Introduction: During the COVID-19 pandemic, disruptions in harm reduction services, housing, and mental health care are suspected to have exacerbated substance use risks amid a dynamic illicit drug market. Understanding and responding to trends in drug use is needed to meet the needs of under-served clients at risk of HIV and HCV infection.

Methods: The Per-SVR study is a prospective cohort study that assesses re-infection rates, health care engagement and outcomes among adults living in British Columbia, Canada who have recently completed direct-acting antiviral (DAA) HCV therapy. Utilizing Per-SVR data (survey and urine drug screen (UDS)), we included participants who completed at least one interview before July 1st, 2021 with a positive UDS sample. A trend analysis of the proportional use of substances by year was performed using a generalized estimating equation model. Participants who completed surveys between March 2019 – March 2020 and July 2020 – July 2021 were included in a pre-post COVID sub-analysis (t-test).

Results: We identified 164/230 participants with a positive UDS at baseline (median age: 52 years (44-58), 65.9% male, 11.0% homeless in previous 3 months). In the annual trend analysis (2017-2021), the proportion of clients using marijuana decreased (66.7% 2017 vs 46.3% 2021, p=0.042) while amphetamines (18.2% 2017 vs 41.5% 2021, p=0.022) and ecstasy (3.0% 2017 vs 36.6% 2021, p <0.001) increased. Fentanyl was the only substance that increased (20.9% pre-COVID vs. 32.3% post-COVID, p=0.008) in the pre-post COVID analysis (n=129). There was no significant change in self-reported overall non-injection substance use and injection substance use pre-post COVID.

Conclusions: Temporal trends in drug use show that stimulants account for an increasing proportion of substances used while the proportion of participants using marijuana has decreased. The proportion of participants using fentanyl has increased since the start of COVID-19, highlighting important implications for harm reduction services.

Background: The COVID-19 pandemic has resulted in many changes in healthcare service delivery. We examined perspectives on health service access due to COVID-19 of people living with HIV (PLWH) in BC and potential resulting effects on antiretroviral treatment interruptions (TIs).

Methods: From January 2016 - September 2018, we used purposive sampling to enrol PLWH aged ≥19 years across BC into the STOP HIV/AIDS Program Evaluation (SHAPE) study. Participants completed surveys at enrollment, 18 and 36 months. In October 2020, additional COVID-19 questions were added to surveys. We examined trends in TIs (defined as >60 days late for ART refill using data from the BC HIV Drug Treatment Program) in six-month periods among all SHAPE participants between March 2019 and August 2021. We examined associations of TIs with reported health service access using generalized linear mixed models.

Results: Of 644 PLWH in the SHAPE study, 595 were alive in March 2019 and had been receiving ART for at least three months since SHAPE enrollment. Of these, 3.4-7.4% participants had a TI in any six-month period. A total of 196 participants completed the COVID questions of whom 33% reported having difficulty accessing healthcare during COVID-19, 10.9% reported avoiding a continuing healthcare service due to COVID-19 related concerns and 72.9% reported using virtual healthcare services since March 2020. In multivariable analysis, the odds of interrupting treatment in any six-month period were not significantly different from March – August 2019, except for March – August 2021, where they were lower (adjusted odds ratio [AOR]= 0.25; 95% CI 0.06-0.99). None of the reported challenges to health care services were associated with TIs.

Conclusion: While some participants reported challenges to accessing services or avoidance of services due to COVID-19, TIs were not more likely during COVID-19 than before. None of these challenges were associated with TIs.

Background HPV-associated anal cancer is a leading cause of non-AIDS defining mortality in men who have sex with men (MSM) living with HIV and occurs at rates up to 100-times greater than in the general population. Despite recent indications that screening reduces the incidence and severity of anal cancer, there are no widespread, publicly funded, anal cancer screening programs. We examined familiarity with screening strategies for anal cancer among MSM living with HIV.

Methods The HPV-SAVE study is a national study examining anal cancer screening among MSM living with HIV in Canada. Between 02/2016 to 05/2021, participants completed a questionnaire at study entry including items related to prior anal cancer screening familiarity and experience, which we report using descriptive statistics.

Results Among the 750 individuals who completed the questionnaire, the majority were white (70.7%), over 50 years old (52.4%) and unpartnered (53.8%). A minority reported previous awareness of targeted anal cancer screening that is accessible in the community (137/715; 19.2%). Experience with screening included having had a digital anal exam (493/715; 69.0%), previous anal pap for cancer screening (129/673; 19.2%), or anoscopy (96/649; 14.8%). Previous self-examination for anal lesions was reported by 322 individuals (45.2%), and 97 individuals (13.9%) reported examination by their partner. Most (89.8%) were comfortable discussing health issues related to their anus with their doctor and 92.7% perceived anal cancer screening as important. Following enrolment in HPV-SAVE, 236 individuals (33.1%) reported being more concerned about anal cancer than they used to be.

