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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

A Multi-State Model Examining Patterns of Transitioning Among States of Engagement in Care in HIV-Positive Individuals Initiating Combination Antiretroviral Therapy.

BACKGROUND: Common measures of engagement in care fail to acknowledge that infrequent follow-up may occur either intentionally among patients with sustained virologic suppression or unintentionally among patients with poor clinical outcomes. METHODS: Five states of HIV care were defined within the Canadian Observational Cohort Collaboration following combination antiretroviral therapy (cART) initiation: (1) guidelines HIV care [suppressed viral load (VL) and CD4 >200 cells per cubic millimeter, no gaps in cART >3 months, no gaps in CD4 or VL measurement >6 months], (2) successful care with decreased frequency of follow-up (as above except no gaps in CD4 or VL measurement >12 months), (3) suboptimal care (unsuppressed VL, CD4 <200 cells per cubic millimeter on 2 consecutive visits, ≥1 gap in cART >3 months, or ≥1 gap in CD4 or VL measurement >12 months), (4) loss to follow-up (no contact for 18 months), and (5) death. Multi-state models were used to determine factors associated with transitioning among states. RESULTS: In total, 7810 participants were included. Younger age, female gender, Indigenous ethnicity, and people who have injected drugs were associated with increased likelihoods of transitioning from guidelines to suboptimal care and decreased likelihoods of transitioning from suboptimal to guidelines care. One-fifth of individuals in successful, decreased follow-up after cART initiation (mean sojourn time 0.72 years) were in suboptimal care in subsequent years. CONCLUSIONS: Using routinely collected data, we have developed a flexible framework that characterizes patient transitions among states of HIV clinical care. We have demonstrated that multi-state models provide a useful approach to supplement "cascade of care" work.

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.

Adherence to Post-Exposure Prophylaxis (PEP) and Incidence of HIV Seroconversion in a Major North American Cohort.

BACKGROUND: There is limited evidence on the efficacy of post-exposure prophylaxis (PEP) for sexual exposures. We sought to determine the factors associated with adherence to treatment and describe the incidence of PEP failures in a Montreal clinic. METHODS: We prospectively assessed all patients consulting for PEP following sexual exposures from October 2000 to July 2014. Patients were followed at 4 and 16 weeks after starting PEP. Treatment adherence was determined by self-report at week 4. Multivariable logistic regression was used to estimate the factors predicting adherence to treatment. RESULTS: 3547 PEP consults were included. Patients were mainly male (92%), MSM (83%) and sought PEP for anal intercourse (72%). Seventy-eight percent (n = 2772) of patients received a prescription for PEP, consisting of Tenofovir/Emtracitabine (TVD) + Lopinavir/Ritonavir (LPV) in 74% of cases, followed by Zidovudine/Lamivudine (CBV) + LPV (10%) and TVD + Raltegravir (RAL) (8%). Seventy percent of patients were adherent to treatment. Compared to TVD+LPV, patients taking CBV+LPV were less likely to adhere to treatment (OR 0.58, 95% CI 0.44-0.75), while no difference was observed for patients taking TVD+RAL (OR 1.15, 95% CI 0.83-1.59). First-time PEP consults, older and male patients were also more adherent to treatment. Ten treated patients seroconverted (0.37%) during the study period, yet only 1 case can be attributed to PEP failure (failure rate = 0.04%). CONCLUSION: PEP regimen was associated with treatment adherence. Patients were more likely to be adherent to TVD-based regimens. Ten patients seroconverted after taking PEP; however, only 1 case was a PEP failure as the remaining patients continued to engage in high-risk behavior during follow-up. One month PEP is an effective preventive measure to avoid HIV infection.

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.

Late initiation of combination antiretroviral therapy in Canada: a call for a national public health strategy to improve engagement in HIV care.

