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The logistic regression model for a binary outcome with a continuous covariate can be expressed equivalently as a two-sample density ratio model for the covariate. Utilizing this equivalence, we study a change-point logistic regression model within the corresponding density ratio modeling framework. We investigate estimation and inference methods for the density ratio model and develop maximal score-type tests to detect the presence of a change point. In contrast to existing work, the density ratio modeling framework facilitates the development of a natural Kolmogorov-Smirnov type test to assess the validity of the logistic model assumptions. A simulation study is conducted to evaluate the finite-sample performance of the proposed tests and estimation methods. We illustrate the proposed approach using a mother-to-child HIV-1 transmission data set and an oral cancer data set., (© 2024 Wiley‐VCH GmbH.)

Objective: The immunogenic nature of coronavirus disease 2019 (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: Sixty-two participants were sampled prevaccination, 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 (lower limit of quantification: 20 copies/ml). The province-wide analysis included all 290 401 pVL performed in British Columbia, Canada between 2012 and 2022., Results: Prevaccination, the median intact reservoir size was 77 [interquartile range (IQR): 20-204] HIV copies/million CD4 + T-cells, compared to 74 (IQR: 27-212) and 65 (IQR: 22-174) postfirst and -second dose, respectively (all comparisons P > 0.07). Prevaccination, 82% of participants had pVL <20 copies/ml (max: 110 copies/ml), compared to 79% postfirst dose (max: 183 copies/ml) and 85% postsecond 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., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Women living with HIV commonly experience low areal bone mineral density (BMD), but whether this is affected by low ovarian hormonal states (prolonged amenorrhea or menopause) is unknown. We compared rates of BMD loss between women living with HIV and HIV-negative control women and investigated its association with low ovarian hormonal states., Setting: Women living with HIV were enrolled from Vancouver Canada and controls from 9 Canadian sites., Methods: This longitudinal analysis included age-matched women living with HIV in the Children and Women: AntiRetrovirals and Markers of Aging cohort and controls in the population-based Canadian Multicentre Osteoporosis Study. Rate of change/year in BMD at the total hip and lumbar spine (L1-L4) between 3 and 5 years was compared between groups, adjusting for sociodemographic and clinical variables., Results: Ninety-two women living with HIV (median [interquartile range] age: 49.5 [41.6-54.1] years and body mass index: 24.1 [20.7-30.8] kg/m 2 ) and 278 controls (age: 49.0 [43.0-55.0] years and body mass index: 25.8 [22.9-30.6] kg/m 2 ) were included. Total hip BMD loss was associated with HIV (β: -0.003 [95% CI: -0.006 to -0.0001] g/cm 2 /yr), menopause (β: -0.007 [-0.01 to -0.005] g/cm 2 /yr), and smoking (β: -0.003 [-0.006 to -0.0002] g/cm 2 /yr); BMD gain was linked with higher body mass index (β: 0.0002 [0.0007-0.0004] g/cm 2 /yr). Menopause was associated with losing L1-L4 BMD (β: -0.01 [-0.01 to -0.006] g/cm 2 /yr). Amenorrhea was not associated with BMD loss., Conclusions: HIV and menopause negatively influenced total hip BMD. These data suggest women living with HIV require hip BMD monitoring as they age., Competing Interests: J.C.P. is the Center Director of the ongoing CeMCOR-funded BC CaM os Center. The remaining authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

There is mixed evidence on whether experiences of HIV-related stigma are mitigated with lived experience. We sought to examine whether people living with HIV (PLWH) with longer living experience reported varying levels of HIV-related stigma. Between January 2016-September 2018, we used purposive sampling to enrol PLWH aged ≥19 across British Columbia, Canada, where participants completed the 10-item Berger HIV Stigma Scale. We conducted bivariate analyzes examining key sociodemographic characteristics and HIV-related stigma scores. Multivariable linear regression modelled the association between year of HIV diagnosis by treatment era and HIV-related stigma scores. We enrolled 644 participants; median age at enrolment was 50 years (Q1-Q3: 42-56), with 37.4% ( n  = 241) diagnosed before the year 2000. The median HIV-stigma scores of all participants (19.0, Q1-Q3: 13-25, range 0-40) stratified by treatment era were: 17.0 (pre-1996), 20.0 (1996-1999), 20.0 (2000-2009), 19.0 (2010-2018) ( p  = 0.03). While there was a significant association at the univariate level, year of HIV diagnosis by treatment era was not associated with stigma scores after controlling for age, gender, HIV key populations, ethnicity, relationship status, social support, and ever having a mental health disorder diagnosis. This suggests that PLWH still experience HIV-related stigma today, compared to those diagnosed in earlier time periods.

We sought to characterize overdose and non-overdose mortality among PLWH amidst the illicit drug toxicity crisis in British Columbia, Canada. A population-based analysis of PLWH (age ≥19) in British Columbia accessing healthcare from April 1996 to March 2017 was conducted using data from the Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) cohort linkage. Underlying causes of deaths were stratified into overdose and non-overdose causes. We compared (bivariate analysis) health-related characteristics and prescription history between PLWH died of overdose and non-overdose causes between April 2009 and March 2017. Among 9,180 PLWH, we observed 962 deaths (142 [14.7%] overdoses; 820 [85.2%] other causes). Compared to those who died from other causes, those who died of overdose were significantly younger (median age [Q, Q3]: 46 years [42, 52] vs. 54 years [48, 63]); had an indication of chronic pain (35.9% vs. 27.1%) and hepatitis C virus (64.8% vs. 50.4%), but fewer experienced hospitalization in the year before death. PLWH who died were most likely to be prescribed with opioids (>50%) and least likely with opioid agonist therapy (<10%) in a year before death. These findings highlight the syndemic of substance use, HCV, and chronic pain, and how the crisis is unqiuely impacting females and younger people.

Background: Using data from a national cohort study and focus groups, the Women-Centred HIV Care (WCHC) Model was developed to inform care delivery for women living with HIV., Methods: Through an evidence-based, integrated knowledge translation approach, we developed 2 toolkits based on the WCHC Model for service providers and women living with HIV in English and French (Canada's national languages). To disseminate, we distributed printed advertising materials, hosted 3 national webinars and conducted 2 virtual capacity-building training series., Results: A total of 315 individuals attended the webinars, and the average WCHC knowledge increased by 29% (SD 4.3%). In total, 131 service providers engaged in 22 virtual capacity-building training sessions with 21 clinical cases discussed. Learners self-reported increased confidence in 15/15 abilities, including the ability to provide WCHC. As of December 2023, the toolkits were downloaded 7766 times., Conclusions: We successfully developed WCHC toolkits and shared them with diverse clinical and community audiences through various dissemination methods., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

We integrated safer conception care into a Ugandan HIV clinic. People with HIV (PWH), or partnered with a PWH, and desiring children were eligible for the Healthy Families Clinic Program. Clients completed quarterly safer conception counselling visits and questionnaires to provide information around method preferences and outcomes (partner pregnancy, partner seroconversion). We used clinic level data to evaluate longitudinal viral suppression among PWH. Between November 2016 and January 2020, 361 clients (53% men) accessed services. 75% were PWH (51% women, 96% men): 99% were on antiretroviral therapy (ART) and most reported HIV-sero-different partnerships (97%). Frequently selected safer conception methods included ART (86%), timed condomless sex (74%), and PrEP (40%) with important differences by HIV-serostatus and gender. 22.5% reported pregnancy. Most (97%) PWH were virally suppressed at enrolment and 81% of non-virally suppressed PWH were virally suppressed at 15 months. Two HIV-negative clients (2%) had HIV seroconversion. There is demand for safer conception care in a public sector HIV-clinic in Uganda. Men and women have unique safer conception care preferences. The majority of clients engaged in safer conception care had viral suppression at follow up.

