DISCOVER trial demonstrated noninferior efficacy of F/TAF to F/TDF for HIV prevention with improved bone mineral density (BMD) and renal safety biomarkers at the primary endpoint at week (W) 48 and at W96. Here we report W144 outcomes for participants randomized to F/TAF and continued F/TAF in the open-label extension (OLE) phase.
We evaluated HIV incidence in participants on F/TAF through W144 and assessed changes in hip and spine bone mineral density (BMD) and in glomerular function (eGFR) from baseline to W144. 2,080 of the 2,694 participants initially randomized to F/TAF opted into the OLE phase, and 1,933 were on study drug through W144, leading to a total of 7,885 person-years (PY) of follow-up on F/TAF. Eight participants taking F/TAF acquired HIV in the blinded phase and 3 in the OLE phase. Dried blood spot analyses on the 3 OL infections found tenofovir diphosphate levels consistent with low adherence. There were no relevant resistance mutations for the 3 new infections. Among participants taking F/TAF, HIV incidence was 0.16/100 PY (95% CI 0.06-0.33) at the primary endpoint, 0.16/100 PY (95% CI 0.07-0.31) through 96 weeks and 0.14/100 PY (95% CI 0.07-0.25) through 144 weeks. Participants taking F/TAF had increases in hip (mean percentage change +0.54%) and spine (mean percentage change +1.02%) BMD from baseline to W144. Median eGFR increased by a median of 2.6 mL/min from baseline to week 144. Participants taking F/TAF gained a median 2.3 kg (IQR -0.9-5.8) over 3 years of follow up.
HIV incidence remained low with stable BMD and renal function parameters through 144 weeks of follow-up demonstrating that/TAF is a safe and effective option for long-term use in people who would benefit from PrEP.

BICSTaR Canada (GS-CA-380-4574/NCT03580668) is an ongoing, observational cohort study evaluating the effectiveness, safety and tolerability of B/F/TAF in antiretroviral treatment‐naïve (TN) or treatment‐experienced (TE) adults living with HIV in Canada. This analysis includes HIV‐1 RNA (missing=excluded analysis), drug‐related (DR) adverse events (AEs), weight changes and treatment persistence in participants who completed a 24M visit.

159 persons (10 TN/149 TE) were included in the analysis (August 2021). Most were male (88%), white (72%) and 51% were ≥50 years old. Baseline comorbidities were prevalent (90%), including neuropsychiatric disorders (40%), hyperlipidemia (30%), and hypertension (22%). Amongst TE persons, 68%/22%/12% switched from INSTI, NNRTI, PI regimens to B/F/TAF, respectively; 46% switched from TDF-containing regimens. 19 participants (13%; 2 TN and 17 TE) had baseline primary resistance (8% NRTI [6 M184V/I, 1 K65R] and 6% NNRTI [7 K103N/S] mutations). Of those with HIV-1 RNA data at 24M (n=126), 8/8 (100%) TN and 117/118 (99%) TE had HIV-1 RNA <50 copies/ml, with no emergent resistance to the components of B/F/TAF. Median CD4+ cell counts (cells/µl) increased in TN (355 to 699) and were stable in TE (588 to 610) from baseline to 24M. Persistence with B/F/TAF at 24M was 89%; 3 TN and 15 TE discontinued (TN: 2 participant/investigator decision, 1 death; TE: 5 AEs, 5 participant/investigator decision, 1 death, 1 lack of efficacy). No discontinuations occurred due to renal/bone/hepatic AEs and no recorded serious DRAEs. DRAEs occurred in 10 TE participants (7%), with weight increase (n=4) and psychiatric symptoms (abnormal dreams [n=1], anxiety [n=1] and major depression [n=1]) being most common. Median (Q1, Q3) weight change was +1.1 kg (−0.9, 4.3) for TE (n=99), with modest BMI changes +0.4 kg/m2 [−0.3, 1.4].

B/F/TAF was highly effective and well-tolerated through two years in this real-world Canadian cohort of adults living with HIV and multiple comorbidities.

Introduction: In British Columbia, antiretrovirals are provided free-of-charge through a publicly-funded HIV Drug Treatment Program (DTP). When available, generic equivalents are substituted for brand-name products, per Health Ministry policies. We describe the incidence and type of adverse reactions attributed to generic antiretrovirals (product substitution issues, “PSIs”), reported to DTP Pharmacovigilance.
Methods: We included persons living with HIV (PLWH) age ≥19 years who received generic antiretroviral(s) between 01-Jun-2017 and 30-Jun-2021, during the first year following brand-to-generic transition: abacavir-lamivudine (ABC-3TC), emtricitabine-tenofovir disoproxil fumarate (FTC-TDF), efavirenz-FTC-TDF (EFV-FTC-TDF), atazanavir and darunavir. Antiretroviral dispensing and PSI data were extracted from DTP databases. PSI incidence rate (95% confidence interval [95%CI], Poisson regression), symptoms, and post-PSI management were described.
Results: During the study period, 4904 PLWH received ≥1 first-year generic product. Median age was 52 (Q1-Q3=44-59) years and 83% were male.
The Table summarizes generic usage, PSI details and management. Most PLWH (≥93%) had previously used the brand-name equivalent. Prior generic antiretroviral experience increased over time (7% at ABC-3TC rollout 2017, 72% at darunavir rollout 2020). Fifty first-year PSIs were reported. PSI rates were low (≤1.45/100 person-years) for most generics. EFV-FTC-TDF had a higher PSI rate (3.09/100 person-years, CI95%=1.83-5.23) due to neuropsychiatric side-effects, while generic darunavir had no reported PSIs.
PSI-related symptoms included mild-moderate gastrointestinal (26/50, 52%), neuropsychiatric (26%), dermatologic (12%) effects, and general fatigue/malaise (14%). Two-thirds of PLWH with generic PSIs switched to the brand-name equivalent.
Conclusion: We report low rates (generally ≤1.45/100 person-years) of generic product substitution-related adverse events in the year following brand-to-generic transition.

