Short report: Characterizing HIV care among a clinical sample of transgender women living with HIV.

INTRODUCTION: This study aimed to characterize and identify factors associated with HIV care among transgender (trans) women living with HIV (TWLWH) in two urban centres in Canada. METHODS: Retrospective data were collected from clinic charts of TWLWH aged 16 years and older across seven family medicine, endocrinology and/or HIV clinics in Montreal and Toronto, Canada, from 2018 to 2019 (n = 86). We assessed the proportion of individuals being ever engaged in HIV care [defined as having any recorded antiretroviral therapy (ART) regimen and/or viral load], current ART use, and most recent viral load (suppressed [<200 copies/ml] vs. unsuppressed) overall and compared across subgroups using χ2 tests. RESULTS: All TWLWH in our sample [100.0%, 95% confidence interval (CI): 95.8-100.0%] were engaged in HIV care; most (93.0%, 95% CI: 85.4-97.4%) were currently using ART and most (93.4%, 95% CI: 85.3-97.8%) with complete data (n = 71/76) were virally suppressed. A higher proportion of trans women of colour (100.0%) reported current ART use compared with white trans women (76.9%, p = 0.017). A higher proportion of those with no documented history of injection drug use (IDU; 96.6%) were virally suppressed compared with those with a history of IDU (66.7%, p = 0.022). Although not statistically significant, 96.2% of those currently reporting feminizing hormone use were virally suppressed, compared with 85.0% of those not reporting use (p = 0.202). CONCLUSIONS: Once engaged in HIV care, TWLWH in Canada appear to have excellent ART use and viral suppression. Findings can be leveraged to identify target populations to enhance HIV care and to further explore the relationship between gender-affirming medical care and HIV care.

Characteristics and outcomes of antiretroviral-treated HIV-HBV co-infected patients in Canada?

BACKGROUND: Hepatitis B (HBV) and Human Immunodeficiency Virus (HIV) share common risk factors for exposure. Co-infected patients have an increased liver-related mortality risk and may have accelerated HIV progression. The epidemiology and demographic characteristics of HIV-HBV co-infection in Canada remain poorly defined. We compared the demographic and clinical characteristics and factors associated with advanced hepatic fibrosis between HIV and HIV-HBV co-infected patients. METHODS: A retrospective cohort analysis was conducted using data from the Canadian Observational Cohort (CANOC) Collaboration, including eight sites from British Columbia, Quebec, and Ontario. Eligible participants were HIV-infected patients who initiated combination ARV between January 1, 2000 and December 14, 2014. Demographic and clinical characteristics were compared between HIV-HBV co-infected and HIV-infected groups using chi-square or Fisher exact tests for categorical variables, and Wilcoxon's Rank Sum test for continuous variables. Liver fibrosis was estimated by the AST to Platelet Ratio Index (APRI). RESULTS: HBV status and APRI values were available for 2419 cohort participants. 199 (8%) were HBV co-infected. Compared to HIV-infected participants, HIV-HBV co-infected participants were more likely to use injection drugs (28% vs. 21%, p = 0.03) and be HCV-positive (31%, vs. 23%, p = 0.02). HIV-HBV co-infected participants had lower baseline CD4 T cell counts (188 cells/mm3, IQR: 120-360) compared to 235 cells/mm3 in HIV-infected participants (IQR: 85-294) (p = 0.0002) and higher baseline median APRI scores (0.50 vs. 0.37, p < 0.0001). This difference in APRI was no longer clinically significant at follow-up (0.32 vs. 0.30, p = 0.03). HIV-HBV co-infected participants had a higher mortality rate compared to HIV-infected participants (11% vs. 7%, p = 0.02). CONCLUSION: The prevalence, demographic and clinical characteristics of the HIV-HBV co-infected population in Canada is described. HIV-HBV co-infected patients have higher mortality, more advanced CD4 T cell depletion, and liver fibrosis that improves in conjunction with ARV therapy. The high prevalence of unknown HBV status demonstrates a need for increased screening among HIV-infected patients in Canada.

Comparison of atazanavir/ritonavir and darunavir/ritonavir based antiretroviral therapy for antiretroviral naïve patients.