Conclusion Despite being disproportionately impacted by anal cancer, most MSM living with HIV were unaware of anal cancer screening and few had prior experience with anoscopy or anal cytology. A high proportion of participants reported previous informal self-examination, suggesting that programs to increase patient-driven anal cancer screening would be well received.

Background
People with HIV (PWH) are at risk for compensated advanced chronic liver disease (cACLD) and liver-related events. Non-invasive tools, including liver stiffness measurement (LSM) by transient elastography, are used to identify patients with cACLD at risk of hepatic decompensation and mortality, but these remain not validated in PWH.

Method
This was an international multicenter cohort study including PWH with available LSM and no previous hepatic decompensation. Non-invasive tests included LSM, LSM to Platelets (LPR), LSM/spleen diameter-to-platelets ratio (LSPS), and Portal Hypertension risk score (PHRS). Non-invasive tests were assessed using area under the curve (AUC) and Cox-regression analysis to predict events. Patients were stratified in four groups based on thrombocytopenia (platelets≤150 G/L) and presence of cACLD (LSM≥10kPa): group1=LSM<10kPa/platelets>150; group2=LSM<10kPa/Platelets≤150; group3=LSM≥10kPa/Platelets>150; group4=LSM≥10kPa/Platelets≤150. Incidence of death and liver-related events (ascites, encephalopathy, variceal bleeding, hepatocellular carcinoma) was assessed.

Results
We included 1488 PWH (mean age 48.5 years, 64.9% co-infected with hepatitis C). When compared to group1, the incidence rate ratio of liver-related events was 9.79 (95%CI 2.4-47.7) for group2, 17.22 (95%CI 5.9-73.3) for group3, and 44.79 (95%CI 16.7-183.1) for group4. Based on AUC, LSM [0.828 (95%CI 0.776-0.881)], LPR [0.831 (95%CI 0.784-0.878)], LSPS [0.832 (95%CI 0.785-0.884)], and PHRS [0.835 (95%CI 0.785-0.879)] all performed well to predict any event. Using separate models for each test, LSM, LPR, LSPS, and PHRS remained independent predictors of any event (see Table).

Conclusion
In PWH, non-invasive tools are predictive of liver-related events and death, particularly when used in combination. The combination of LSM, platelet count and spleen diameter provides better assessment of this risk as compared to single non-invasive tools.

Background: Non-alcoholic fatty liver disease (NAFLD) affects 35% of people with HIV (PWH). Significant liver fibrosis develops in 15% of these PWH. Developing strategies to identify PWH at risk for NAFLD-related liver fibrosis related is imperative to reduce complications. Transient elastography (TE) is not widely accessible to evaluate liver fibrosis. A two-tier pathway using simple fibrosis biomarkers initially could reduce the need for specialist tests like TE.

Methods: A two-tier care pathway was applied to three prospective cohorts of PWH without viral hepatitis in Canada and Italy who underwent screening for NAFLD. Significant liver fibrosis was defined as TE reading >7.1 kPa. Five simple fibrosis biomarkers (FIB-4<1.3, BARD score 0-1, NAFLD fibrosis score<-1.455, AST:ALT ratio<0.8 and APRI<0.5) were applied as first-tier tests to exclude significant liver fibrosis and evaluate the reduction in TE referrals and costs.

Results: Of the included 1749 PWH (mean age 50.2 years, prevalence of diabetes 34%), 15.1% had significant liver fibrosis by TE. Application of simple fibrosis biomarkers as first tier tests would have resulted in 24.9-86.3% decrease in TE referrals (see Table). After adjusting for age, sex, diabetes, CD4 cell count, BMI (adjusted odds ratio [aOR] 1.12 (95% CI 1.08-1.17) and triglycerides (aOR 1.26, 95% CI 1.11-1.44) were independent predictors of discordance for APRI<0.5 with TE>7.1.

Conclusion: A two-tier pathway could save over 80% of TE examinations and related costs, helping resource optimization in HIV medicine. Patients stratified as low risk by APRI but with metabolic comorbidities should be considered for referral for TE examination.