Background: Integrase strand transfer inhibitors (INSTIs) have been associated with excess weight gain in adults living with HIV. This study assessed the effect of INSTIs on BMI percentile of children living with perinatally acquired HIV (CLWPH).

Methods: EPIC4 prospectively enrolled and followed CLWPH from 7 Canadian centres from 2014-2018. Spline regression analysis was used to compare trends in BMI for patients with INSTI containing regimens versus age- and sex-matched INSTI naive patients. Data points were assessed at time of initiation and 1 & 2 years before and after starting INSTI containing regimens.

Results: 197 children (113 INSTI-exposed; 84 controls) were included, with median age 13 years at start of INSTI (range 0.4-18.5); 53% were female. 75% had normal BMI at baseline; 20% were overweight or obese, 5% were underweight. Dolutegravir, raltegravir and elvitegravir were prescribed for 33 (29%), 43 (38%), and 37 (33%), respectively. Viral load was detectable in 43/113 (39%) in INSTI group versus 9/84 (11%) in non-INSTI group at baseline, and in 7/61 (11.5%) and 13/73 (17.8%) after 2 years. Median CD4 count was 694 cells/uL in INSTI group vs 772 cells/uL in non-INSTI group at baseline, and 772 cells/uL vs 780 cells/uL after 2 years. Comparing BMI percentile over time in INSTI and control groups, modest increases in BMI percentile from baseline were noted in both groups. Regression analysis demonstrated no statistically significant difference in BMI percentiles between INSTI and non-INSTI groups (p=0.276), except in those taking INSTI plus protease inhibitors (n=27; difference in change in BMI percentile compared to non-INSTI at 1 and 2 years of 0.05 [p=0.014] and 0.12 [p=0.014], respectively).

Conclusion: INSTI-containing regimens do not appear to be associated with increase in BMI percentile in children living with perinatally acquired HIV in Canada.

Objectives
To engage people living with HIV (PLHIV) in their care and support their HIV self-management, we developed a bilingual (EN/FR) Chatbot MARVIN using artificial intelligence. MARVIN answers patients’ questions about antiretrovirals 24/7 with expert-validated information. In this study, we gauged MARVIN’s usability and acceptability.

Methods
We recruited 30 adult PLHIV receiving care at the McGill University Health Centre for a 4-week trial. Participants were asked to 1) have at least 20 conversations with MARVIN on predetermined topics and complete a usability and acceptability questionnaire and 2) participate in a semi-structured focus group in week 4 to discuss their experiences with MARVIN. Usability and acceptability were measured using the Usability Metric for User Experience-lite (UMUX-lite) and Acceptability E-Scale (AES), considering their predetermined thresholds of 68 and 24 respectively. We then compared the qualitative and the quantitative results on the four sub-constructs of the Technology Acceptance Model (TAM): perceived ease of use, perceived usefulness, attitude toward use, and behavioral intention.

Results
From April to December 2021, 26 participants completed the study. Their mean age was 40.8 years (SD=11.9), most were male (n=23/26), and over half (n=14/26) preferred to communicate with MARVIN in English. Mean scores for the UMUX-lite and AES were 69.8 and 23.7. Proximity to the predetermined thresholds indicates that MARVIN is usable and acceptable. Preliminary qualitative results suggest that MARVIN is easy to use and useful when it provides the correct answers. However, participants noted the lack of breadth and depth of conversations and requested several additional topics, including antiretroviral side effects, drug interactions, community support group information, and HIV research updates.

Conclusion
Our preliminary results suggest that the current MARVIN Chatbot is usable and acceptable for PLHIV and is a promising telehealth companion. Adding new conversational topics will be a main priority for the next phase.

Background

PrEP stigma is an expression of social power which uses stereotypes (e.g., promiscuity) to devalue PrEP users. Using thematic analysis, we characterized participants’ experiences of PrEP stigma within the Ontario PrEP Cohort Study.

Methods

Adults initiating or using PrEP completed 6-monthly electronic questionnaires for up to two years from 02/2018-06/2021, including annual questions about anticipated and enacted PrEP stigma. Using inductive thematic analysis techniques, we developed a codebook of socioecological PrEP stigma themes based on participants’ responses and pre-existing literature. Participants’ written responses were then iteratively coded by theme, with disagreements resolved by a third author.