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Social support has previously been found to be associated with improved health outcomes of individuals managing chronic illnesses, including amongst people living with HIV (PLWH). For women and people who use injection drugs who continue to experience treatment disparities in comparison to other PLWH, social support may have potential in facilitating better treatment engagement and retention. In this analysis, we examined determinants of social support as measured by the Medical Outcomes Study - Social Support Survey (MOS-SSS) scale, and quantified the relationship between MOS-SSS and HIV treatment interruptions (TIs) among PLWH in British Columbia, Canada., Methods: Between January 2016 and September 2018, we used purposive sampling to enroll PLWH, 19 years of age or older living in British Columbia into the STOP HIV/AIDS Program Evaluation study. Participants completed a baseline survey at enrolment which included the MOS-SSS scale, where higher MOS-SSS scores indicated greater social support. Multivariable linear regression modeled the association between key explanatory variables and MOS-SSS scores, whereas multivariable logistic regression modeled the association between MOS-SSS scores and experiencing TIs while controlling for confounders., Results: Among 644 PLWH, we found that having a history of injection drug use more than 12 months ago but not within the last 12 months, self-identifying as Indigenous, and sexual activity in the last 12 months were positively associated with MOS-SSS, while being single, divorced, or dating (vs. married), experiences of lifetime violence, and diagnosis of a mental health disorder were inversely associated. In a separate multivariable model adjusted for gender, ethnicity, recent homelessness, sexual activity in the last 12 months, and recent injection drug use, we found that higher MOS-SSS scores, indicating more social support, were associated with a lower likelihood of HIV treatment interruptions (adjusted odds ratio: 0.90 per 10-unit increase, 95% confidence interval: 0.83, 0.99)., Conclusions: Social support may be an important protective factor in ensuring HIV treatment continuity among PLWH. Future research should examine effective means to build social support among communities that have potential to promote increased treatment engagement., (© 2023. The Author(s).)

Background: HIV-related stigma, gender discrimination, and racial discrimination harm mental health and hamper HIV treatment access for women living with HIV. Maladaptive coping strategies, such as substance use, can further worsen HIV treatment outcomes, whereas resilience can improve HIV outcomes. We examined resilience and depression as mediators of the relationship between multiple stigmas and HIV treatment outcomes among women living with HIV., Setting: Ontario, British Columbia, and Quebec, Canada., Methods: We conducted a longitudinal study with 3 waves at 18-month intervals. We used structural equation modeling to test the associations of multiple stigmas (HIV-related stigma, racial discrimination, and gender discrimination) or an intersectional construct of all 3 stigmas at wave 1 on self-reported HIV treatment cascade outcomes (≥95% antiretroviral treatment [ART] adherence, undetectable viral load) at wave 3. We tested depression and resilience at wave 2 as potential mediators and adjusted for sociodemographic factors., Results: There were 1422 participants at wave 1, half of whom were Black (29%) or Indigenous (20%). Most participants reported high ART adherence (74%) and viral suppression (93%). Racial discrimination was directly associated with having a detectable viral load, while intersectional stigma was directly associated with lower ART adherence. Resilience mediated associations between individual and intersectional stigmas and HIV treatment cascade outcomes, but depression did not. Racial discrimination was associated with increased resilience, while intersectional and other individual stigmas were associated with reduced resilience., Conclusion: Race, gender and HIV-related stigma reduction interventions are required to address intersectional stigma among women living with HIV. Including resilience-building activities in these interventions may improve HIV treatment outcomes., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Although the Netherlands, Canada and Australia were early adopters of harm reduction for people who inject drugs (PWID), their respective HIV and hepatitis C (HCV) epidemics differ. We measured the pooled effect of needle and syringe program (NSP) and opioid agonist therapy (OAT) participation on HIV and HCV incidence in these settings., Design: For each cohort, we emulated the design and statistical analysis of a target trial using observational data., Setting and Participants: We included PWID at risk of HIV or HCV infection from the Amsterdam Cohort Studies (1985-2013), Vancouver Injection Drug Users Study (1997-2009) and Melbourne Injecting Drug User Cohort Study (SuperMIX) (2010-2021)., Measurements: Separately for each infection and cohort (only HCV in SuperMIX), marginal structural models were used to compare the effect of comprehensive (on OAT and 100% NSP coverage or on OAT only if no recent injection drug use) versus no/partial NSP/OAT (no OAT and/or <100% NSP coverage) participation. Pooled hazard ratios (HR) and 95% CI were calculated using random-effects meta-analysis., Findings: We observed 94 HIV seroconversions and 81 HCV seroconversions among 2023 and 430 participants, respectively. Comprehensive NSP/OAT led to a 41% lower risk of HIV acquisition (pooled HR = 0.59, 95% CI = 0.36-0.96) and a 76% lower risk of HCV acquisition (pooled HR = 0.24, 95% CI = 0.11-0.51), compared with no/partial NSP/OAT, with little heterogeneity between studies for both infections (I 2  = 0%)., Conclusions: In the Netherlands, Canada and Australia, comprehensive needle and syringe program and opioid agonist therapy participation appears to substantially reduce HIV and hepatitis C acquisition compared with no or partial needle and syringe program/opioid agonist therapy participation. These findings from an emulated trial design reinforce the critical role of comprehensive access to harm reduction in optimizing infection prevention for people who inject drugs., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Although prevalent among people living with human immunodeficiency virus (HIV) (PLWH) and people who use unregulated drugs (PWUD), pain and its possible links to substance use patterns and engagement in HIV treatment remains poorly characterized. We sought to evaluate the prevalence and correlates of pain among a cohort of PLWH who use un-regulated drugs. Between December 2011 and November 2018, 709 participants were recruited, and data were analyzed using generalized linear mixed-effects (GLMM). At baseline, 374 (53 percent) individuals reported moderate-to-extreme pain in the previous 6 months. In a multivariable model, pain was significantly associated with nonmedical prescrip-tion-opioid use (adjusted odds ratio (AOR) = 1.63, 95 percent confidence interval (CI): 1.30-2.05), nonfatal overdose (AOR = 1.46, 95 percent CI: 1.11-1.93), self-managing pain (AOR = 2.25, 95 percent CI: 1.94-2.61), requesting pain medication in the previous 6 months (AOR = 2.01, 95 percent CI: 1.69-2.38), and ever being diagnosed with a mental illness (AOR = 1.47, 95 percent CI: 1.11-1.94). Establishing accessible pain management interventions that address the complex intersection of pain, drug use, and HIV-infection has potential to improve quality of life outcomes among this population.

