Objective: Orthopaedic surgery is essential to populations worldwide. Due to reduced CD4 counts, HIV+ patients may be at an increased risk of infection by perioperative pathogens. However, the risk of surgical site infection (SSI), and the effect of an extended antibiotic course on reducing postoperative infections in this population, remains unclear. Therefore, we systematically reviewed the literature in order to describe the influence of HIV status on the risk of developing SSIs after orthopaedic surgery, and to determine if such risk is altered by an antibiotic course.

Methods: Searches were conducted in five different databases. Articles that included HIV+ patients who underwent clean implant orthopaedic surgery, and provided a description of clinical outcomes, were eligible. The following data was extracted: patient sex, age, HIV status (+/-), type of orthopaedic procedure, follow-up period, presence of postoperative SSIs, and type of antibiotic course.

Results: Searches generated 1,440 articles, with 22 of those articles being eligible for review. There were 2,616 patients included, 78.9% of whom were male. Mean patient age was 39.4 years (SD = 5.9). Prior to surgery, 23.9% of patients were HIV+. Knee and hip arthroplasty were the most common procedures, and the mean follow-up period was 51.2 months (SD = 41.0). 14.5% of HIV+ patients and 7.8% of HIV- patients developed postoperative SSIs. The most frequent antibiotic course was a second- or third-generation cephalosporin regimen dosed once preoperatively and three times postoperatively.

Conclusion: HIV-positivity has been shown to increase the risk of SSI after clean implant orthopaedic surgery. Unfortunately, the effect of a prolonged antibiotic course on reducing infection risk is inconclusive. Our findings emphasize the need for subsequent studies to analyze infection rates based on CD4 counts and to compare antibiotic regimens for the purpose of developing safe orthopaedic surgical protocols for HIV patients.

Background:
HIV pre-exposure prophylaxis (PrEP) is recommended for populations at high ongoing risk of infection. Research evidence shows that PrEP acceptance in Toronto among Blacks at risk of HIV is particularly low. Previous studies to optimize use of PrEP has focused on adherence, without consideration for the decision-making process required for adoption of PrEP as HIV preventive measure. This study examined the decision conflict and the decision support needs of Black patients that were offered PrEP for HIV prevention.
Methods:
The Ottawa Decision Support Framework (ODSF) was used to guide the development of a key informant guide used for qualitative data collection. Black patients assessed by healthcare providers as meeting the basic criteria for starting PrEP were recruited through the St. Michael’s Hospital Academic Family Health Team and clinical and community agencies in Toronto. Participants were interviewed by trained research staff. Qualitative content analysis was guided by the ODSF, and analysis was done using the Nvivo.
Results:
Twenty-nine women and men (including men who have sex with men) were interviewed. Participants reported having difficulty in decision making regarding adoption of PrEP. The main reasons for decision-conflict regading PrEP adoption were: lack of adequate information about PrEP, concerns about the side effects of PrEP, inability to ascertain the benefits or risk of taking PrEP, provider’s lack of adequate time for interaction during clinical consultation, and perceived pressure from healthcare provider. Participants identified detailed information about PrEP, and the ability to clarify how their values align with the risks and side effects of PrEP as their decision support needs.
Conclusion:
PrEP-eligible Black patients that are prescribed PrEP have decision conflict. A decision support tool that incorporates the decision support needs of Black patients will reduce decision conflict and improve the decision making process for adoption of PrEP for HIV prevention.

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Background :
COVID-19 has disrupted the lifestyle of PWUD. To understand the effects of the pandemic on their overall wellbeing, and to improve response to the crisis, engaging with PWUD and hearing their stories is important. «Nothing about us, without us” is branded by advocacy groups and evidence shows the value of involving PWLE in research, substance use program, service, and policy development.

Objective:
To assess the challenges of PWUD, during the second wave of the pandemic, 150 PWUD in Montreal were to be recruited in 15 weeks for phone interviews (September-December 2020), amidst restrictive public health measures.

Recruitment strategies:
1) Contacting PWUD from a cohort study contact list (phone, email, post; passive recruitment in 3 community resources).
When this failed to yield recruitment objectives, a research assistant with lived experience (RAWLE) was mandated to intervene which led to:
2) Optimizing and tailoring recruitment products and 23 added resources, based on RAWLE’S first-hand knowledge and experience.
3) Facilitating access to phone interviews by having RALWE on site with a research-issued cell phone.
4) Offering in-person interview option.

Results:
Strategy 1: 6 interviews from Sept. 7-28
Strategies 1 and 2: 6 interviews from Sept. 29-Nov 1
Strategies 1, 2 and 3: 38 interviews from Nov 2-24
Strategies 2, 3 and 4: 77 interviews from Nov 25-Dec 18

Completed interviews = 128; Targeted N: 150.

Although we missed our target, the exponential growth of interviews after integrating a RAWLE in the recruitment strategies was significant. It required applying for an ethics amendment allowing in-person data collection, executing IPE protocols, training the RAWLE to be an interviewer.

Conclusion:
Involving a RAWLE was the key to increasing weekly recruitment targets by 12 in a restricted context, contributing to the arguments for the implication of PWLE in research on substance use with PWUD.

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Introduction: The newer generation of non-nucleoside reverse transcriptase inhibitors (NNRTIs), doravirine and rilpivirine, demonstrate high potency and can overcome resistance caused by K103N, Y181C and G190A point mutations, Phase 2 trials showed that the doravirine, combined with islatravir, the first nucleoside reverse transcriptase translocation inhibitor, maintained viral suppression through 96 weeks. Here, we performed in vitro drug selections to compare the drug resistance profiles of doravirine, alone & paired with lamivudine (3TC) or islatravir.

Methods: Subtype B (n=4) and non-B subtype (n=3) clinical isolates were passaged in cord blood mononuclear cells with progressively increasing concentrations of doravirine, doravirine + islatravir, doravirine + 3TC, rilpivirine, rilpivirine + islatravir, and rilpivirine + 3TC. Genotypic analysis monitored the acquisition and accumulation of drug resistance mutations at weeks 8 and 24 following selective drug pressure. Cell-based phenotypic assays assessed levels of cross-resistance conferred by acquired resistance mutations.

Results: Doravirine pressure resulted in the acquisition of V108I (6/7) and V106A/I/M (5/7) mutations at weeks 8, followed by F227L (4/7), Y318F (4/7), M230L (2/7) and L234I (2/7) by weeks 24. In contrast, rilpivirine favoured the appearance of E138K (5/7), L100I (3/7) and.M230L (1/7). Doravirine-resistant variants retained sensitivity to rilpivirine and etravirine, whereas rilpivirine-resistant variants showed intermediate resistance (12-152-fold) to doravirine. There was a delay and diminution in the emergence of resistance when doravirine was combined with islatravir or 3TC. At 24 weeks, the V108I mutation (9/15) prevailed with fewer or no other changes. There was a lesser delay in emergent resistance to rilpivirine when combined islatravir or lamivudine selections. The M184I/V mutation, conferring islatravir and lamivudine resistance, rarely occurred in dual (2/28) selections.

Conclusion: Doravirine showed a more robust resistance profile compared to other NNRTIs. The high potency and long intracellular half-life of islatravir, provide the opportunity for long-acting and low dosing treatment options.

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The DISCOVER trial randomized men who have sex with men and transgender women at risk for HIV to receive blinded daily emtricitabine plus tenofovir alafenamide (F/TAF) or tenofovir disoproxil fumarate (F/TDF) for HIV pre-exposure prophylaxis (PrEP) for at least 96 weeks. DISCOVER included participants already taking F/TDF for PrEP at baseline (BL), creating a unique opportunity to investigate estimated glomerular filtration rate (eGFR), markers of renal proximal tubular function (RBP and β2M to creatinine ratios), and fasting cholesterol levels and bone mineral density (BMD).