BACKGROUND: Atazanavir/ritonavir and darunavir/ritonavir are common protease inhibitor-based regimens for treating patients with HIV. Studies comparing these drugs in clinical practice are lacking. METHODS: We conducted a retrospective cohort study of antiretroviral naïve participants in the Canadian Observational Cohort (CANOC) collaboration initiating atazanavir/ritonavir- or darunavir/ritonavir-based treatment. We used separate Fine and Gray competing risk regression models to compare times to regimen failure (composite of virologic failure or discontinuation for any reason). Additional endpoints included virologic failure, discontinuation due to virologic failure, discontinuation for other reasons, and virologic suppression. RESULTS: We studied 222 patients treated with darunavir/ritonavir and 1791 patients treated with atazanavir/ritonavir. Following multivariable adjustment, there was no difference between darunavir/ritonavir and atazanavir-ritonavir in the risk of regimen failure (adjusted hazard ratio 0.76, 95% CI 0.56 to 1.03) Darunavir/ritonavir-treated patients were at lower risk of virologic failure relative to atazanavir/ritonavir treated patients (aHR 0.50, 95% CI 0.28 to 0.91), findings driven largely by high rates of virologic failure among atazanavir/ritonavir-treated patients in the province of British Columbia. Of 108 discontinuations due to virologic failure, all occurred in patients starting atazanavir/ritonavir. There was no difference between regimens in time to discontinuation for reasons other than virologic failure (aHR 0.93; 95% CI 0.65 to 1.33) or virologic suppression (aHR 0.99, 95% CI 0.82 to 1.21). CONCLUSIONS: The risk of regimen failure was similar between patients treated with darunavir/ritonavir and atazanavir/ritonavir. Although darunavir/ritonavir was associated with a lower risk of virologic failure relative to atazanavir/ritonavir, this difference varied substantially by Canadian province and likely reflects regional variation in prescribing practices and patient characteristics.

Predictors of viral suppression and rebound among HIV-positive men who have sex with men in a large multi-site Canadian cohort.

BACKGROUND: Gay, bisexual and other men who have sex with men (MSM) are disproportionately affected by HIV in Canada. Combination antiretroviral therapy has been shown to dramatically decrease progression to AIDS, premature death and HIV transmission. However, there are no comprehensive data regarding combination antiretroviral therapy outcomes among this population. We sought to identify socio-demographic and clinical correlates of viral suppression and rebound. METHODS: Our analysis included MSM participants in the Canadian Observational Cohort, a multi-site cohort of HIV-positive adults from Canada's three most populous provinces, aged ≥18 years who first initiated combination antiretroviral therapy between 2000 and 2011. We used accelerated failure time models to identify factors predicting time to suppression (2 measures <50 copies/mL ≥30 days apart) and subsequent rebound (2 measures >200 copies/mL ≥30 days apart). RESULTS: Of 2,858 participants, 2,448 (86 %) achieved viral suppression in a median time of 5 months (Q1-Q3: 3-7 months). Viral suppression was significantly associated with later calendar year of antiretroviral therapy initiation, no history of injection drug use, lower baseline viral load, being on an initial regimen consisting of non-nucleoside reverse-transcriptase inhibitors, and older age. Among those who suppressed, 295 (12 %) experienced viral rebound. This was associated with earlier calendar year of antiretroviral therapy initiation, injection drug use history, younger age, higher baseline CD4 cell count, and living in British Columbia. CONCLUSIONS: Further strategies are required to optimize combination antiretroviral therapy outcomes in men who have sex with men in Canada, specifically targeting younger MSM and those with a history of injection drug use.

Removing inactive NRTIs in a salvage regimen is safe, maintains virological suppression and reduces treatment costs: results from the VERITAS study (TMC114HIV4054).

BACKGROUND: Despite the benefit of maintaining inactive Nucleotide/side reverse transcriptase inhibitors (NRTIs) in salvage regimens, they are associated with increased toxicity and treatment costs. Current evidence suggests that NRTI-sparing regimens in patients failing ART are non-inferior to NRTI-including regimens. This study aimed to evaluate the impact of removing at least one inactive NRTI on virologic, safety, and financial outcomes. METHODS: Drug-resistant, virologically suppressed patients with CD4 >250 cells/ml on a stable regimen of four or more antiretrovirals (ARVs) were enrolled in a 48-week prospective, open-label pilot trial. One inactive NRTI was removed at baseline. Patients taking over five ARVs had a second inactive NRTI removed at 24 weeks. Viral load, CD4 count, and adverse events were assessed at baseline, 24, and 48 weeks. RESULTS: Thirty-one male patients participated. Twenty-nine (94%) patients had lamivudine (3TC) or emtricitabine (FTC) removed and four patients had an additional NRTI removed. One patient was excluded at week 26 for discontinuing an active NRTI. All patients maintained undetectable viral loads at weeks 24 (100%) and 48 [PP = 100%; Intent-to-treat (ITT) = 97%]. At 48 weeks, patients had a median gain of 20 CD4 (IQR: - 50, +133; mean +39) compared to baseline. Three patients exhibited Grade III bilirubin elevation (two Grade II and one Grade III at baseline), which returned to baseline levels. No serious adverse events were observed. Removal of one or two ARVs equated to a mean annual savings of $3319 CDN (11%) and $8630 CDN (24%), respectively. CONCLUSION: Removing inactive NRTIs in patients with a controlled viral load appears to be safe, maintains virological suppression, and reduces treatment costs.

Explaining the appeal for immigrant men who have sex with men of a community-based rapid HIV-testing site in Montreal (Actuel sur Rue).

