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.

Depressive Symptoms, the Impact on ART Continuation, and Factors Associated with Symptom Improvement Among a Cohort of People Living with HIV in British Columbia, Canada.

Depressive symptoms among people living with HIV (PLWH) are associated with poorer overall health outcomes. We characterized depressive symptoms and improvements in symptomology among PLWH (≥ 19 years old) in British Columbia (BC), Canada. We also examined associations between depressive symptomology and antiretroviral therapy (ART) treatment interruptions. Depressive symptoms were measured using the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10), within a longitudinal cohort study with three surveys administered 18-months apart. We used multivariable logistic regression to model factors associated with improvements in depressive symptoms (CES-D-10 scores from ≥ 10 to < 10). Of the 566 participants eligible for analysis 273 (48.2%) had CES-D scores indicating significant depressive symptoms (score ≥ 10) at enrollment. Improvements in symptoms at first follow-up were associated with greater HIV self-care on the Continuity of Care Scale (adjusted odds ratio: 1.17; 95% CI 1.03-1.32), and not having a previously reported mental health disorder diagnosis (aOR 2.86; 95% CI 1.01-8.13). Those reporting current cocaine use (aOR 0.33; 95% CI 0.12-0.91) and having a high school education, vs. less than, (aOR 0.25; 95% CI 0.08-0.82) had lower odds of improvement in depressive symptomatology. CES-D scores ≥ 10 were not significantly associated with ART treatment interruptions during follow-up (aOR: 1.08; 95% CI:0.65-1.8). Supporting greater self-care and consideration of mental health management strategies in relation to HIV may be useful in promoting the wellbeing of PLWH who experience depressive symptoms.

Risk of Multiple Sclerosis in People Living with HIV: An International Cohort Study.

OBJECTIVE: There has been interest in a possible negative association between HIV and multiple sclerosis (MS). We aimed to compare the risk of MS in a cohort of individuals living with HIV to that in the general population. METHODS: Population-based health data were accessed for 2 cohorts of HIV-positive persons from Sweden and British Columbia, Canada. Incident MS was identified using MS registries or a validated algorithm applied to administrative data. Individuals with HIV were followed from 1 year after the first clinical evidence of HIV or the first date of complete administrative health data (Canada = April 1, 1992 and Sweden = January 1, 2001) until the earliest of incident MS, emigration, death, or study end (Canada = March 31, 2020 and Sweden = December 31, 2018). The observed MS incidence rate in the HIV-positive cohort was compared to the expected age-, sex-, calendar year-, income-specific, and region of birth-specific rates in a randomly selected sample of >20% of each general population. The standardized incidence ratio (SIR) for MS following the first antiretroviral therapy exposure ("ART-exposed") was also calculated. RESULTS: The combined Sweden-Canada cohort included 29,163 (75% men) HIV-positive persons. During 242,248 person-years of follow-up, 14 incident MS cases were observed in the HIV-positive cohort, whereas 26.19 cases were expected. The SIR for MS in the HIV-positive population was 0.53 (95% confidence interval [CI] = 0.32-0.90). The SIR for MS following the first ART exposure was 0.55 (95% CI = 0.31-0.96). INTERPRETATION: This international population-based study demonstrated a lower risk of MS among HIV-positive individuals, and HIV-positive ART-exposed individuals. These findings provide support for further exploration into the relationship among HIV, ART, and MS. ANN NEUROL 2024;95:487-494.

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.

Identification of people with low prevalence diseases in administrative healthcare records: A case study of HIV in British Columbia, Canada.

