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We explored attitudes of gay, bisexual, and other men who have sex with men (GBM) toward their amphetamine-use and associations with reduced use over time. We recruited sexually-active GBM aged 16+ years in Montreal, Toronto, and Vancouver, Canada, from 02-2017 to 08-2019, with follow-up visits every 6–12 months until November 2020. Among participants who reported past-six-month (P6M) amphetamine-use at enrollment, we used logistic regression to identify demographic, psychological, social, mental health, other substance-use, and behavioral factors associated with reporting needing help reducing their substance-use. We used mixed-effects logistic regression to model reduced P6M amphetamine-use with perceived problematic-use as our primary explanatory variable. We enrolled 2,449 GBM across sites. 15.5-24.7% reported P6M amphetamine-use at enrollment and 82.6 − 85.7% reported needing no help or only a little help in reducing their substance use. Reporting needing a lot/of help or completely needing help in reducing substance-use was associated with group sex participation (AOR = 2.35, 95%CI:1.25–4.44), greater anxiety symptomatology (AOR = 2.11, 95%CI:1.16–3.83), greater financial strain (AOR = 1.35, 95%CI:1.21–1.50), and greater Escape Motive scores (AOR = 1.07, 95%CI:1.03–1.10). Reductions in P6M amphetamine-use were less likely among GBM who perceived their amphetamine-use as problematic (AOR = 0.17 95% CI 0.10 − 0.29). Most amphetamine-using GBM did not feel they needed help reducing their substance use, and many reported reduced amphetamine-use at subsequent visits. Those who perceived their use as problematic were less likely to reduce their use. Further interventions to assist GBM in reducing their use are needed to assist those who perceive their use as problematic. [ABSTRACT FROM AUTHOR]

In mid-2022, a global mpox epidemic emerged that was concentrated in gay, bisexual and other men who have sex with men, prompting the WHO to declare a public health emergency of international concern. Shortly after cases were first identified in Canada, we established the Mpox Prospective Observational Cohort Study (MPOCS) to characterize clinical, psychosocial, epidemiologic and virologic characteristics of this re-emerging infection. Community members were engaged in identifying research priorities, creating participant-facing materials, and forming a community advisory board. This article outlines the MPOCS study protocol. Although cases of mpox in Canada have rapidly declined, our research procedures may serve as a template for rapidly studying emerging infectious disease threats in the future, particularly among sexual networks. [ABSTRACT FROM AUTHOR]

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

Objective: To characterize the incidence of select chronic comorbidities in the era of modern (pre-integrase-inhibitor) highly active antiretroviral therapy (HAART) in British Columbia, Canada. Methods: We used data from the Comparative Outcomes And Service Utilization Trends (COAST) study, a population-based cohort study of people living with HIV (PLWH), to determine incidence rates of six key chronic diseases among PLWH receiving HAART in BC from 2000 to 2012. The selected diseases included cardiovascular disease (CVD), diabetes mellitus (DM), hypertension (HTN), asthma/chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD) and chronic liver disease (CLD) defined using ICD-9 and -10 codes. Disease incidence was determined by number of new cases per year. We used Poisson regression to measure trends in incidence rates. Results: The study sample (n = 10,210) was predominantly male (83%), white (72%) and younger than 50 years of age at HAART initiation (88%). Incidence rates of HTN per 1000 person-years (PY) increased significantly between 2000 and 2012, after adjusting for age, sex, baseline-weighted Charlson Comorbidity Index, CD4 cell count and viral load (p < .001); incidence rates of CKD and CLD decreased significantly over time (p < .001). Unadjusted incidence rates of DM increased over time (p < .01), but remained stable in the adjusted model. Incidence rate patterns for CVD and COPD/asthma were stable over the study period. Conclusions: Population-level increases in incidence rates for HTN, and decreases for CLD and CKD, were observed among PLWH on modern (pre-integrase-inhibitor) HAART from 2000 to 2012. Overall, the increasing incidence of several of these chronic comorbidities in our study suggests that further efforts are needed to maximize the potential for healthy aging among PLWH receiving modern (pre-integrase-inhibitor) HAART. [ABSTRACT FROM AUTHOR]

