Prevalence and Correlates of Reporting Difficulty Taking Antiretroviral Treatment Among HIV-Positive Illicit Drug Users in Vancouver, Canada: A Longitudinal Analysis.

People living with HIV who use illicit drugs continue to experience high rates of suboptimal treatment outcomes from antiretroviral therapy (ART). Although previous studies have identified important behavioural, social and structural barriers to ART adherence, the effects of patient-level factors have not been fully evaluated. Thus, we sought to investigate the prevalence and correlates of reporting ART was difficult to take among a cohort of illicit drug users in Vancouver, Canada. We accessed data from the AIDS Care Cohort to evaluate Exposure to Survival Services (ACCESS), an ongoing prospective cohort of HIV-positive illicit drug users linked to comprehensive HIV clinical monitoring records. We used generalized linear mixed-effects modeling to identify factors longitudinally associated with periods in which individuals reported they found ART difficult to take. Between December 2005 and May 2014, 746 ART-exposed illicit drug users were recruited and contributed at least one study interview. Finding ART hard to take was reported by 209 (28.0%) participants at baseline, and 460 (61.7%) participants throughout the study period. Patients ingesting a greater daily pill count (adjusted odds ratio [AOR] = 1.12 per pill, 95% confidence interval [CI] 1.08-1.17) and experiencing barriers to healthcare (AOR = 1.64, 95% CI 1.34-2.01) were more likely to report difficulty taking ART. Patients less likely to report satisfaction with their HIV physician (AOR = 0.76, 95% CI 0.58-1.00) and achieve a non-detectable HIV viral load (AOR = 0.62, 95% CI 0.51-0.74) were more likely to report finding ART hard to take. In this community-recruited cohort of ART-exposed illicit drug users, a substantial proportion reported they found HIV treatment hard to take, which was clearly linked to higher dissatisfaction with healthcare experiences and, most importantly, a lower likelihood of experiencing optimal virologic outcomes. Our findings reveal a number of opportunities to improve HIV treatment experiences and outcomes for people who use illicit drugs, including the use of treatment regimens with lower pill burdens, as well as reducing barriers to healthcare access.

Drug use and phylogenetic clustering of hepatitis C virus infection among people who use drugs in Vancouver, Canada: A latent class analysis approach.

This study estimated latent classes (ie, unobserved subgroups in a population) of people who use drugs in Vancouver, Canada, and examined how these classes relate to phylogenetic clustering of hepatitis C virus (HCV) infection. HCV antibody-positive people who use drugs from two cohorts in Vancouver, Canada (1996-2012), with a Core-E2 sequence were included. Time-stamped phylogenetic trees were inferred, and phylogenetic clustering was determined by time to most common recent ancestor. Latent classes were estimated, and the association with the phylogenetic clustering outcome was assessed using an inclusive classify/analyse approach. Among 699 HCV RNA-positive participants (26% female, 24% HIV+), recent drug use included injecting cocaine (80%), injecting heroin (70%), injecting cocaine/heroin (ie, speedball, 38%) and crack cocaine smoking (28%). Latent class analysis identified four distinct subgroups of drug use typologies: (i) cocaine injecting, (ii) opioid and cocaine injecting, (iii) crack cocaine smoking and (iv) heroin injecting and currently receiving opioid substitution therapy. After adjusting for age and HIV infection, compared to the group defined by heroin injecting and currently receiving opioid substitution therapy, the odds of phylogenetic cluster membership was greater in the cocaine injecting group (adjusted OR [aOR]: 3.06; 95% CI: 1.73, 5.42) and lower in the crack cocaine smoking group (aOR: 0.06; 95% CI: 0.01, 0.48). Combining latent class and phylogenetic clustering analyses provides novel insights into the complex dynamics of HCV transmission. Incorporating differing risk profiles associated with drug use may provide opportunities to further optimize and target HCV treatment and prevention strategies.

Non-HIV-related health care utilization, demographic, clinical and laboratory factors associated with time to initial retention in HIV care among HIV-positive individuals linked to HIV care.

