M-J Milloy

Female gender predicts lower access and adherence to antiretroviral therapy in a setting of free healthcare

BackgroundBarriers to HIV treatment among injection drug users (IDU) are a major public health concern. However, there remain few long-term studies investigating key demographic and behavioral factors - and gender differences in particular - that may pose barriers to antiretroviral therapy (ART), especially in settings with universal healthcare. We evaluated access and adherence to ART in a long-term cohort of HIV-positive IDU in a setting where medical care and antiretroviral therapy are provided free of charge through a universal healthcare system.MethodsWe evaluated baseline antiretroviral use and subsequent adherence to ART among a Canadian cohort of HIV-positive IDU. We used generalized estimating equation logistic regression to evaluate factors associated with 95% adherence to antiretroviral therapy estimated based on prescription refill compliance.ResultsBetween May 1996 and April 2008, 545 IDU participants were followed for a median of 23.8 months (Inter-quartile range: 8.5 - 91.6), among whom 341 (63%) were male and 204 (37%) were female. Within the six-month period prior to the baseline interview, 133 (39%) men and 62 (30%) women were on ART (p = 0.042). After adjusting for clinical characteristics as well as drug use patterns measured longitudinally throughout follow-up, female gender was independently associated with a lower likelihood of being 95% adherent to ART (Odds Ratio [OR] = 0.70; 95% Confidence Interval: 0.53-0.93).ConclusionsDespite universal access to free HIV treatment and medical care, female IDU were less likely to access and adhere to antiretroviral therapy, a finding that was independent of drug use and clinical characteristics. These data suggest that interventions to improve access to HIV treatment among IDU must be tailored to address unique barriers to antiretroviral therapy faced by female IDU.

Estimated drug overdose deaths averted by North America's first medically-supervised safer injection facility.

Background Illicit drug overdose remains a leading cause of premature mortality in urban settings worldwide. We sought to estimate the number of deaths potentially averted by the implementation of a medically supervised safer injection facility (SIF) in Vancouver, Canada. Methodology/Principal Findings The number of potentially averted deaths was calculated using an estimate of the local ratio of non-fatal to fatal overdoses. Inputs were derived from counts of overdose deaths by the British Columbia Vital Statistics Agency and non-fatal overdose rates from published estimates. Potentially-fatal overdoses were defined as events within the SIF that required the provision of naloxone, a 911 call or an ambulance. Point estimates and 95% Confidence Intervals (95% CI) were calculated using a Monte Carlo simulation. Between March 1, 2004 and July 1, 2008 there were 1004 overdose events in the SIF of which 453 events matched our definition of potentially fatal. In 2004, 2005 and 2006 there were 32, 37 and 38 drug-induced deaths in the SIFs neighbourhood. Owing to the wide range of non-fatal overdose rates reported in the literature (between 5% and 30% per year) we performed sensitivity analyses using non-fatal overdose rates of 50, 200 and 300 per 1,000 person years. Using these model inputs, the number of averted deaths were, respectively: 50.9 (95% CI: 23.6–78.1); 12.6 (95% CI: 9.6–15.7); 8.4 (95% CI: 6.5–10.4) during the study period, equal to 1.9 to 11.7 averted deaths per annum. Conclusions/Significance Based on a conservative estimate of the local ratio of non-fatal to fatal overdoses, the potentially fatal overdoses in the SIF during the study period could have resulted in between 8 and 51 deaths had they occurred outside the facility, or from 6% to 37% of the total overdose mortality burden in the neighborhood during the study period. These data should inform the ongoing debates over the future of the pilot project.