Background: Inflammation has been associated with increased morbidity and mortality in HIV-positive patients. We compared inflammatory biomarkers with dual therapy using lopinavir/ritonavir plus lamivudine (LPV/r+3TC) versus triple therapy using LPV/r plus two nucleoside reverse transcriptase inhibitors (LPV/r+2NRTIs) in treatment-naïve HIV-positive adults. Methods: This was a substudy among Argentinian participants in the randomized trial GARDEL. We measured hsCRP, IL-6, MCP-1, TNF, D-dimer and sCD14 from plasma collected at baseline, week 24 and week 48. Generalized estimating equations with an identity/logit link were used to model the average impact of dual versus triple therapy on each biomarker over time, controlling for baseline levels. Additional models estimated the average effect of virologic suppression on biomarker levels over time, adjusting for age, sex, and baseline CD4 count. Results: Of 191 trial participants enrolled in Argentina, 172 had baseline and follow-up measurements and were included. Median (IQR) age was 35.5 (28.5, 45) years and CD4 cell count was 310 (219, 414) cells/mm3. Dual therapy was not associated with significantly different biomarker levels over 48 weeks relative to triple therapy. Virologic suppression was associated with statistically significant decreases in MCP-1, TNF and D-dimer levels and an unexpected increase in sCD14 levels. No change was observed in hsCRP or the proportion of participants with undetectable IL-6 levels. Conclusions: In addition to having virologic non-inferiority, LPV/r+3TC dual therapy is generally associated with similar inflammatory biomarker levels over 48 weeks compared to LPV/r+2NRTIs triple therapy in treatment-naïve adults. Further study of dual treatment regimens is warranted. [ABSTRACT FROM AUTHOR]

Background: Late HIV diagnosis is associated with increased AIDS-related morbidity and mortality as well as an increased risk of HIV transmission. In this study, we quantified and characterized missed opportunities for earlier HIV diagnosis in British Columbia (BC), Canada. Design: Retrospective cohort. Methods: A missed opportunity was defined as a healthcare encounter due to a clinical manifestation which may be caused by HIV infection, or is frequently present among those with HIV infection, but no HIV diagnosis followed within 30 days. We developed an algorithm to identify missed opportunities within one, three, and five years prior to diagnosis. The algorithm was applied to the BC STOP HIV/AIDS population-based cohort. Eligible individuals were ≥18 years old, and diagnosed from 2001–2014. Multivariable logistic regression identified factors associated with missed opportunities. Results: Of 2119 individuals, 7%, 12% and 14% had ≥1 missed opportunity during one, three and five years prior to HIV diagnosis, respectively. In all analyses, individuals aged ≥40 years, heterosexuals or people who ever injected drugs, and those residing in Northern health authority had increased odds of experiencing ≥1 missed opportunity. In the three and five-year analysis, individuals with a CD4 count <350 cells/mm3 were at higher odds of experiencing ≥1 missed opportunity. Prominent missed opportunities were related to recurrent pneumonia, herpes zoster/shingles among younger individuals, and anemia related to nutritional deficiencies or unspecified cause. Conclusions: Based on our newly-developed algorithm, this study demonstrated that HIV-diagnosed individuals in BC have experienced several missed opportunities for earlier diagnosis. Specific clinical indicator conditions and population sub-groups at increased risk of experiencing these missed opportunities were identified. Further work is required in order to validate the utility of this proposed algorithm by establishing the sensitivity, specificity, positive and negative predictive values corresponding to the incidence of the clinical indicator conditions among both HIV-diagnosed and HIV-negative populations. [ABSTRACT FROM AUTHOR]

Gay, bisexual, and other men who have sex with men (gbMSM) are at the highest risk for HIV infection in British Columbia (BC). Pre-exposure prophylaxis (PrEP) has been recently licensed but is currently not publicly funded in BC. Using respondent-driven sampling, we recruited a cohort of gbMSM to complete a computer-assisted self-interview with follow-up every 6 months. Stratified by HIV status, we examined trends in awareness of PrEP from 11/2012 to 02/2016 and factors associated with PrEP awareness. 732 participants responded to the PrEP awareness question. Awareness of PrEP among HIV-negative men increased from 18 to 80% (p < 0.0001 for trend); among HIV-positive men, awareness increased from 36 to 77% (p < 0.0001). PrEP awareness was associated with factors related to HIV risk including sero-adaptive strategies and sexual sensation seeking. Eight HIV-negative men reported using PrEP. Low PrEP uptake highlights that PrEP access should be expanded for at-risk gbMSM in BC. [ABSTRACT FROM AUTHOR]