OBJECTIVES: The aim of the study was to explore non-HIV-related health care service (NHRHS) utilization, demographic, clinical and laboratory factors associated with timely initial "retention" in HIV care among individuals "linked" to HIV care in British Columbia (BC), Canada. METHODS: We conducted a Weibull time-to-initial-retention analysis among BC Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) cohort participants linked in 2000-2010, who had ≥ 1 year of follow-up. We defined "linked" as the first HIV-related service accessed following HIV diagnosis and "retained" as having, within a calendar year, either: (i) at least two HIV-related physician visits/diagnostic tests or (ii) at least two antiretroviral therapy (ART) dispensations, ≥ 3 months apart. Individuals were followed until they were retained, died, their last contact date, or until 31 December 2011, whichever occurred first. RESULTS: Of 5231 linked individuals (78% male; median age 39: (Q1-Q3: 32-46) years], 4691 (90%) were retained [median time to initial retention of 9 (Q1-Q3: 5-13) months] by the end of follow-up and 540 (10%) were not. Eighty-four per cent of not retained and 96% of retained individuals used at least one type of NHRHS during follow-up. Individuals who saw a specialist for NHRHS during follow-up had a shorter time to initial retention than those who did not [adjusted hazard ratio (aHR) 2.79; 95% confidence interval (CI): 2.47-3.16]. However, those who saw a general practitioner (GP) for NHRHS (aHR 0.79; 95% CI: 0.74-0.84) and those admitted to the hospital for NHRHS (aHR 0.60; 95% CI: 0.54-0.67), versus those who did/were not, respectively, had longer times to initial retention, as did female patients, people who inject drugs (PWID) and individuals < 40 years old. CONCLUSIONS: Overall, 84% of not retained individuals used some type of NHRHS during follow-up. Given that 71% of not retained individuals used GP NHRHS, our results suggest that GP-targeted interventions may be effective in improving time to initial retention.

Cancer incidence among HIV-positive women in British Columbia, Canada: Heightened risk of virus-related malignancies.

OBJECTIVES: We used population-based data to identify incident cancer cases and correlates of cancer among women living with HIV/AIDS in British Columbia (BC), Canada between 1994 and 2008. METHODS: Data were obtained from a retrospective population-based cohort created from linkage of two province-wide databases: (1) the database of the BC Cancer Agency, a province-wide population-based cancer registry, and (2) a database managed by the BC Centre for Excellence in HIV/AIDS, which contains data on all persons treated with antiretroviral therapy in BC. This analysis included women (≥ 19 years old) living with HIV in BC, Canada. Incident cancer diagnoses that occurred after highly active antiretroviral therapy (HAART) initiation were included. We obtained a general population comparison of cancer incidence among women from the BC Cancer Agency. Bivariate analysis (Pearson χ(2) , Fisher's exact or Wilcoxon rank-sum test) compared women with and without incident cancer across relevant clinical and sociodemographic variables. Standardized incidence ratios (SIRs) were calculated for selected cancers compared with the general population sample. RESULTS: We identified 2211 women with 12 529 person-years (PY) of follow-up who were at risk of developing cancer after HAART initiation. A total of 77 incident cancers (615/100 000 PY) were identified between 1994 and 2008. HIV-positive women with cancer, in comparison to the general population sample, were more likely to be diagnosed with invasive cervical cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma and Kaposi's sarcoma and less likely to be diagnosed with cancers of the digestive system. CONCLUSIONS: This study observed elevated rates of cancer among HIV-positive women compared to a general population sample. HIV-positive women may have an increased risk for cancers of viral-related pathogenesis.

Predictors of unstructured antiretroviral treatment interruption and resumption among HIV-positive individuals in Canada.