Background: Depression and anxiety are commonly experienced among gay, bisexual and other men-who-have-sex-with-men (gbMSM). We explored factors associated with improvements in mental health symptoms among gbMSM with abnormal depression and anxiety scores over a period of four years, in Vancouver, Canada., Methods: Sexually active gbMSM ≥16 years of age were recruited using respondent-driven sampling from February 2012 to February 2015. Participants completed a computer-assisted questionnaire which included the Hospital Anxiety and Depression Scale (HADS), and psychometric scales to measure loneliness, self-esteem and social connectedness, every 6 months until July 2019. Generalized linear mixed models were used to assess factors associated with normal/borderline HADS scores (<11) following a previous abnormal score (≥11) for each of anxiety and depression subscales., Results: We recruited 694 participants, of whom 580 had at least one follow-up visit. Across all visits, 43.6 % of participants ever had abnormal anxiety scores and 16.2 % ever had abnormal depression scores. Among those with abnormal anxiety scores, 34.9 % of follow-up visits demonstrated reductions in anxiety scores. Among those with abnormal depression scores 51.0 % of follow-up visits demonstrated reductions in depression scores. Reductions in anxiety scores were associated with increased self-esteem, decreased loneliness and the number of gbMSM seen/spoken to in the previous month. Reductions in depression scores were associated with increased self-esteem, decreased loneliness and having a regular partner., Conclusion: Improvements in mental health symptoms were frequently observed. Social connectedness was related with improved anxiety and depression symptoms. Interventions to improve social connectedness may help to improve mental health for gbMSM., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

Little is known about how the co-occurrence of psychosocial factors affect sub-populations of people living with HIV (PLWH). We used cross-sectional data from 999 PLWH, aged ≥19, accessing antiretroviral therapy (ART) in British Columbia, Canada (2007-2010) to examine associations between psychosocial factors and ART-related outcomes separately for trans/cis inclusive women; heterosexual men; and gay, bisexual, and other men who have sex with men (gbMSM). Multivariable logistic regression examined associations between psychosocial factors (0-3): any violence in the past 6 months, depressive symptoms in the past week, and current street drug use (heroin, crack, meth or speedball) with sub-optimal adherence (outcome 1: average annual ART adherence <95% from interview until end of follow-up, death, or December 31st, 2018) and ever viral rebound (outcome 2) adjusting for potential confounders. Of 999 PLWH (264 women, 382 heterosexual men, and 353 gbMSM), women and heterosexual men had significantly higher median counts than gbMSM. Overall, higher counts were associated with sub-optimal adherence (adjusted odds ratio [aOR] = 1.26/1-unit increase, 95%CI = 1.07-1.49). All effect estimates were of a greater magnitude among gbMSM, but not significant for women or heterosexual men, highlighting the need for population (e.g., gender and sexual orientation)-centered care and research.

Objectives: We estimated the effectiveness of COVID-19 vaccines against laboratory-confirmed SARS-CoV-2 infection among people living with HIV (PLWH) and compared the estimates with a matched HIV-negative cohort., Methods: We used the British Columbia COVID-19 Cohort, a population-based data platform, which integrates COVID-19 data on SARS-CoV-2 tests, laboratory-confirmed cases, and immunizations with provincial health services data. The vaccine effectiveness (VE) was estimated with a test-negative design using the multivariable logistic regression., Results: The adjusted VE against SARS-CoV-2 infection was 71.1% (39.7, 86.1%) 7-59 days after two doses, rising to 89.3% (72.2, 95.9%) between 60 and 89 days. VE was preserved 4-6 months after the receipt of two doses, after which noticeable waning was observed (51.3% [4.8, 75.0%]). In the matched HIV-negative cohort (n = 375,043), VE peaked at 91.4% (90.9, 91.8%) 7-59 days after two doses and was sustained for up to 4 months, after which evidence of waning was observed, dropping to 84.2% (83.4, 85.0%) between 4 and 6 months., Conclusion: The receipt of two COVID-19 vaccine doses was effective against SARS-CoV-2 infection among PLWH pre-Omicron. VE estimates appeared to peak later in PLWH than in the matched HIV-negative cohort and the degree of waning was relatively quicker in PLWH; however, peak estimates were comparable in both populations., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

HIV treatment interruptions are a major public health concern that demonstrate a lack of engagement in care and is detrimental to the health of people living with HIV. Community connectedness have demonstrated a protective effect for psychosocial health but are not well understood for HIV treatment outcomes. We explored associations between community connectedness and treatment interruptions among gay, bisexual and other men who have sex with men (gbMSM) living with HIV in Vancouver, British Columbia. We analyzed survey data from the Momentum Health Study and identified treatment interruptions through data linkages with the provincial HIV Drug Treatment Program as episodes lasting more than 60 days beyond an expected antiretroviral therapy refill date from February 2012 to July 2019. We built a mixed-effects logistic regression model, adjusting for confounders. Of 213 gbMSM living with HIV, 54 experienced treatment interruption (25.4%) over a median five-year follow-up. Multivariable results found the number gbMSM who spoken to in the past month (aOR = 0.995; 95% CI = 0.991, 1.000 (per 100-unit increase)) and attending a gay community meeting more than once per month (aOR = 0.32; 95% CI = 0.11, 0.89) were associated with lower odds of treatment interruptions. These results highlight the importance of social connections in facilitating effective HIV care.

The lung is an understudied site of HIV persistence. We isolated 898 subgenomic proviral sequences (nef) by single-genome approaches from blood and lung from nine individuals on long-term suppressive antiretroviral therapy (ART), and characterized genetic diversity and compartmentalization using formal tests. Consistent with clonal expansion as a driver of HIV persistence, identical sequences comprised between 8% to 86% of within-host datasets, though their location (blood vs. lung) followed no consistent pattern. The majority (77%) of participants harboured at least one sequence shared across blood and lung, supporting the migration of clonally-expanded cells between sites. The extent of blood proviral diversity on ART was also a strong indicator of diversity in lung (Spearman's ρ = 0.98, p<0.0001). For three participants, insufficient lung sequences were recovered to reliably investigate genetic compartmentalization. Of the remainder, only two participants showed statistically significant support for compartmentalization when analysis was restricted to distinct proviruses per site, and the extent of compartmentalization was modest in both cases. When all within-host sequences (including duplicates) were considered, the number of compartmentalized datasets increased to four. Thus, while a subset of individuals harbour somewhat distinctive proviral populations in blood and lung, this can simply be due to unequal distributions of clonally-expanded sequences. For two participants, on-ART proviruses were also phylogenetically analyzed in context of plasma HIV RNA populations sampled up to 18 years prior, including pre-ART and during previous treatment interruptions. In both participants, on-ART proviruses represented the most ancestral sequences sampled within-host, confirming that HIV sequences can persist in the body for decades. This analysis also revealed evidence of re-seeding of the reservoir during treatment interruptions. Results highlight the genetic complexity of proviruses persisting in lung and blood during ART, and the uniqueness of each individual's proviral composition. Personalized HIV remission and cure strategies may be needed to overcome these challenges., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Shahid et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Momentum is funded through the National Institute on Drug Abuse (R01DA031055-01A1) and the Canadian Institutes for Health Research (MOP-107544, FDN-143342, PJT-153139). HLA was supported by a Postdoctoral Fellowship Award from the Canadian Institutes of Health Research (Grant # MFE-152443). NJL was supported by a CANFAR/CTN Postdoctoral Fellowship Award. DMM and NJL are supported by Scholar Awards from the Michael Smith Foundation for Health Research (#5209, #16863). KGC is supported by a Canadian HIV Trials Network / Canadian Foundation for AIDS Research Postdoctoral Fellowship award, a Michael Smith Foundation for Health Research Trainee award, and a Canadian Institutes of Health Research Health Systems Impact Fellowship award. JMS is supported by a Michael Smith Foundation for Health Research Trainee award and a CTN CIHR Canadian HIV/AIDS Trials Network postdoctoral fellowship award.JM is supported with grants paid to his institution by the British Columbia Ministry of Health and by the US National Institutes of Health (R01DA036307). He has also received limited unrestricted funding, paid to his institution, from Abbvie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. The remaining authors report no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The British Columbia Centre for Excellence in HIV/AIDS (BC-CfE) may, upon meeting all legislative and policy obligations, provide de-identified data used in the manuscript for external research use. Identifiable data will not be provided to external researchers. Requests for access to the research dataset must be directed to the Data Analysis Team using the BC-CfE Data Analysis Research Form. The Data Analysis Team and the Privacy Officer will review external data access requests and if approved, the de-identified research dataset will be provided via Secure File Transfer Protocol to the researcher.