Background: Daily tenofovir disoproxil fumarate (TDF)/emtricitabine as HIV pre-exposure prophylaxis (PrEP) causes subclinical decreases in bone mineral density (BMD). We surveyed PrEP users to assess feasibility for a clinical trial of vitamin D supplementation to mitigate TDF-induced BMD loss. Methods: We recruited participants using or starting PrEP in Toronto and Vancouver. The primary objective was to assess the acceptability of daily or weekly vitamin D supplementation. We also assessed the acceptability of calcium supplementation, existing use of non-pharmacological bone health interventions, prevalence of osteoporosis risk factors, and bone health knowledge (Osteoporosis Knowledge Test, OKT). Results: Of 161 participants, 72.1% were current PrEP users, 18.0% were starting PrEP, and 9.9% did not indicate their PrEP status. All identified as males, 88.8% as gays, and 67.1% as Whites. Median (IQR) age was 32.0 (29.0, 40.0) years, and 62.1% reported family income ≥$60,000/year. Among those not already using the interventions, willingness to supplement with daily vitamin D, weekly vitamin D, or daily calcium was very high at 90.9%, 96.4%, and 93.0 %, respectively. Only 31.0% reported adequate dietary calcium intake, while 42.9% reported ≥1 osteoporosis risk factor (most commonly, alcohol and smoking). Overall bone health knowledge was low, as median (IQR) OKT score was 16/32. In post hoc comparisons, current PrEP users may have been more likely than new PrEP users to engage in bone loading exercise (Bone-specific Physical Activity Questionnaire score=12.5 vs 3.6, P=0.001) and have greater bone health knowledge (OKT=17 vs 14, P=0.08), but they had similar levels of current vitamin D supplementation (37.4% vs 21.4%, P=0.11), calcium supplementation (11.2% vs 13.8%, P=0.70), and adequate dietary calcium intake (32.7% vs 25.0%, P=0.43). Discussion: The high acceptability of vitamin D and calcium supplementation in this cohort suggests that enrollment into a clinical trial of such interventions to mitigate PrEP-induced BMD loss is feasible. [ABSTRACT FROM AUTHOR]

Advances in HIV therapies have transformed HIV infection into a manageable chronic disease. Accordingly, hospital admission trends among people living with HIV may have evolved over time. This study describes discharge diagnoses from the dedicated HIV/AIDS ward at St. Paul’s Hospital in Vancouver, Canada. A retrospective database review of admissions to the HIV/AIDS ward between 1 July 2005 and 30 June 2014 was conducted. Primary discharge diagnoses were manually categorized by condition and reviewed by two physicians. Data were analysed in 12-month intervals. Trends were fitted using generalized estimating equations. A total of 1595 individuals with 3919 admissions were included. The median age was 46 years, 77.1% identified as male, 63.6% had a history of injection drug use (IDU) and 61.8% had a history of hepatitis C virus exposure. The most common reasons for admission included non-opportunistic respiratory tract infections (18.2%), cellulitis (7.3%), gastroenteritis (6.0%), endocarditis/bacteremia (4.9%) and bone/joint infections (3.5%). The proportion of admissions attributable to opportunistic infections declined from 16.2% in 2005 to 5.5% in 2014. Over this period, the proportion of individuals on antiretroviral therapy and with virologic suppression increased (odds ratio 1.19 [95% confidence interval 1.16, 1.23] and 1.22 [95% confidence interval 1.17, 1.26], respectively). These results demonstrate a decline in admissions related to opportunistic infections but increased admissions due to other infections among people living with HIV. Preventive and outpatient care for respiratory infections and complications of IDU may further improve health care outcomes and decrease hospital admissions in this setting. [ABSTRACT FROM AUTHOR]

Purpose The Comparative Outcomes And Service Utilization Trends (COAST) Study in British Columbia (BC), Canada, was designed to evaluate the determinants of health outcomes and health care services use among people living with HIV (PLHIV) as they age in the period following the introduction of combination antiretroviral therapy (cART). The study also assesses how age-associated comorbidities and health care use among PLHIV may differ from those observed in the general population. Participants COAST was established through a data linkage between two provincial data sources: The BC Centre for Excellence in HIV/AIDS Drug Treatment Program, which centrally manages cART dispensation across BC and contains prospectively collected data on demographic, immunological, virological, cART use and other clinical information for all known PLHIV in BC; and Population Data BC, a provincial data repository that holds individual event-level, longitudinal data for all 4.6 million BC residents. COAST participants include 13 907 HIV-positive adults (≥19 years of age) and a 10% random sample inclusive of 516 340 adults from the general population followed from 1996 to 2013. Findings to date For all participants, linked individual-level data include information on demographics, health service use (eg, inpatient care, outpatient care and prescription medication dispensations), mortality, and HIV diagnostic and clinical data. Publications from COAST have demonstrated the significant mortality reductions and dramatic changes in the causes of death among PLHIV from 1996 to 2012, differences in the amount of time spent in a healthy state by HIV status, and high levels of injury and mood disorder diagnosis among PLHIV compared with the general population. Future plans To capture the dynamic nature of population health parameters, regular data updates and a refresh of the data linkage are planned to occur every 2 years, providing the basis for planned analysis to examine age-associated comorbidities and patterns of health service use over time. [ABSTRACT FROM AUTHOR]