Immigrant men who have sex with men (MSM) are vulnerable to HIV. In the last decade, several rapid HIV-testing facilities targeting MSM have been established around the world and seem popular among immigrants. This study analyzes factors contributing to immigrant MSM's use of Actuel sur Rue (AsR), a community-based rapid HIV-testing site in Montreal's gay village, where 31% of clients are immigrants. From October 2013 to January 2014, AsR staff compiled a list of new clients born outside of Canada. With their consent, 40 immigrant MSM were reached among these new clients for a 15-minute phone survey entailing open-ended and multiple-choice questions. The survey sought immigrant MSM's reasons for visiting AsR; satisfaction with service and staff; and open comments. An inductive thematic analysis was conducted with the qualitative data, and descriptive statistics were produced with the quantitative data. The qualitative findings indicate that the main reasons for seeking an HIV test were a recent risk, routine testing, or being in a new relationship. Clients chose AsR mainly because it is easily accessible, service is fast or they heard about it from a friend. The quantitative findings indicate that rates of satisfaction were high (over 90% were satisfied about all aspects except for openings hours) and more than 80% felt comfortable while receiving services at AsR. Nevertheless, this study's findings have implications for improving services. They stress the importance of offering rapid yet comprehensive service and of taking into account immigrant MSM's concerns for confidentiality.

Factors associated with the frequency of monitoring of liver enzymes, renal function and lipid laboratory markers among individuals initiating combination antiretroviral therapy: a cohort study.

BACKGROUND: As the average age of the HIV-positive population increases, there is increasing need to monitor patients for the development of comorbidities as well as for drug toxicities. METHODS: We examined factors associated with the frequency of measurement of liver enzymes, renal function tests, and lipid levels among participants of the Canadian Observational Cohort (CANOC) collaboration which follows people who initiated HIV antiretroviral therapy in 2000 or later. We used zero-inflated negative binomial regression models to examine the associations of demographic and clinical characteristics with the rates of measurement during follow-up. Generalized estimating equations with a logit link were used to examine factors associated with gaps of 12 months or more between measurements. RESULTS: Electronic laboratory data were available for 3940 of 7718 CANOC participants. The median duration of electronic follow-up was 3.5 years. The median (interquartile) rates of tests per year were 2.76 (1.60, 3.73), 2.55 (1.44, 3.38) and 1.42 (0.50, 2.52) for liver, renal and lipid parameters, respectively. In multivariable zero-inflated negative binomial regression models, individuals infected through injection drug use (IDU) were significantly less likely to have any measurements. Among participants with at least one measurement, rates of measurement of liver, renal and lipid tests were significantly lower for younger individuals and Aboriginal Peoples. Hepatitis C co-infected individuals with a history of IDU had lower rates of measurement and were at greater risk of having 12 month gaps between measurements. CONCLUSIONS: Hepatitis C co-infected participants infected through IDU were at increased risk of gaps in testing, despite publicly funded health care and increased risk of comorbid conditions. This should be taken into consideration in analyses examining factors associated with outcomes based on laboratory parameters.

Life expectancy of HIV-positive individuals on combination antiretroviral therapy in Canada.

BACKGROUND: We sought to evaluate life expectancy and mortality of HIV-positive individuals initiating combination antiretroviral therapy (ART) across Canada, and to consider the potential error introduced by participant loss to follow-up (LTFU). METHODS: Our study used data from the Canadian Observational Cohort (CANOC) collaboration, including HIV-positive individuals aged ≥18 years who initiated ART on or after January 1, 2000. The CANOC collaboration collates data from eight sites in British Columbia, Ontario, and Quebec. We computed abridged life-tables and remaining life expectancies at age 20 and compared outcomes by calendar period and patient characteristics at treatment initiation. To correct for potential underreporting of mortality due to participant LTFU, we conservatively estimated 30% mortality among participants lost to follow-up. RESULTS: 9997 individuals contributed 49,589 person-years and 830 deaths for a crude mortality rate of 16.7 [standard error (SE) 0.6] per 1000 person-years. When assigning death to 30% of participants lost to follow-up, we estimated 1170 deaths and a mortality rate of 23.6 [SE 0.7] per 1000 person-years. The crude overall life expectancy at age 20 was 45.2 [SE 0.7] and 37.5 [SE 0.6] years after adjusting for LTFU. In the LTFU-adjusted analysis, lower life expectancy at age 20 was observed for women compared to men (32.4 [SE 1.1] vs. 39.2 [SE 0.7] years), for participants with injection drug use (IDU) history compared to those without IDU history (23.9 [SE 1.0] vs. 52.3 [SE 0.8] years), for participants reporting Aboriginal ancestry compared to those with no Aboriginal ancestry (17.7 [SE 1.5] vs. 51.2 [SE 1.0] years), and for participants with CD4 count <350 cells/µL compared to CD4 count ≥350 cells/µL at treatment initiation (36.3 [SE 0.7] vs. 43.5 [SE 1.3] years). Life expectancy at age 20 in the calendar period 2000-2003 was lower than in periods 2004-2007 and 2008-2012 in the LTFU-adjusted analyses (30.8 [SE 0.9] vs. 38.6 [SE 1.0] and 54.2 [SE 1.4]). CONCLUSIONS: Life expectancy and mortality for HIV-positive individuals receiving ART differ by calendar period and patient characteristics at treatment initiation. Failure to consider LTFU may result in underestimation of mortality rates and overestimation of life expectancy.

