The Ontario HIV Treatment Network Cohort Study (OCS) is an observational, open dynamic cohort of people who are receiving medical care for human immunodeficiency virus (HIV) infection in Ontario, Canada. Established in the mid-1990s, the OCS has its roots in AIDS activists' demands for research that would improve the quality of life of people living with HIV while respecting their privacy. It is a collaborative and community-driven study, including a Governance Committee made up of people with HIV and other stakeholders that evaluates analysis project proposals for community relevance and ethics. From 1995 to 2010, a total of 5644 participants were enrolled and 27,720 person-years of observation were accumulated; follow-up will continue until at least 2015. In the initial years of study, the focus was on clinical data from medical chart reviews. It has since evolved into a comprehensive study that collects extensive de-identified information on clinical, laboratory and psychosocial and behavioural measures based on medical chart abstractions, interviews using a standardized questionnaire and linkage with external administrative health databases in Ontario. Interested collaborators are encouraged to submit analysis project proposals as instructed on the study website (www.ohtncohortstudy.ca).
Background Although HIV pre-exposure prophylaxis (PrEP) substantially diminishes the likelihood of HIV acquisition, poor adherence can decrease the HIV-protective benefits of PrEP. The present investigation sought to identify the extent to which alcohol consumption, substance use, and depression were linked to PrEP nonadherence among gay, bisexual, and other men-who-have-sex-with-men (gbMSM). Methods gbMSM (age ≥ 18, prescribed PrEP for ≥3 months) were recruited from two clinics in Toronto, Canada for an e-survey assessing demographics; PrEP nonadherence (4-day PrEP-focused ACTG assessment); hazardous and harmful alcohol use (AUDIT scores of 8–15 and 16+, respectively); moderate/high risk substance use (NIDA M-ASSIST scores > 4); depression (CESD-10 scores ≥10); and other PrEP-relevant factors. The primary outcome, PrEP nonadherence, entailed missing one or more PrEP doses over the past 4 days. A linear-by-linear test of association assessed whether increasing severity of alcohol use (i.e., based on AUDIT categories) was linked to a greater occurrence of PrEP nonadherence. Univariate logistic regression was employed to determine factors associated with PrEP nonadherence, and factors demonstrating univariate associations at the p < .10 significance level were included in a multivariate logistic regression model. Additive and interactive effects involving key significant factors were assessed through logistic regression to evaluate potential syndemic-focused associations. Results A total of 141 gbMSM (Mean age = 37.9, white = 63.1%) completed the e-survey. Hazardous/harmful drinking (31.9%), moderate/high risk substance use (43.3%), and depression (23.7%) were common; and one in five participants (19.9%) reported PrEP nonadherence. Increasing alcohol use level was significantly associated with a greater likelihood of nonadherence (i.e., 15.6, 25.0, and 44.4% of low-risk, hazardous, and harmful drinkers reported nonadherence, respectively (χ2(1) = 4.79, p = .029)). Multivariate logistic regression demonstrated that harmful alcohol use (AOR = 6.72, 95%CI = 1.49–30.33, p = .013) and moderate/high risk cocaine use (AOR = 3.11, 95%CI = 1.01–9.59, p = .049) independently predicted nonadherence. Furthermore, an additive association emerged, wherein the likelihood of PrEP nonadherence was highest among those who were hazardous/harmful drinkers and moderate/high risk cocaine users (OR = 2.25, 95%CI = 1.19–4.25, p = .013). Depression was not associated with nonadherence. Conclusions Findings highlight the need to integrate alcohol- and substance-focused initiatives into PrEP care for gbMSM. Such initiatives, in turn, may help improve PrEP adherence and reduce the potential for HIV acquisition among this group.
The present study describes the clinical presentation and management of CA-MRSA infections occurring in Toronto among men who have sex with men. The infections appear to have been caused by CMRSA-10, which has caused the majority of CA-MRSA outbreaks elsewhere.
Information on the virologic durability of modern antiretroviral regimens is important to clinicians. We aimed to describe virologic durability of first-line integrase strand transfer inhibitor (INSTI)-, nonnucleoside reverse transcriptase inhibitor (NNRTI)-, or protease inhibitor (PI)-based antiretroviral regimens. This was a retrospective study of antiretroviral-naïve patients that initiated first-line antiretroviral regimens with two nucleoside reverse transcriptase inhibitors and an INSTI, NNRTI, or PI between January 2006 and June 2016. The outcome was time to virologic failure, which was assessed by Kaplan–Meier survival analysis and Cox regression models. There were 780 patients (median age = 37 years [interquartile range (IQR) = 30–45], 93.3% male, 56.2% Caucasian, median HIV duration = 1.8 years [IQR = 0.4–5.4], baseline log10 viral load [VL]=4.6 [IQR = 4.1–5.1], and baseline CD4+ cell count = 320 cells/µl [IQR = 217–440]). In total, 189/780 were on a third agent INSTI, 339/780 on a third agent NNRTI, and 252/780 on a third agent PI. Kaplan–Meier survival probability revealed longer time to virologic failure for INSTI, followed by NNRTI then PI (p < 0.001). Multivariable Cox regression revealed that being on an INSTI regimen (aHR = 0.27; 95%CI = 0.18–0.41) or NNRTI regimen (aHR = 0.64; 95%CI = 0.47–0.87) versus PI regimen, frequent VL testing (per year), (aHR = 0.64; 95%CI = 0.47–0.87), and duration of ART (aHR = 0.22; 95%CI = 0.17–0.30) (years) were inversely associated with time to virologic failure, and log10 of baseline VL (aHR = 1.94; 95%CI = 1.58–2.39 per log10) increased risk. Virologic failure was delayed and virologic durability prolonged for INSTI- compared to NNRTI- and PI-based regimens, supporting current antiretroviral therapy guidelines.
Although coinfection with hepatitis C (HCV) is an established risk factor for hepatotoxicity in HIV-positive patients receiving combination antiretroviral therapy (cART), specific variables that may be predictive of severe hepatotoxicity among co-infected patients receiving cART remain poorly defined. A retrospective cohort study of HIV/HCV coinfected adults from two HIV treatment centers covering the period between December 1998 and December 2003 was conducted to address this question. The primary endpoint of the study was the occurrence of grade 3 or 4 elevation of serum alanine aminotransferase (ALT) during follow-up and the primary predictors of interest were specific antiretrovirals. One hundred five coinfected patients receiving cART for a median of 70 months (interquartile range [IQR], 37, 83) were included in the analysis. Twenty-three (22%) patients developed a grade 3 or 4 increase in serum ALT at least once in follow-up. In univariate analysis, current receipt of lopinavir/ritonavir (LPV/r) (odds ratio [OR] 3.09, 95% confidence interval [CI] 1.14-8.34, p = 0.03), baseline ALT (OR 1.01, 95% CI 1.00-1.02, p = 0.004), and current use of boosting ritonavir (OR 2.84, 95% CI 1.16-7.00, p = 0.02) were significantly associated with a grade 3 or 4 increase in serum ALT, although most patients receiving boosting ritonavir were on lopinavir/ritonavir based regimens. Patients receiving LPV/r had been previously exposed to significantly more antiretrovirals (p < 0.0001), protease inhibitors (p < 0.0001), and nucleoside analogues (p = 0.0009) compared to the rest of the cohort. Further research to better clarify risk factors for hepatotoxicity in coinfected patients is warranted given the challenges in treating this population.
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