The article discusses the guideline on pre-exposure prophylaxis (PrEP) and non-occupational post-exposure prophylaxis (nPEP) for the prevention of HIV infection in Canada. Topics discussed include PrEP using tenofovir disoproxil fumarate/emtricitabine, indications for PrEP including men who have sex with men (MSM), heterosexual exposure and people who inject drugs (PWID) exposure, and preferred and alternate agents for nPEP.

Background: As a simplification strategy for treatment-experienced HIV-infected patients who have achieved virologic suppression on a multi-drug, multi-class antiretroviral regimen, the aim of this study was to evaluate the safety, efficacy, and pharmacokinetics of once-daily elvitegravir/cobicistat/emtricitabine/tenofovir disproxil fumarate (E/C/F/ TDF) with darunavir. Methods: A single arm, open-label 48-week study was conducted of regimen simplification to E/C/F/TDF plus darunavir 800 mg daily from stable therapy including two nucleoside/nucleotide reverse transcriptase inhibitors, a ritonavir-boosted protease inhibitor, and an integrase inhibitor. Participants had plasma HIV viral load consistently < 200 copies/mL for ≥ 6 months, estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, and no genotypic resistance to major components of the study regimen. Plasma viral load was measured at weeks 2 and 4, then every 4 weeks throughout the study. Safety laboratory assessments were conducted at baseline and at weeks 12, 24, 36, and 48. Antiretroviral drug concentrations were measured at baseline and once ≥ 2 weeks after the regimen change. Results: Ten HIV-infected adults (8 male and 2 female; median age 50.5 years) were enrolled. All maintained virologic suppression on the new regimen for 48 weeks. One subject experienced a decrease in eGFR from 62 mL/min at baseline to 52 mL/min at week 12; study medications were continued and his eGFR remained stable (50--59 mL/min) thereafter. No subjects discontinued study medications for renal function changes or other adverse events. Darunavir trough concentration were lower on the new regimen than on darunavir/ritonavir 800/100 mg (n = 5; p < 0.05). Conclusions: Despite low darunavir trough concentrations, treatment simplification to a two-pill, once-daily regimen of E/C/F/TDF plus darunavir was safe and effective for 48 weeks among 10 selected treatment-experienced HIV-infected patients. Trial registration The study protocol was registered with ClinicalTrials.gov (NCT02199613) on July 22, 2014 [ABSTRACT FROM AUTHOR]

Rurally located people living with HIV (PLWH) face unique challenges associated with remoteness that may negatively affect their HIV care outcomes. The Programmatic Compliance Score (PCS) has been used previously as a quality of care metric, and is predictive of mortality for treatment-naïve individuals initiating combination antiretroviral therapy (cART). This study looked at whether the rurality of PLWH impacted their PCS. PCS was calculated for PLWH (≥19 years old) initiating cART in British Columbia between 2000 and 2013. Rurality was determined at the time of cART initiation using two methodologies: (1) a categorical postal code method; and (2) the General Practice Rurality Index (GPRI), a score representing an individual’s degree of rurality. Ordinal logistic regression modeling was used to assess the relationship between rurality and PCS. Among 4616 PLWH with an evaluable PCS, 176 were classified as rural and 3512 as urban (928 had an unknown postal code). After adjusting for age, sex, hepatitis C status, Indigenous ancestry, and year of cART initiation, categorical rurality was not associated with a worse PCS (adjusted odds ratio (AOR) 1.04; 95% CI: 0.77–1.39). However, an increasing degree of rurality was associated with a worse PCS (AOR (per 10 increase in GPRI) 1.13; 95% CI: 1.06–1.20). Given that a poor PCS has been shown to be predictive of all-cause mortality for individuals initiating cART, strategies to improve access to HIV care for rural individuals should be evaluated. [ABSTRACT FROM PUBLISHER]