905/5387 (16.8%) participants were on BL F/TDF for PrEP for a median duration of 399 days. HIV incidence was low in participants taking BL PrEP. There was one HIV infection among BL PrEP users, in a participant randomized to F/TDF who had intermittent low adherence.

Participants on BL PrEP randomized to F/TAF had improvements in eGFR and markers of proximal tubular function compared to F/TDF. Median change in BMD was not statistically different for BL PrEP users assigned to F/TAF vs F/TDF, however de novo F/TAF participants had improved BMD profiles compared to F/TDF. BL PrEP users in the F/TAF arm had increases in LDL cholesterol (median +6mg/dL) compared to F/TDF, while changes in HDL and total:HDL ratio were similar. Lipid-modifying agent (LMA) initiation in BL PrEP users was more frequent in the F/TAF arm, while LMA initiation in de novo PrEP participants was similar between arms.

Participants who switched from F/TDF to F/TAF had improvements in renal biomarkers and there was no difference in BMD among BL PrEP users. The observed lipid changes in BL PrEP users are consistent with the LDL and HDL suppressive effect of TDF, and the small but higher rate of LMA initiation with F/TAF is likely related to withdrawal of this effect.

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Background:
Limited data is available concerning the impact of pregnancy on raltegravir (RAL) plasma concentrations. Furthermore, the relevance of therapeutic drug monitoring (TDM) for pregnant women is not demonstrated. This study aims to describe RAL minimum concentrations (Cmin). during pregnancy and their clinical significance, and to review the impact of RAL TDM during pregnancy on the management of HIV care.

Methods:
In the prospective cohort of the Mother and Children’s Infectious Diseases Center (Quebec, Canada), pregnant women living with HIV who used RAL at any time during their pregnancy between January 2011 and August 2020 were selected. RAL Cmin were assessed by liquid chromatography / tandem mass spectrometry. Undetectable viral load was set to < 50 HIV RNA copies/mL.

Results:
We analyzed 76 pregnancies of which 47 underwent TDM. In this subgroup, we observed a significant difference in the distribution of RAL Cmin between the women with a detectable or undetectable viral load (p=0.025). A new RAL Cmin target of 0.032 mg/L showed the best area under the curve for undetectable viral load (specificity: 81%, sensitivity: 75 %, AUC: 0.819, p=0.037). No significant differences were observed between Cmin at each trimester or compared with a non-pregnant state. When comparing pregnancies with and without TDM, there was no statistical difference in the rate of viral suppression during pregnancy nor with the prescription of a prophylaxis antiretroviral triple therapy in newborns.

Conclusions:
The RAL Cmin target of 0.032 mg/L should be confirmed. The impact of TDM monitoring could not be demonstrated.

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Background:
While major integrase strand transfer inhibitor (INSTI) resistance mutations have been identified, the effect of mutation combinations is less clear. We identified a clinical HIV sequence with four major integrase resistance mutations, and characterized in vitro INSTI phenotypic susceptibility of all combinations thereof to deconstruct their individual and combined effects.
Methods:
Routine clinical testing identified an integrase sequence harboring T97A, E138K, G140S and Q148H. We constructed chimeric NL4-3 viruses harboring i) all possible combinations of 0- to 4-mutations in the autologous integrase backbone, and ii) NL4-3 with all four mutations. Chimeric viruses were grown in reporter CD4+ T-cells in the presence of 0.01-1,000nM raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG), cabotegravir (CAB), and bictegravir (BIC), where infection was measured by imaging cytometry.
Results:
Viruses engineered with Q148H without G140S either failed to propagate, or propagated only after in vitro mutation. In the autologous viral backbone, T97A, E138K, or G140S alone conferred 2.4 to 15.4-fold decreased susceptibility to EVG but not to other INSTI. Two-mutation combinations conferred low to moderate resistance, except G140S/Q148H which eliminated RAL and EVG activity and conferred 8.3-, 50.9-, and 3.1-fold reduced susceptibility to DTG, CAB, and BIC respectively. Addition of E138K to G140S/Q148H conferred 12.1-, 98.6- and 4.6-fold reduced susceptibility to DTG, CAB, and BIC respectively, while addition of T97A to G140S/Q148H reduced susceptibility by >100, >100 and 47.7-fold. The T97A/E138K/G140S/Q148H clinical sequence displayed >100-fold reduced susceptibility to all INSTIs. The quadruple NL4.3 mutant displayed >100-fold reduced susceptibility to RAL, EVG and CAB but only 66.2-, and 8.2-fold less to DTG, and BIC respectively, while the clinical revertant retained 2.8-fold decreased susceptibility to EVG. Measured EC50s correlated strongly with Stanford HIVdB resistance scores (Spearman r>0.87; p<0.0001 for all INSTIs).
Conclusion:
High-level resistance to DTG, CAB and BIC requires multiple integrase substitutions including compensatory mutations.

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BACKGROUND
We hypothesized that prior syphilis would be associated with worse neurocognitive outcomes among HIV+ adults.

METHODS
We performed a retrospective analysis of adults enrolled in the OHTN Cohort Study between 2008-2017. Neurocognitive measures included: 1) MOS-HIV 4-item scale; 2) average T-score (ATS) using complex attention, speed of processing, and learning/memory data; 3) global deficit score (GDS) dichotomized into impaired/unimpaired. Prior syphilis was determined through chart review/lab data while number of episodes used lab data. We compared the most recent MOS-HIV and ATS among those with/without syphilis using Wilcoxon rank-sum tests, and the proportion impaired on GDS using Chi-Square/Fisher tests. Multivariable models were adjusted for age, education, race, income, years of HIV, nadir and most recent CD4 count, most recent viral load, methamphetamine use, depression, and number of prior neurocognitive tests performed.

RESULTS
Of 1434 participants, 228 had prior syphilis. Median age was 47(IQR: 37,54), 76.4% were male, median CD4 count was 517.5 (IQR: 360,678) cells/mm3, and 80.2% had HIV viral load <50 copies/mL. Median lab-confirmed episodes in the syphilis group was 1 (IQR: 0,1). There was no significant difference in median MOS-HIV (85 vs. 80, p=0.58), median ATS (45.8 vs. 45.8, p=0.87), or the proportion with neurocognitive impairment on GDS (53.0% vs. 51.9%, p=0.87), between syphilis and non-syphilis groups. Multivariable models found no significant relationship between syphilis or the number of episodes of syphilis and the neurocognitive outcomes (Table).

CONCLUSION
Among HIV+ adults in care, there was no association between prior syphilis/number of episodes of syphilis and neurocognitive outcomes.

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Background: Compared to HIV-uninfected individuals, people living with HIV (PLWH) may be expected to have increased risk of developing symptomatic or severe COVID-19 disease due to underlying immunodeficiency. We characterized PLWH followed at a tertiary care clinic in Montreal who acquired COVID-19 and described their outcome during the first wave of the pandemic.

Methods: A retrospective chart review was performed for PLWH followed at the Chronic Viral Illness Service (CVIS) clinic with a positive COVID-19 nasopharyngeal PCR or symptoms suggestive of COVID-19 between March and June 2020. Data on demographics, socioeconomic status, co-morbidities, severity of COVID-19 and outcomes were extracted.

Results: Of 1702 individuals, 27 (1.6%) presented with a positive COVID-19 test (n=24) or symptoms suspicious for COVID-19 (n=3). Median age was 51 years [IQR 39, 58], 14(52%) were black, 9 (33%) had hypertension and 25 (93%) had been prescribed combined antiretroviral therapy. Most individuals (96%) earned $35000 dollars or less annually. Nine (35%) individuals worked in long-term care (LTC) homes while 3 (7%) lived in LTC homes and 4 (15%) were homeless. Median CD4 count was 596 cells/mm3 [342, 811] and 5 had detectable plasma HIV viral loads. Four persons were asymptomatic and most symptomatic individuals (86%) had mild disease.