INTRODUCTION: Case-finding algorithms can be applied to administrative healthcare records to identify people with diseases, including people with HIV (PWH). When supplementing an existing registry of a low prevalence disease, near-perfect specificity helps minimize impacts of adding in algorithm-identified false positive cases. We evaluated the performance of algorithms applied to healthcare records to supplement an HIV registry in British Columbia (BC), Canada. METHODS: We applied algorithms based on HIV-related diagnostic codes to healthcare practitioner and hospitalization records. We evaluated 28 algorithms in a validation sub-sample of 7,124 persons with positive HIV tests (2,817 with a prior negative test) from the STOP HIV/AIDS data linkage-a linkage of healthcare, clinical, and HIV test records for PWH in BC, resembling a disease registry (1996-2020). Algorithms were primarily assessed based on their specificity-derived from this validation sub-sample-and their impact on the estimate of the total number of PWH in BC as of 2020. RESULTS: In the validation sub-sample, median age at positive HIV test was 37 years (Q1: 30, Q3: 46), 80.1% were men, and 48.9% resided in the Vancouver Coastal Health Authority. For all algorithms, specificity exceeded 97% and sensitivity ranged from 81% to 95%. To supplement the HIV registry, we selected an algorithm with 99.89% (95% CI: 99.76% - 100.00%) specificity and 82.21% (95% CI: 81.26% - 83.16%) sensitivity, requiring five HIV-related healthcare practitioner encounters or two HIV-related hospitalizations within a 12-month window, or one hospitalization with HIV as the most responsible diagnosis. Upon adding PWH identified by this highly-specific algorithm to the registry, 8,774 PWH were present in BC as of March 2020, of whom 333 (3.8%) were algorithm-identified. DISCUSSION: In the context of an existing low prevalence disease registry, the results of our validation study demonstrate the value of highly-specific case-finding algorithms applied to administrative healthcare records to enhance our ability to estimate the number of PWH living in BC.

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.

People With Human Immunodeficiency Virus Receiving Suppressive Antiretroviral Therapy Show Typical Antibody Durability After Dual Coronavirus Disease 2019 Vaccination and Strong Third Dose Responses.

BACKGROUND: Longer-term humoral responses to 2-dose coronavirus disease 2019 (COVID-19) vaccines remain incompletely characterized in people living with human immunodeficiency virus (HIV) (PLWH), as do initial responses to a third dose. METHODS: We measured antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain, angiotensin-converting enzyme 2 (ACE2) displacement, and viral neutralization against wild-type and Omicron strains up to 6 months after 2-dose vaccination, and 1 month after the third dose, in 99 PLWH receiving suppressive antiretroviral therapy and 152 controls. RESULTS: Although humoral responses naturally decline after 2-dose vaccination, we found no evidence of lower antibody concentrations or faster rates of antibody decline in PLWH compared with controls after accounting for sociodemographic, health, and vaccine-related factors. We also found no evidence of poorer viral neutralization in PLWH after 2 doses, nor evidence that a low nadir CD4+ T-cell count compromised responses. Post-third-dose humoral responses substantially exceeded post-second-dose levels, though Omicron-specific responses were consistently weaker than responses against wild-type virus. Nevertheless, post-third-dose responses in PLWH were comparable to or higher than controls. An mRNA-1273 third dose was the strongest consistent correlate of higher post-third-dose responses. CONCLUSION: PLWH receiving suppressive antiretroviral therapy mount strong antibody responses after 2- and 3-dose COVID-19 vaccination. Results underscore the immune benefits of third doses in light of Omicron.

Antibody response durability following three-dose coronavirus disease 2019 vaccination in people with HIV receiving suppressive antiretroviral therapy.

BACKGROUND: Limited data exist regarding longer term antibody responses following three-dose coronavirus disease 2019 (COVID-19) vaccination, and the impact of a first SARS-CoV-2 infection during this time, in people with HIV (PWH) receiving suppressive antiretroviral therapy (ART). We quantified wild-type-specific, Omicron BA.1-specific and Omicron BA.5-specific responses up to 6 months post-third dose in 64 PWH and 117 controls who remained COVID-19-naive or experienced their first SARS-CoV-2 infection during this time. DESIGN: Longitudinal observational cohort. METHODS: We quantified wild-type-specific and Omicron-specific anti-Spike receptor-binding domain IgG concentrations, ACE2 displacement activities and live virus neutralization at 1, 3 and 6 months post-third vaccine dose. RESULTS: Third doses boosted all antibody measures above two-dose levels, but BA.1-specific responses remained significantly lower than wild-type-specific ones, with BA.5-specific responses lower still. Serum IgG concentrations declined at similar rates in COVID-19-naive PWH and controls post-third dose (median wild-type-specific and BA.1-specific half-lives were between 66 and 74 days for both groups). Antibody function also declined significantly yet comparably between groups: 6 months post-third dose, BA.1-specific neutralization was undetectable in more than 80% of COVID-19 naive PWH and more than 90% of controls. Breakthrough SARS-CoV-2 infection boosted antibody concentrations and function significantly above vaccine-induced levels in both PWH and controls, though BA.5-specific neutralization remained significantly poorer than BA.1 even post-breakthrough. CONCLUSION: Following three-dose COVID-19 vaccination, antibody response durability in PWH receiving ART is comparable with controls. PWH also mounted strong responses to breakthrough infection. Due to temporal response declines, however, COVID-19-naive individuals, regardless of HIV status, would benefit from a fourth dose within 6 months of their third.