OBJECTIVES: Sustained optimal use of combination antiretroviral therapy (cART) has been shown to decrease morbidity, mortality and HIV transmission. However, incomplete adherence and treatment interruption (TI) remain challenges to the full realization of the promise of cART. We estimated trends and predictors of treatment interruption and resumption among individuals in the Canadian Observational Cohort (CANOC) collaboration. METHODS: cART-naïve individuals ≥ 18 years of age who initiated cART between 2000 and 2011 were included in the study. We defined TIs as ≥ 90 consecutive days off cART. We used descriptive analyses to study TI trends over time and Cox regression to identify factors predicting time to first TI and time to treatment resumption after a first TI. RESULTS: A total of 7633 participants were eligible for inclusion in the study, of whom 1860 (24.5%) experienced a TI. The prevalence of TI in the first calendar year of cART decreased by half over the study period. Our analyses highlighted a higher risk of TI among women [adjusted hazard ratio (aHR) 1.59; 95% confidence interval (CI) 1.33-1.92], younger individuals (aHR 1.27; 95% CI 1.15-1.37 per decade increase), earlier treatment initiators (CD4 count ≥ 350 vs. <200 cells/µL: aHR 1.46; 95% CI 1.17-1.81), Aboriginal participants (aHR 1.67; 95% CI 1.27-2.20), injecting drug users (aHR 1.43; 95% CI 1.09-1.89) and users of zidovudine vs. tenofovir in the initial cART regimen (aHR 2.47; 95% CI 1.92-3.20). Conversely, factors predicting treatment resumption were male sex, older age, and a CD4 cell count <200 cells/µL at cART initiation. CONCLUSIONS: Despite significant improvements in cART since its advent, our results demonstrate that TIs remain relatively prevalent. Strategies to support continuous HIV treatment are needed to maximize the benefits of cART.

Successes and gaps in uptake of regular, voluntary HIV testing for hidden street- and off-street sex workers in Vancouver, Canada.

Despite evidence globally of the heavy HIV burden among sex workers (SWs) as well as other poor health outcomes, including violence, SWs are often excluded from accessing voluntary, confidential and non-coercive health services, including HIV prevention, treatment, care and support. This study therefore assessed the prevalence and association with regular HIV testing among street- and off-street SWs in Vancouver, Canada. Cross-sectional baseline data were used from a longitudinal cohort known as "An Evaluation of Sex Worker's Health Access" (AESHA; January 2010-July 2012). This cohort included youth and adult SWs (aged 14+ years). We used multivariable logistic regression to assess the relationship between explanatory variables and having a recent HIV test (in the last year). Of the 435 seronegative SWs included, 67.1% reported having a recent HIV test. In multivariable logistic regression analysis, having a recent HIV test remained significantly independently associated with elevated odds of inconsistent condom use with clients [adjusted (multivariable) odds ratios, AOR: 2.59, 95% confidence intervals [95% CIs]: 1.17-5.78], injecting drugs (AOR: 2.33, 95% CIs: 1.17-4.18) and contact with a mobile HIV prevention programme (AOR: 1.76, 95% CIs: 1.09-2.84) within the last six months. Reduced odds of having a recent HIV test was also significantly associated with being a migrant/new immigrant to Canada (AOR: 0.33, 95% CIs: 0.19-0.56) and having a language barrier to health care access (AOR: 0.26, 95% CIs: 0.09-0.73). Our results highlight successes of reaching SWs at high risk of HIV through drug and sexual pathways. To maximize the effectiveness of including HIV testing as part of comprehensive HIV prevention and care to SWs, increased mobile outreach and safer-environment interventions that facilitate access to voluntary, confidential and non-coercive HIV testing remain a critical priority, in addition to culturally safe services with language support.

Social and Structural Factors Shaping High Rates of Incarceration among Sex Workers in a Canadian Setting.

In light of the emphasis on enforcement-based approaches towards sex work, and the well-known negative impacts of these approaches on women's health, safety and well-being, we conducted a study to investigate the prevalence and correlates of recent incarceration among a cohort of women sex workers in Vancouver, Canada. Data were obtained from an open prospective community cohort of female and transgender women sex workers, known as An Evaluation of Sex Workers' Health Access (AESHA). Bivariate and multivariable logistic regression analyses, using generalized estimating equations (GEE), were used to model the effect of social and structural factors on the likelihood of incarceration over the 44-month follow-up period (January 2010-August 2013). Among 720 sex workers, 62.5 % (n = 450) reported being incarcerated in their lifetime and 23.9 % (n = 172) being incarcerated at least once during the study period. Of the 172 participants, about one third (36.6 %) reported multiple episodes of incarceration. In multivariable GEE analyses, younger age (adjusted odds ratio [AOR] = 1.04 per year younger, 95 % confidence interval [CI] 1.02-1.06), being of a sexual/gender minority (AOR = 1.62, 95 % CI 1.13-2.34), heavy drinking (AOR = 1.99, 95 % CI 1.20-3.29), being born in Canada (AOR = 3.28, 95 % CI 1.26-8.53), living in unstable housing conditions (AOR = 4.32, 95 % CI 2.17-8.62), servicing clients in public spaces (versus formal sex work establishments) (AOR = 2.33, 95 % CI 1.05-5.17) and experiencing police harassment without arrest (AOR = 1.82, 95 % CI 1.35-2.45) remain independently correlated with incarceration. This prospective study found a very high prevalence and frequency of incarceration among women sex workers in Vancouver, Canada, with the most vulnerable and marginalized women at increased risk of incarceration. Given the well-known social and health harms associated with incarceration, and associations between police harassment and incarceration in this study, our findings further add to growing calls to move away from criminalized and enforcement-based approaches to sex work in Canada and globally.