Non-Fatal Overdose Among a Cohort of Active Injection Drug Users Recruited from a Supervised Injection Facility

Non-fatal overdose among injection drug users (IDU) is a source of significant morbidity. Since it has been suggested that supervised injecting facilities (SIF) may increase risk for overdose, we sought to evaluate patterns of non-fatal overdose among a cohort of SIF users. We examined recent non-fatal overdose experiences among participants enrolled in a prospective study of IDU recruited from within North Americas first medically supervised safer injecting facility. Correlates of recent non-fatal overdoses were identified using generalized estimating equations (GEE). There were 1,090 individuals recruited during the study period of which 317 (29.08%) were female. At baseline, 638 (58.53%) reported a history of non-fatal overdose and 97 (8.90%) reported at least one non-fatal overdose in the last six months. This proportion remained approximately constant throughout the study period. In the multivariate GEE analysis, factors associated with recent non-fatal overdose included: sex-trade involvement (Adjusted Odds Ratio [AOR]: 1.45 [95% Confidence Interval [CI] 1.07–1.99], p = 0.02) and public drug use (AOR: 1.50 [95% CI 1.09–2.06]; p = 0.01). Using the SIF for ≥ 75% of injections was not associated with recent non-fatal overdose in univariate (Odds Ratio: 1.05, p = 0.73) or multivariate analyses (AOR: 1.01, p = 0.96). The proportion of individuals reporting recent non-fatal overdose did not change over the study period. Our findings indicate that a sub-population of IDU might benefit from overdose prevention interventions. Our findings refute the suggestion that the SIF may increase the likelihood of overdose.

Social and Environmental Predictors of Plasma HIV RNA Rebound Among Injection Drug Users Treated With Antiretroviral Therapy

IntroductionEvidence is needed to improve HIV treatment outcomes for individuals who use injection drugs (IDU). Although studies have suggested higher rates of plasma viral load (PVL) rebound among IDU on antiretroviral therapy (ART), risk factors for rebound have not been thoroughly investigated. MethodsWe used data from a long-running community-recruited prospective cohort of IDU in Vancouver, Canada, linked to comprehensive ART and clinical monitoring records. Using proportional hazards methods, we modeled the time to confirmed PVL rebound above 1000 copies per milliliter among IDU on ART with sustained viral suppression, defined as 2 consecutive undetectable PVL measures. ResultsBetween 1996 and 2009, 277 individuals had sustained viral suppression. Over a median follow-up of 32 months, 125 participants (45.1%) experienced at least 1 episode of virologic failure for an incidence of 12.6 [95% confidence interval (CI): 10.5 to 15.0] per 100 person-years. In a multivariate model, PVL rebound was independently associated with sex-trade involvement [adjusted hazard ratio (AHR) = 1.40, 95% CI: 1.08 to 1.82) and recent incarceration (AHR = 1.83, 95% CI: 1.33 to 2.52). Methadone maintenance therapy (AHR = 0.79, 95% CI: 0.66 to 0.94) was protective. No measure of illicit drug use was predictive. ConclusionsIn this setting of free ART, several social and environmental factors predicted higher risks of viral rebound among IDU, including sex-trade involvement and incarceration. These findings should help inform efforts to identify individuals at risk of viral rebound and targeted interventions to treat and retain individuals in effective ART.

Elevated HIV risk behaviour among recently incarcerated injection drug users in a Canadian setting: a longitudinal analysis

BackgroundWhile incarceration has consistently been associated with a higher risk of HIV infection for individuals who use injection drugs (IDU), the effect of incarceration on the post-release risk environment remains poorly described. We sought to assess the impact of incarceration on risk factors for HIV infection after release from prison in a sample of active IDU in Vancouver, Canada.MethodsUsing a prospective cohort of community-recruited IDU followed from May 1, 1996 to November 30, 2005, we examined contingency tables and performed linear growth curve analyses to assess changes in the prevalence of independent risk factors for HIV infection from before to after a period of incarceration among participants reporting incarceration and a matched control group.ResultsOf the 1603 participants followed-up over the study period, 147 (9.2%) were eligible for an analysis of post-incarceration risk behaviours and 742 (46.3%) were used as matched controls. Significant differences were found in one or both groups for the prevalence of frequent cocaine injection, requiring help injecting, binge drug use, residence in the HIV outbreak epicentre, sex-trade participation and syringe sharing (all p < 0.05) after incarceration. In linear growth curve adjusted for age, gender and ethnicity, syringe sharing was significantly more common in those recently released from prison (p = 0.03) than in the control group.ConclusionIn a sample of Canadian IDU, we did not observe any effect of incarceration on the prevalence of several behaviours that are risk factors for HIV infection, including intensity of drug use or participation in the sex trade. However, those recently released from prison were more likely to report syringe sharing that those in a matched control group.