Background: Non-HIV/AIDS-related diseases are gaining prominence as important causes of morbidity and mortality among people living with HIV. The purpose of this study was to characterize and compare changes over time in mortality rates and causes of death among a population-based cohort of persons living with and without HIV in British Columbia (BC), Canada.Methods: We analysed data from the Comparative Outcomes And Service Utilization Trends (COAST) study; a retrospective population-based study created via linkage between the BC Centre for Excellence in HIV/AIDS and Population Data BC, and containing data for HIV-infected individuals and the general population of BC, respectively. Our analysis included all known HIV-infected adults (≥ 20 years) in BC and a random 10% sample of uninfected BC adults followed from 1996 to 2012. Deaths were identified through Population Data BC - which contains information on all registered deaths in BC (BC Vital Statistics Agency dataset) and classified into cause of death categories using International Classification of Diseases (ICD) 9/10 codes. Age-standardized mortality rates (ASMR) and mortality rate ratios were calculated. Trend test were performed.Results: 3401 (25%), and 47,647 (9%) individuals died during the 5,620,150 person-years of follow-up among 13,729 HIV-infected and 510,313 uninfected individuals, respectively. All-cause and cause-specific mortality rates were consistently higher among HIV-infected compared to HIV-negative individuals, except for neurological disorders. All-cause ASMR decreased from 126.75 (95% CI: 84.92-168.57) per 1000 population in 1996 to 21.29 (95% CI: 17.79-24.79) in 2011-2012 (83% decline; p < 0.001 for trend), compared to a change from 7.97 (95% CI: 7.61-8.33) to 6.87 (95% CI: 6.70-7.04) among uninfected individuals (14% decline; p < 0.001). Mortality rates from HIV/AIDS-related causes decreased by 94% from 103.85 per 1000 population in 1996 to 6.72 by the 2011-2012 era (p < 0.001). Significant ASMR reductions were also observed for hepatic/liver disease and drug abuse/overdose deaths. ASMRs for neurological disorders increased significantly over time. Non-AIDS-defining cancers are currently the leading non-HIV/AIDS-related cause of death in both HIV-infected and uninfected individuals.Conclusions: Despite the significant mortality rate reductions observed among HIV-infected individuals from 1996 to 2012, they still have excess mortality risk compared to uninfected individuals. Additional efforts are needed to promote effective risk factor management and appropriate screening measures among people living with HIV. [ABSTRACT FROM AUTHOR]

Objectives:To assess safety and efficacy of a switch to unboosted atazanavir (ATV) among HIV-infected adults receiving ATV/ritonavir (r) and tenofovir disoproxil fumarate (TDF). Methods:HIV-infected adults with viral load (VL) <40 copies/mL at screening and <150 copies/mL consistently for ≥3 months while receiving a regimen including ATV/r and TDF were randomized to continue ATV/r 300/100 mg daily (control) or change to ATV 400 mg daily (switch), while maintaining their TDF backbone. The primary outcome was proportion of subjects without treatment failure (regimen switch or VL > 200 copies/mL twice consecutively) at 48 weeks. Results: Fifty participants (46 male, median age 47 years) were randomized, 25 to each arm. At week 48, treatment success occurred in 76% in the control arm and 92% in the switch arm (ITT,p = 0.25). ATV trough levels at week 9 were higher in controls (median 438 ng/mL) than in the switch arm (median 124 ng/mL) (p = 0.003), as was total bilirubin at week 48 (median 38 μmol/L and 28 μmol/L, respectively;p = 0.02). Estimated glomerular filtration rate (eGFR) decreased in the control arm (p = 0.007), but did not change in the switch arm. At week 48, eGFR was higher in the switch arm (median 96 mL/min) than in the control arm (median 85 mL/min) (p = 0.035), but the arms were similar with respect to fasting glucose, C-reactive protein, and lipid parameters. Conclusions:Switching from ATV/r to unboosted ATV appears to be safe and effective in selected virologically suppressed patients receiving TDF-containing regimens, and may have favorable effects on bilirubin and renal function. [ABSTRACT FROM AUTHOR]