Performance of HIV-1 drug resistance testing at low-level viremia and its ability to predict future virologic outcomes and viral evolution in treatment-naive individuals.

BACKGROUND: Low-level viremia (LLV; human immunodeficiency virus [HIV-1] RNA 50-999 copies/mL) occurs frequently in patients receiving antiretroviral therapy (ART), but there are few or no data available demonstrating that HIV-1 drug resistance testing at a plasma viral load (pVL) <1000 copies/mL provides potentially clinically useful information. Here, we assess the ability to perform resistance testing by genotyping at LLV and whether it is predictive of future virologic outcomes in patients beginning ART. METHODS: Resistance testing by genotyping at LLV was attempted on 4915 plasma samples from 2492 patients. A subset of previously ART-naive patients was analyzed who achieved undetectable pVL and subsequently rebounded with LLV (n = 212). A genotypic sensitivity score (GSS) was calculated based on therapy and resistance testing results by genotyping, and stratified according to number of active drugs. RESULTS: Eighty-eight percent of LLV resistance assays produced useable sequences, with higher success at higher pVL. Overall, 16 of 212 (8%) patients had pretherapy resistance. Thirty-eight of 196 (19%) patients without pretherapy resistance evolved resistance to 1 or more drug classes, primarily the nucleoside reverse transcriptase (14%) and/or nonnucleoside reverse transcriptase (9%) inhibitors. Patients with resistance at LLV (GSS <3) had a 2.1-fold higher risk of virologic failure (95% confidence interval, 1.2- to 3.7-fold) than those without resistance (P = .007). Progressively lower GSS scores at LLV were associated with a higher increase in pVL over time (P < .001). Acquisition of additional resistance mutations to a new class of antiretroviral drugs during LLV was not found in a subset of patients. CONCLUSIONS: Routine HIV-1 genotyping of LLV samples can be performed with a reasonably high success rate, and the results appear predictive of future virologic outcomes.

Modelling clinical progression and health care utilization of HIV-positive patients in British Columbia prior to death.

OBJECTIVES: The extent to which clinical progression of HIV-positive patients leads to an increase in health care utilization, especially prior to their death, is unknown. Thus, we modelled trends in CD4 cell count and emergency department utilization and the likelihood of an emergency department visit leading to a transfer to an acute care-level facility prior to a patient's death from nonaccidental causes. METHODS: Eligible patients initiated highly active antiretroviral therapy (HAART) in British Columbia between August 1996 and June 2006 (n = 457). Patients were followed until their death, which occurred on or before 30 June 2007 (period in which the emergency department visit data were available). Trends were modelled using generalized mixed effects. RESULTS: Patients experienced a significantly steep decline in CD4 cell count and a corresponding increase in the number of emergency department visits and transfers to acute-level facilities in the 5 years prior to death. For every 6-month interval prior to death, the CD4 cell count decreased by 13.22 cells/µL, the risk of experiencing an emergency department visit increased by 9%, and among those ever admitted, the odds ratio of being transferred to an acute care-level facility increased by 3%. CONCLUSIONS: We showed that patients experienced a steep decline in CD4 cell count, which was associated with an increase in health care utilization prior to their death. These findings highlight the substantial residual avoidable burden that unsuccessfully managed HIV disease poses, even in the HAART era. Further strategies to enhance sustained and successful engagement in care are urgently needed to mitigate high health care utilization.