INTRODUCTION: Combination antiretroviral therapy (ART) significantly decreases morbidity, mortality and HIV transmission. We aimed to characterize the timing of ART initiation based on CD4 cell count from 2000 to 2012 and identify factors associated with late initiation of treatment. METHODS: Participants from the Canadian Observational Cohort (CANOC), a multi-site cohort of HIV-positive adults initiating ART naively after 1 January 2000, in three Canadian provinces (British Columbia, Ontario and Québec) were included. Late initiation was defined as a CD4 count <200 cells/mm(3) or an AIDS-defining illness before ART initiation (baseline). Temporal trends were assessed using the Cochran-Armitage test, and independent correlates of late initiation were identified using logistic regression. RESULTS: In total, 8942 participants (18% female) of median age 40 years (Q1-Q3 33-47) were included. The median baseline CD4 count increased from 190 cells/mm(3) (Q1-Q3 80-320) in 2000 to 360 cells/mm(3) (Q1-Q3 220-490) in 2012 (p<0.001). Overall, 4274 participants (48%) initiated ART with a CD4 count <200 cells/mm(3) or AIDS-defining illness. Late initiation was more common among women, non-MSM, older individuals, participants from Ontario and BC (vs. Québec), persons with injection drug use (IDU) history and individuals starting ART in earlier calendar years. In sub-analysis exploring recent (2008 to 2012) predictors using an updated CD4 criterion (<350 cells/mm(3)), IDU and residence in BC (vs. Québec) were no longer significant correlates of late initiation. CONCLUSIONS: This analysis documents increasing baseline CD4 counts over time among Canadians initiating ART. However, CD4 counts at ART initiation remain below contemporary treatment guidelines, highlighting the need for strategies to improve earlier engagement in HIV care.

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.

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.

Tolerability is more important than simplicity for treatment durability.

INTRODUCTION: Many studies have shown the superiority of single tablet regimens (STRs) of antiretrovirals for the treatment of HIV in terms of efficacy, adherence and rate of hospitalisation as they offer a low pill burden and once daily dosing. Our objective was to compare the duration of first-line STRs to multi-tablet regimens. METHODS: From our clinical database, we selected patients initiating any of the major first-line regimens between 2007 and 2013. Two STRs, Atripla (ATP) and Complera (CPLR), were compared to three non-STRs: two NRTIs and raltegravir (RAL), atazanavir/ritonavir (ATV/r) or darunavir/ritonavir (DRV/r). The primary outcome was time to discontinuation of the first-line regimen. The association between regimen type and duration was estimated using Cox proportional hazards models adjusted for age, gender, baseline CD4, baseline viral load, risk factor, site and year of treatment initiation. RESULTS: A total of 743 patients (281 on STRs and 462 on non-STRs) were included. 693 (93%) were male and median age was 43 years. Median length of follow-up was 3.2 years. 56% of patients were MSM, 6% IDU and 6% from endemic countries. Patients on an STR were less likely to be IDU (p<0.024) and have a baseline HIV-RNA ≥100,000 copies/mL (p<0.011). Overall, 321 (43%) patients discontinued their regimen during the study period. The rate of discontinuation one year after starting ARV depends on the regimen: 29% for patients on 2NRTIs+DRV/r, 26% on ATP, 25% on 2NRTIs+ATV/r, 17% on 2NRTIs+RAL and 10% on CPLR (p<0.001). In the adjusted model, durability for STR and non-STR was equivalent (aHR=0.83, p=0.108). Compared to patients on ATP, patients on CPLR were less likely to discontinue (HR=0.58, p=0.070). No difference between ATP and the other regimens was observed: HR for 2NRTIs+RAL=0.92 (p=0.66), 2NRTIs+ DRV/r=1.16 (p=0.36), 2NRTIs+ATV/r=1.11 (p=0.46). CONCLUSIONS: Our findings suggest that STRs do not necessarily result in a more durable treatment. Even with a higher pill burden and/or twice daily dosing, patients initiating therapy with RAL or boosted-PI based regimens were not more likely to discontinue the first-line regimen compared to patients on an STR. Among the STR subgroups, the regimen with better known tolerability conferred more durable treatment. Limitations included our inability to adjust for the patient's adherence to a given regimen.