Virological suppression among gay, bisexual, and other men who have sex with men living with HIV in Vancouver, Canada: A longitudinal cohort study from 2012-2017.

INTRODUCTION: In 2010, British Columbia (BC) implemented HIV Treatment as Prevention (TasP) as policy. We examined trends in virologic suppression and determinants of significant viremia among a prospective biobehavioural cohort of men who have sex with men (gbMSM) in Vancouver from 2012-2017. METHODS: Respondent-driven sampling was used to recruit sexually active gbMSM (≥16 years) who completed biannual study visits with a computer-assisted self-interview and clinical CD4 and viral load (VL) testing. We linked participant data with the BC HIV Drug Treatment Program to obtain antiretroviral dispensing and VL data. We conducted a trend analysis of VL suppression using univariable generalized estimating equation (GEE) multi-level modelling and multivariable GEE to identify factors associated with episodes of VL ≥200 copies/mL. RESULTS: Of 774 participants, 223 were living with HIV at baseline and 16 were diagnosed during follow-up (n = 239). We observed a significant trend towards reduced levels of unsuppressed VL (>200 copies/mL) from 22% (07/2012-12/2012) to 12% (07/2016-12/2016) (OR:0.87; 95%CI:0.83-0.91 for each 6-month period). Among those with at least one follow-up visit, (n = 178, median follow-up = 3.2 years, median age = 46.9 years), younger age (aOR:0.97; 95%CI:0.94-0.99, per year), ecstasy use (aOR:1.69; 95%CI:1.13-2.53), crystal methamphetamine use (aOR:1.71; 95%CI:1.18-2.48), seeking sex via websites (aOR:1.46; 95%CI:1.01-2.12), and lower HIV treatment optimism (aOR:0.94; 95%CI:0.90-0.97) were associated with episodes of elevated viremia. CONCLUSIONS: During a period when TasP policy was actively promoted, we observed a significant trend towards reduced levels of unsuppressed VL. Continued efforts should promote HIV treatment optimism and engagement, especially among younger gbMSM and those who use ecstasy and crystal methamphetamine.

Evolving patterns of antiretroviral drug interactions in people with HIV in British Columbia, Canada.

OBJECTIVES: To characterize the annual prevalence of antiretroviral/nonantiretroviral drug interactions in relation to antiretroviral therapy (ART)-prescribing patterns, and to describe drug interaction-related ART changes. DESIGN/METHODS: This cohort study included ART-treated adults in British Columbia, Canada between 01 January 2010 and 31 December 2016. Medication dispensing records were abstracted from a population-based, linked administrative-health dataset and used to identify antiretroviral-comedication drug interactions ('caution'/'avoid' drug interactions in HIV-focused drug interaction checkers). We identified temporal trends in annual drug interaction prevalence and quantified the association between taking higher drug interaction-risk ART and receiving nonrecommended antiretroviral-comedication combinations using Poisson regression models, modified for binary outcomes and correlated data. Clinician-reported, drug interaction-related ART changes and associated adverse events were abstracted from an HIV drug treatment registry and summarized descriptively. RESULTS: Among 8571 ART-treated adults who received nonantiretroviral comedications, prevalence of having any drug interaction or receiving nonrecommended drug combination(s) significantly declined from 85 to 71% and 5.6 to 3.2%, respectively, between 2010 and 2016 ( P  < 0.001). This paralleled a shift from higher drug interaction-risk ART (e.g. ritonavir/cobicistat-boosted protease inhibitors) to lower drug interaction-risk ART (e.g. unboosted integrase inhibitors). Risk of receiving a nonrecommended antiretroviral-comedication combination was greater for persons taking higher vs. lower drug interaction-risk ART [adjusted risk ratio (aRR) 3.12, 95% confidence interval (CI) 2.24-4.35]. Boosted antiretroviral-inhaled corticosteroid drug interactions accounted for the most commonly dispensed, nonrecommended drug combinations, and the most commonly reported drug interaction-related adverse events (adrenal insufficiency). CONCLUSION: The prevalence of antiretroviral-comedication drug interactions is declining as ART shifts towards antiretrovirals with lower drug interaction potential but nonrecommended drug combinations remain a concern. Healthcare providers should screen for drug interactions whenever drugs are prescribed or dispensed.

People with HIV receiving suppressive antiretroviral therapy show typical antibody durability after dual COVID-19 vaccination, and strong third dose responses.