Characteristics and determinants of T-cell phenotype normalization in HIV-1-infected individuals receiving long-term antiretroviral therapy.

OBJECTIVES: Although combination antiretroviral therapy (cART) can restore CD4 T-cell numbers in HIV infection, alterations in T-cell regulation and homeostasis persist. We assessed the incidence and predictors of reversing these alterations with cART. METHODS: ART-naïve adults (n = 4459) followed within the Canadian Observational Cohort and exhibiting an abnormal T-cell phenotype (TCP) prior to cART initiation were studied. Abnormal TCP was defined as having (1) a low CD4 T-cell count (< 532 cells/µL), (2) lost T-cell homeostasis (CD3 < 65% or > 85%) or (3) CD4:CD8 ratio dysregulation (ratio < 1.2). To thoroughly evaluate the TCP, CD4 and CD8 T-cell percentages and absolute counts were also analysed for a median duration of 3.14 years [interquartile range (IQR) 1.48-5.47 years]. Predictors of TCP normalization were assessed using adjusted Cox proportional hazards models. RESULTS: At baseline, 96% of pateints had CD4 depletion, 32% had lost homeostasis and 99% exhibited ratio dysregulation. With treatment, a third of patients had normalized CD4 T-cell counts, but only 85 individuals (2%) had normalized their TCP. In a multivariable model adjusted for age, measurement frequency and baseline regimen, higher baseline CD4 T-cell counts and time-dependent viral suppression independently predicted TCP normalization [hazard ratio (HR) for baseline CD4 T-cell count = 1.42 (1.31-1.54) per 100 cells/µL increase; P ≤ 0.0001; HR for time-dependent suppressed viral load = 3.69 (1.58-8.61); P-value ≤ 0.01]. CONCLUSIONS: Despite effective cART, complete TCP recovery occurred in very few individuals and was associated with baseline CD4 T-cell count and viral load suppression. HIV-induced alterations of the TCP are incompletely reversed by long-term ART.

A comparison of computational models with and without genotyping for prediction of response to second-line HIV therapy.

OBJECTIVES: We compared the use of computational models developed with and without HIV genotype vs. genotyping itself to predict effective regimens for patients experiencing first-line virological failure. METHODS: Two sets of models predicted virological response for 99 three-drug regimens for patients on a failing regimen of two nucleoside/nucleotide reverse transcriptase inhibitors and one nonnucleoside reverse transcriptase inhibitor in the Second-Line study. One set used viral load, CD4 count, genotype, plus treatment history and time to follow-up to make its predictions; the second set did not include genotype. Genotypic sensitivity scores were derived and the ranking of the alternative regimens compared with those of the models. The accuracy of the models and that of genotyping as predictors of the virological responses to second-line regimens were compared. RESULTS: The rankings of alternative regimens by the two sets of models were significantly correlated in 60-69% of cases, and the rankings by the models that use a genotype and genotyping itself were significantly correlated in 60% of cases. The two sets of models identified alternative regimens that were predicted to be effective in 97% and 100% of cases, respectively. The area under the receiver-operating curve was 0.72 and 0.74 for the two sets of models, respectively, and significantly lower at 0.55 for genotyping. CONCLUSIONS: The two sets of models performed comparably well and significantly outperformed genotyping as predictors of response. The models identified alternative regimens predicted to be effective in almost all cases. It is encouraging that models that do not require a genotype were able to predict responses to common second-line therapies in settings where genotyping is unavailable.

Cost-effectiveness analysis along the continuum of HIV care: how can we optimize the effect of HIV treatment as prevention programs?

The cascade of HIV care has been proposed as a useful tool to monitor health system performance across the key stages of HIV care delivery to reduce morbidity, mortality, and HIV transmission, the focal points of HIV Treatment as Prevention campaigns. Interventions to improve the cascade at its various stages may vary substantially in their ability to deliver health value per amount expended. In order to meet global antiretroviral treatment access targets, there is an urgent need to maximize the value of health spending by prioritizing cost-effective interventions. We executed a literature review on economic evaluations of interventions to improve specific stages of the cascade of HIV care. In total, 33 articles met the criteria for inclusion in the review, 22 (67 %) of which were published within the last 5 years. Nonetheless, substantial gaps in our knowledge remain, particularly for interventions to improve linkage and retention in HIV care in developed and developing-world settings and generalized and concentrated epidemics. We make the case here that the attention of scientists and policymakers needs to turn to the development, implementation, and rigorous evaluation of interventions to improve the various stages of the cascade of HIV care.