Conclusion: As has been observed in the general population, PLWH attending the CVIS with COVID-19 had lower socioeconomic status and had employment or living conditions that put them at high risk for infection. Rather than stage of HIV infection, social determinants of health seem to have been a principal factor predisposing PLWH to COVID-19 during this first wave. Work is ongoing to identify additional cases of COVID-19 which may not have been captured during wave 1 due to lost patient contact, in addition to subsequent cases of COVID-19 during waves 2 and 3 of the pandemic.

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Background: Both HIV and ART affect mitochondrial DNA (mtDNA) which may contribute to high rates of preterm birth (PTB) among women living with HIV (WLWH). The causes of PTB remain poorly understood, but hypoxia, oxidative stress, and impaired placenta mitochondrial function are believed to play a role. Factors such as maternal smoking and older age, both associated with risk of PTB, have also been associated with increased mtDNA mutation burden in blood cells. The objective of this pilot study was to explore associations between placenta mtDNA mutation burden and maternal HIV status, smoking, age, or PTB.

Methods: Placenta tissue specimens were obtained from two cohorts of pregnant women: Children & Women AntiRetroviral therapy and Markers of Aging (CARMA-PREG), and the Pregnancy Study. Specimens selected included 37 WLWH (13/37 PTB) and 27 HIV-negative controls (10/27 PTB). A 264bp region of the mitochondrial D-loop was sequenced using molecular barcoding to detect rare substitutions; mtDNA mutation burden was expressed as substitutions per 10kb and analyzed using Mann Whitney or Spearman’s correlation test.

Results: Univariately, increased placenta mtDNA mutation burden was associated with older maternal age and with smoking throughout pregnancy, although the latter was mitigated in women who quit smoking during pregnancy. No significant associations was detected with HIV status or PTB, however, a signal toward higher placenta mtDNA mutation burden among WLWH emerged in a sub-analysis restricted to the 252/264 fully conserved positions of the 64 mtDNA sequences.

Conclusions: This study suggests that older age, smoking, and HIV may be associated with increased placenta mtDNA mutations. Although all three factors are associated with increased risk of PTB, we failed to detect an association between PTB and mtDNA mutations. A larger study is needed to confirm independent associations, including with other pregnancy complications, and to investigate possible associations with ART.

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Abstract
There is a growing consensus that COVID-19 disproportionately affects vulnerable communities in Canada characterised by lower socioeconomic standing, recent immigration, as well neighbourhood factors. There is no socio-demographic information on COVID-19 infections at neighbourhood level in Canada.
Objectives: To explore the sociodemographic characteristics associated with higher numbers of COVID-19 cases at neighbourhood level in Ottawa guided by social determinants of health framework.
Methodology: Outcome variable of the total number of COVID-19 cases were extracted from a publicly available Ottawa Neighbourhood study (ONS). Explanatory variables included demographic (median age, population density, percentage of single parent family), socioeconomic (percentage of population with no high school diploma, speaks neither English nor French, recently immigrant, percentage of refugee population, percentage of black population), and neighbourhood level factors (perceived walkability score, percent of population living within 50m walking distance to healthcare centres). Data were analysed using linear regression methods.
Results: The neighbourhoods with relatively higher number of total COVID-19 cases were Hunt Club, Hintonburg, and Hawthorne Meadows. According to the findings, higher percentage of: newcomers (β=0.12, 95%CI=0.01-0.23), population aged 65 years and above (β=0.08, 95%CI=0.02,0.16), population density (β=0.12, 95%CI= 0.01-0.23) showed positive association with higher number of cases, while percentage of population living within 50m walking distance to healthcare centres (β=-0.19, 95%CI=-0.36, -0.03) showed an inverse association.
Conclusion: Higher proportion of newcomers, senior residents, and higher population density are significant risk factors of higher COVID-19 cases, and living within 50m of walking distance to the nearest health facility appeared to be a protective factor. It is important to note that and there is serious data gap on COVID-19 at neighbourhood level in most Canadian cities. This is an imperative for policy priority.
Key words: COVID-19 cases, socioeconomic risk factors, neighbourhood study, Ottawa.

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Background:
Persons living with HIV-1 (PLWH) who achieve viral suppression (VS) on ART may experience viral blips (VB) or low-level viremia (LLV). We described a cohort of individuals who achieved VS and subsequently developed VB or LLV and factors associated to VB.
Methods:
ART-naïve adults ≥19 years who commenced ART in British Columbia between January 1st 2010 and December 31st 2018 and achieved durable VS (3 consecutive plasma viral loads (pVL)<40 c/ml) with a minimum follow-up period of 12 months were included. VB was defined as an isolated pVL between 40 to 1000 c/ml returning to pVL <40 c/ml within 3 months, while LLV included those with persistent detectable pVL below 1000 c/ml. Multivariable Cox proportional hazard models adjusting for demographic and clinical variables, including ART were used to model the hazard of experiencing VB.
Results:
Of 2405 participants, 84% were male. At baseline median age was 41 years (Q1-Q3:32-49), CD4 count 360 cells/μL (Q1-Q3:219-540) pVL 4.73 log10 copies/mL (Q1-Q3:4.2-5.0), and 10% had ART resistance. During the study period 1507(63%) maintained VS, 322 (13%) had VB, 381 (16%) had LLV, 132 (5%) had viral failure and 63 (3%) lost to follow-up. The incidence rate for VB was 5.62 per 100 person years (95% CI:5.06-6.22). Only 4% of participants with VB and 2% with LLV experienced subsequent virologic failure. Factors associated with increased risk of VB included higher baseline pVL, (adjusted HR 2.38 [95% CI:1.75-3.24]) and longer time to VS, (adjusted HR 1.03 [95% CI:1.01-1.05]). ART was not associated with increased risk of VB.
Discussion:
This cohort of ART-naïve individuals who achieved VS had low incidence of viral blips that were associated with higher baseline pVL and longer time to VS. Subsequent virologic failure in individuals with VB or LLV was infrequently observed.

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Background: People ageing with HIV now face both HIV- and age-related health challenges with frailty being one of these concerns. Fried’s Frailty Phenotype (FFP) is the predominant way of defining frailty based on meeting 3/5 criteria: weight loss, slow gait speed, week grip strength, exhaustion, and low physical activity. The pattern among these criteria may suggest different frailty phenotypes with potentially different causes and therefore different treatment approaches
Objectives: The purpose is to identify whether different frailty profiles emerge from five criteria of FFP and factors associated with emergent profiles.
Methods: Positive Brain Health Now cohort (n=856) was the data source. Item patterns of FFP were analyzed using latent class analysis. The main outcome was frailty profiles derived from self-report items were matching the original 5 criteria: BMI<21, exhaustion, low physical activity, limitation in walking several blocks and in lifting and carrying. The effects of explanatory variables, sex, pain, numbness, mood, CRP, CD4-count, and co-morbidities were estimated using multinominal regression yielding odds ratios (OR) and 95% confidence intervals.
Results: Five profiles emerged: (A) low physical activity (62%), (B)-fatigue (14%), (C) arm/not leg weakness (11%), (D) arm and leg weakness (5%); and (E) global frailty (8%). People in profiles (C,D,E), 24%, would be classified as frail (3 items). In comparison to profile A, a typical aging profile, the three frailty profiles (C,D,E) were explained by: pain (OR-range:6.1-10.8), numbness (OR-range:3.0-6.2), anxiety/depression (OR-range:3.0-3.3), arthritis (OR-range:2.3-4.1), and thyroid (OR-range:2.7-6.7).
Conclusion: People meet frailty criteria through different impairment profiles. Research data cannot determine whether the person is frail or whether their co-morbidities and impairments are the reasons for meeting the criteria to determine frailty. Frailty is considered something that has to been seen to be believed and a simple classification method may not be sufficient to quantify frailty for research purposes.