Magnitude of virologic blips is associated with a higher risk for virologic rebound in HIV-infected individuals: a recurrent events analysis.

BACKGROUND: The importance of human immunodeficiency virus (HIV) blip magnitude on virologic rebound has been raised in clinical guidelines relating to viral load assays. METHODS: Antiretroviral-naive individuals initiating combination antiretroviral therapy (cART) after 1 January 2000 and achieving virologic suppression were studied. Negative binomial models were used to identify blip correlates. Recurrent event models were used to determine the association between blips and rebound by incorporating multiple periods of virologic suppression per individual. RESULTS: 3550 participants (82% male; median age, 40 years) were included. In a multivariable negative binomial regression model, the Amplicor assay was associated with a lower blip rate than branched DNA (rate ratio, 0.69; P < .01), controlling for age, sex, region, baseline HIV-1 RNA and CD4 count, AIDS-defining illnesses, year of cART initiation, cART type, and HIV-1 RNA testing frequency. In a multivariable recurrent event model controlling for age, sex, intravenous drug use, cART start year, cART type, assay type, and HIV-1 RNA testing frequency, blips of 500-999 copies/mL were associated with virologic rebound (hazard ratio, 2.70; P = .002), whereas blips of 50-499 were not. CONCLUSIONS: HIV-1 RNA assay was an important determinant of blip rates and should be considered in clinical guidelines. Blips ≥500 copies/mL were associated with increased rebound risk.

Feminizing hormone therapy in a Canadian cohort of transgender women with and without HIV.

BACKGROUND: Potential bidirectional drug-drug interactions between feminizing hormone therapy (FHT) and antiretroviral therapy (ART) are of concern for trans women with HIV and their healthcare providers. This study aimed to characterize patterns of FHT and ART among trans women with HIV and to compare serum hormone levels to trans women without HIV. METHODS: Charts of trans women were reviewed at seven HIV primary care or endocrinology clinics in Toronto and Montreal from 2018 to 2019. ART regimens, FHT use, serum estradiol, and serum testosterone levels were compared on the basis of HIV status (positive, negative, missing/unknown). RESULTS: Of 1495 trans women, there were 86 trans women with HIV, of whom 79 (91.8%) were on ART. ART regimens were most commonly integrase inhibitor-based (67.4%), many boosted with ritonavir or cobicistat (45.3%). Fewer (71.8%) trans women with HIV were prescribed FHT, compared to those without HIV (88.4%) and those with missing/unknown status (90.2%, p < 0.001). Among trans women on FHT with recorded serum estradiol (n = 1153), there was no statistical difference in serum estradiol between those with HIV (median: 203 pmol/L, IQR: 95.5, 417.5) and those with negative (200 mol/L [113, 407]) or missing/unknown HIV status (227 pmol/L [127.5, 384.5) (p = 0.633). Serum testosterone concentrations were also similar between groups. CONCLUSIONS: In this cohort, trans women with HIV were prescribed FHT less often than trans women with negative or unknown HIV status. There was no difference in serum estradiol or testosterone levels of trans women on FHT regardless of HIV status, providing reassurance regarding potential drug-drug interactions between FHT and ART.

Abacavir/lamivudine fixed-dose combination with ritonavir-boosted darunavir: a safe and efficacious regimen for HIV therapy.

BACKGROUND: Current treatment guidelines recommend the use of tenofovir (TDF) and emtricitabine (FTC) along with a third agent to treat HIV-positive adults. However, other treatment options, including the use of abacavir (ABC) and lamivudine (3TC) when used with ritonavir-boosted darunavir (DRV/r), have rarely been studied. OBJECTIVE: We evaluated the safety and efficacy of the coformulation of ABC/3TC administered with DRV/r in treatment-naïve and treatment-experienced patients. METHODS: HIV-infected adults who received an open-label combination of ABC/3TC/ DRV/r were followed in a community clinic in Montréal. Patients had no resistance to any of the compounds in their regimen. Viral load (VL), CD4 cell count, AST, ALT, and creatinine levels were examined throughout the 48 weeks of follow-up. RESULTS: Sixty-seven patients with a mean age of 45 years were enrolled. Two did not return for follow-up and were excluded. Thirty-five (52%) were treatment- experienced and the remaining were treatment-naïve. HLA-B*5701 test results were available for 56 patients and none were positive. At baseline, mean VL was 4.8 log for treatment-naïve and 2.3 log for experienced patients. Twelve patients discontinued the study regimen prior to reaching the endpoint. At week 48, 79% had a VL <50. Median CD4 cell gain was higher among treatment-naïve patients (273 cells) than among treatment-experienced patients (102 cells) (P = .002). No patient experienced any grade 2 or higher liver enzyme elevation throughout the study. CONCLUSIONS: The new combination of ABC/3TC/DRV/r demonstrates a high rate of antiviral activity with no major toxicity. The drug combination appears to be generally safe and well tolerated.

