating PEP within the preceding five days for a confirmed or potential sexual exposure to HIV were randomized to either receive short message service (SMS) check-ins using the WelTel platform, or standard care. At randomization, all participants were switched to B/F/TAF to complete 28 days. CBC, ALT and creatinine were assessed at week 2; HIV status at weeks 6 and 12; and adverse events at all visits. We report preliminary results from the week 4 assessment.
Results: 85 participants have been enrolled to date, of whom 81 have completed the week 4 visit and are included in this analysis. Median (interquartile range) age was 29.9 (26.2, 34.5) years. Most (96.3%) were assigned male sex at birth and 23.5% had previously used PEP. At week 4, 84.2% of participants reported completing 28 days of PEP. B/F/TAF was well tolerated, with only 10% experiencing adverse events of grade ≥2 severity (Table). There were no laboratory abnormalities deemed at least probably related to study drug.
Conclusions: We observed excellent tolerability and adherence with B/F/TAF as HIV PEP. These data support the use of this single tablet regimen as PEP after sexual exposures.

Background: Ritonavir-boosted darunavir (DRV/r) is a preferred protease inhibitor in pregnant women living with HIV (WLWH). Current practice at British Columbia’s referral centre (the Oak Tree Clinic) is to dose DRV/r as 800/100 mg daily throughout pregnancy, although guidelines recommend DRV/r 600/100 mg twice daily due to altered pharmacokinetics with once daily dosing.

Objectives: We describe the effect of once daily DRV/r on viral suppression, perinatal HIV transmission, adverse drug effects and adherence in pregnant WLWH.

Methods: This was a retrospective analysis of pregnant WLWH in British Columbia (BC). Eligible patients gave birth between January 2015 and August 2021, and took DRV/r 800/100 mg daily at any time during pregnancy.

Results: Thirty-four patients were included in this study. The mean age was 33 years (SD = 5). Thirty (88%) patients were diagnosed with HIV prior to pregnancy, with 22 (73%) having viral suppression at baseline. Four (12%) patients were diagnosed in pregnancy, with a median baseline viral load of 9,616 copies/mL (range 8,370 – 165,000 copies/mL). Viral suppression was achieved by 16 (100%), 24 (75%), and 26 (74%) patients in first, second, and third trimester, respectively. No perinatal HIV transmission occurred. This regimen was well-tolerated, with adverse drug effects that did not result in discontinuation or change in therapy. The majority of patients maintained at least 75% adherence to once daily DRV/r at all times during pregnancy.

Conclusions: DRV/r 800/100 mg daily appears to be an appropriate dosing strategy for pregnant WLWH who are able to maintain optimal adherence.

PURPOSE:Online forms of community-based exercise (CBE) may help to manage disability experienced by adults living with HIV during the COVID-19 pandemic. Our aim was to describe characteristics of adults living with HIV who engaged in a six-month online CBE intervention and their participation in the intervention.
METHODS:We conducted a longitudinal intervention study with adults living with HIV in Toronto who considered themselves safe to engage in exercise between October 2021 and December 2022. Participants engaged in a 6-month online CBE intervention involving a) exercise thrice weekly, b) personalized online coaching sessions with a trainer biweekly, and c) online group educational sessions monthly, using d) home exercise equipment, e) an exercise app and f) wireless physical activity monitor. We documented loss to follow-up and reasons for withdrawal. We characterized participants using descriptive statistics. We assessed biweekly coaching session adherence and reasons for missed sessions using a trainer-completed log.
RESULTS:Of 33 participants who enrolled in the study, 32(97%) initiated the intervention. Most (69%) were men (n=22/32), median age of 53 years (interquartile range[IQR]:43,60), and median of 3 concurrent non-HIV health conditions (IQR:1,7). Twenty-two (69%) participants(n=22/32) completed the intervention. Reasons for non-completion (n=10 participants) were: busy schedule (4 participants); unknown (4 participants); episodic health issues (1 participant); and dissatisfaction with the study (1 participant). Participants (n=32) attended a median of 11 out of 13 (IQR:6,12) biweekly online coaching sessions. Ten of the 32 participants (31%) extended their coaching sessions beyond 6 months due to scheduling issues (holiday break, trainer-participant scheduling conflicts)(6 participants), and/or missed session(s) for unknown reasons (4 participants), or for health reasons (2 participants).
CONCLUSION:Most (69%) participants who initiated, completed the online CBE intervention. Factors that influenced retention and adherence to the online coaching sessions highlight the potential episodic health with HIV, and factors influencing implementation to address in future research.