Introduction: Tenofovir disoproxil fumarate (TDF)–associated renal dysfunction may abate when TDF is replaced with abacavir (ABC). The extent to which the third drug atazanavir contributes to renal dysfunction is unclear.Methods: A retrospective analysis was conducted on adults who had plasma viral load (pVL)<200 copies/mL for≥six months while receiving TDF/lamivudine (3TC) – or TDF/emtricitabine (FTC)–based antiretroviral therapy (ART), then switched to ABC/3TC while retaining the third drug in the ART regimen. CD4, pVL, creatinine, estimated glomerular filtration rate (eGFR), serum phosphorus, urine albumin to creatinine ratio and serum lipids were compared between pre-switch baseline and 3, 6 and 12 months after the switch to ABC.Results: A total of 286 patients switched from TDF to ABC between 2004 and 2014: 232 (81%) male, median age 48 years (interquartile range (IQR) 42, 56). The third drug was atazanavir (± ritonavir) in 141 (49%) cases. The pVL was<50 copies/mL in 93 to 96% at all time points. Median serum creatinine was 93 µmol/L (IQR 80–111) at baseline and decreased to 88 µmol/L (IQR 78–98) at 12 months after the switch to ABC. Median eGFR increased from 74 (IQR 60–88) mL/min at baseline to 80 mL/min (IQR 69–89) at 12 months. Results were not significantly different between patients on atazanavir versus those on another third drug.Conclusions: Viral suppression was maintained among patients who switched from TDF/3TC or TDF/FTC to ABC/3TC. Serum creatinine and eGFR improved up to 12 months after switching to ABC/3TC, irrespective of whether or not patients were also receiving atazanavir±ritonavir. [ABSTRACT FROM AUTHOR]

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

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Introduction: HIV-1 plasma viral load during treatment can be highly variable. Thus, there is the need to find a measure of cumulative viremia that can be used to assess both the short- and long-term efficacy of highly active antiretroviral therapy (HAART). Here, we validate a measure of cumulative viremia to evaluate HAART efficacy. Methods: We accessed HAART efficacy using data from a randomized clinical trial conducted in Mexico. We compared the proportion of individuals achieving a viral load <50 and <400 copies/mL at week 48, against the cumulative plasma viral load, estimated as the area under the plasma viral load curve (AUVLC). High AUVLC indicates high cumulative viremia. Results and discussion: There was a strong and significant association between the proportion of individuals achieving a viral load <50 and <400 copies/mL at week 48, with individuals suppressed having significant lower cumulative viremia. The median area was 7513 (25th–75th percentile [Q1–Q3] 6634−8180) if viral load <50 copies/mL and 7679 (Q1–Q3 6899−9373) if viral load ≥50 copies/mL (p-value 0.0284). When the analysis was stratified by study arm, individuals on efavirenz had lower cumulative viremia than those on boosted lopinavir. Conclusions: Our findings suggest that cumulative viremia should be explored further as a tool to simultaneously evaluate the individual and public health efficacy of HAART. This is particularly relevant to the implementation and evaluation of the Treatment 2.0 strategy recently proposed by UNAIDS and the WHO, as a means to maximize the individual and public health benefit of HAART. [ABSTRACT FROM AUTHOR]

Discordance between absolute CD4 cell count and CD4 cell percentage is common in patients coinfected with human immunodeficiency virus and hepatitis C virus. Discordance is associated with markers of fibrosis, an aspartate transaminase to platelet ratio index of >1.5, and end-stage liver disease and thus may be useful in identifying patients for liver disease staging.Background. Liver cirrhosis has been associated with decreased absolute CD4 cell counts but preserved CD4 cell percentage in human immunodeficiency virus (HIV)–negative persons. We evaluated factors associated with discordance between the absolute CD4 cell count and the CD4 cell percentage in a cohort of patients coinfected with HIV and hepatitis C virus (HCV).Methods. Baseline data from 908 participants in a prospective, Canadian, multisite cohort of individuals with HIV-HCV coinfection were analyzed. Absolute CD4 cell count and CD4 cell percentage relationships were evaluated. We defined low and high discordance between absolute CD4 cell count/CD4 cell percentage relationships as CD4 cell percentages that differed from the expected CD4 cell percentage, given the observed absolute CD4 cell count, by ±7 percentage points; we defined very low and very high discordance as differences of ±14 percentage points. Factors associated with high or very high discordance, including either end-stage liver disease or aspartate transaminase to platelet ratio index (APRI) of >1.5, were analyzed using multivariate logistic regression models and compared to groups with concordant and low discordant results.Results. High/very high discordance was seen in 31% (n = 286), while 35% (n = 321) had concordant values. Factors associated with very high discordance at baseline included history of end-stage liver disease (adjusted odds ratio [aOR], 6.52; 95% confidence interval [CI], 2.27–18.67) and APRI of >1.5 (aOR 4.69; 95% CI, 1.64–13.35). Compared with those with detectable HCV RNA, those who cleared HCV spontaneously were less likely to have very high discordance.Conclusions. Discordance between absolute CD4 cell count and CD4 cell percentage is common in an HIV/HCV-coinfected population and is associated with advanced liver disease and ongoing HCV replication. [ABSTRACT FROM AUTHOR]