Trends in Use of Combination Antiretroviral Therapy and Treatment Response from 2000 to 2016 in the Canadian Observational Cohort (CANOC): A Longitudinal Cohort Study.

Background: Advances in treatment have turned HIV from a terminal illness to a more manageable condition. Over the past 20 years, there have been considerable changes to HIV treatment guidelines, including changes in preferred antiretrovirals and timing of initiation of combination antiretroviral therapy (cART). Objective: To examine real-world trends in cART utilization, viral control, and immune reconstitution among people living with HIV in Canada. Methods: Data were obtained from the Canadian Observational Cohort (CANOC). CANOC participants were eligible if they were antiretroviral therapy-naive at entry and initiated 3 or more antiretrovirals on or after January 1, 2000; if they were at least 18 years of age at treatment initiation; if they were residing in Canada; and if they had at least 1 viral load determination and CD4 count within 1 year of CANOC entry. Baseline and annual mean CD4 counts were categorized as less than 200, 200-350, 351-500, and more than 500 cells/mm3. Annual mean viral loads were reported as suppressed (< 50 copies/mL), low (50-199 copies/mL), or high detectable (≥ 200 copies/mL). The cART regimens were reported yearly. Results: All CANOC participants were included (n = 13 040). Over the study period, the proportion of individuals with an annual mean CD4 count above 500 cells/mm3 increased from 16.3% to 65.8%, while the proportion of individuals with an undetectable mean viral load increased from 10.6% to 83.2%. As of 2007, the most commonly prescribed 2-agent nucleoside reverse transcriptase inhibitor backbone was tenofovir disoproxil fumarate and emtricitabine. In terms of third agents, non-nucleoside reverse transcriptase inhibitors were the most common class in the periods 2000-2003 and 2014-2015, protease inhibitors were most common in the period 2004-2013, and integrase inhibitors were most common in 2016. Conclusions: Concordance with treatment guidelines was demonstrated over time with respect to cART prescribing and immunologic and virologic response.

Contexte: Les progrès effectués dans le domaine des traitements ont transformé le VIH. Celui-ci est passé d'une maladie en phase terminale à une maladie plus gérable. Au cours des 20 dernières années, des changements considérables ont eu lieu dans les directives de traitement du VIH, y compris des changements dans les antirétroviraux privilégiés et le moment de l'initiation de la thérapie antirétrovirale combinée (TARc). Objectif: Examiner les tendances réelles de l'utilisation de la TARc, du contrôle viral et de la reconstitution immunitaire chez les personnes vivant avec le VIH au Canada. Méthodes: Les données ont été obtenues auprès de la Canadian Observational Cohort (CANOC). Les participants à la CANOC étaient admissibles s'ils n'avaient jamais reçu de traitement antirétroviral à l'entrée et avaient commencé la prise de 3 antirétroviraux ou plus le 1er janvier 2000 ou après cette date; s'ils avaient au moins 18 ans au moment du début du traitement; s'ils résidaient au Canada; et s'ils avaient au moins 1 charge virale et un nombre de CD4 dans l'année suivant l'entrée à la CANOC. Les numérations initiales et annuelles moyennes de CD4 ont été classées comme inférieures à 200, 200 à 350, 351 à 500, et supérieures à 500 cellules/mm3. Les charges virales moyennes annuelles ont été signalées comme supprimées (< 50 copies/mL), faibles (50 à 199 copies/mL) ou élevées détectables (≥ 200 copies/mL). Les régimes de la TARc ont été rapportés chaque année. Résultats: Tous les participants à la CANOC ont été inclus (n = 13040). Au cours de la période d'étude, la proportion de personnes ayant une numération CD4 moyenne annuelle supérieure à 500 cellules/mm3 est passée de 16,3 % à 65,8 %, tandis que la part de personnes ayant une charge virale moyenne indétectable est passée de 10,6 % à 83,2 %. En 2007, la bithérapie de base d'inhibiteurs nucléosidiques de la transcriptase inverse la plus couramment prescrite était le fumarate de ténofovir disoproxil et l'emtricitabine. En matière de troisièmes agents, la classe la plus courante dans les périodes 2000­2003 et 2014­2015 était les inhibiteurs non nucléosidiques de la transcriptase inverse; les plus courants dans la période 2004­2013 étaient les inhibiteurs de protéase; et les inhibiteurs de l'intégrase étaient les plus courants en 2016. Conclusions: La concordance avec les directives de traitement a été démontrée au fil du temps en ce qui concerne la prescription de la cART et la réponse immunologique et virologique.