BACKGROUND: Post-exposure prophylaxis (PEP) is an effective HIV prevention tool involving 28 days of antiretroviral medications taken within 72 hours of suspected high-risk HIV exposure. We conducted a systematic review of PEP clinical trials and cohort studies to inform a forthcoming update to Canadian PEP guidelines.

METHODS: We searched MEDLINE, EMBASE, and CINAHL for PEP clinical trials and cohort studies published July 2017-July 2022 reporting on at least one of: PEP completion, adverse events (AEs) leading to discontinuation, and/or HIV seroconversion. Abstracts were screened by two independent reviewers via Covidence. Articles that fit eligibility criteria underwent full-text review and data extraction onto standardized electronic forms.

RESULTS: We identified 5081 abstracts, of which 568 were duplicates and 4513 were screened. 74 articles underwent full-text review; 15 met eligibility criteria, including 1 randomized trial (n=157), 7 prospective cohort studies (n=2617), and 7 retrospective cohort studies (n=20975). Exposure types included sexual (n=13 studies) and non-sexual/parenteral (n=5 studies) exposures. Regimens including tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) or tenofovir alafenamide/emtricitabine (TAF/FTC) backbones generally had higher completion rates and fewer AEs compared to regimens with zidovudine/lamivudine (AZT/3TC). Regimens containing rilpivirine (RPV, n=2 studies), raltegravir (RAL, n=4), elvitegravir/cobicistat (EVG/c, n=6), dolutegravir (DTG, n=3) or bictegravir (BIC, n=1) generally showed higher completion rates and/or fewer AEs compared to atazanavir or lopinavir/ritonavir (LPV/r). One study demonstrated high completion rates with long-acting intravenous albuvirtide-containing regimens. AEs were most commonly reported in TDF/FTC or AZT/3TC regimens with LPV/r. Only 3 cases of seroconversion were reported out of all studies; one case involved early PEP discontinuation, and two cases involved multiple HIV exposures after starting PEP.

CONCLUSION: Newer PEP regimens containing TAF/FTC or TDF/FTC backbones and RAL, RPV, ELV/c, DTG, BIC, and long-acting intravenous albuvirtide are associated with high completion rates and minimal side effects. Findings will support decision-making when updating Canadian guidelines.

INTRODUCTION
Cervical cancer is the most common cancer among women living with HIV, with recent research citing a six-fold higher risk of developing cervical cancer in this population. Screening programs (i.e. Pap tests) reduce the incidence of cervical cancer. Refugees often have a higher prevalence of abnormal Pap tests and a greater cervical cancer risk due to immunocompromise from a disproportionate HIV burden, limited screening, and/or higher HPV infection rates. Most refugees in Canada have never had cervical cancer screening, despite having Interim Federal Health Program (IFHP) coverage. Our study aims to compare the grade of cervical dysplasia by histology at the initial colposcopy clinic visit between patients billing through IFHP as a proxy for refugee status and through Ontario Health Insurance Plan (OHIP). We hypothesize that refugees present with a higher grade of dysplasia compared to Ontario residents.

METHODS
Following REB approval, a multi-center, retrospective review of all IFHP patients presenting to their first colposcopy clinic at two academic urban centres between Jan. 2015 and Apr. 2020 was conducted. Each IFHP patient meeting inclusion criteria was age-matched to two OHIP patients meeting inclusion criteria (N=154; 52 IFHP, 104 OHIP).

RESULTS
Approximately one-third (30.7%, n=16) of IFHP patients were living with HIV. Histologically, IFHP patients were significantly more likely to have a biopsy result showing HSIL or LSIL compared to OHIP patients (χ^2=13.43, p<0.01). OHIP patients are significantly more likely than IFHP patients to have had at least 1 dose of an HPV-vaccine as opposed to no recorded immunization (28% vs 2%, χ^2=15.42, p<0.001).