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Background: Deaths attributable to drug abuse are on the rise across Canada with more than 17,602 opioid-related deaths in 2020. Dispensing take-home naloxone (THN) and initiating opioid agonist treatment (OAT) can help prevent overdose, including programs for ED patients who are at risk for opioid overdose (ROO). In 2018, a multidisciplinary group of clinical experts set goals to implement a clinical algorithm for dispensing THN and prescribing buprenorphine/naloxone (B/n) for at ROO patients in 3 Québec EDs: SuboxED project.
Methods: This project had two phases i) implementation process and ii) evaluation process. The first phase named an expert group, identified 3 EDs, OAT, and pharmacy partnerships, and developed training tools and the ED algorithm. In phase 2, we performed a retrospective review of ED electronic medical records flagged as at ROO. The implementation process was from April 1, 2018 to April 30, 2019, and the evaluation, from May 1 to December 31, 2019. We also administered satisfaction surveys to medical teams and patients.
Results: In phase 1, the expert group trained over 328 ED staff. In phase 2877 (36.2%) patient records were included in the analysis. Of these, 62% had a confirmed diagnostic of opioid use disorder (OUD), and 70.8% met eligibility criteria for naloxone prescriptions. However, only 7.7% were given a prescription or THN in the ED, and 12.4% were initiated on B/n in the ED/the community after their visit. Seven patients and 125 health care providers from EDs, clinics, and retail pharmacies completed the survey.
Conclusion: The SuboxED project demonstrated the feasibility of implementing a clinical algorithm for dispensing THN and initiating B/n in ED, and identified the challenges. In addition to advocating for free access to THN in EDs, scaling up the uptake of the algorithm in EDs is the next challenge.

Buprenorphine/naloxone, take-home naloxone, implementation, overdose

Objective: Using a Virtual Classroom (VC) model to address the demand for HIV medical education and to enhance capacity to test and treat HIV among Saskatchewan’s primary care providers.

Approach: The novel VC was launched in 2018 as an online, small-group platform to deliver HIV medical education to Saskatchewan health care providers. Despite the COVID-19 pandemic, interest for the VC has grown. Due to this, four sessions were offered (two more than originally planned) between April-December 2020 to a total of 39 participants. A post-evaluation survey was developed and sent by email to the first cohort. The survey administered to the last three sessions was modified slightly. The data were analyzed using descriptive techniques.

Results: A total of 22 surveys (56% response rate) from all four sessions were collected. Results from these surveys together indicate that 95% of participants (21/22) either “strongly agree” or “agree” that they know: how to order an HIV test and interpret the results; the various methods of HIV prevention; which tests to order for early visits; how to counsel patients on medical adherence; and approaches to long-term HIV management. All survey respondents either “strongly agreed” or “agreed” that they are aware of what issues to consider when starting anti-retroviral (ARV) treatment; can identify complicated situations and special populations; and can assess readiness to begin ARV treatment. All 18 participants from the last three sessions showed an average 4-point increase (scale:1-10) in confidence providing HIV primary care. Since the beginning of the HIV VC, 18 primary care providers have become approved ARV prescribers for Saskatchewan (10 in 2019; 8 in 2020).

Conclusion: These findings suggest that the VC continues to be a promising and effective model for educating primary care providers and enrolling new ARV prescribers in Saskatchewan despite an ongoing global pandemic.

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Background: Drug interactions (DI) between antiretroviral (ARV) and non-ARV drugs can lead to toxicity or treatment failure. The Toronto General Hospital Immunodeficiency Clinic (Toronto) and University of Liverpool (Liverpool) maintain web-based, HIV-focused DI checkers. We evaluated the comprehensiveness and concordance of these databases using a “real-world” sample of medications dispensed to HIV patients.

Methods: A list of non-ARV drugs dispensed to HIV-infected, ARV-treated British Columbians age ≥19 years was extracted from the population-based Seek and Treat for Optimal Prevention of HIV/AIDS cohort. Drugs included outpatient dispensing between 01-Jan-2010 and 31-Dec-2016. Four HIV healthcare providers checked each non-ARV drug for DI with all available ARVs using the Toronto and Liverpool databases (accessed May-September 2019).
Database comprehensiveness was calculated as the percentage of non-ARV drugs included. ARV+non-ARV pairs having the same DI severity classification in both databases were considered concordant (see Table). Comprehensiveness and concordance were calculated overall, and by non-ARV drug class.

Results: Of 659 non-ARV drugs, Toronto included 378 (57%) and Liverpool 432 (66%), with 316 (48%) in both. Overall, 75% of drugs were present in at least one database, with 9% only in Toronto and 18% only in Liverpool. Of 15,058 ARV+non-ARV pairs evaluated, 5,254 (35%) were listed in both databases, with 4,219 (80%) concordant (see Table). Discordant classifications were due to international differences between drug monographs and/or interpretation of DI literature.

Conclusions: Combined use of Liverpool and Toronto HIV DI-checkers enhances the comprehensiveness of DI information. Discordance is infrequent, and provides insight into different interpretations of DI literature.

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Background:
People living with HIV who have precarious or no health care coverage face major barriers in accessing health care, treatment and support. This group makes up a significant proportion of the 10-10-10% gaps in the HIV care engagement cascade. In response, a coalition of 10 health and community agencies in the Greater Toronto collaborated to develop the Blue Door Clinic to offer timely primary care, access to treatment, social supports, and linkage to long-term stable health services.
Method:
Launched in August 2019, the Blue Door Clinic operates a bimonthly half-day clinic in downtown Toronto, staffed with physicians, nurses, case managers and peer navigators all donated in-kind from partner agencies. Our clinicians provide clients with primary care, access to HIV treatment, immunizations, and monitoring tests. Our case managers and peer navigators connect them to needed legal, social and mental health supports. Since inception, the Blue Door Clinic has served 91 clients. This abstract will report on client service data from our first year of operation.
Results:
Our clients include: 38 (42%) people on temporary work or visitor permits, 26 (28.5%) with pending immigration processes; 18 (20%) international students, and 9 (10%) with lapsed immigration status. Of those we served, 26 (29%) were newly diagnosed with HIV; 9 (10%) presented with advanced HIV disease with AIDS-related complications, and the rest were people with known HIV who faced imminent risks of treatment disruptions.
To date, 39 (43%) of our clients were successfully referred to other health services and 56 (61%) were connected to additional community support services.
Conclusion:
The Blue Door Clinic successfully bridged a critical gap in the HIV care continuum. Results from our service evaluation research study underway will provide further insights on its long-term health impact and the replicability and sustainability of its model to benefit other marginalized populations.

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Older individuals are at increased risk of co-morbidities and polypharmacy, so ensuring the safety and tolerability of ART in older PLWH is critical. In this ongoing 96-week study, we evaluated the efficacy and safety of switching participants ≥65 years to single-tablet B/F/TAF in a phase 3b open-label study.

Virologically suppressed (HIV-1 RNA <50 copies/mL) participants >65 years old currently receiving either E/C/F/TAF or a TDF-based regimen were switched to B/F/TAF. The primary endpoint was HIV-1 RNA <50 copies/mL at Week(W) 24 as defined by the FDA Snapshot algorithm. Here we report efficacy and safety outcomes at W72.

86 participants were enrolled at sites from 5 European countries; median age was 69 years (range 65-80); 13% were female, and 99% were White; 92% were receiving E/C/F/TAF at baseline.