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.

Clinical and demographic predictors of antiretroviral efficacy in HIV-HBV co-infected patients.

Background: The clinical and demographic characteristics that predict antiretroviral efficacy among patients co-infected with HIV and hepatitis B virus (HBV) remain poorly defined. We evaluated HIV virological suppression and rebound in a cohort of HIV-HBV co-infected patients initiated on antiretroviral therapy. Methods: A retrospective cohort analysis was performed with Canadian Observation Cohort Collaboration data. Cox proportional hazards models were used to determine the factors associated with time to virological suppression and time to virological rebound. Results: HBV status was available for 2,419 participants. A total of 8% were HBV co-infected, of whom 95% achieved virological suppression. After virological suppression, 29% of HIV-HBV co-infected participants experienced HIV virological rebound. HBV co-infection itself did not predict virological suppression or rebound risk. The rate of virological suppression was lower among patients with a history of injection drug use or baseline CD4 cell counts of <199 cells per cubic millimetre. Low baseline HIV RNA and men-who-have-sex-with-men status were significantly associated with a higher rate of virological suppression. Injection drug use and non-White race predicted viral rebound. Conclusions: HBV co-infected HIV patients achieve similar antiretroviral outcomes as those living with HIV mono-infection. Equitable treatment outcomes may be approached by targeting resources to key subpopulations living with HIV-HBV co-infection.

Historique: Les caractéristiques cliniques et démographiques prédictives de l'efficacité antirétrovirale chez les patients co-infectés par le virus de l'immunodéficience humaine (VIH) et le virus de l'hépatite B (VHB) demeurent mal définies. Les chercheurs ont évalué la suppression et le rebond virologiques du VIH dans une cohorte de patients co-infectés par le VIH et le VHB chez qui on avait entrepris un traitement antirétroviral. Méthodologie: Les chercheurs ont réalisé une analyse rétrospective de cohorte à l'aide des données de la Canadian Observation Cohort Collaboration. Ils ont utilisé le modèle à risques proportionnels de Cox pour déterminer les facteurs associés à la période jusqu'à la suppression et au rebond virologiques. Résultats: Les chercheurs ont obtenu le statut de VHB de 2 419 participants. Au total, 8 % étaient co-infectés par le VHB, dont 95 % présentaient une suppression virologique. Après la suppression virologique, 29 % des participants co-infectés par le VIH et le VHB ont subi un rebond virologique du VIH. En elle-même, la co-infection par le VHB n'était pas prédictive de la suppression virologique ou du risque de rebond. Le taux de suppression virologique était plus faible chez les patients ayant des antécédents de consommation de drogues injectables ou une numération des cellules CD4 de référence de moins de 199 cellules par millimètre cube. Un ARN du VIH de référence bas et les hommes ayant des relations sexuelles avec des hommes étaient associés de manière significative avec un taux plus élevé de suppression virologique. La consommation de drogues injectables et les races non blanches étaient prédictives d'un rebond viral. Conclusion: Les patients atteints du VHB co-infectés par le VIH obtenaient des résultats antirétroviraux semblables à ceux qui étaient seulement infectés par le VIH. On peut anticiper des résultats cliniques équitables des traitements en ciblant les ressources vers les sous-populations atteintes d'une co-infection par le VIH et le VHB.

Regional differences in rates of HIV-1 viral load monitoring in Canada: Insights and implications for antiretroviral care in high income countries.

BACKGROUND: Viral load (VL) monitoring is an essential component of the care of HIV positive individuals. Rates of VL monitoring have been shown to vary by HIV risk factor and clinical characteristics. The objective of this study was to determine whether there are differences among regions in Canada in the rates of VL testing of HIV-positive individuals on combination antiretroviral therapy (cART), where the testing is available without financial barriers under the coverage of provincial health insurance programs. METHODS: The Canadian Observational Cohort (CANOC) is a collaboration of nine Canadian cohorts of HIV-positive individuals who initiated cART after January 1, 2000. The study included participants with at least one year of follow-up. Generalized Estimating Equation (GEE) regression models were used to determine the effect of geographic region on (1) the occurrence of an interval of 9 months or more between two consecutive recorded VL tests and (2) the number of days between VL tests, after adjusting for demographic and clinical covariates. Overall and regional annual rates of VL testing were also reported. RESULTS: 3,648 individuals were included in the analysis with a median follow-up of 42.9 months and a median of 15 VL tests. In multivariable GEE logistic regression models, gaps in VL testing >9 months were more likely in Quebec (Odds Ratio (OR) = 1.72, p < 0.0001) and Ontario (OR = 1.78, p < 0.0001) than in British Columbia and among injection drug users (OR = 1.68, p < 0.0001) and were less likely among older individuals (OR = 0.77 per 10 years, p < 0.0001), among men having sex with men (OR = 0.62, p < 0.0001), within the first year of cART (OR = 0.15, p < 0.0001), among individuals on cART at the time of the blood draw (OR = 0.34, p < 0.0001) and among individuals with VL < 50 copies/ml at the previous visit (OR = 0.56, p < .0001). CONCLUSIONS: Significant variation in rates of VL testing and the probability of a significant gap in testing were related to geographic region, HIV risk factor, age, year of cART initiation, type of cART regimen, being in the first year of cART, AIDS-defining illness and whether or not the previous VL was below the limit of detection.