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/mm 3 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).

Gay and bisexual men's (GBM) group sex parties are considered HIV risk environments due to their association with concurrent sexual partners, condomless anal sex, and polysubstance use. The possibility of group sex party hosts acting as gatekeepers to minimize risks has been suggested, but remains understudied. We analyzed qualitative data from 20 in-depth interviews with North American GBM who recently attended private group sex parties to determine if hosts' actions constitute harm reduction strategies. Results showed hosts acting as gatekeepers before parties by establishing and disseminating themes and rules, screening applicants, and selecting guests. During parties hosts enforced rules and rejected uninvited guests. By their actions, hosts established a more controlled environment compared to public sex-on-premises bathhouses, and facilitated boundary play, the paradoxical behavior of simultaneously desiring risk and safety, previously noted for GBM circuit parties. Results suggest initiating education programs focusing on private group sex party hosts as gatekeepers.

Motivation: A key process in anti-viral adaptive immunity is that the human leukocyte antigen (HLA) system presents epitopes as major histocompatibility complex I (MHC I) protein-peptide complexes on cell surfaces and in this way alerts CD8+ cytotoxic T-lymphocytes (CTLs). This pathway exerts strong selection pressure on viruses, favoring viral mutants that escape recognition by the HLA/CTL system. Naturally, such immune escape mutations often emerge in highly variable viruses, e.g. HIV or HBV, as HLA-associated mutations (HAMs), specific to the hosts MHC I proteins. The reliable identification of HAMs is not only important for understanding viral genomes and their evolution, but it also impacts the development of broadly effective anti-viral treatments and vaccines against variable viruses. By their very nature, HAMs are amenable to detection by statistical methods in paired sequence/HLA data. However, HLA alleles are very polymorphic in the human host population which makes the available data relatively sparse and noisy. Under these circumstances, one way to optimize HAM detection is to integrate all relevant information in a coherent model. Bayesian inference offers a principled approach to achieve this., Results: We present a new Bayesian regression model for the detection of HAMs that integrates a sparsity-inducing prior, epitope predictions and phylogenetic bias assessment, and that yields easily interpretable quantitative information on HAM candidates. The model predicts experimentally confirmed HAMs as having high posterior probabilities, and it performs well in comparison to state-of-the-art models for several datasets from individuals infected with HBV, HDV and HIV., Availability and Implementation: The source code of this software is available at https://github.com/HAMdetector/Escape.jl under a permissive MIT license. The data underlying this article were provided by permission. Data will be shared on request to the corresponding author with permission of the respective co-authors., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Opioid use is escalating in North America and comes with a multitude of health consequences, including HIV and hepatitis C virus (HCV) outbreaks among persons who inject drugs (PWID). HIV pre-exposure prophylaxis (PrEP) and HCV treatment regimens have transformative potential to address these co-occurring epidemics. Evaluation of innovative multi-modal approaches, integrating harm reduction, opioid agonist therapy (OAT), PrEP, and HCV treatment is required. The aim of this study is to assess the effectiveness of an on-site integrated care model where delivery of PrEP and HCV treatment for PWID takes places at syringe service programs (SSP) and OAT programs compared with referring PWID to clinical services in the community through a patient navigation model and to examine how structural factors interact with HIV prevention adherence and HCV treatment outcomes., Methods: The Miami-Montreal Hepatitis C and Pre-Exposure Prophylaxis trial (M 2 HepPrEP) is an open-label, multi-site, multi-center, randomized, controlled, superiority trial with two parallel treatment arms. A total of 500 persons who injected drugs in the prior 6 months and are eligible for PrEP will be recruited in OAT clinics and SSP in Miami, FL, and Montréal, Québec. Participants will be randomized to either on-site care, with adherence counseling, or referral to off-site clinics assisted by a patient navigator. PrEP will be offered to all participants and HCV treatment to those HCV-infected. Co-primary endpoints will be (1) adherence to pre-exposure prophylaxis medication at 6 months post-randomization and (2) HCV sustained virological response (SVR) 12 weeks post-treatment completion among participants who were randomized within the HCV stratum. Up to 100 participants will be invited to participate in a semi-structured interview regarding perceptions of adherence barriers and facilitators, after their 6-month assessment. A simulation model-based cost-effectiveness analysis will be performed to determine the comparative value of the strategies being evaluated., Discussion: The results of this study have the potential to demonstrate the effectiveness and cost-effectiveness of offering PrEP and HCV treatment in healthcare venues frequently attended by PWID. Testing the intervention in two urban centers with high disease burden among PWID, but with different healthcare system dynamics, will increase generalizability of findings., Trial Registration: Clinicaltrials.gov NCT03981445 . Trial registry name: Integrated HIV Prevention and HCV Care for PWID (M2HepPrEP). Registration date: June 10, 201., (© 2022. The Author(s).)

Background: Hepatitis C virus (HCV) education may be changing following the simplification of HCV treatment and emergence of direct acting antiviral (DAA). We aimed to characterize HCV knowledge among people who recently completed DAA therapy., Methods: The Per-SVR (Preservation of Sustained Virologic Response) is a prospective cohort of patients who achieved a sustained virologic response upon successful completion of DAA therapy. The per-SVR study provided the sampling frame of participants who completed a psychometrically validated 19-item HCV knowledge scale at cohort entry (n = 227). To score the questionnaire, for each correct response one point was awarded, with no point for incorrect response. We assessed mean HCV knowledge score in the overall sample and mutually exclusive populations: people who inject drug (PWID) (n = 71); people with co-occurring HIV (n = 23); PWID and co-occurring HIV (n = 29), and others (n = 104) Using a latent class analysis based on distal outcome, we identified unobserved subgroups and assessed HCV knowledge amongst them., Results: Total mean (SD) percent of correct responses were 83 (11) in the overall sample; 83 (10) in PWID; 79 (12) in people with co-occurring HIV; 81 (10) in PWID and co-occurring HIV, and 84 (11) in rest of the sample Three latent groups were identified: baby boomers who ever experienced homelessness (n = 126); women sex workers who ever experienced homelessness (n = 68); men who inject drug, ever experienced homelessness and had ever diagnosis of mental health disorders (n = 18). Mean percent of correct responses were 85 (8), 82 (11), 85 (10), in latent class 1, 2, and 3, respectively., Conclusion: Patients successfully treated with DAAs had a high HCV knowledge. High knowledge and awareness of reinfection among complex patient groups often facing barriers to HCV care is encouraging and emphasizes the positive outcomes of universal access to treatment., Competing Interests: The authors have declared that no competing interests exist.

In this paper, we present the findings of a qualitative study aimed at conceptualizing the service needs of aging gay men living with HIV (GMLH). Our analysis is based on interview data from 16 gay-identified men living with HIV, ages 50 and over. Drawing on a framework of intersectionality, which theoretically accounts for interlocking expressions of marginalization in groups affected by multiple systems of oppression, we highlight the practical, social, and mental health needs of this population, as well as services that could be designed or adapted to address these concerns. We also emphasize the relevance of specialized training for caring professionals serving older GMLH, and articulate the need for initiatives that more fully engage gay men aging with HIV in the development and delivery of services intended for their use.

