Adverse drug reactions attributed to generic substitution of antiretroviral medications among HIV treatment and pre-exposure prophylaxis clients in British Columbia, Canada.

BACKGROUND: In British Columbia, antiretrovirals (ARVs) for HIV treatment (HIV-Tx) and pre-exposure prophylaxis (PrEP) are free-of-charge through publicly-funded Drug Treatment Programs (DTPs). When available, less costly generics are substituted for brand-name ARVs. We describe the incidence and type of product substitution issue (PSI) adverse drug reactions (ADRs) attributed to generic ARVs. METHODS: Cohorts included DTP clients ≥19 years who received generic ARVs for HIV-Tx (abacavir-lamivudine, emtricitabine-tenofovir DF, efavirenz-emtricitabine-tenofovir DF, atazanavir or darunavir between 01 Jun 2017 and 30 Jun 2022) or PrEP (emtricitabine-tenofovir DF, 01 Apr 2018 to 30 Jun 2022). Demographic, ARV and ADR data were extracted from DTP databases and summarized by descriptive statistics. PSI incidence was calculated for each product during the year following brand-to-generic and generic-to-generic transitions (first-year-post-rollout), and compared between generic versions using generalized estimating equations. For context, incidence of any ARV product-related ADR was calculated in the same 1-year periods. RESULTS: During first-year-post-rollout periods, 5339 HIV-Tx (83% male, median age 52 years) and 8095 PrEP (99% male, median 33 years) clients received generic ARVs, and reported 78 and 23 generic PSIs, respectively. PSI incidence was <1% for most generic ARVs, with mild-moderate symptoms including gastrointestinal upset, headache, dizziness, fatigue/malaise and skin rash. In HIV-Tx clients, the efavirenz-containing product had higher PSI incidence than other ARVs (2.2%, p = .004), due to more neuropsychiatric adverse reactions. Any ADR incidence was stable across measurement periods, and generic PSIs represented less than one third of all product-related ADRs. CONCLUSIONS: Generic substitution of antiretrovirals for HIV-Tx and PrEP was well tolerated, with ≤2% incidence of mild-moderate PSI ADRs.

Effects of COVID-19 mRNA vaccination on HIV viremia and reservoir size.

OBJECTIVE: The immunogenic nature of COVID-19 mRNA vaccines led to some initial concern that these could stimulate the HIV reservoir. We analyzed changes in plasma HIV loads (pVL) and reservoir size following COVID-19 mRNA vaccination in 62 people with HIV (PWH) receiving antiretroviral therapy (ART), and analyzed province-wide trends in pVL before and after the mass vaccination campaign. DESIGN: Longitudinal observational cohort and province-wide analysis. METHODS: 62 participants were sampled pre-vaccination, and one month after their first and second COVID-19 immunizations. Vaccine-induced anti-SARS-CoV-2-Spike antibodies in serum were measured using the Roche Elecsys Anti-S assay. HIV reservoirs were quantified using the Intact Proviral DNA Assay; pVL were measured using the cobas 6800 (LLOQ:20 copies/mL). The province-wide analysis included all 290,401 pVL performed in British Columbia, Canada between 2012-2022. RESULTS: Pre-vaccination, the median intact reservoir size was 77 (IQR:20-204) HIV copies/million CD4+ T-cells, compared to 74 (IQR:27-212) and 65 (IQR:22-174) post-first and -second dose, respectively (all comparisons p>0.07). Pre-vaccination, 82% of participants had pVL<20 copies/mL (max:110 copies/mL), compared to 79% post-first dose (max:183 copies/mL) and 85% post-second dose (max:79 copies/mL) (p > 0.4). There was no evidence that the magnitude of the vaccine-elicited anti-SARS-CoV-2-Spike immune response influenced pVL nor changes in reservoir size (p > 0.6). We found no evidence linking the COVID-19 mass vaccination campaign to population-level increases in detectable pVL frequency among all PWH in the province, nor among those who maintained pVL suppression on ART. CONCLUSION: We found no evidence that COVID-19 mRNA vaccines induced changes in HIV reservoir size nor plasma viremia.

Effects of COVID-19 mRNA vaccination on HIV viremia and reservoir size.