At W72, HIV RNA <50 copies/mL was 93% (80/86); 6 (7%) had no virologic data in window (4 discontinued study drug due to AE but had last available HIV-1 RNA <50 copies/mL and 2 had no data within the window but were still on study drug). Using the missing=excluded analysis, HIV RNA <50 copies/mL was 100% at W72. There were no virologic failures or emergent resistance. Median change in CD4 count was 53 cells/mm3 (IQR: -49, 120). There were 2 (2%) Grade 3-4 study drug-related adverse events (AEs). Four AEs led to premature study drug discontinuation; 1) abdominal discomfort (grade 2, drug-related), 2) alcohol withdrawal, 3) benzodiazepine withdrawal, 4) suicide. There were no serious AEs that were study drug-related. There were 7 Grade 3 and 1 Grade 4 laboratory-related AEs reported, with the Grade 4 being hyperkalemia. There were no discontinuations for renal, bone or hepatic AEs.

Through W72, B/F/TAF was safe, well tolerated with high rates of virologic suppression in PLWH ≥65 years who switched to B/F/TAF.

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Objectives: To assess pregnancy outcomes among women living with HIV (WLWH) vaccinated against HPV during pregnancy or near conception (within three months of last menstrual period).

Methods: This is a sub-analysis from a multi-centre Canadian study of qHPV vaccination in WLWH. Participants were not pregnant at the time of study enrolment (by urine pregnancy test) and were willing to avoid pregnancy for the vaccination phase. If conception did occur prior to or shortly after a vaccine dose was administered, pregnancy and infant outcomes were documented.

Results: 353 WLWH received ≥1 dose of qHPV vaccine. At baseline, median age was 36 years (IQR: 27-43), median CD4 count was 523 cells/mm3 (IQR: 384-710), median CD4 nadir was 242 cells/mm3 (IQR: 123-367), and 67% had a suppressed HIV viral load (<50 copies/mL). Seventeen WLWH received a dose of qHPV vaccine while pregnant (n=8, all within the first month) or within 3 months of conception (n=9). Among the 17 pregnancies, there were 9 live births (53%; 4 among women vaccinated while pregnant and 5 among women vaccinated near conception), 7 therapeutic abortions (41%; 3 among women vaccinated while pregnant and 4 among women vaccinated near conception), 1 spontaneous abortion in a woman vaccinated while pregnant, and 0 stillbirths. Among the 9 live born infants, median gestational age at delivery was 39.4 weeks (IQR: 38.6-40.1), median birth weight was 2830g (IQR: 2698-3755), and median Apgar scores at first and second assessment were both 9.

Conclusions: Although the number of pregnancies among WLWH vaccinated during/near pregnancy was too low to compare their specific pregnancy outcomes with those of controls not vaccinated during/near pregnancy, adverse pregnancy outcomes were uncommon among qHPV-vaccinated WLWH in our cohort. These findings are consistent with reproductive safety data for qHPV vaccines in cohorts of women not living with HIV.

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BACKGROUND: Islatravir (ISL, MK-8591) is the first nucleoside reverse transcriptase translocation inhibitor (NRTTI) in development for the treatment of HIV-1 infection. We evaluated changes in bone mineral density (BMD), body fat distribution, and related metabolic endpoints (weight, body mass index [BMI], fasting glucose and lipid levels), in a double-blind, dose-ranging trial of ISL in a combination antiretroviral regimen.

METHODS: Treatment-naïve adults with HIV-1 were randomized to once-daily ISL (0.25mg, 0.75mg, or 2.25mg) with doravirine (DOR, 100mg) and lamivudine (3TC, 300mg) or to the fixed-dose combination DOR/3TC/TDF. Participants receiving ISL who achieved HIV-1 RNA <50copies/mL at Week 20 or later stopped 3TC (usually at Week 24) and continued DOR+ISL at their initial dosage. Hip BMD, spine BMD, peripheral fat, and trunk fat were assessed by dual-energy x-ray absorptiometry (DEXA) at Weeks 0 and 48 and evaluated by a central imaging reader. Change from baseline to Week 48 was calculated for each DEXA endpoint, weight, BMI, and fasting plasma glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides.

RESULTS: 121 participants (92.6% male, 76.0% white, mean age 31 years) received study therapy and were included in the analyses. At baseline, the mean CD4+ T-cell count was 492cells/mm3 and 22% of participants had HIV-1 RNA>100,000copies/mL. Changes in metabolic endpoints from baseline to Week 48 are shown below (see table).

CONCLUSIONS: The ISL regimens, regardless of dose, demonstrated minimal BMD impact and similar changes in fat distribution, weight, and BMI compared to the DOR/3TC/TDF group, through 48 weeks of treatment.

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Background/objectives: Forty to 60% of persons with HIV (PHW) report having experienced loneliness and 5 to 29% of PWH are frail depending on the method of study. Recently it has been shown that the hazard ratio of death in individuals who are frail and lonely or frail and socially isolated is 1.8-fold that of individuals who are neither frail, nor lonely or socially isolated.

Design: A cross-sectional study of PWH ≥ 50 years. Routine frailty assessment was performed using the Clinical Frailty Scale. Individuals who scored 4+ on the CFS completed a questionnaire to elucidate additional factors present in frail PWH, including loneliness, falls, impaired gait and balance, polypharmacy, unintentional weight loss, food insecurity, and subjective cognitive concerns.

Setting: An urban outpatient clinic in Calgary, Canada.
Participants Individuals with HIV aged 50+ years living in Southern Alberta, Canada.
Measurements Frailty screening was performed using the Clinical Frailty Scale. Loneliness was measured with 3-item Loneliness Scale. Descriptive statistics were performed using Stata version 16.

Results: Two-hundred and ninety-four PWH were screened for frailty using the CFS. The mean age was 59 years (range 50-86 years). Sixteen percent were female. Fifteen percent were frail based on a score of 4+ on the CFS. Of the frail PWH, 42% endorsed feelings of loneliness, 42% had fallen in the past one year and 55% reported impaired gait or balance. One-fifth reported unintentional weight loss and 33% experienced food insecurity. Nearly 40% reported subjective memory concerns.

Conclusion: In aging PWH, frailty and loneliness are prevalent. Given the increased risk of death when both are present, upstream and targeted interventions are urgently needed. These may include addressing loneliness, falls risk, weight loss, food insecurity and memory concerns.
Key Words: frailty, loneliness, social vulnerability, aging, Human Immunodeficiency Virus (HIV)

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BACKGROUND
Second generation integrase strand transfer inhibitor (INSTI) cabotegravir is in late clinical trial as oral and long injectable, and bictegravir (BIC) is becoming accessible in settings with high HIV-1 non-B subtype viruses. Data on impact of INSTIs drug resistance mutations (DRMs) on integration site preference and susceptibility to BIC and CAB remains very scarce especially in HIV-1 non-B subtypes.

METHODS
Phenotypic assays on HIV-1 integrase recombinant subtype A and D viruses from 8 patients failing RAL-based third-line in Uganda was done in TZM-bl cells. HIV-1 integration capacity into human genome was assessed in MT4 cells. Integration site profiles were analyzed from total genomic DNA of antiretroviral therapy naïve (n=30), raltegravir failing (n=30) and protease inhibitor failing patients (n=30) using Illumina MiSeq sequencing.

RESULTS
HIV-1 integrase recombinant viruses harboring single N155H or Y143R/S mutations or in combination with secondary INSTIs mutations were susceptible to both BIC and CAB. However, multiple primary INSTIs DRMs in form of E138A/G140A/G163R/Q148R, and E138K/G140A/S147G/Q148K mutations led to increased fold-change in EC50 to both CAB (FC, 429->1000) and BIC (FC, 60->100). Reduced susceptibility in presence of multiple primary INSTIs DRMs was significantly high with CAB compared to BIC (P < 0.0023). Contrary to ART naïve, viruses carrying INSTIs DRMs significantly integrated into lamina associated domains (P < 0.0001) and oncogenes (P < 0.05). All viruses had impaired integration capacity, (<50%) relative to the wild type.