Computational models can predict response to HIV therapy without a genotype and may reduce treatment failure in different resource-limited settings.

OBJECTIVES: Genotypic HIV drug-resistance testing is typically 60%-65% predictive of response to combination antiretroviral therapy (ART) and is valuable for guiding treatment changes. Genotyping is unavailable in many resource-limited settings (RLSs). We aimed to develop models that can predict response to ART without a genotype and evaluated their potential as a treatment support tool in RLSs. METHODS: Random forest models were trained to predict the probability of response to ART (≤400 copies HIV RNA/mL) using the following data from 14 891 treatment change episodes (TCEs) after virological failure, from well-resourced countries: viral load and CD4 count prior to treatment change, treatment history, drugs in the new regimen, time to follow-up and follow-up viral load. Models were assessed by cross-validation during development, with an independent set of 800 cases from well-resourced countries, plus 231 cases from Southern Africa, 206 from India and 375 from Romania. The area under the receiver operating characteristic curve (AUC) was the main outcome measure. RESULTS: The models achieved an AUC of 0.74-0.81 during cross-validation and 0.76-0.77 with the 800 test TCEs. They achieved AUCs of 0.58-0.65 (Southern Africa), 0.63 (India) and 0.70 (Romania). Models were more accurate for data from the well-resourced countries than for cases from Southern Africa and India (P < 0.001), but not Romania. The models identified alternative, available drug regimens predicted to result in virological response for 94% of virological failures in Southern Africa, 99% of those in India and 93% of those in Romania. CONCLUSIONS: We developed computational models that predict virological response to ART without a genotype with comparable accuracy to genotyping with rule-based interpretation. These models have the potential to help optimize antiretroviral therapy for patients in RLSs where genotyping is not generally available.

Relationship of chronic hepatitis C infection to rates of AIDS-defining illnesses in a Canadian cohort of HIV seropositive individuals receiving highly active antiretroviral therapy.

BACKGROUND: The influence of chronic hepatitis C virus (HCV) infection on the risk, timing, and type of AIDS-defining illnesses (ADIs) is not well described. To this end, rates of ADIs were evaluated in a Canadian cohort of HIV seropositive individuals receiving highly active antiretroviral therapy (HAART). METHODS: ADIs were classified into 6 Centers for Disease Control and Prevention (CDC)-defined etiological subgroups: non-Hodgkin lymphoma, viral infection, bacterial infection, HIV-related disease, protozoal infection, and mycotic infection. Generalized estimating equation (GEE) Poisson regression models were used to estimate the effect of HCV on rates of ADIs after adjusting for covariates. RESULTS: Among 2,706 HAART recipients, 768 (28%) were HCV coinfected. Rates of all ADIs combined and of bacterial infection, HIV-related disease, and mycotic infection were increased in HCV-coinfected persons and among those with CD4 counts <200 cells/mm3 HCV was associated with an increased risk of ADIs (rate ratio [RR], 1.38; 95% CI, 1.01-1.88) and a 2-fold increased risk of mycotic infections (RR, 2.21; 95% CI, 1.35-3.62) in univariate analyses and after adjusting for age, baseline viral load, baseline CD4 count, and region of Canada. However, after further adjustment for HAART interruptions, HCV was no longer associated with an increased rate of ADIs overall (RR, 1.13; 95% CI, 0.80-1.59), but remained associated with an increased rate of mycotic infections (RR, 1.97, 95% CI, 1.08-3.61). CONCLUSION: Although HCV coin-fected individuals are at increased risk of developing ADIs overall, our analysis suggests that behavioral variables associated with HCV (including rates of retention on HAART), and not biological interactions with HCV itself, are primarily responsible.

Factors associated with virological suppression among HIV-positive individuals on highly active antiretroviral therapy in a multi-site Canadian cohort.