Purpose: This study aimed at determining to what extent sexual minority status modifies the association between HIV risk behavior and prevalent mood or anxiety disorder diagnosis in British Columbia (BC), Canada, using a population-based survey., Methods: This analysis was based on the cross-sectional 2013-2014 Canadian Community Health Survey. The sample was restricted to respondents in BC with valid responses to the survey items considered. A multivariable logistic model, where the behavioral HIV risk score exposure was nested into the sexual minority status modifier, estimated the odds of having a prevalent mood or an anxiety disorder. The behavioral HIV risk score (0, 1, 2, ≥ 3) included the following five measures: (1) age at first intercourse < 14 years, (2) condom use during last intercourse, (3) history of sexually transmitted infections, (5) number of sexual partners in the past 12 months (< 4, ≥ 4), and substance use in the past 12 months., Results: Of the weighted sample (2,521,252), 97% (95% confidence interval (CI) 97-98) were heterosexual, while 3% (95% CI 2-3) were lesbian, gay, and bisexual (LGB). The prevalence of a mood or anxiety disorder diagnosis was 12% (95% CI 11-13). For every 1-level increment in the behavioral HIV risk score, the adjusted odds ratio of having a prevalent mood or anxiety disorder diagnosis was 1.29 (95% CI 1.03-1.54) for heterosexual respondents and 2.37 (95% CI 1.84-2.90) for LGB respondents., Conclusion: Sexual minority status modified the relationship between HIV risk behavior and prevalent mood or anxiety disorders, with a stronger association among LGB respondents. Healthcare providers should prioritize integrated care that addresses the intersectionality between sexual risk, substance use, and mood or anxiety disorders., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: People living with HIV who use drugs commonly experience chronic pain and often use illicit opioids to manage pain. Recent research suggests people living with HIV use cannabis for pain relief, including as an adjunct to opioids. This underscores the need to better understand how people living with HIV who use drugs use cannabis for pain management, particularly as cannabis markets are undergoing changes due to cannabis legalisation., Methods: From September 2018 to April 2019, we conducted in-depth interviews with 25 people living with HIV who use drugs in Vancouver, Canada to examine experiences using cannabis to manage pain. Interviews were audio-recorded, transcribed and coded. Themes were identified using inductive and deductive approaches., Results: Most participants reported that using cannabis for pain management helped improve daily functioning. Some participants turned to cannabis as a supplement or periodic alternative to prescription and illicit drugs (e.g. benzodiazepines, opioids) used to manage pain and related symptoms. Nonetheless, participants' access to legal cannabis was limited and most continued to obtain cannabis from illicit sources, which provided access to cannabis that was free or deemed to be affordable., Discussion and Conclusions: Cannabis use may lead to reduced use of prescription and illicit drugs for pain management among some people living with HIV who use drugs. Our findings add to growing calls for additional research on the role of cannabis in pain management and harm reduction, and suggest the need for concrete efforts to ensure equitable access to cannabis., (© 2021 Australasian Professional Society on Alcohol and other Drugs.)

Background: Women with an undetectable viral load can become pregnant and have children with no risk of HIV transmission to their sexual partners and low risk of transmission to their infants. Contemporary pregnancy intentions of women living with HIV in Canada are poorly understood, evidenced by high rates of unintended pregnancy and low uptake of contraceptives., Methods: We used longitudinal survey data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) to measure and compare pregnancy intentions (Yes vs No vs Unsure) at baseline, 18-months and 36-months follow-up (from 2013 to 2018) among women living with HIV of reproductive age (16-49 years) and potential. We used Sankey diagrams to depict changes in pregnancy intentions over time and multivariable logistic regression to examine the relationship between pregnancy intention within 2 years and subsequent pregnancy., Results: At baseline, 41.9% (119/284) of women intended to become pregnant, 43.3% did not, and 14.8% were unsure. Across 36-months of follow-up, 41.9% (119/284) of women changed their pregnancy intentions, with 25% changing from intending to not intending to become pregnant and 13.1% vice versa. Pregnancy intentions were not strongly associated with subsequent pregnancy between baseline and 18-months (aOR 1.44; 95% CI 0.53, 3.72) or between 18 and 36-months (aOR 2.17; 95% CI 0.92, 5.13)., Conclusions: Our findings underscore the need for healthcare providers to engage in ongoing discussions with women living with HIV to support their dynamic pregnancy intentions., (© 2021. The Author(s).)

Background: A remarkable reduction in AIDS-related mortality has been achieved through the widespread use of triple combination antiretroviral therapy, considerably increasing the life expectancy of people living with HIV (PLWH). However, these survival gains are now at risk in North America due to an unprecedented public health emergency: the deadly drug overdose epidemic. Drug overdoses are now the leading cause of unintentional death in British Columbia (BC), Canada and the United States due to synthetic opioids (e.g., fentanyl) in illegal markets. This manuscript aimed to estimate the effect of overdose mortality on life expectancy and identify covariates associated with the hazard for overdose mortality in the presence of competing risk among PLWH in BC., Methods: Those eligible were aged ≥20 years, initiated antiretroviral therapy from 1-Apr-1996 to 30-Dec-2017, and were followed until 31-Dec-2017, last contact or death date. We estimated the potential gains in life expectancy from abridged life tables. We modelled the association between covariates and the cause-specific hazard for overdose mortality, accounting for mortality of other causes as a competing risk., Results: Among the 10,362 PLWH, 3% experienced overdose mortality. The life expectancy at age 20 increased by 8.7 years from 2002-2007 to 2008-2013 compared to only 3.0 years from 2008-2013 to 2014-2017. The potential gain in life expectancy was 3.3 years at age 20 during the ongoing overdose epidemic (2014-2017). There were gender differences in life expectancies throughout the study period. People who have ever injected drugs, women and viral load monitoring non-compliance were key covariates associated with an increased hazard of overdose mortality., Conclusion: Survival gains among PLWH have been considerably reduced due to the ongoing overdose epidemic., Competing Interests: Declarations of Interest JSGM has received institutional grants from Gilead Sciences, J&J, Merck, ViiV Healthcare, and a Knowledge Translation Award from the Canadian Institutes of Health Research. JSGM also served as an advisor to the Government of Canada and the Government of British Columbia in the last year. All other authors declare no competing interests., (Copyright © 2021. Published by Elsevier B.V.)

We examined temporal trends and factors associated with reporting partner's serostatus and viral load among a sample of gay, bisexual and other men who have sex with men (gbMSM) in Vancouver, Canada. Participants were recruited using respondent-driven sampling and we collected prospective cohort data from 09/2014 to 02/2017 using a computer-assisted questionnaire and nurse-administered STI/HIV testing. Our study included 481 participants reporting on 3780 sexual events. Among HIV-negative/unknown gbMSM we found a trend towards decreased proportions of sexual events reporting an unknown HIV-status partner (42-19%; p =  < 0.001) and found increased proportions among gbMSM living with HIV (11-27%; p = 0.043). More participants living with HIV reported sex with undetectable partners, compared to HIV-negative/unknown participants (14.8% versus 5%). Our multivariable model found that compared with unknown status partners, undetectable partners were older, were from longer sexual relationships and were more likely to engage in condomless anal sex. Findings indicate that HIV-negative gbMSM seem more aware of the serostatus of their partners over time, but knowledge of partners' viral load over time was not significant. Further research should assess the degree to which new campaigns such as Undetectable = Untransmittable (U = U) are associated with discussions about HIV disclosure and viral load status.