Background: Longer-term humoral responses to two-dose COVID-19 vaccines remain incompletely characterized in people living with HIV (PLWH), as do initial responses to a third dose. Methods: We measured antibodies against the SARS-CoV-2 spike protein receptor-binding domain, ACE2 displacement and viral neutralization against wild-type and Omicron strains up to six months following two-dose vaccination, and one month following the third dose, in 99 PLWH receiving suppressive antiretroviral therapy, and 152 controls. Results: Though humoral responses naturally decline following two-dose vaccination, we found no evidence of lower antibody concentrations nor faster rates of antibody decline in PLWH compared to controls after accounting for sociodemographic, health and vaccine-related factors. We also found no evidence of poorer viral neutralization in PLWH after two doses, nor evidence that a low nadir CD4+ T-cell count compromised responses. Post-third-dose humoral responses substantially exceeded post-second-dose levels, though anti-Omicron responses were consistently weaker than against wild-type.Nevertheless, post-third-dose responses in PLWH were comparable to or higher than controls. An mRNA-1273 third dose was the strongest consistent correlate of higher post-third-dose responses. Conclusion: PLWH receiving suppressive antiretroviral therapy mount strong antibody responses after two- and three-dose COVID-19 vaccination. Results underscore the immune benefits of third doses in light of Omicron.

Prevalence and incidence of hepatitis C infection amongst men who have sex with men in a population-based pre-exposure prophylaxis program in British Columbia, Canada.

BACKGROUND: Men who have sex with men (MSM) are at risk for sexually-transmitted hepatitis C (HCV). Evidence for HCV infection in the context of pre-exposure prophylaxis (PrEP) use in North America is limited. We sought to characterize baseline HCV prevalence and incidence in MSM receiving PrEP in British Columbia (BC), Canada. METHODS: We followed individuals in the BC PrEP program from January 2018 to August 2019. We evaluated baseline prevalence and incident seroconversions (newly positive HCV antibody). A multivariable logistic regression model was performed in MSM for factors associated with HCV prevalence at enrollment, including reported prior sexually transmitted infection (STI), HIV Incidence Risk Index for MSM score, PrEP use because of a partner living with HIV, and location of residence. RESULTS: The median age of the cohort was 33 years, 98.3% male, with 3058 person years (PY) of follow-up. Baseline HCV prevalence was 0.82% (31/3907 MSM enrollees) and HCV incidence (n = 3) was 0.15 per 100 PY (95% confidence interval [CI] 0.03-0.45). In multivariable analysis, initiating PrEP because of a partner living with HIV (adjusted odds ratio [aOR] 5.02; 95% CI 1.87-13.47) and prior STI (aOR 2.34; 95% CI 1.04-5.24) were associated with positive HCV status. CONCLUSIONS: Baseline HCV prevalence and incidence was low amongst MSM in a population-based PrEP program in BC, Canada. HCV was associated with bridging from populations living with HIV and evidence of a reported prior STI as a PrEP indicator condition amongst MSM. PrEP initiation may be an opportunity for linkage to HCV screening and treatment.

Neighbourhood-level material deprivation and response to combination antiretroviral therapy in the Canadian Observational Cohort (CANOC): a longitudinal cohort study.

BACKGROUND: Socioeconomic status has been associated with higher viral loads and lower CD4 cell counts among people living with HIV. The objective of this study was to evaluate the relation between neighbourhood-level material deprivation and immunologic and virologic response to combination antiretroviral therapy (ART) among people living with HIV in Canada. METHODS: The Canadian Observational Cohort (CANOC) is a longitudinal cohort of people living with HIV, containing data from 2000-2016 from 5 Canadian provinces. We defined response to combination ART as positive if the CD4 cell count increased by 50 cells/mm3 (0.05 cells × 109/L) or more (CD4+) and viral load decreased to 50 copies/mL or less (VL+) within 6 months of treatment initiation. We further categorized response to therapy as concordant positive (CD4+/VL+), concordant negative (CD4-/VL-) or discordant (CD4+/VL- or CD4-/VL+). We used adjusted multinomial logistic regression to quantify the relation between neighbourhood-level material deprivation and immunologic and virologic response. RESULTS: This study included 8274 people living with HIV, of which 1754 (21.2%) lived in the most materially deprived neighbourhoods. Most individuals (62.2%) showed a concordant positive response to combination ART. After adjustment, living in the most materially deprived neighbourhoods was associated with a CD4-/VL+ discordant response (adjusted odds ratio [OR] 1.31, 95% confidence interval [CI] 1.06-1.62) and a concordant negative response (adjusted OR 1.45, 95% CI 1.13-1.86), using a concordant positive response as the reference. No other deprivation quartile was independently associated with a particular response. INTERPRETATION: People living with HIV from the most materially deprived neighbourhoods had increased odds of poor immunologic or virologic response to combination ART. These results motivate further study of the specific socioeconomic factors that potentially affect response to combination ART among people living with HIV in Canada.