Impact of previous HIV resistance and virologic failures on virologic outcome following a switch to dolutegravir with 2 NRTIs among people living with HIV.

There is uncertainty regarding the potential virologic outcome associated with a change in antiretroviral therapy (ARV) among PLHIV who had previous documented virologic failure or who have been exposure to mono/dual nucleoside reverse transcriptase inhibitors (NRTI) therapy. The objective was to measure the potential impact of exposure to previous virologic failure or mono/dual NRTI regimen on virologic outcome of PLHIV following a switch to dolutegravir with 2 NRTIs from a viremia suppressive ARV therapy.Data from the Quebec HIV Cohort including 10219 PLHIV were collected through routine clinical care at 4 clinical sites in Montreal, Canada. This study includes patients whose ARV therapy was switched to dolutegravir with 2 NRTIs since 2013 with undetectable viral load for ≥6 months before switch. The association between exposure and post-switch virologic outcome was measured by marginal hazard ratio estimated using the Inverse probability weighting Cox model.Among the 1199 eligible PLHIV, 478 (39.9%) previously experienced at least one virologic failure or were exposed to mono/dual therapy before dolutegravir switch. Post-switch virologic failure after 30 months occurred in 4.1% (95% CI 2.1-7.9) of exposed compared to 4.1% (95% CI 2.3-7.4) in unexposed participants. The adjusted hazard ratio for the association between exposure and post-switch virologic failure was 0.84 (95% CI 0.35-2.01).Our findings suggest that switch to dolutegravir with 2 NRTIs from a suppressive therapy is a safe option for PLHIV with documented virologic failure and/or previous exposure to mono/dual NRTI therapy.

Treatment Switch to Dolutegravir With 2 Nucleoside Reverse-Transcriptase Inhibitors (NRTI) in Comparison to Continuation With Protease Inhibitor/Ritonavir Among Patients With Human Immunodeficiency Virus at Risk for Prior NRTI Resistance: A Cohort Analysis of Real-World Data.

BACKGROUND: Switching antiretroviral regimens when human immunodeficiency virus (HIV) viremia is controlled for a new regimen is challenging when there is the potential for prior nucleoside reverse-transcriptase inhibitor (NRTI) resistance. The objective was to study virologic outcomes after switching to dolutegravir compared with remaining on a boosted protease inhibitor (protease inhibitor/ritonavir [PI/r]) regimen in people with HIV (PWH) with prior documented virologic failure and/or exposure to mono/dual NRTIs. METHODS: We used the Quebec HIV Cohort including 10 219 PWH whose data were collected at 4 sites in Montreal, Canada. We included all PWH with documented virologic failure or exposure to mono/dual NRTI therapy who were virologically suppressed on a PI/r-based regimen for at least 6 months on or after January 1, 2014 (n = 532). A marginal structural Cox model analysis was used to estimate the effect of the switch to dolutegravir on virologic outcome compared with remaining on PI/r. The outcome was defined as 2 consecutive viral loads (VLs) >50 copies/mL or 1 VL >50 copies/mL if it occurred at the last VL available. RESULTS: Among 532 eligible participants, 216 (40.6%) had their regimen switched to dolutegravir with 2 NRTIs, whereas 316 (59.4%) remained on the PI/r with 2 NRTIs. The weighted hazard ratio for the effect of dolutegravir switch on virologic failure compared with patients whose regimen remained on PI/r was 0.57 (95% confidence interval, 0.21-1.52). CONCLUSIONS: We did not find evidence of an increased risk for virologic failure after switching to dolutegravir from PI/r among patients with previous virologic failure or prior exposure to mono/dual NRTI.

Characterization of drug resistance in antiretroviral-treated patients infected with HIV-1 CRF02_AG and AGK subtypes in Mali and Burkina Faso.