OBJECTIVE: The aim of the study was to evaluate time to virological suppression in a cohort of individuals who started highly active antiretroviral therapy (HAART), and to explore the factors associated with suppression. METHODS: Eligible participants were HIV-positive individuals from a multi-site Canadian cohort of antiretroviral-naïve patients initiating HAART on or after 1 January 2000. Viral load and CD4 measurements within 6 months prior to HAART initiation were assessed. Univariate and multivariate analyses were conducted using piecewise survival exponential models where time scale was divided into intervals (<10 months; ≥10 months). Virological suppression was defined as the time to the first of at least two consecutive viral load measurements <50 HIV-1 RNA copies/mL. RESULTS: A total of 3555 individuals were included in the study, of median age 40 years [interquartile range (IQR) 34-47 years]. Eighty per cent were male, 18% had a history of injecting drug use (IDU), and 13% presented with an AIDS-defining illness at baseline. The median time to suppression was 4.55 months (IQR 2.99-7.89 months). In multivariate analyses, older age, male sex, treatment in Ontario rather than British Columbia, non-IDU history, and having an AIDS diagnosis at baseline predicted increased likelihood of suppression. Patients with low baseline viral load were more likely to have suppression [4-5 log(10) copies/mL, hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.18-1.38; <4 log(10) copies/mL, HR 1.49, 95% CI 1.32-1.68] than patients with baseline viral load ≥5 log(10) copies/mL; however, this effect ceased after 18 months of follow-up. Suppression was more likely with nonnucleoside reverse transcriptase inhibitors and ritonavir-boosted HAART. CONCLUSION: Identification of patients at risk for diminished likelihood of virological suppression will allow focusing of efforts and the utilization of resources to maximize the benefits of HAART.

High prevalence of food insecurity among HIV-infected individuals receiving HAART in a resource-rich setting.

This study aimed to assess the prevalence and correlates of food insecurity in a cohort of HIV-infected individuals on highly active antiretroviral therapy (HAART) in British Columbia (BC), Canada. Adults receiving HAART voluntarily enrolled into the Longitudinal Investigations into Supportive and Ancillary Health Services (LISA) cohort. Individual food insecurity was measured using a modified version of the Radimer/Cornell Questionnaire. We performed bivariate analyses to determine differences between explanatory variables for individuals who were food secure and food insecure. We performed logistic regression to determine independent predictors of food insecurity. Of the 457 individuals enrolled in the LISA cohort, 324 (71.0%) were found to be food insecure. Multivariate analysis indicated that individuals who had an annual incomes less than $15,000 (odds ratio [OR] 3.15, 95% confidence interval [CI] 1.83, 5.44), used illicit drugs (OR 1.85, 95% CI 1.03, 3.33), smoked tobacco (OR 2.30, 95% CI 1.30, 4.07), had depressive symptoms (OR 2.34, 95% CI 1.38, 3.96), and were younger (OR 0.95, 95% CI, 0.92, 0.98) were more likely to be food insecure. Our results demonstrated a high (71%) prevalence of food insecurity among HIV-infected individuals receiving HAART in this resource-rich setting, and that food insecurity is associated with a compendium of environmental and behavioral factors. More research is needed to understand the biological and social pathways linking food insecurity to these variables in order to identify program strategies that can effectively improve food security among HIV-infected populations.

Suboptimal use of HIV drug resistance testing in a universal health-care setting.

HIV drug resistance testing is recommended as routine part of clinical practice in HIV/AIDS treatment and care. Our objective is to assess the determinants of accessing HIV drug resistance testing and examine the factors associated with resistance testing prior to or after starting highly active antiretroviral therapy (HAART) in a setting where access to HIV care is free and universal. The Longitudinal Investigation into Supportive and Ancillary health services (LISA) study is an open prospective cohort of HIV-positive persons on HAART in British Columbia (BC), Canada. Non-clinical data were collected through an interviewer-administered survey and clinical data were obtained through the BC Centre for Excellence in HIV/AIDS Drug Treatment Program. Independent associations between key explanatory variables and resistance testing were analyzed using logistic regression. We restricted our post-HAART analyses to those patients who met the criteria for resistance testing after HAART initiation. Of 359 LISA participants who started HAART after 2000 and at a time when resistance testing was available free of charge, almost half did not receive a baseline resistance test. Post-HAART initiation, 165 of 359 study subjects met the criteria for resistance testing based on current therapeutic guidelines due to virological failure. About 37.6% of them remain untested for resistance. Multivariable analyses show that baseline testing was less likely performed for persons of Aboriginal ethnicity and more likely performed for patients initiating HAART in 2004 or after. Additionally, persons initiating HAART in 2004 or after were less likely to have received a resistance test after virologic failure. Our results show that despite existing clinical guidelines, resistance testing is underused, even in an environment where the service is available free of charge. Further, resistance testing is particularly underutilized among vulnerable populations. Urgent efforts are needed to ensure the optimal use of resistance testing at baseline and at the time of virologic failure as recommended by current guidelines.