The advent of combination antiretroviral therapy has led to significant improvement in the care of HIV-infected patients. Originally designed as a protease inhibitor (PI), ritonavir is currently exclusively used as a pharmacokinetic enhancer of other protease inhibitors, predominantly due to ritonavir's potent inhibition of the cytochrome P450 3A4 isoenzyme. Ritonavir-boosting of PIs decrease pill burden and frequency of dosing. Boosted PIs are recommended for first-line therapy in treatment and play a key role in the management of treatment-experienced patients. Potential problems associated with PIs include metabolic abnormalities (e.g. dyslipidemia), increased cardiovascular risk, and drug interactions. [ABSTRACT FROM AUTHOR]

Guidelines recommend that when soft-gelatin capsules of lopinavir/ritonavir are co-administered with CYP3A4- inducing agents, doses should be increased to 4 capsules (533 mg/133 mg) twice daily. No evidence is available to guide dosing of lopinavir/ritonavir in tablet formulation in this setting. A single-center study is conducted to compare the pharmacokinetics of high-dose lopinavir/ritonavir in 34 patients on stable HAART regimens including 4 soft-gelatin capsules twice daily who then switch to 3 tablets (600 mg/150 mg) twice daily. Median C[submin] on soft-gelatin capsule and tablets is 4700 ng/mL (interquartile range [IQR] 2310, 6000 ng/mL) and 5640 ng/mL (IQR 4290, 8080 ng/mL), respectively, for those on inducing agents (n = 17). For patients not on inducing agents (n = 17), median C[submin] on soft-gelatin capsule and tablets is 5170 ng/mL (IQR 3640, 6210 ng/mL) and 5640 ng/mL (IQR 4290, 8080 ng/mL), respectively. Among treatment-experienced patients on lopinavir/ritonavir capsules 533/133 mg twice daily, a switch to tablets 600/150 mg twice daily produces comparable pharmacokinetics, regardless of whether they receive concomitant CYP3A4-inducing antiretroviral agents. [ABSTRACT FROM AUTHOR]

The article discusses the transforming worldwide epidemiology of pulmonary manifestations of HIV/AIDS. Infections such as bacteria pneumonias remain common, while opportunistic agents such as Pneumocystis jirovecii remain a concern. The tuberculosis epidemic has been re-energized by the spread of HIV. Atypical inflammatory responses due to a phenomenon of immune reconstitution are now recognized as a result of highly active antiretroviral therapy (HAART).

Background. Streptococcus pneumoniae is a common cause of sporadic invasive infections, but outbreaks of invasive pneumococcal disease are infrequent. In August 2006, a sudden increase in the number of patients presenting with invasive pneumococcal disease was noted at St. Paul's Hospital (Vancouver, Canada). Most patients with severe disease resided in an area referred to as the Downtown Eastside, a neighborhood known for its high rates of poverty and illicit drug use. Methods. Prospective, laboratory-based surveillance for invasive pneumococcal disease was initiated, including on-site serotyping of S. pneumoniae isolates. A vaccination campaign using 23-valent polysaccharide pneumococcal vaccine was launched in the Downtown Eastside. Multiple logistic regression was used to examine the association of sociodemographic variables and medical risk factors with S. pneumoniae serotype status. Results. A single S. pneumoniae serotype (serotype 5) was responsible for 78% of invasive pneumococcal disease cases (137 of 175 cases) during the outbreak period of August 2006-July 2007. The outbreak strain, although fully susceptible to penicillin, caused significant morbidity and placed considerable strain on the acute care system within the Vancouver Coastal Health region. Crack cocaine use was found to be the main independent risk factor associated with invasive pneumococcal disease due to S. pneumoniae serotype 5 (odds ratio, 12.4; 95% confidence interval, 2.22-69.5). Conclusions. A targeted vaccination campaign using polysaccharide pneumococcal vaccine appeared to help control this outbreak. In urban centers with high rates of illicit drug use, vaccination strategies for preventing invasive pneumococcal disease may need to be refined to include individuals who use crack cocaine. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the author discusses the use of efavirenz and boosted atazanavir in combination with tenofovir/ emtricitabine as initial therapy for treatment against HIV infection.