BACKGROUND: In a multicentred cohort of patients on antiretroviral therapy (ART) in Burkina Faso and Mali, we analysed the prevalence of HIV drug resistance mutations in patients failing a modified directly observed therapy (mDOT) protocol. METHODS: Patients on ART >6 months and with viral load (VL) >500 copies/ml were enrolled in a mDOT protocol. Genotypic resistance testing was performed on pre- and post-mDOT plasma samples of patients who still had VL >500 copies/ml after mDOT. RESULTS: Eight hundred and one patients from seven sites participated in the study. One hundred and thirteen patients (14.1%) had VL >500 copies/ml. Most patients were treated with lamivudine along with zidovudine or stavudine and efavirenz or nevirapine. Genotypes were available for 46 patients. The predominant HIV-1 subtypes were CRFO2_AG in 26 (56.5%) and AGK/K/AK in 12 (26.1%) patients. The prevalence of drug resistance mutations by class were as follows for nucleoside reverse transcriptase inhibitors: 1841/V (82.6%), 215Y/F (32.6%), 219E/Q (19.6%), 70R (19.6%), 67N (21.7%), 41L (15.2%) and 151M(2.2%). For non-nucleoside reverse transcriptase inhibitors the prevalence was: 103N (50%) and 181C/I (19.6%). Phylogenetic analysis showed that, although the genetic distances were small among isolates, there was no clustering of a particular subtype in a specific region and that the high prevalence of AGK subtype in our drug-resistant population was not due to a circulating resistant strain. CONCLUSION: Although CRFO2_AG is the dominant clade in the Burkina Faso/Mali region, isolates with subtype K reverse transcriptase were frequent in our cohort. Drug resistance mutation pathways in subtype K reverse transcriptase need to be further evaluated in a larger cohort of non-B HIV-infected individuals.

A comparison of virological suppression and rebound between Indigenous and non-Indigenous persons initiating combination antiretroviral therapy in a multisite cohort of individuals living with HIV in Canada.

BACKGROUND: This study compared time to virological suppression and rebound between Indigenous and non-Indigenous individuals living with HIV in Canada initiating combination antiretroviral therapy (cART). METHODS: Data were from the Canadian Observational Cohort collaboration; eight studies of treatment-naive persons with HIV initiating cART after 1/1/2000. Fine and Gray models were used to estimate the effect of ethnicity on time to virological suppression (two consecutive viral loads [VLs] <50 copies/ml at least 3 months apart) after adjusting for the competing risk of death and time until virological rebound (two consecutive VLs >200 copies/ml at least 3 months apart) following suppression. RESULTS: Among 7,080 participants were 497 Indigenous persons of whom 413 (83%) were from British Columbia. The cumulative incidence of suppression 1 year after cART initiation was 54% for Indigenous persons, 77% for Caucasian and 80% for African, Caribbean or Black (ACB) persons. The cumulative incidence of rebound 1 year after suppression was 13% for Indigenous persons, 6% for Caucasian and 7% for ACB persons. Indigenous persons were less likely to achieve suppression than Caucasian participants (aHR=0.58, 95% CI 0.50, 0.68), but not more likely to experience rebound (aHR=1.03, 95% CI 0.84, 1.27) after adjusting for age, gender, injection drug use, men having sex with men status, province of residence, baseline VL and CD4+ T-cell count, antiretroviral class and year of cART initiation. CONCLUSIONS: Lower suppression rates among Indigenous persons suggest a need for targeted interventions to improve HIV health outcomes during the first year of treatment when suppression is usually achieved.

Increased mortality among Indigenous persons in a multisite cohort of people living with HIV in Canada.

OBJECTIVE: Compare all-cause mortality between Indigenous participants and participants of other ethnicities living with HIV initiating combination antiretroviral therapy (cART) in an interprovincial multi-site cohort. METHODS: The Canadian Observational Cohort is a collaboration of 8 cohorts of treatment-naïve persons with HIV initiating cART after January 1, 2000. Participants were followed from the cART initiation date until death or last viral load (VL) test date on or before December 31, 2012. Cox proportional hazard models were used to estimate the effect of ethnicity on time until death after adjusting for age, gender, injection drug use, being a man who has sex with men, hepatitis C, province of origin, baseline VL and CD4 count, year of cART initiation and class of antiretroviral medication. RESULTS: The study sample consisted of 7080 participants (497 Indigenous, 2471 Caucasian, 787 African/Caribbean/Black (ACB), 629 other, and 2696 unknown ethnicity). Most Indigenous persons were from British Columbia (BC) (83%), with smaller numbers from Ontario (13%) and Québec (4%). During the study period, 714 (10%) participants died. The five-year survival probability was lower for Indigenous persons (0.77) than for Caucasian (0.94), ACB (0.98), other ethnicities (0.96) and unknown ethnicities (0.85) (p < 0.0001). In an adjusted proportional hazard model for which missing data were imputed, Indigenous persons were more likely to die than Caucasian participants (hazard ratio = 2.69, p < 0.0001). CONCLUSION: The mortality rate for Indigenous persons was higher than for other ethnicities and is largely reflective of the BC population. Addressing treatment challenges and identifying HIV- and non-HIV-related causes for mortality among Indigenous persons is required to optimize their clinical management.