CONCLUSIONS
IFHP patients are significantly more likely to have higher grade histology results and less likely to have at least one dose of an HPV vaccine. Our findings signify the importance of advocating for primary (HPV vaccination) and secondary prevention (screening) for refugees living in Ontario.

Purpose: The present study investigated working memory, an aspect of executive functioning, in children who are HIV-exposed uninfected (CHEU) and children who are HIV-unexposed uninfected (CHUU).

Methods: CHEU and CHUU 6 to 10 years of age underwent developmental assessments through the Kids Imaging and Neurocognitive Development (KIND) study at the Hospital for Sick Children. Two working memory subtest scores (digit and picture span) and Full-Scale IQ (FSIQ) were evaluated with the Wechsler Intelligence Scale for Children – Fifth Edition (WISC). A spatial working memory (SWM) task was administered using the Cambridge Neuropsychological Testing Automated Battery (CANTAB). Five SWM measures were obtained, which included the number of incorrect decisions within four trials of increasing difficulty (cognitive load) and a search strategy score. Group differences and analyses with age were evaluated. Significance was held at p <0.05.

Results: Forty CHEU (23 female, 8.61 ±1.56 years) and 28 CHUU (11 female, 8.69 ±1.52 years) were included. There were no between-group differences in FSIQ. The digit span subtest was lower in the CHEU (p=0.048) compared to CHUU, but not the picture span subtest or SWM measures. Older age was related to better decision performance on two trials with the highest cognitive load (p=0.032 and p<0.01, respectively) across groups. When the groups were separated, older age was significantly related to better decision performance on the highest cognitive load trial (p <0.01) only in the CHEU group.

Conclusions: In this preliminary analysis, the CHEU demonstrated lower verbal working memory scores than CHUU on assessment measures. On the SWM task, the CHEU demonstrated age-related performance on the highest difficulty trial, possibly indicating protracted development of more complex non-verbal working memory abilities compared to CHUU. These results suggest a vulnerability in working memory abilities, and further research on other aspects of executive functioning is needed.

Background: Gay, bisexual, and other sexual minority men (GBM) report high rates of sexual minority stress and alcohol misuse, but findings regarding their relationship are inconsistent. Inconsistent findings may be attributed to the differential impact of minority stress on alcohol misuse among GBM living with HIV versus HIV-negative GBM.

Method: We analyzed the baseline data of 2,449 GBM from Engage, a study of sexually active GBM recruited (02/2017-08/2019) using respondent-driven-sampling (RDS) in Montreal, Toronto, and Vancouver. Sexual minority stress was measured using the Lesbian, Gay, and Bisexual Identity (LGBI) and the Heterosexist Harassment, Rejection, and Discrimination (HHRD) scales. Alcohol misuse was measured using the Alcohol Use Disorders Identification Test-Concise (AUDIT-C), with scores ≥ 4 indicating a positive screen for alcohol misuse. We used multiple logistic regression to model associations between sexual minority stress and alcohol misuse, and whether HIV serostatus moderated this relationship. RDS-adjusted analyses controlled for age, income, sexual orientation, ethnicity, and city.

Results: HIV serostatus moderated only the association between heterosexist harassment and alcohol misuse, β = .36, 95% CI [.04, .69], p = .03. The odds of alcohol misuse increased by 45% for every one unit increase in heterosexist harassment among GBM living with HIV, OR = 1.45, 95% CI [1.08, 1.95], p = .01, but not among HIV-negative GBM, OR = 1.01, 95% CI [.89, 1.15], p = .83.

Discussion: GBM living with HIV had 45% greater odds than HIV-negative GBM to screen positive for alcohol misuse related to increases in experiences of heterosexist harassment. It is possible that other stressors unique to people living with HIV, particularly HIV stigma, are contributing to their increased risk for alcohol misuse. Future mental health research with GBM may wish to stratify by HIV serostatus to examine differences in risk factors for alcohol misuse.