Objective: The immunogenic nature of COVID-19 mRNA vaccines led to some initial concern that these could stimulate the HIV reservoir. We analyzed changes in plasma HIV loads (pVL) and reservoir size following COVID-19 mRNA vaccination in 62 people with HIV (PWH) receiving antiretroviral therapy (ART), and analyzed province-wide trends in pVL before and after the mass vaccination campaign. Design: Longitudinal observational cohort and province-wide analysis. Methods: 62 participants were sampled pre-vaccination, and one month after their first and second COVID-19 immunizations. Vaccine-induced anti-SARS-CoV-2-Spike antibodies in serum were measured using the Roche Elecsys Anti-S assay. HIV reservoirs were quantified using the Intact Proviral DNA Assay; pVL were measured using the cobas 6800 (LLOQ:20 copies/mL). The province-wide analysis included all 290,401 pVL performed in British Columbia, Canada between 2012-2022. Results: Pre-vaccination, the median intact reservoir size was 77 (IQR:20-204) HIV copies/million CD4+ T-cells, compared to 74 (IQR:27-212) and 65 (IQR:22-174) post-first and -second dose, respectively (all comparisons p>0.07). Pre-vaccination, 82% of participants had pVL<20 copies/mL (max:110 copies/mL), compared to 79% post-first dose (max:183 copies/mL) and 85% post-second dose (max:79 copies/mL) (p>0.4). The magnitude of the vaccine-elicited anti-SARS-CoV-2-Spike antibody response did not correlate with changes in reservoir size nor detectable pVL frequency (p>0.6). We found no evidence linking the COVID-19 mass vaccination campaign to population-level increases in detectable pVL frequency among all PWH in the province, nor among those who maintained pVL suppression on ART. Conclusion: We found no evidence that COVID-19 mRNA vaccines induced changes in HIV reservoir size nor plasma viremia.

Process description of developing HIV prevention monitoring indicators for a province-wide pre-exposure prophylaxis (PrEP) program in British Columbia, Canada.

In 2018, the pre-exposure prophylaxis (PrEP) program was initiated in British Columbia (BC), Canada, providing PrEP at no cost to qualifying residents. This observational study discussed the steps to develop key evidence-based monitoring indicators and their calculation using real-time data. The indicators were conceptualized, developed, assessed and approved by the Technical Monitoring Committee of representatives from five health authority regions in BC, the BC Ministry of Health, the BC Centre for Disease Control, and the BC Centre for Excellence in HIV/AIDS. Indicator development followed the steps adopted from the United States Centers for Disease Control and Prevention framework for program evaluation in public health. The assessment involved eight selection criteria: data quality, indicator validity, existing scientific evidence, indicator informativeness, indicator computing feasibility, clients' confidentiality maintenance capacity, indicator accuracy, and administrative considerations. Clients' data from the provincial-wide PrEP program (January 2018-December 2020) shows the indicators' calculation. The finalized 14 indicators included gender, age, health authority, new clients enrolled by provider type and by the health authority, new clients dispensed PrEP, clients per provider, key qualifying HIV risk factor(s), client status, PrEP usage type, PrEP quantity dispensed, syphilis and HIV testing and incident cases, and adverse drug reaction events. Cumulative clients' data (n = 6966; 99% cis-gender males) identified an increased new client enrollment and an unexpected drop during the COVID-19 pandemic. About 80% dispensed PrEP from the Vancouver Coastal health authority. The HIV incidence risk index for men who have sex with men score ≥10 was the most common qualifying risk factor. The framework we developed integrating indicators was applied to monitor our PrEP program, which could help reduce the public health impact of HIV.

Healthcare and treatment experiences among people diagnosed with HIV before and after a province-wide treatment as prevention initiative in British Columbia, Canada.

INTRODUCTION: In 2010, the Canadian province of British Columbia (BC) initiated the Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) program to improve HIV testing, linkage to care, and treatment uptake, thereby operationalizing the HIV Treatment as Prevention (TasP) framework at the population-level. In this analysis, we evaluated self-reported HIV care experiences and therapeutic outcomes among people diagnosed with HIV prior to and after implementation of this provincial program. METHODS: A cross-sectional analysis was performed on the baseline data of a cohort of people living with HIV (PLWH) (19 years and older) in the province of BC sampled from July 2016 to September 2018. All participants consented to linking their survey data to the provincial HIV treatment registry. Individuals diagnosed with HIV from January 1 2000-December 31 2009 were classified as pre-intervention and those diagnosed January 1 2010-December 31 2018 as post-intervention cohorts. Bivariate analyses were run using Chi-square and Wilcoxon Rank Sum tests. Cox proportional hazards regression model demonstrates time to antiretroviral therapy (ART) initiation (from HIV baseline) and virological suppression (2 consecutive plasma viral load measurements < 200 copies/ml). RESULTS: Of the 325 participants included in this analysis, 198 (61%) were diagnosed with HIV in the pre-intervention era and 127 (39%) in the post-intervention era. A higher proportion of participants in post-intervention era were diagnosed at walk-in clinics (45% vs. 39%) and hospitals (21% vs. 11%) (vs pre-intervention) (p = 0.042). Post-intervention participants had initiated ART with less advanced HIV disease (CD4 count 410 vs. 270 cells/ul; p = 0.001) and were less likely to experience treatment interruptions at any point in the 5 years after HIV diagnosis (17% vs. 48%; p < 0.001). The post-intervention cohort had significantly more timely ART initiation (aHR: 5.97, 95%CI 4.47, 7.97) and virologic suppression (aHR: 2.03, 95%CI 1.58, 2.60) following diagnosis, after controlling for confounders. CONCLUSIONS: We found favourable treatment experiences and more timely ART initiation and virologic suppression after a targeted TasP provincial program. Our results illustrate the importance of accessible low-barrier HIV testing and treatment in tackling the HIV epidemic.