Results

Of 167 participants who provided a written description of PrEP stigma, median age was 35.6 (IQR, 29.3-41.2) years, 154 (92.2%) identified as male, and 142 (85.0%) as gay. Across 211 responses, 18 themes of PrEP stigma were identified across three socioecological levels: community, interpersonal, and institutional. Community-level stigma was the most common, with themes including: promiscuity (38.4% of all 211 responses), risk promotion (25.6%), general (13.7%), HIV-related stigma (4.2%), PrEP efficacy distrust (2.8%), responsibility to educate peers (2.8%), and homophobia/transphobia (0.0%). Interpersonal-level stigma was the next most common, with themes being: general (11.3%), risk promotion (10.9%), HIV-related stigma (6.6%), promiscuity (6.1%), PrEP efficacy distrust (5.7%), de-stigmatization (reverse-coded) (5.2%), and homophobia/transphobia (2.4%). Institutional-level stigma was the least common socioecological level, with themes being: healthcare discrimination (2.8%), healthcare distrust (2.4%), governmental distrust (1.9%), and governmental discrimination (0.0%).

Conclusion

While PrEP users most commonly reported stigmatization related to promiscuity and risk-promotion, other expressions of stigma (e.g., HIV-related stigma) were not rare. By identifying these varying expressions of PrEP stigma, this research can help address stigmatization by providing services a socioecological framework of how PrEP users experience stigma.

Background
Healthcare-related factors may influence future PrEP use. We explored whether first experiences with PrEP-related healthcare differed between GBM on PrEP and GBM who discontinued PrEP.

Methods
We used data from the PrEP implementation project (PRIMP), a cross-sectional survey from July 2019 to August 2020 in Toronto, Ottawa, Hamilton, Vancouver and Victoria. Our analytic sub-sample was GBM who met criteria for PrEP according to the Canadian PrEP guidelines. We asked about their first experience seeking PrEP.

Results
Of 522 respondents, 147 had stopped PrEP and 375 were taking PrEP. GBM who discontinued PrEP were younger than those taking PrEP (30.3 (SD=7.8) vs. 35.3 years (SD=10), p<0.001) and earned less (26% earned >$60.000/year versus 45%, p<0.001). Those who discontinued PrEP were more likely to have sought PrEP from their family doctor (instead of a sexual health clinic) more often than those who continued PrEP (42% vs 27%, p=0.004). Participants who stopped PrEP waited a median of 11.5 days (IQR= 7-16) for their first prescription versus 19 days (IQR= 7-60) for those currently on PrEP (p<0.001).
Those still taking PrEP felt more comfortable discussing their sexual health with their healthcare provider (HCP) (86% vs 75%, p=0.003) and were more often instructed to take PrEP daily (91%) versus on-demand (58%, p<0.001). Participants currently on PrEP reported greater satisfaction with their first experience seeking PrEP (Figure).

Conclusion
GBM who discontinued PrEP were less satisfied with PrEP-related healthcare than GBM who stayed on PrEP. Initial experiences seeking PrEP may have lasting implications on PrEP persistence.

Background: Women living with HIV are increasingly overrepresented within correctional settings and experience sub-optimal HIV health outcomes post-release from incarceration. To identify specific areas of intervention, we used path analysis to investigate pathways from recent incarceration to optimal antiretroviral therapy (ART) adherence through mediators of homelessness, criminalized substance use, and gender-based violence.

Methods: We drew on 9 years (2010-2019) of data from the SHAWNA (Sexual Health and HIV/AIDS: Women’s Longitudinal Needs Assessment) Project, a longitudinal community-based research cohort with self-identified cis and trans women living with HIV in Metro Vancouver, Canada. Using path analysis, we tested direct effects between recent incarceration, mediating variables, and ART adherence, along with indirect effects between incarceration and ART adherence through each mediator. Model fit was assessed using chi-square, root mean square error of approximation (RMSEA), and comparative fit index (CFI).

Results: Among 336 participants at baseline, Indigenous women accounted for 57% of the sample, 9% were Black or otherwise racialized, and 34% were white; 7% reported trans identity. Within the last 6 months at baseline, 9% had been incarcerated, 22% had experienced homelessness, 70% had used criminalized substances, and 19% had experienced gender-based violence. Path analysis model fit indicated our hypothesized model fit well to the data (χ2(1)=1.100; p=0.2943; CFI=1.000; RMSEA=0.007). In the final model recent homelessness, recent criminalized substance use, and recent gender-based violence fully mediated the pathway between recent incarceration and optimal ART adherence.

Conclusions: To improve ART adherence and subsequent health outcomes among women living with HIV post-release from incarceration, there is an urgent need for expanded options for safe and supportive housing, alongside tailored supports for criminalized substance use. Services and programs must be rooted in cultural safety and trauma and violence-informed practice, and be sensitive to the ongoing impacts of gender-based violence among marginalized women.