Humoral immune responses to COVID-19 vaccination in people living with HIV receiving suppressive antiretroviral therapy.

Humoral responses to COVID-19 vaccines in people living with HIV (PLWH) remain incompletely characterized. We measured circulating antibodies against the SARS-CoV-2 spike protein receptor-binding domain (RBD), ACE2 displacement and viral neutralization activities one month following the first and second COVID-19 vaccine doses, and again 3 months following the second dose, in 100 adult PLWH and 152 controls. All PLWH were receiving suppressive antiretroviral therapy, with median CD4+ T-cell counts of 710 (IQR 525-935) cells/mm3, though nadir CD4+ T-cell counts ranged as low as <10 cells/mm3. After adjustment for sociodemographic, health and vaccine-related variables, HIV infection was associated with lower anti-RBD antibody concentrations and ACE2 displacement activity after one vaccine dose. Following two doses however, HIV was not significantly associated with the magnitude of any humoral response after multivariable adjustment. Rather, older age, a higher burden of chronic health conditions, and dual ChAdOx1 vaccination were associated with lower responses after two vaccine doses. No significant correlation was observed between recent or nadir CD4+ T-cell counts and responses to two vaccine doses in PLWH. These results indicate that PLWH with well-controlled viral loads and CD4+ T-cell counts in a healthy range generally mount strong initial humoral responses to dual COVID-19 vaccination. Factors including age, co-morbidities, vaccine brand, response durability and the rise of new SARS-CoV-2 variants will influence when PLWH will benefit from additional doses. Further studies of PLWH who are not receiving antiretroviral treatment or who have low CD4+ T-cell counts are needed, as are longer-term assessments of response durability.

The impact of lookback windows on the prevalence and incidence of chronic diseases among people living with HIV: an exploration in administrative health data in Canada.

BACKGROUND: We described the impact of different lengths of lookback window (LW), a retrospective time period to observe diagnoses in administrative data, on the prevalence and incidence of eight chronic diseases. METHODS: Our study populations included people living with HIV (N = 5151) and 1:5 age-sex-matched HIV-negative individuals (N = 25,755) in British Columbia, Canada, with complete follow-up between 1996 and 2012. We measured period prevalence and incidence of diseases in 2012 using LWs ranging from 1 to 16 years. Cases were deemed prevalent if identified in 2012 or within a defined LW, and incident if newly identified in 2012 with no previous cases detected within a defined LW. Chronic disease cases were ascertained using published case-finding algorithms applied to population-based provincial administrative health datasets. RESULTS: Overall, using cases identified by the full 16-year LW as the reference, LWs ≥8 years and ≥ 4 years reduced the proportion of misclassified prevalent and incidence cases of most diseases to < 20%, respectively. The impact of LWs varied across diseases and populations. CONCLUSIONS: This study underscored the importance of carefully choosing LWs and demonstrated data-driven approaches that may inform these choices. To improve comparability of prevalence and incidence estimates across different settings, we recommend transparent reporting of the rationale and limitations of chosen LWs.

Tobacco smoking and HIV-related immunologic and virologic response among individuals of the Canadian HIV Observational Cohort (CANOC).

We assessed the relationship between tobacco smoking and immunologic and virologic response among people living with HIV (PLWH) initiating combination antiretroviral therapy (cART) in the Canadian HIV Observational Cohort (CANOC). Positive immunologic and virologic response, respectively, were defined as ≥50 cells/mm3 CD4 count increase (CD4+) and viral suppression ≤50 copies/mL (VL+) within 6 months of cART initiation. Using multinomial regression, we examined the relationship between smoking, immunologic, and virologic response category. Model A adjusted for birth sex, baseline age, enrolling province, and era of cohort entry; models B and C further adjusted for neighbourhood level material deprivation and history of injection drug use (IDU), respectively. Among 4267 individuals (32.7%) with smoking status data, concordant positive (CD4+/VL+) response was achieved by 64.2% never, 66.9% former, and 59.4% current smokers. In the unadjusted analysis, current smoking was significantly associated with concordant negative response (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.40-2.45). Similarly, models A and B showed an increased odds of concordant negative response in current smokers (adjusted OR [aOR] 1.78, 95% CI 1.32-2.39 and 1.74, 95% CI 1.29-2.34, respectively). The association between current smoking and concordant negative response was no longer significant in model C (aOR 1.18, 95%CI 0.85-1.65).