CONCLUSIONS
Single N155H or Y143S/R or in combination with secondary mutations, remain susceptible to both BIC and CAB, however, multiple primary INSTIs DRMs leads to increased resistance to CAB and BIC. Though not currently indicated, BIC offers alternative option to patients with single primary and/ or in combination with secondary mutations. INSTIs DRMs may encourage formation of latent reservoirs and malignancies in patients failing RAL with resistance.

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Background: Tenofovir disoproxil fumarate (TDF) is a commonly used component of ART for the treatment of HIV. However, TDF has been associated with nephrotoxicity and reduction in bone mineral density (BMD). Tenofovir alafenamide (TAF) is a newer formulation with proposed benefit of fewer adverse effects (ADEs). Although TAF has been extensively studied, less than 20% of included participants are women. The primary objective of this study is to describe the proportion of women experiencing ADEs from TAF. Secondary objectives include: to describe changes in renal function, liver enzymes, lipid profile, weight, CD4+ cell count, BMD and virologic suppression before and after starting TAF, and describe the frequency of monitoring for ADEs and effectiveness following initiation of TAF.

Methods: Retrospective cohort chart review of HIV positive women initiated on TAF-containing regimens prior to August 31st, 2019 at the British Columbia’s Women’s Hospital Oak Tree Clinic. Inclusion criteria include those who received a TAF regimen for at least 30 days and patient reported adherence of ≥ 80%.

Results: A total of 35 women were included. ADEs were reported in 63% of patients, with majority defined as mild in severity. Overall mean (SD) change in weight was 1.4 ± 4.2 kg, with weight gain greater than 3% within the first year of therapy occurring in 9 (26%) patients. No clinically significant changes in laboratory values were observed. Median (IQR) change in T/Z-score from baseline was 0.6 ± 0.5 for lumbar spine, 0.3 ± 0.4 for femur, and 0 ± 0.1 for femoral neck. Virologic suppression was maintained in 95% of patients.

Conclusion: In this cohort of women TAF was well tolerated and effective. No clinically significant changes in renal function, liver enzymes, lipid profile or BMD was observed. Risk factors for weight gain within the first year of therapy may warrant further investigations.

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Objective: Goal setting is an important component of self-management interventions such as exercise among people living with chronic disease. Our aim was to describe goal setting and achievement among adults living with HIV engaged in a community-based exercise (CBE) intervention.

Methods: We administered the Goal Attainment Scale (GAS) to participants living with HIV pre-CBE intervention (month 0), post-CBE intervention (month 6) and follow-up (month 14). The CBE intervention included exercise 3 times/week with weekly supervised coaching (Intervention), followed by thrice-weekly independent exercise (Follow-Up). Goals were established in collaboration with the research coordinator (months 0 and 6) and shared among participants and coaches, were independent from the CBE intervention and considered an exploratory outcome of our larger study. We conducted a content analysis to describe the type of goals set at baseline (month 0) and post-CBE intervention (month 6). We described the extent of goal achievement (frequency;%) at the end of intervention (month 6) and end of follow-up (month 14).

Results: Of 82 participants who completed the baseline GAS, 60 (75%) completed it post-intervention and 46 (56%) at end of follow-up (similar to participant retention in the CBE study). Of 275 goals set at baseline, 133 (48%) were achieved at month 6; most (76%) were physical goals (common physical goals achieved: improve balance, endurance, strength/muscle capacity, incorporate exercise into routine (# achieved/# articulated ≥50%). Of 162 goals set at month 6, 80 (49%) were achieved at month 14; most (74%) were physical goals similar to baseline (common physical goals achieved: improve overall fitness, endurance, flexibility, body tone/physique, and balance, activity-specific goals, incorporate exercise into routine (#achieved/# articulated ≥50%).

Conclusion: Collaborative goal setting can be used as a motivating factor when implementing self-management interventions and offer a potential outcome for evaluating the impact of exercise interventions for adults living with HIV.

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Objective: To describe uncertainty experienced by adults living with HIV and self-care living strategies used during the COVID-19 pandemic.

Methods: We conducted a cross-sectional web-based survey between June-August 2020 with adults living with HIV. We recruited participants from a previous exercise study, supplemented by word of mouth. Participants completed questionnaires about disability (HIV Disability Questionnaire), living strategies (frequency of strategy use and change since the pandemic in the following areas: maintaining control and healthy lifestyle; attitudes and beliefs; blocking the pandemic out of the mind, and social interaction), demographics, and COVID-19. We calculated median and interquartile ranges (IQR) for HDQ domain scores (range 0-100), higher scores indicating greater severity. We reported the proportion of participants who engaged in each living strategy ‘a few times a week’ or ‘everyday’ and the change in strategy use during the pandemic (increase/decrease/no change).

Results: Of 63 respondents, most (84%) were men, median age was 57 years (IQR:45,60), most (62%) were living alone, and few (25%) were working during the pandemic. Highest median HDQ severity scores were in the domains of uncertainty (median 30; IQR:16,43) and mental-emotional health (median 25: IQR:14,41). The majority (>50%) reported using 22 (60%) of 37 positive strategies ‘a few times a week’ or ‘everyday’ (most common pertained to maintaining a healthy lifestyle and positive outlook). Of the nine strategies (18%) reportedly changed during the pandemic, the most common related to social interaction (decreasing time spent with friends, colleagues or seeking company with others, increasing isolation, and increasing time interacting with others on the internet (27% engaged in this strategy ‘a few times a week’ or ‘everyday’).

Conclusion: Uncertainty and mental-emotional health challenges were the most severe dimensions of disability experienced by participants. Results can help to provide an understanding of disability and self-care strategy use during the COVID-19 pandemic.

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Background: People living with HIV are at higher risk of age-related comorbidities, even when treated with cART. There are limited data describing multiple comorbidity risk prediction scores in women living with HIV (WLWH). Our objective was to compare risk scores and immune aging markers-- leukocyte telomere length (LTL) and mitochondrial DNA (mtDNA) content--between WLWH and HIV-negative control women.
Methods: Demographic and clinical data from 122 WLWH and 81 controls aged >45y with visits between 2008-2018 in the Children and Women: AntiRetrovirals and Markers of Aging (CARMA) cohort were retrospectively reviewed. Framingham Risk Score (FRS), aspartate aminotransferase-to-platelet ratio (APRI), and Canadian Association of Radiologists and Osteoporosis Canada (CAROC) score were calculated for all participants. Liver-related death risk (LRD) score, Veterans Aging Cohort Study (VACS) index, and Chronic Kidney Disease (CKD) prediction scores were calculated for WLWH only. LTL and mtDNA were measured by qPCR.
Results: WLWH were younger than controls (median[IQR] 53[49-57] vs. 55[(50-59], p=0.028) but more likely to be current/past smokers (63% vs. 45%, p=0.016). A larger proportion of WLWH had APRI>0.7 (21% vs. 4%, p<0.001), and moderate/high CAROC scores (39% vs. 19%, p=0.029) compared to controls, indicating higher risks for hepatic fibrosis and 10-year fracture, respectively. FRS, which estimates 10-year risk of cardiovascular disease, did not differ between groups. Among WLWH, LRD (n=47) was 5.5[4.5-6.5] with 18.4% at medium-to-high risk, and CKD risk score was 7.0[3.0-12.0] with 68% at high risk of CKD. The VACS index predicted a 10.8[6.2-21.2]% risk of 5-year mortality. WLWH had shorter LTL than controls (6.6[6.1-7.3] vs. 7.4[6.8-8.0], p<0.0001), but no difference in mtDNA content was detected.
Conclusions: Among WLWH vs. controls, we observed shorter LTL as well as higher risk scores for liver and bone, but not cardiovascular disease. Further research is needed to determine how to better predict and prevent aging comorbidities in this population.