In Canada, im/migrant sex workers face stigma, health access barriers, and overlapping marginalisation, with end-demand law reforms in 2014 postulated to exacerbate these inequities. Yet, little quantitative evidence on how immigration status shapes HIV/STI risk exists. Drawing on community-based longitudinal cohort data (AESHA, 2010-2018), we used multivariable confounder models with logistic regression to model (1) the independent effect of precarious immigration status (any status revocable under criminal charges: permanent residency/temporary residency/undocumented) on client condom refusal, and (2) the moderating effect of precarious status on the relationship between condom refusal and exposure to end-demand law reform (2015-2018). Over this 8-year study involving 758 sex workers in Metro Vancouver, 16.0% were im/migrants, of whom 57% had precarious immigration status at baseline. 16.5% of participants experienced client condom refusal. Precarious immigration was associated with increased odds of facing condom refusal (adjusted odds ratio [AOR] 2.53, 95% confidence interval [CI] 1.37-4.68), and these odds were heightened post-end-demand law reforms (AOR 4.35, 95%CI 1.21-15.66). Our findings suggest that lack of citizenship rights may enhance barriers to safer sex negotiation and increase HIV/STI risk among sex workers, highlighting the need for sex work and immigration policy reforms.

Our study aims to define and identify correlates of social isolation among people living with HIV (PLHIV). The Longitudinal Investigation into Supportive and Ancillary health services (LISA) study provided a cross-sectional analytic sample of 996 PLHIV in British Columbia, Canada (sampled between 2007 and 2010). Individuals marginalized by socio-structural inequities were oversampled; sampling bias was addressed through inverse probability of participation weighting. Through latent class analysis, three groups were identified: Socially Connected (SC) ( n = 364, 37%), Minimally Isolated (MI) ( n = 540, 54%) and Socially Isolated (SI) ( n = 92, 9%). Correlates of the SI and MI classes, determined through multivariable multinomial regression using the SC class as a reference, include: recent violence (aOR 1.61, 95%CI 1.28-2.02 [MI vs. SC]; aOR 2.04, 95%CI 1.41-2.96 [SI vs. SC]) and a mental health diagnosis (aOR 1.50, 95% CI 1.31-1.72 [MI vs. SC]; aOR 1.43, 95%CI 1.11-1.83 [SI vs. SC]). Women (aOR 0.47; 95%CI 0.32-0.68 [SI vs. SC]), individuals of Indigenous ancestry (aOR 0.59; 95%CI 0.40-0.87 [SI vs. SC]) and people identifying as gay or lesbian (aOR 0.37; 95%CI 0.26-0.52 [SI vs. SC]) were less likely to experience isolation. These findings highlight the importance of supporting communities fostering connectedness and identifies populations susceptible to isolation.

Social isolation, a risk factor for poor health within the general population, may be exacerbated by unique challenges faced by people living with HIV (PLHIV). This analysis examines the association between social isolation and all-cause mortality among a cohort of PLHIV experiencing multiple social vulnerabilities. The analytical sample included 936 PLHIV ≥ 19 years, living in British Columbia, Canada, and enrolled in the Longitudinal Investigation into Supportive and Ancillary Health Services (LISA) Study (2007-2010). Participants were classified as Socially Connected (SC), Minimally Isolated (MI) or Socially Isolated (SI) via latent class analysis. Cross-sectional survey data was linked to longitudinal clinical data from a provincial HIV treatment database. Mortality was assessed longitudinally up to and including December 31st, 2017. Through multivariable logistic regression, an association between SI and all-cause mortality was found (adjusted OR: 1.48; 95% CI 1.08, 2.01). These findings emphasize the need to mitigate effects of social isolation among PLHIV.

Antiretroviral therapy adherence among transgender (trans) women living with HIV (WLWH) is negatively impacted by depression and post-traumatic stress disorder (PTSD). Yet, little is known about factors associated with depression or PTSD among trans WLWH. Using cross-sectional data from a national community-based study of 1422 WLWH ( n  = 53 trans women), we characterized the prevalence of depressive and PTSD symptoms among trans WLWH and examined associations between factors (e.g., Trans stigma) and depressive and PTSD symptoms. Nearly half of participants reported clinically significant PTSD (45.3%) and depressive symptoms (45.3%) [mean Post-traumatic Stress Disorder Civilian Checklist Version-C score 13.8 (SD = 5.8); mean Center for Epidemiological Studies - Depression score 9.4 (SD = 8.0)]. Univariate linear regression analyses showed that <95% adherence, higher internalized HIV-related stigma, frequency of past-month hazardous alcohol use, and current injection drug use were significantly associated with both higher PTSD and depressive symptom scores, and higher resilience and social support with lower scores. A history of violence in adulthood was associated with higher depressive symptoms scores, whereas sexual relationship power and less difficulty meeting housing costs were associated with lower scores. Findings suggest a need for multi-level interventions to reduce barriers to mental wellbeing while fostering resilience and social support.

Over half of people living with HIV (PLHIV) engaged in care in British Columbia (BC) are age ≥50. The public home and community care (HCC) system offers formal support that PLHIV may turn to as they age, but little is known about access specific to PLHIV. Using data from the STOP HIV/AIDS cohort, which includes linked treatment and demographic records for PLHIV accessing care in BC, we compared older PLHIV (defined as those age ≥50) who did and did not access HCC services. We estimated adjusted odds ratios (aORs) for factors associated with HCC service utilization using logistic regression. This study included 5,603 PLHIV age ≥50, 837 (14.94%) of whom accessed any HCC service between 2005 and 2015. Services most commonly used were community nursing (8.98%, n  = 503) and rehabilitation (7.73%, n  = 433). Those who received HCC were more likely to be female (aOR = 1.56, 95% CI = 1.24, 1.98), have a history of injection drug use (aOR = 1.88, 95% CI = 1.57, 2.25), have a higher Charlson comorbidity score (aOR = 1.11, 95% CI:1.07, 1.15) and to have visited a general practitioner in the past year (aOR = 2.17, 95% CI = 1.77, 2.67). Approximately 15% of older PLHIV have accessed HCC, but the extent of potential unmet need for these services requires further research.

In Canada, women make up 25% of the prevalent HIV cases and represent an important population of those living with HIV, as a high proportion are racialized and systemically marginalized; furthermore, many have unmet healthcare needs. Using the knowledge-to-action framework as an implementation science methodology, we developed the "Women-Centred HIV Care" (WCHC) Model to address the needs of women living with HIV. The WCHC Model is depicted in the shape of a house with trauma- and violence-aware care as the "foundation". Person-centred care with attention with attention to social determinants of health and family make up the "first" floor. Women's health (including sexual and reproductive health and rights) and mental and addiction health care are integrated with HIV care, forming the "second" floor. Peer support, leadership, and capacity building make up the "roof". To address the priorities of women living with HIV in all their diversity and across their life course, the WCHC Model should be flexible in its delivery (e.g., single provider, interdisciplinary clinic or multiple providers) and implementation settings (e.g., urban, rural).

HIV-1 strains harboring immune escape mutations can persist in circulation, but the impact of selection by multiple HLA alleles on population HIV-1 dynamics remains unclear. In Japan, HIV-1 Reverse Transcriptase codon 135 (RT135) is under strong immune pressure by HLA-B*51:01-restricted and HLA-B*52:01-restricted T cells that target a key epitope in this region (TI8; spanning RT codons 128-135). Major population-level shifts have occurred at HIV-1 RT135 during the Japanese epidemic, which first affected hemophiliacs (via imported contaminated blood products) and subsequently non-hemophiliacs (via domestic transmission). Specifically, threonine accumulated at RT135 (RT135T) in hemophiliac and non-hemophiliac HLA-B*51:01+ individuals diagnosed before 1997, but since then RT135T has markedly declined while RT135L has increased among non-hemophiliac individuals. We demonstrated that RT135V selection by HLA-B*52:01-restricted TI8-specific T-cells led to the creation of a new HLA-C*12:02-restricted epitope TN9-8V. We further showed that TN9-8V-specific HLA-C*12:02-restricted T cells selected RT135L while TN9-8T-specific HLA-C*12:02-restricted T cells suppressed replication of the RT135T variant. Thus, population-level accumulation of the RT135L mutation over time in Japan can be explained by initial targeting of the TI8 epitope by HLA-B*52:01-restricted T-cells, followed by targeting of the resulting escape mutant by HLA-C*12:02-restricted T-cells. We further demonstrate that this phenomenon is particular to Japan, where the HLA-B*52:01-C*12:02 haplotype is common: RT135L did not accumulate over a 15-year longitudinal analysis of HIV sequences in British Columbia, Canada, where this haplotype is rare. Together, our observations reveal that T-cell responses to sequentially emerging viral escape mutants can shape long-term HIV-1 population dynamics in a host population-specific manner., Competing Interests: The authors have declared that no competing interests exist.