Longitudinal Analysis of HIV Risk and Substance Use Patterns for Men Who Have Sex with Men and Women and Men Who Have Sex with Men Only.

Men Who Have Sex with Men and Women (MSMW) experience discrimination from same-sex and heterosexual communities partially because of perceptions they feature high-risk sexual behavior, elevated polysubstance use levels, and constitute an HIV bridge population. We used a longitudinal multivariate generalized linear mixed model comparing sexual risk and substance use patterns for Men Who Have Sex with Men Only (MSMO) with MSMW in the same cohort study. Data consisted of 771 men reporting 3,705 sexual partnerships from 2012-2017. For high-risk sexual behavior multivariate results showed non-significant (p>0.05) differences for partner number and commercial sex work, and significantly less (p<0.05) HIV prevalence and condomless anal sex. However, MSMW had significantly higher levels of hallucinogen and prescription opioid use, and substance treatment histories. Only one HIV-positive MSMW had a transmittable viral load, negating the concept of an HIV bridge population. Results indicate the need for additional longitudinal studies comparing MSMO and MSMW.

Factors associated with lost to follow-up after hepatitis C treatment delivered by primary care teams in an inner-city multi-site program, Vancouver, Canada.

BACKGROUND: Treatment of hepatitis c virus (HCV) with direct-acting-antivirals (DAAs) by family physicians in primary care and addiction settings may allow treatment expansion to inner-city populations, including people who inject drugs (PWID). Real-world data however, suggests high rates of non-attendance to SVR 12 testing. This study examines outcomes of HCV treatment delivered by family physicians working in interdisciplinary treatment programs, integrated into inner-city primary care clinics. METHODS: In this prospective cohort, participants completed baseline questionnaires, including questions on demographics and substance use. Participants were recorded as achieving a sustained virologic response (SVR 12) if HCV RNA was undetectable 12 weeks following end of therapy, and were recorded as lost to follow-up (LTFU) if they did not present for an HCV follow-up visit. SVR was calculated in intention to treat (ITT) as well as modified intention to treat (mITT) analysis, which excluded those who completed treatment but had no SVR 12 result. A logistic regression model assessed factors associated with LTFU. RESULTS: Of 138 individuals included in the analysis, 52% were on opioid agonist therapy (OAT), 75% reported a history of injection drug use (IDU), with 25% reporting IDU in the month prior to treatment initiation. ITT SVR across all sites and genotypes was 86% and mITT was 95%. There was a significant difference in mITT for those reporting recent IDU compared to those who did not (87% vs 99% p = 0.03). While 13% were LTFU at SVR 12, participants receiving OAT in the same clinic as HCV treatment were less likely to be LTFU (aOR 0.09(0.02-0.46)). CONCLUSION: HCV treatment by family physicians, along with interdisciplinary teams, can be successful in inner-city populations in the era of DAAs; however, follow-up after treatment is a challenge. Integrating OAT in the same location as HCV treatment may help to improve follow-up.

Viral suppression and viral rebound among young adults living with HIV in Canada.

Describe the prevalence and covariates of viral suppression and subsequent rebound among younger (≤29 years old) compared with older adults.A retrospective clinical cohort study; eligibility criteria: documented HIV infection; resident of Canada; 18 years and over; first antiretroviral regimen comprised of at least 3 individual agents on or after January 1, 2000.Viral suppression and rebound were defined by at least 2 consecutive viral load measurements <50 or >50 HIV-1 RNA copies/mL, respectively, at least 30 days apart, in a 1-year period. Time to suppression and rebound were measured using the Kaplan-Meier method and Life Table estimates. Accelerated failure time models were used to determine factors independently associated with suppression and rebound.Younger adults experienced lower prevalence of viral suppression and shorter time to viral rebound compared with older adults. For younger adults, viral suppression was associated with being male and later era of combination antiretroviral initiation (cART) initiation. Viral rebound was associated with a history of injection drug use, Indigenous ancestry, baseline CD4 cell count >200, and initiating cART with a protease inhibitor (PI) containing regimen.The influence of age on viral suppression and rebound was modest for this cohort. Our analysis revealed that key covariates of viral suppression and rebound for young adults in Canada are similar to those of known importance to older adults. Women, people who use injection drugs, and people with Indigenous ancestry could be targeted by future health interventions.