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Background: People living with HIV (PLWH) are living longer, but there is evidence that these individuals are experiencing an accentuated aging process. Physical impairments have not received much attention in the literature in comparison with the other consequences of aging with HIV. It is critical to study physical deficits in this population, as they can have an impact on mortality, falls risk, and health-related quality of life.
Objectives: In this critical review, we explore which factors contribute to physical
impairments, report common physical impairments and activity limitations, describe physical performance measures, and provide recommendations for rehabilitation professionals for
exercise prescription among PLWH.
Methods: Using Embase, MEDLINE, and CINAHL, we identified relevant studies by searching
databases for terms related to physical function among PLWH. We also hand-searched reference lists for additional studies.
Results: Among PLWH, inflammation, HIV severity markers (CD4+ count and viral load), comorbidities, and oxidative stress are contributing factors to physical impairments and activity limitations. Gait, static and dynamic balance, aerobic capacity, diminished muscle strength and mass, and frailty are common and can have a negative impact on fall risk and functional performance in this population. Some physical performance measures from the limited available literature can be used for screening and assessment, including the Short Physical Performance Battery, Six-Minute Walk Test, 5-times sit-to-stand test, Community Mobility and Balance Scale, and gait speed tests. The Berg Balance Scale is not recommended for use with PLWH as it is susceptible to ceiling effects.
Conclusions: Physical impairments are common among PLWH. Aerobic exercise, resistance training, and balance exercise appear to benefit PLWH. Future work should investigate which outcome measures should be used in clinical practice to measure physical performance. Rehabilitation professionals should identify PLWH who are at risk of developing physical impairments using available physical performance measures.

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Background
The evidence shows that many older people living with HIV (PLWH) could protect or improve their brain health through lifestyle change. Sustained lifestyle change is difficult for those with a chronic condition that affects cognitive ability, eroding the very executive functions needed for effective goal-directed behavior. Thus, the key question is how we can improve adherence to the most promising interventions. Goal Management Training (GMT) is an intervention that involves goal-setting, sustained attention, and feedback.
Objective
To estimate the extent to which GMT before a healthy lifestyle program (HLP) is associated with greater uptake of health recommendations, achievement of health-related goals, and better brain health among PLWH compared to the HLP alone.

Methods
Brain Health Now cohort members are eligible for this study. The main outcome will be adherence to the HLP, which is the number of physical activity weeks where adherence targets were met, (150 minutes per week) using an activity monitor. Social activities per week will be captured through self-report with confidential photo validation. The MyHealth app will be used to send pain, anxiety, depression, sleep, distress, fatigue and health perception questionnaires to the participants. Downstream outcomes will include health-related quality of life, cognitive ability, vascular risk profile, and social network size. All participants will receive a list of relevant local resources, a health coach, a goal-setting application, and access to an online goal-setting workshop. The intervention group will participate in 9 GMT sessions. All participants will enter the HLP for 52 weeks. Data will be analyzed using a linear regression model.
Implications
This work will contribute to the current literature regarding adherence to exercise interventions aimed at improving brain health. If successful, behavioural interventions such as GMT could be implemented as an adjunct to exercise interventions for people with cognitive impairment across many clinical populations.

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Background:
Pharmacists contribute to HIV patient care in different settings. The purpose of this study is to describe the roles of clinic- and community-based pharmacists in HIV care in Canada, and to understand how pharmacists within these settings can effectively collaborate to improve pharmaceutical care.

Methods:
A mixed-methods approach was utilized. A cross-sectional survey was distributed electronically to the Canadian HIV and Viral Hepatitis Pharmacists Network in September 2020. A convenience sample of interested respondents was selected for semi-structured interviews. Survey data were analyzed descriptively and triangulated with interview transcript data, which were analyzed independently by two researchers using an inductive approach.

Results:
Thirty-two pharmacists from cities across British Columbia, Alberta, Saskatchewan, Ontario, and Quebec responded to the survey and 3 pharmacists were interviewed. Survey respondents were primarily clinic-based pharmacists (75%) or community pharmacists (12.5%); interviewed pharmacists were clinic-based. Two thirds of survey respondents reported both clinic- and community-based pharmacist involvement in caring for HIV patients, but 62% would like community pharmacists to increase capacity for HIV care. Clinic-based pharmacists described a desire for greater sharing of clinical tasks such as medication counselling in order to increase clinic-based pharmacists’ capacity to focus more on complex clinical cases. While community pharmacists can play important roles in adherence and safety monitoring, the level of collaboration between HIV clinics and community pharmacies varies. For community pharmacists to be better utilized in HIV care, they require increased HIV knowledge, access to more clinical information about patients, and improved communication with clinics.

Conclusions:
Most HIV clinic-based pharmacists regularly collaborate with community pharmacists to deliver care, but barriers limit the degree to which collaboration occurs. HIV training for community pharmacists and a communication system that enables information sharing across healthcare settings could enhance pharmacist collaboration in HIV care, but more input from community pharmacists is needed.

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Background
The incidence of HHV8-induced Kaposi sarcoma (KS) in people living with HIV (PLWH) has dramatically decreased with antiretroviral treatments (ART). However, reemergence of KS in ART-treated PLWH with restored CD4 T-cell count and sustained HIV control is reported, raising concerns on HHV-8 pathogenesis and optimal management of these patients.

Method
We performed a pilot study including ART-treated PLWH (KS ART HIV+) and uninfected people (KS HIV-) with KS. We assessed clinical characteristics, CD4 and CD8 counts. In plasma and PBMCs, viral loads of HHV-8, CMV and EBV were quantified by digital droplet PCR.

Results
19 patients with KS have been recruited, including 11 KS ART HIV+ with undetectable HIV viremia and 8 KS HIV-. Cases of KS ART HIV+ were all men who have sex with men (MSM), whereas 7/8 KS HIV- were male including 3 MSM. KS ART HIV+ were younger than KS HIV- (52 years vs 79, p=0.0005). Despite similar CD4 T-cell count in the two groups (579 vs 472 cells/µL, p=0.30), KS ART HIV+ had a higher CD8 T-cell count (608 vs 374 cells/µL, p=0.007) and lower CD4/CD8 ratio (0.7 vs 1.8, p=0.03). HHV-8 DNA in PBMCs was detected in none (0/9) of KS ART HIV+ while in 3/7 KS HIV-. In contrast, EBV and CMV DNA was detected at similar levels in PBMCs of all KS patients, HIV+ or HIV-.

Conclusion
ART-treated PLWH with KS exhibited similar CD4 T-cell counts but higher CD8 T-cell counts and younger age compared to HIV-uninfected KS patients. Irrespectively of HIV infection, other herpesviruses EBV and CMV DNA was detected in PBMCs of all KS participants. We are now assessing the influence of aging, inflammation, microbial translocation as well as host and viral factors in KS pathogenesis. Such insights will help reducing KS-induced stigma and developing preventive and therapeutical strategies.

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Background: Bictegravir/emtricitabine/tenofovir alafenamide (BFT) is approved for treatment of HIV without known resistance to its 3 components. Several studies have demonstrated efficacy of BFT in patients with NRTI resistance associated mutations (RAMs), mainly identified by proviral DNA, a technique not available in Canada. We evaluated BFT in patients with NRTI RAMs identified by routine genotyping.

Methods: Retrospective analysis of adults receiving BFT. Patients were identified through a search of electronic health records, and eligibility confirmed by review of individual patient records. Included patients had genotypically documented 2019 IAS-USA major RAMs affecting NRTIs and at least one HIV viral load (VL) after starting BFT.

Results: 42 patients met study criteria. The mean age was 54 years, the mean proximal CD4 count was 634 cells/mm3, and 28 (67%) were male. 39 were virologically suppressed when BFT was initiated, two were treatment naïve and one had a VL of 961 copies/mL on antiretroviral therapy (ART). 25 had one NRTI RAM (20 were M184V/I), 8 had 2 NRTI RAMs, 3 had 3 NRTI RAMs, 3 had 4 NRTI RAMs, 2 had 5 NRTI RAMs and 1 had 7 NRTI RAMs plus a 69 insertion. No patient had K65R/E/N. 19 patients also had major NNRTI RAMs and 15 had major protease RAMs, but none had documented integrase resistance. At the last VL measurement on BFT, a mean of 8 months after starting BFT, 41 of 42 had VL <40 copies/mL. One patient who had a VL <40 copies/mL two months after starting BFT, had a VL of 67 copies/mL 14 months after starting BFT. This patient had well documented past history of poor adherence and had no new RAMs identified in the sample 13 months after starting BFT.