Background: Women living with HIV in Canada experience barriers to comprehensive HIV care. We sought to describe care gaps across a typology of care. Methods: We analyzed baseline data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS). A typology of care was characterized by primary HIV physician and care setting. Quality-of-care indicators included the following: Pap test, Pap test discussions, reproductive goal discussions, breast cancer screening, antiretroviral therapy (ART) use, adherence, HIV viral load, and viral load discussions. We defined comprehensive care with three indicators: Pap test, viral load, and either reproductive goal discussions over last 3 years or breast cancer screening, as indicated. Multivariable logistic regression analyses measured associations between care types and quality-of-care indicators. Results: Among women living with HIV accessing HIV care, 56.4% (657/1,164) experienced at least one gap in comprehensive care, most commonly reproductive goal discussions. Women accessed care from three types of care: (1) physicians (specialist and family physicians) in HIV clinics (71.6%); (2) specialists in non-HIV clinics (17.6%); and (3) family physicians in non-HIV clinics (10.8%), with 55.5%, 63.9%, and 50.8% gaps in comprehensive care, respectively. Type 3 care had double the odds of not being on ART: adjusted odds ratio (AOR 2.09, 95% confidence interval [CI] 1.16-3.75), while Type 2 care had higher odds of not having discussed the importance of Pap tests (AOR 1.48, 95% CI 1.00-2.21). Discussion: Women continue to experience gaps in care, across types of care, indicating the need to evaluate and strengthen women-centered models of care.

HIV-1-specific CD8+ T cells are an important component of HIV-1 curative strategies. Viral variants in the HIV-1 reservoir may limit the capacity of T cells to detect and clear virus-infected cells. We investigated the patterns of T cell escape variants in the replication-competent reservoir of 25 persons living with HIV-1 (PLWH) durably suppressed on antiretroviral therapy (ART). We identified all reactive T cell epitopes in the HIV-1 proteome for each participant and sequenced HIV-1 outgrowth viruses from resting CD4+ T cells. All non-synonymous mutations in reactive T cell epitopes were tested for their effect on the size of the T cell response, with a≥50% loss defined as an escape mutation. The majority (68%) of T cell epitopes harbored no detectable escape mutations. These findings suggest that circulating T cells in PLWH on ART could contribute to control of rebound and could be targeted for boosting in curative strategies., Competing Interests: JW, SZ, YX, MM, DM, OC, JK, JS, NR, AA, SJ, JK, CG, DM, NA, ZB, NG No competing interests declared, RS UNC is pursuing IP protection for Primer ID, and Ronald Swanstrom is listed as a coinventor and has received nominal royalties., (© 2020, Warren et al.)

HIV Nef counteracts cellular host restriction factors SERINC3 and SERINC5, but our understanding of how naturally occurring global Nef sequence diversity impacts these activities is limited. Here, we quantify SERINC3 and SERINC5 internalization function for 339 Nef clones, representing the major pandemic HIV-1 group M subtypes A, B, C and D. We describe distinct subtype-associated hierarchies for Nef-mediated internalization of SERINC5, for which subtype B clones display the highest activities on average, and of SERINC3, for which subtype B clones display the lowest activities on average. We further identify Nef polymorphisms that modulate its ability to counteract SERINC proteins, including substitutions in the N-terminal domain that selectively impair SERINC3 internalization. Our findings demonstrate that the SERINC antagonism activities of HIV Nef differ markedly among major viral subtypes and between individual isolates within a subtype, suggesting that variation in these functions may contribute to global differences in viral pathogenesis., Competing Interests: The authors have declared that no competing interests exist.

Background: While previous research has identified how criminalization of HIV non-disclosure can have deleterious effects on those living with HIV, the perspectives of people who use drugs - a population disproportionately affected by HIV- should be more meaningfully considered in these discussions., Methods: Using constant comparative techniques, data from 60 interviews with men and women living with and without HIV and who use drugs in Vancouver were analyzed to explore their perceptions about Canada's HIV non-disclosure legal framework., Results: Participants' perspectives on the framework involved three themes: understandings of HIV risk; HIV-related stigma; and their own experiences with HIV. While several participants favored the punitive character of the legal framework, these arguments were premised on misinformed and stigmatized assumptions regarding HIV., Conclusions: The paper concludes by discussing the challenges and opportunities for resisting HIV stigma and misconceptions about HIV within the context of personal accounts that, at times, support criminalization of non-disclosure.

Male and female condoms are the only available Multipurpose Prevention Technologies (MPTs) that can prevent unintended pregnancy and sexually transmitted infections including HIV. If used correctly and consistently, condoms can provide levels of pregnancy protection similar to many hormonal methods. Condoms remain one of the most common methods used at first sexual intercourse and are relied on as a current use of contraception by adolescents in many regions of the world. Male and female condoms are safe and require no prescription; in particular male condoms are generally easy to access at low cost. Female condoms are more expensive than male condoms and less accessible; however, they have the advantage of being a female-initiated method. Condom users may experience some common challenges; however, recent advances in condom technology have led to new designs and modifications of existing products to improve quality and make them more attractive, acceptable and pleasurable for consumers and increase its use., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: Food insecurity, or self-reports of inadequate food access due to limited financial resources, remains prevalent among people living with HIV (PLHIV). We examined the impact of food insecurity on combination antiretroviral therapy (cART) adherence within an integrated care programme that provides services to PLHIV, including two meals per day., Design: Adjusted OR (aOR) were estimated by generalized estimating equations, quantifying the relationship between food insecurity (exposure) and cART adherence (outcome) with multivariable logistic regression., Setting: We drew on survey data collected between February 2014 and March 2016 from the Dr. Peter Centre Study based in Vancouver, Canada., Participants: The study included 116 PLHIV at baseline, with ninety-nine participants completing a 12-month follow-up interview. The median (quartile 1-quartile 3) age was 46 (39-52) years at baseline and 87 % (n 101) were biologically male at birth., Results: At baseline, 74 % (n 86) of participants were food insecure (≥2 affirmative responses on Health Canada's Household Food Security Survey Module) and 67 % (n 78) were adherent to cART ≥95 % of the time. In the adjusted regression analysis, food insecurity was associated with suboptimal cART adherence (aOR = 0·47, 95 % CI 0·24, 0·93)., Conclusions: While food provision may reduce some health-related harms, there remains a relationship between this prevalent experience and suboptimal cART adherence in this integrated care programme. Future studies that elucidate strategies to mitigate food insecurity and its effects on cART adherence among PLHIV in this setting and in other similar environments are necessary.