Introduction: The prevalence of hepatitis C virus (HCV) is far higher in prison settings than in the general population; thus, micro‐elimination strategies must target people in prison to eliminate HCV. We aimed to examine incarceration patterns and determine whether incarceration impacts HCV treatment uptake among Canadian HIV‐HCV co‐infected individuals in the direct‐acting antiviral (DAA) era. Methods: The Canadian Co‐Infection Cohort prospectively follows HIV‐HCV co‐infected people from 18 centres. HCV RNA‐positive participants with available baseline information on incarceration history were included and followed from 21 November 2013 (when second‐generation DAAs were approved by Health Canada) until 30 June 2017. A Cox proportional hazards model was used to assess the effect of time‐updated incarceration status on time to treatment uptake, adjusting for patient‐level characteristics known to be associated with treatment uptake in the DAA era. Results: Overall, 1433 participants (1032/72% men) were included; 67% had a history of incarceration and 39% were re‐incarcerated at least once. Compared to those never incarcerated, previously incarcerated participants were more likely to be Indigenous, earn <$1500 CAD/month, report current or past injection drug use and have poorly controlled HIV. There were 339 second‐generation DAA treatment initiations during follow‐up (18/100 person‐years). Overall, 48% of participants never incarcerated were treated (27/100 person‐years) compared to only 31% of previously incarcerated participants (15/100 person‐years). Sustained virologic response (SVR) rates at 12 weeks were 95% and 92% respectively. After adjusting for other factors, participants with a history of incarceration (adjusted hazard ratio (aHR): 0.7, 95% CI: 0.5 to 0.9) were less likely to initiate treatment, as were those with a monthly income <$1500 (aHR: 0.7, 95% CI: 0.5 to 0.9) or who reported current injection drug use (aHR: 0.7, 95% CI: 0.4 to 1.0). Participants with undetectable HIV RNA (aHR: 2.1, 95% CI: 1.6 to 2.9) or significant fibrosis (aHR: 1.5, 95% CI: 1.2 to 1.9) were more likely to initiate treatment. Conclusions: The majority of HIV‐HCV co‐infected persons had a history of incarceration. Those previously incarcerated were 30% less likely to access treatment in the DAA era even after accounting for several patient‐level characteristics. With SVR rates above 90%, HCV elimination may be possible if treatment is expanded for this vulnerable and neglected group. [ABSTRACT FROM AUTHOR]

Background: The burden of HCV among those living with HIV remains a major public health challenge. We aimed to characterize trends in healthcare-related visits (HRV) of people living with HIV (PLW-HIV) and those living with HIV and HCV (PLW-HIV/HCV), in British Columbia (BC), and to identify risk factors associated with the highest HRV rates over time.Methods: Eligible individuals, recruited from the BC Seek and Treat for Optimal Prevention of HIV/AIDS population-based retrospective cohort (N = 3955), were ≥ 18 years old, first started combination antiretroviral therapy (ART) between 01/01/2000-31/12/2013, and were followed for ≥6 months until 31/12/2014. The main outcome was HRV rate. The main exposure was HIV/HCV co-infection status. We built a confounder non-linear mixed effects model, adjusting for several demographic and time-dependent factors.Results: HRV rates have decreased since 2000 in both groups. The overall age-sex standardized HRV rate (per person-year) among PLW-HIV and PLW-HIV/HCV was 21.11 (95% CI 20.96-21.25) and 41.69 (95% CI 41.51-41.88), respectively. The excess in HRV in the co-infected group was associated with late presentation for ART, history of injection drug use, sub-optimal ART adherence and a higher number of comorbidities. The adjusted HRV rate ratio for PLW-HIV/HCV in comparison to PLW-HIV was 1.18 (95% CI 1.13-1.24).Conclusions: Although HRV rates have decreased over time in both groups, PLW-HIV/HCV had 18% higher HRV than those only living with HIV. Our results highlight several modifiable risk factors that could be targeted as potential means to minimize the disease burden of this population and of the healthcare system. [ABSTRACT FROM AUTHOR]

A response from the author of the article "Factors associated with discordance between absolute CD4 cell count and CD4 cell percentage in patients coinfected with HIV and hepatitis C virus" in the 2012 issue is presented.