Conclusions: BFT was effective in maintaining HIV VL suppression in patients with genotypically documented NRTI RAMs.

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Background: With ART, long-term comorbidities, quality of life, and longevity are priority concerns for people living with HIV. Findings from the Children and Women: AntiRetroviral Therapy and Markers of Aging (CARMA) study, which investigated biological aging, indicate that women living with HIV (WLWH) experience higher rates of comorbidities, hormonal abnormalities, and accelerated cellular aging compared to HIV-negative women. These outcomes are potentiated by high HIV viral loads and smoking. The Canadian HIV WOmen’s Sexual and Reproductive Health Cohort Study (CHIWOS) operationalized “women-centered care” and “Meaningful Involvement of Women Living with HIV/AIDS”, while investigating psychosocial and structural factors that impact women’s healthy aging. Utilizing the strengths of CARMA and CHIWOS, BCC3 will comprehensively investigate intersecting factors that influence aging in WLWH using a cell-to-society and health equity approach.

Community collaboration: WLWH and community partners are engaged throughout all stages of this study, including Peer Research Associates and a Community Advisory Board representing WLWH, HIV/AIDS organizations, and clinicians.

Methods: We aim to enrol n=350 WLWH and n=350 HIV-negative women from 2020-2023. Participants will first attend a clinical visit, where biospecimens, anthropometric measurements, and clinical data will be collected. Biospecimens will be analyzed for markers of cellular aging and inflammation, hormone levels, and other chronic/latent viral infections. Within one month, participants will attend a community visit, where a Peer Research Associate will administer a comprehensive questionnaire regarding psychosocial and structural determinants of health. Using biospecimens and survey data, we will analyze how chronic inflammation, co-infection with chronic/latent viruses, hormonal irregularities, and psychosocial, behavioral, and structural factors impact markers of aging in immune cells and the development of comorbidities in WLWH and HIV-negative women.

Significance: The BCC3 study is uniquely positioned to investigate how these factors intersect as WLWH age, and inform best practices for comprehensive, holistic, women-centered care throughout their life course.

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Lenacapavir (LEN, GS-6207) is a first-in-class subcutaneous (SC) long acting inhibitor of HIV-1 capsid protein (CA) function, which can be administered every 6 months. We conducted a phase 1b proof-of-concept study in which people with HIV (PWH) received a single SC injection of LEN 20, 50, 150, 450, or 750 mg. LEN demonstrated potent antiviral activity with up to 2.3 log10 decline in HIV-1 RNA after 9 days of monotherapy. Here we describe the resistance analyses for all participants.

Study 4072 is a double-blind, placebo-controlled, dose-ranging, randomized (3:1; n=8/group) study in PWH who were capsid inhibitor-naive. Resistance analyses were performed for all participants prior to study entry and at the end of monotherapy using genotypic and phenotypic Gag-Pro assays (Monogram Biosciences) and next-generation sequencing (NGS; Seq-IT). Samples were evaluated for the emergence of CA mutations and/or change in phenotypic susceptibility to LEN.

Thirty-nine PWH enrolled in the study, 29 receiving LEN and 10 receiving placebo. All PWH responded to LEN with no rebound. In the pre-treatment analysis, none had HIV-1 harboring resistance mutations to LEN, with all having wild-type (WT) phenotypic susceptibility to LEN. Post-monotherapy analyses revealed the emergence of CA mutation Q67H at Day 10 in 2 participants. One participant (20 mg group) had a Q67Q/H mixture detected both by population and NGS analysis, and another participant (50 mg group) had a Q67H mutation, detected only by the NGS analysis. No other substitutions were observed in the CA protein.

Overall, emergence of resistance to LEN was rare and only occurred well below exposures expected to be achieved in Ph2/3 studies, with the emergence of a single mutation Q67H. These results support further evaluation of LEN as a long-acting antiretroviral agent in PWH.

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Background: Nearly 50% of people living with HIV in the US are ≥50 years old. Doravirine (DOR) is a next-generation NNRTI with activity against first-generation NNRTI-associated mutations, a neutral impact on lipids, and few drug-drug interactions with commonly used medications. We compared Week 96 results in treatment-naïve adults ≥50 vs <50 years old from 3 DOR trials (P007, P018, P021).

Methods: 855 participants received DOR 100mg +2 NRTIs or fixed-combination DOR/3TC/TDF; 383 participants received ritonavir-boosted darunavir (DRV) +2 NRTIs; and 472 received efavirenz (EFV) 600mg +FTC/TDF. Participants who received ≥1 dose of study drug were included. All analyses were done by descriptive statistics; the Observed Failure approach was used for missing efficacy data.

Results: Of 1710 participants, 187 (11%) were 50-70 (median 54) years old at study entry. The older cohorts (age ≥50 years) had more women, more participants with AIDS, and lower median CD4+T-cell counts than the younger cohorts (table). Hypertension and analgesic use were also more common in older participants. At Week 96, the older cohorts had more participants with HIV-1 RNA<50copies/mL and fewer discontinuations due to lack of efficacy. Mean change in CD4+T-cell count was similar between age cohorts in the DOR group. Rates of drug-related AEs and serious drug-related AEs were similar between age cohorts across all treatment groups. Discontinuations due to drug-related AEs were similar between age cohorts in the DOR group.

Conclusions: DOR is a beneficial option for adults ≥50 years old, given its similar efficacy and favorable safety profile compared to younger adults.

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Background: Islatravir (ISL; MK-8591) is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) with multiple mechanisms of action. ISL has potent activity against nucleos(t)ide reverse transcriptase inhibitor (NRTI) resistance-associated variants and inhibitory quotients (IQs) that suggest it will have a high barrier to resistance in the clinic. We conducted studies to increase understanding of resistance pathways that alter susceptibility to ISL.

Materials and methods: Viral resistance selection studies were conducted with HIV-1 subtype B in MT4-green fluorescent protein (GFP) cells and with subtypes A and C in MT4-GFP/CCR5 cells with escalating ISL concentrations. Antiviral activity of ISL on variants bearing emergent substitutions, or NRTI resistance-associated substitutions, was assessed in MT4-GFP cells and/or PBMCs. Replication capacity was examined for select variants.

Results: In subtype A, B, and C viruses, ISL selected for M184I and M184V mutations; however, these mutations conferred modest impacts on ISL antiviral activity (6.2- and 6.8-fold potency (IC50) reductions, respectively). In subtype B virus, a rare A114S variant (observed in a single replicate experiment at passage 38) was detected. Phenotypic analysis showed A114S conferred a marginal potency loss (≤2-fold) to ISL while variants containing A114S+M184V conferred a >24-fold potency loss to ISL. Variants containing A114S+M184V had profoundly reduced replicative capacity consistent with being rarely observed in the clinic. In contrast to the decreased susceptibility to ISL, A114S increased susceptibility to NRTIs, tenofovir disoproxil fumarate, zidovudine, lamivudine, and emtricitabine, by 1.6- to 14.3-fold in PBMCs. Combinations of A114S and thymidine analog mutations enhanced susceptibility to NRTIs but not ISL suggesting distinct inhibitory mechanisms on reverse transcription.

Conclusions: Variants selected by ISL selective pressure in vitro exhibit low replicative capacity and confer modest foldshifts on antiviral activity of ISL. The high potency of ISL coupled with its high IQs, continue to support a high barrier to the development of ISL resistance.

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