Adherence and plasma HIV RNA response to antiretroviral therapy among HIV-seropositive injection drug users in a Canadian setting

Abstract HIV-positive individuals who use injection drugs (IDU) may have lower rates of adherence to highly active antiretroviral therapy (ART). However, previous studies of factors associated with adherence to ART among IDU have been limited primarily to samples drawn from clinical settings and in areas with financial barriers to healthcare.We evaluated patterns of ART adherence and rates of plasma HIV RNA response among a Canadian cohort of community-recruited IDU. Using data from a community-recruited cohort of antiretroviral-naive HIV-infected IDU, we investigated ART adherence patterns based on prescription refill compliance and factors associated with time to plasma HIV-1 RNA suppression (<500 copies/mL) using Cox proportional hazards regression in a setting with universal health care, including free ART. Between 1996 and 2008, 267 antiretroviral-naive HIV-infected IDU initiated ART and had a median of 51 months (inter-quartile range: 17–95 months) of follow-up. Overall, 81 (30.3%) were ≥95% adherent during the first year of HAART and 187 (70.0%) achieved HIV RNA suppression at least once over the study period, for an incidence-density of 34.5 (95% confidence interval [CI]: 29.8–39.9) per 100 person-years. The Kaplan-Meier cumulative plasma HIV RNA suppression rates at 12 months after the initiation of ART were 80.8% (95% CI: 71.2–88.7) for adherent and 28.9% (95% CI: 22.8–36.1) for non-adherent participants. While several socio-demographic characteristics and drug-using behaviours were identified as barriers to successful treatment in unadjusted analyses, the factor most strongly associated with time to HIV RNA suppression in multivariate analysis was adherence to ART of at least 95% (adjusted hazard ratio [AHR] = 6.0, 95% CI: 4.2–8.6, p<0.001). These results demonstrate low rates of adherence to ART among a community-recruited cohort of IDU and reinforce the importance of adherence as the key determinant of successful virological response to antiretroviral therapy.

Clinical care of incarcerated people with HIV, viral hepatitis, or tuberculosis

The burden of HIV/AIDS and other transmissible diseases is higher in prison and jail settings than in the non-incarcerated communities that surround them. In this comprehensive review, we discuss available literature on the topic of clinical management of people infected with HIV, hepatitis B and C viruses, and tuberculosis in incarcerated settings in addition to co-occurrence of one or more of these infections. Methods such as screening practices and provision of treatment during detainment periods are reviewed to identify the effect of community-based treatment when returning inmates into the general population. Where data are available, we describe differences in the provision of medical care in the prison and jail settings of low-income and middle-income countries compared with high-income countries. Structural barriers impede the optimal delivery of clinical care for prisoners, and substance use, mental illness, and infectious disease further complicate the delivery of care. For prison health care to reach the standards of community-based health care, political will and financial investment are required from governmental, medical, and humanitarian organisations worldwide. In this review, we highlight challenges, gaps in knowledge, and priorities for future research to improve health-care in institutions for prisoners.

Declining Incidence of Hepatitis C Virus Infection among People Who Inject Drugs in a Canadian Setting, 1996-2012

Background People who inject drugs (PWID) are at high risk of hepatitis C virus (HCV) infection. Trends in HCV incidence and associated risk factors among PWID recruited between 1996 and 2012 in Vancouver, Canada were evaluated. Methods Data were derived from a long-term cohort of PWID in Vancouver. Trends in HCV incidence were evaluated. Factors associated with time to HCV infection were assessed using Cox proportional hazards regression. Results Among 2,589, 82% (n = 2,121) were HCV antibody-positive at enrollment. Among 364 HCV antibody-negative participants with recent (last 30 days) injecting at enrollment, 126 HCV seroconversions were observed [Overall HCV incidence density: 8.6 cases/100 person-years (py); 95% confidence interval (95% CI): 7.2, 10.1; HCV incidence density among those with injecting during follow-up: 11.5 cases/100 py; 95% CI 9.7, 13.6]. The overall HCV incidence density declined significantly from 25.0/100 py (95% CI: 20.2, 30.3) in 1996–99, as compared to 6.0/100 py (95% CI: 4.1, 8.5) in 2000–2005, and 3.1/100 py (95% CI: 2.0, 4.8) in 2006–2012. Among those with injecting during follow-up, the overall HCV incidence density declined significantly from 27.9/100 py (95% CI: 22.6, 33.6) in 1996–99, as compared to 7.5/100 py (95% CI: 5.1, 10.6) in 2000–2005, and 4.9/100 py (95% CI: 3.1, 7.4) in 2006–2012. Unstable housing, HIV infection, and injecting of cocaine, heroin and methamphetamine were independently associated with HCV seroconversion. Conclusions HCV incidence has dramatically declined among PWID in this setting. However, improved public health strategies to prevent and treat HCV are urgently required to reduce HCV-associated morbidity and mortality.