Background: Risk compensation in an HIV Treatment as Prevention (TasP) environment may increase high-risk sexual and substance use behaviors among people living with HIV. Objective: To examine recent crystal methamphetamine (CM) use/initiation in a longitudinal cohort of gay, bisexual, and other men who have sex with men (GBMSM) living with HIV in Metro Vancouver, Canada. Methods: Eligible participants were GBMSM aged >15   years who reported sex with another man in the past six months. Participants were recruited using respondent-driven sampling and self-completed a computer questionnaire every six months. We used multi-level generalized mixed-effect models to evaluate trends in recent CM use (past six months), multivariable logistic regression to identify covariates of recent CM use, and multivariable survival analysis to identify predictors of CM initiation. Results: Of 207 GBMSM living with HIV at enrollment, 44.3% reported recent CM use; there was a statistically non-significant decrease over the study period (41% in first period to 25% in final period, p   =   0.087). HIV treatment optimism was not associated with CM use/initiation. CM use was positively associated with depressive symptomology, sexual escape motivation, transactional sex, number of anal sex partners, condomless anal sex with seroconcordant partners, STIs, and other substance use. Recent CM use was negatively associated with viral load sorting. CM initiation was predicted by escape motivation, transactional sex, and group sex participation. Conclusion: Results suggest that CM use among GBMSM living with HIV is prevalent and increased CM use/initiation is not a consequence of TasP public policy.

Previous maternity experiences may influence subsequent reproductive intentions and motherhood experiences. We used latent class analysis to identify patterns of early motherhood experience reported for the most recent live birth of 905 women living with HIV enrolled in the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS). Four indicators were used: difficulties getting pregnant, feelings when finding out pregnancy, feelings during pregnancy, and feelings during the first year postpartum. Most (70.8%) pregnancies analyzed occurred before HIV diagnosis. A four-class maternity experience model was selected: "overall positive experience" (40%); "positive experience with postpartum challenges" (23%); "overall mixed experience" (14%); and "overall negative experience" (23%). Women represented in the "overall negative experience" class were more likely to be younger at delivery, to not know the HIV status of their pregnancy partner, and to report previous pregnancy termination. Women represented in the "positive experience with postpartum challenges" class were more likely to report previous miscarriage, stillbirth or ectopic pregnancy. We found no associations between timing of HIV diagnosis (before, during or after pregnancy) and experience patterns. Recognition of the different patterns of experiences can help providers offer a more adapted approach to reproductive counseling of women with HIV.

Scant research has explored the engagement of transgender (trans) women living with HIV (WLWH) in the HIV care cascade, particularly in universal health care settings like Canada. This convergent parallel, mixed-methods study drew on cross-sectional quantitative data from 50 trans WLWH in the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) and qualitative semistructured interview data from a subsample of 11 participants. Descriptive analyses were used to describe proportions of trans WLWH at five steps of the HIV care cascade and bivariate analyses to determine associations between hypothesized barriers/facilitators and HIV care cascade outcomes. Framework analysis was used to describe barriers and facilitators to HIV care engagement. Quantitative and qualitative data were then compared and contrasted. While use of purposive sampling, including recruitment through AIDS Service Organizations and HIV clinics, may have led to oversampling of trans WLWH who already had access to care, gaps were still seen in antiretroviral therapy (ART) outcomes (current ART use: 78%; ≥95% adherence among those currently taking ART: 67%). The number of years living with HIV was positively associated with HIV care cascade engagement. Factors associated with lower engagement included: higher health-related quality of life, depressive and post-traumatic stress disorder symptoms, barriers to access to care, transphobia, HIV-related stigma, and housing insecurity. Qualitative findings converged and expanded on how physical health, and social and structural marginalization, influence trans WLWH's engagement in HIV care. Qualitative findings elaborated on the importance of ART-related factors in impeding or facilitating engagement, including concerns about feminizing hormone-ART drug-drug interactions. Mixed-methods findings reveal how trans WLWH experience barriers common to other people living with HIV, and also experience unique barriers as a result of trans and HIV experiences.

Given the disproportionate HIV burden faced by female sex workers FSWs and limited data regarding their engagement in the HIV cascade of care in conflict-affected settings, we characterized the cascade of care and examined associations with new HIV diagnoses and antiretroviral therapy (ART) use in a community-based cohort of FSWs in conflict-affected Northern Uganda. Data were collected via FSW/peer-led time-location sampling and outreach, interview-administered questionnaires, and voluntary HIV testing. Of 400 FSWs, 33.5% were living with HIV, of whom 33.6% were new/previously undiagnosed infections and 32.8% were on ART. Unstable housing and heavy alcohol/drug use were independently associated with increased odds of new HIV diagnoses, whereas exposure to condom demonstrations and number of lifetime pregnancies were negatively associated. In subanalysis among known HIV-positive women, age and time since diagnosis were associated with ART use, whereas sexually transmitted infections were negatively associated. Findings suggest the need for FSW-tailored, peer-based, and integrated HIV and sexual and reproductive health programs to address gaps in HIV testing and treatment for FSWs in conflict-affected communities.

Earlier HIV diagnosis allows for improved treatment outcomes and secondary prevention. It is recommended that all individuals know their HIV status and that those at higher risk test more frequently. Using a representative community sample of gay, bisexual, and other men who have sex with men (GBMSM), we aimed to: (1) determine the proportion of GBMSM who have tested in the past 2 years, (2) determine reasons for testing and never having tested, and (3) explore correlates of testing. Of 535 eligible participants, 80.0% reported having had an HIV test in the past 2 years, most commonly as part of a regular testing schedule. The most common reason for not testing was low perceived HIV risk. Bisexual and older GBMSM, as well as those who lived outside of Vancouver, were less likely to have tested in the past 2 years. Rapid point-of-care testing may help improve testing rates and was shown to effectively engage some hard-to-reach GBMSM (e.g., those who had not tested for other STIs) in this sample.

While combination antiretroviral therapy (cART) has successfully converted HIV to a chronic but manageable infection in many parts of the world, HIV continues to persist within latent cellular reservoirs, which can become reactivated at any time to produce infectious virus. New therapies are therefore needed not only for HIV suppression but also for containing or eliminating HIV reservoirs. Compounds derived from plant, marine, and other natural products have been found to combat HIV infection and/or target HIV reservoirs, and these discoveries have substantially guided current HIV therapy-based studies. Here we summarize the role of natural product-derived compounds in current HIV suppression, remission, and cure strategies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: In North America, women have lower engagement across the HIV cascade of care compared with men. Among women living with HIV (WLWH) in Canada, we measured the prevalence and correlates of attrition across cascade stages overall, and by key subpopulations., Methods: We analyzed baseline survey data regarding 6 nested stages of the HIV cascade among 1424 WLWH enrolled in the Canadian HIV Sexual and Reproductive Health Cohort Study (CHIWOS), including: linked to care, retained in care, initiated antiretroviral therapy (ART), current ART use, ART adherence (≥90%), and viral suppression (<50 copies/mL). Logistic regression identified factors associated with attrition at each stage., Results: Overall, 98% of WLWH were linked to care; 96% retained; 88% initiated ART; 83% were currently on ART; and, among those on ART, 68% were adherent and 72% were virally suppressed, with substantial variability by subpopulation (49%-84%).The largest attrition occurred between current ART use and adherence (-17%), with the greatest losses among indigenous women (-25%), women who use illicit drugs (-32%), and women incarcerated in the past year (-45%). Substantial attrition also occurred between linkage to care and ART initiation (-11%), with the greatest losses among women 16-29 years (-20%) and with unstable housing (-27%). Factors independently associated with attrition at viral suppression included household annual income, racial discrimination, incarceration history, age, and resilience., Conclusions: Overall, 28% of WLWH were lost across the HIV care cascade, with significant differences by stage, subpopulation, and social inequities. Targeted interventions are needed to improve women's retention across the cascade.