Concordance of HIV transmission risk factors elucidated using viral diversification rate and phylogenetic clustering.

BACKGROUND AND OBJECTIVES: Although HIV sequence clustering is routinely used to identify subpopulations experiencing elevated transmission, it over-simplifies transmission dynamics and is sensitive to methodology. Complementarily, viral diversification rates can be used to approximate historical transmission rates. Here, we investigated the concordance and sensitivity of HIV transmission risk factors identified by phylogenetic clustering, viral diversification rate, changes in viral diversification rate and a combined approach. METHODOLOGY: Viral sequences from 9848 people living with HIV in British Columbia, Canada, sampled between 1996 and February 2019, were used to infer phylogenetic trees, from which clusters were identified and viral diversification rates of each tip were calculated. Factors associated with heightened transmission risk were compared across models of cluster membership, viral diversification rate, changes in diversification rate, and viral diversification rate among clusters. RESULTS: Viruses within larger clusters had higher diversification rates and lower changes in diversification rate than those within smaller clusters; however, rates within individual clusters, independent of size, varied widely. Risk factors for both cluster membership and elevated viral diversification rate included being male, young, a resident of health authority E, previous injection drug use, previous hepatitis C virus infection or a high recent viral load. In a sensitivity analysis, models based on cluster membership had wider confidence intervals and lower concordance of significant effects than viral diversification rate for lower sampling rates. CONCLUSIONS AND IMPLICATIONS: Viral diversification rate complements phylogenetic clustering, offering a means of evaluating transmission dynamics to guide provision of treatment and prevention services. LAY SUMMARY: Understanding HIV transmission dynamics within clusters can help prioritize public health resource allocation. We compared socio-demographic and clinical risk factors associated with phylogenetic cluster membership and viral diversification rate, a historical branching rate, in order to assess their relative concordance and sampling sensitivity.

Chronic Hepatitis B Infection Among Preexposure Prophylaxis Users Enrolled in a Population-Based Program in British Columbia, Canada.

Initiation of human immunodeficiency virus preexposure prophylaxis (PrEP) medications will also treat hepatitis B infection (HBV). The prevalence of chronic HBV was 0.86% (n=41/4760) among enrollees in a provincial PrEP program in British Columbia, Canada. Overall, 46.3% lacked follow-up HBV DNA monitoring, underscoring the need for HBV-related education for PrEP prescribers.

Humoral immune responses to COVID-19 vaccination in people living with HIV receiving suppressive antiretroviral therapy.

Humoral responses to COVID-19 vaccines in people living with HIV (PLWH) remain incompletely understood. We measured circulating antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, ACE2 displacement and live viral neutralization activities one month following the first and second COVID-19 vaccine doses in 100 adult PLWH and 152 controls. All PLWH were receiving suppressive antiretroviral therapy, with median CD4+ T-cell counts of 710 (IQR 525-935) cells/mm 3 . Nadir CD4+ T-cell counts ranged as low as <10 (median 280; IQR 120-490) cells/mm 3 . After adjustment for sociodemographic, health and vaccine-related variables, HIV infection was significantly associated with 0.2 log 10 lower anti-RBD antibody concentrations (p=0.03) and ∻11% lower ACE2 displacement activity (p=0.02), but not lower viral neutralization (p=0.1) after one vaccine dose. Following two doses however, HIV was no longer significantly associated with the magnitude of any response measured. Rather, older age, a higher burden of chronic health conditions, and having received two ChAdOx1 doses (versus a heterologous or dual mRNA vaccine regimen) were independently associated with lower responses. After two vaccine doses, no significant correlation was observed between the most recent or nadir CD4+ T-cell counts and vaccine responses in PLWH. These results suggest that PLWH with well-controlled viral loads on antiretroviral therapy and CD4+ T-cell counts in a healthy range will generally not require a third COVID-19 vaccine dose as part of their initial immunization series, though other factors such as older age, co-morbidities, vaccine regimen type, and durability of vaccine responses will influence when this group may benefit from additional doses. Further studies of PLWH who are not receiving antiretroviral treatment and/or who have low CD4+ T-cell counts are needed.