HLA class I sequence-based typing using DNA recovered from frozen plasma

We describe a rapid, reliable and cost-effective method for intermediate-to-high-resolution sequence-based HLA class I typing using frozen plasma as a source of genomic DNA. The plasma samples investigated had a median age of 8.5 years. Total nucleic acids were isolated from matched frozen PBMC (~2.5 million) and plasma (500 μl) samples from a panel of 25 individuals using commercial silica-based kits. Extractions yielded median [IQR] nucleic acid concentrations of 85.7 [47.0-130.0]ng/μl and 2.2 [1.7-2.6]ng/μl from PBMC and plasma, respectively. Following extraction, ~1000 base pair regions spanning exons 2 and 3 of HLA-A, -B and -C were amplified independently via nested PCR using universal, locus-specific primers and sequenced directly. Chromatogram analysis was performed using commercial DNA sequence analysis software and allele interpretation was performed using a free web-based tool. HLA-A, -B and -C amplification rates were 100% and chromatograms were of uniformly high quality with clearly distinguishable mixed bases regardless of DNA source. Concordance between PBMC and plasma-derived HLA types was 100% at the allele and protein levels. At the nucleotide level, a single partially discordant base (resulting from a failure to call both peaks in a mixed base) was observed out of >46,975 bases sequenced (>99.9% concordance). This protocol has previously been used to perform HLA class I typing from a variety of genomic DNA sources including PBMC, whole blood, granulocyte pellets and serum, from specimens up to 30 years old. This method provides comparable specificity to conventional sequence-based approaches and could be applied in situations where cell samples are unavailable or DNA quantities are limiting.

Physician experience and rates of plasma HIV-1 RNA suppression among illicit drug users: an observational study

BackgroundDespite the availability of antiretroviral therapy (ART), suboptimal treatment outcomes have been observed among HIV-seropositive illicit drug users. As there is an urgent need to improve responses to antiretroviral therapy among this population, we undertook this study to evaluate the role of physician experience on rates of plasma HIV-1 RNA suppression following initiation of ART.MethodsUsing data from a community-recruited cohort of HIV-positive illicit drug users, we used Cox proportional hazards regression to model the time to plasma viral HIV RNA < 500 copies/mL among antiretroviral-naïve subjects initiating ART. Physician experience was defined as a continuous variable measured per 100 HIV-infected patients previously enrolled in the province-wide HIV treatment registry by that physician at the time a patient was enrolled.ResultsBetween May 1996 and December 2008, 267 individuals initiated ART among whom 227 (85%) achieved a plasma HIV RNA < 500 copies/mL during the study period. In a multivariate analysis, greater physician experience was independently associated with higher rates of plasma HIV RNA suppression (adjusted hazard ratio [AHR] = 1.17, 95% confidence interval [CI]: 1.03-1.34) after adjustment for adherence to ART. Other factors associated with viral suppression included engagement in methadone maintenance therapy (AHR = 1.61, 95% CI: 1.23-2.09), ≥ 95% adherence to ART (AHR = 2.42, 95% CI: 1.80-3.26), baseline CD4 count (AHR = 0.89, 95% CI: 0.83-0.96) and baseline plasma HIV-1 RNA (AHR = 0.65, 95% CI: 0.53-0.81).ConclusionsIn this setting of universal HIV/AIDS care, illicit drug users with more experienced physicians exhibited faster rates of plasma viral load suppression. These findings argue for specialized services to help optimize HIV treatment outcomes among this population.