Introduction: Chronic inflammation in HIV infection promotes a higher risk of co-morbidities such as cardiovascular disease (CVD), which is a leading cause of mortality in people living with HIV (PLWH). IL-32 is a potent multi-isoform proinflammatory cytokine that we and others have shown to be upregulated in T-cells from blood and coronary arteries in PLWH. In this study, we aimed to investigate the impact of IL-32 isoforms on CD4 T-cells as related to their activation and potential to recruit other immune cells to the site of inflammation.
Methods: IL-32 isoforms (α, β, γ, 500ng/ml) were used to stimulate CD4 T-cells isolated by negative selection (StemCell) from peripheral blood mononuclear cells (PBMCs) from non-infected donors (n=5). RNA was extracted at 12 hours post-activation and subjected to RNA Sequencing (NovaSeq6000). Plasma and PBMC samples were collected from PLWH and non-infected controls participating in the Canadian HIV and Aging Cohort Study (CHACS). Differentially expressed chemokines were validated at the transcriptional and protein levels by RT-qPCR (n=10) and ELISA (n=10), respectively.
Results: Systemic analysis of RNAseq showed that individual IL-32 isoforms had a distinct impact on CD4+ T-cell gene transcription with IL-32β and IL-32γ, but not IL-32α, stimulating the expression of multiple chemokines. Validation at the transcriptional and protein levels in IL-32 stimulated CD4 T-cells in vitro showed that IL-32β and IL-32γ significantly upregulated a signature of CCL22, CXCL1 and CXCL8. These chemokines were also significantly upregulated in plasma from PLWH (n=79) compared to non-infected controls (n=49) (p=0.04, p=0.001, and p=0.023, respectively).
Conclusion: Upregulation of CCL22, CXCL1 and CXCL8 by IL-32 in activated T-cells, if happening in plaque-forming sites in arteries, is likely to promote the recruitment of inflammatory neutrophil, T-cells and monocytes, which could exacerbate local inflammation and CVD. IL-32 may represent a therapeutic target to dampen inflammation and prevent CVD in PLWH.

Background
HIV is associated with diminished fertility, younger age at menopause, and shorter leukocyte telomere length (LTL), a marker of cellular aging. Anti-Mullerian hormone (AMH) is a reliable marker of ovarian reserve. We sought to examine the associations among LTL, AMH, and HIV, to better understand factors associated with ovarian aging in women living with HIV (WLWH), cross sectionally and longitudinally.
Methods
We included 256 WLWH and 206 HIV-negative women 12-50 years of age enrolled in the CARMA cohort with ≥1 study visit(s), >1 year apart. Relative LTL and serum AMH were measured by qPCR and ELISA. Women were separated for analyses in reproductive (<35 years of age) vs. late reproductive (≥35 years of age) life phases. Using multivariable mixed-effects linear regressions or logistic regressions, we assessed factors associated with AMH and ΔAMH/year, while adjusting for relevant confounders including age, ethnicity, and substance use.
Results
WLWH and HIV-negative controls were of similar age (33.5±SD vs. 32.3±SD years, p=0.62) but WLWH had shorter LTL (7.2 vs. 7.5 p=0.0002) and lower AMH (1.5ng/mL vs. 2.3ng/mL p=0.032). After adjusting for relevant confounders including substance use and ethnicity, HIV was associated with 20% lower AMH (p=0.05) in women <35 years and shorter LTL was associated with AMH below the clinical threshold of 2 ng/ml among women ≥35 years (p=0.046). Longitudinally, ΔAMH/year was related to age in younger women, and primarily associated with AMH levels at first visit among older women.
Conclusions
Factors associated with AMH change across the reproductive lifespan. Our data show lower AMH levels among WLWH <35 years, suggesting that HIV infection and/or treatment may have an initial detrimental effect on ovarian reserve. In women ≥35 years, the association between shorter LTL and lower AMH suggests that the immune and reproductive aging connections may be important in this age group.

Background:
Studies suggest that women living with HIV (WLWH) reach menopause earlier than negative controls. However, this may be confounded by hypothalamic amenorrhea, which occurs frequently in WLWH. Follicle stimulating hormone (FSH) can distinguish menopause from hypothalamic amenorrhea. Herein, we compare age at menopause in WLWH and controls by self-report versus biochemical confirmation (FSH).
Methods:
Cross-sectional demographic and medical data were obtained for a subset of women enrolled in CARMA and BCC3. Participants aged ≥35 years and sex-assigned female at birth were included. Women with hysterectomy, bilateral oophorectomy, or hormonal therapy use were excluded. Menopause status was determined by 1) self-report and 2) age at last menstrual period and serum FSH (biochemical confirmation). Participants were compared using descriptive statistics. The Chi2 test was used to compare counts of premenopausal and menopausal women by self-report vs. biochemical confirmation.
Results:
In total, 139 WLWH and 104 controls are included in this interim analysis, of whom 51 WLWH and 49 controls were menopausal. WLWH had lower income, less education, higher parity, and higher rates of hepatitis C infection than controls. Among WLWH, 81.0% had a viral load <40 copies/ml. Self-reported reproductive phase was concordant with biochemical data in 83.8% of WLWH compared with 95.0% of controls (p=0.008). By self-report, mean age at menopause was 48.7 ± 5.7 years in WLWH and 50.2 ± 4.8 years in controls. When FSH measurements were considered, menopause ages were similar (WLWH: 50.1 ±4.3 vs. controls: 50.2 ± 4.9 years).
Conclusion:
This interim analysis suggests no difference in menopause age between WLWH and controls using biochemical confirmation, compared to self-report where WLWH appeared to have slightly earlier menopause. If confirmed in final analyses, these results call to question whether WLWH experience earlier menopause and suggest biochemical confirmation could be an important research tool when assessing menopause in WLWH.