HIV knowledge and perceptions of risk in a young, urban, drug-using population.

BACKGROUND: Educational programs targeted towards youth to prevent HIV transmission are based on a model that increased knowledge equals reduced risk behaviour. This study explored HIV knowledge among a cohort of young drug users, and their perceptions of HIV risk acquisition. METHODS: Between September 2005 and August 2009, youth who used illegal drugs were recruited into a prospective cohort known as the at-risk youth study (ARYS) in Vancouver, Canada. Participants completed an 18 item HIV Knowledge Questionnaire (HIV-KQ-18) and responses were scored dichotomously (i.e., ≥15 indicating high knowledge and <15 indicating low knowledge). We compared high- and low-scoring youth using Pearson's chi-square test and logistic regression. We also examined youths' perceptions of risk for acquiring HIV compared to their peers. RESULTS: Of 589 youth recruited into ARYS, the mean age was 22 (interquartile range [IQR]: 20-24), 186 (31.6%) were female, and 143 (24.3%) were of Aboriginal ancestry. The median score on the HIV-KQ- 18 was 15 (IQR: 12-16). Internal reliability was high (Cronbach's α=0.82). The analyses demonstrated that youth with higher HIV knowledge were more likely to be older (adjusted odds ratio [AOR]=1.08, per year older p=0.031), completed high school (AOR=1.42, p=0.054), and engage in unprotected intercourse (AOR=1.73, p=0.023). The majority of respondents (77.6%) perceived themselves to be at lower risk for acquiring HIV in comparison to their peers. CONCLUSIONS: HIV knowledge scores of participants were surprisingly low for an urban Canadian setting as was their HIV risk perception. Higher HIV knowledge was not associated with reduced sexual risk behaviour. Results demonstrate that education programs are not reaching or impacting this high-risk population. Given the complex forces that promote HIV risk behaviour, prevention programs should be fully evaluated and must recognize the unique characteristics of drug-using youth and factors that drive risk among this population.

Non-medically supervised treatment interruptions among participants in a universally accessible antiretroviral therapy programme.

BACKGROUND: We examined clinical outcomes, patient characteristics and trends over time of non-medically supervised treatment interruptions (TIs) from a free-of-charge antiretroviral therapy (ART) programme in British Columbia (BC), Canada. METHODS: Data from ART-naïve individuals > or =18 years old who initiated triple combination highly active antiretroviral therapy (HAART) between January 2000 and June 2006 were analysed. Participants having > or =3 month gap in HAART coverage were defined as having a TI. Cox proportional hazards modelling was used to examine factors associated with TIs and to examine factors associated with resumption of treatment. RESULTS: A total of 1707 participants were study eligible and 643 (37.7%) experienced TIs. TIs within 1 year of ART initiation decreased from 29% of individuals in 2000 to 19% in 2006 (P<0.001). TIs were independently associated with a history of injection drug use (IDU) (P=0.02), higher baseline CD4 cell counts (P<0.001), hepatitis C co-infection (P<0.001) and the use of nelfinavir (NFV) (P=0.04) or zidovudine (ZDV)/lamivudine (3TC) (P=0.009) in the primary HAART regimen. Male gender (P<0.001), older age (P<0.001), AIDS at baseline (P=0.008) and having a physician who had prescribed HAART to fewer patients (P=0.03) were protective against TIs. Four hundred and eighty-eight (71.9%) participants eventually restarted ART with male patients and those who developed an AIDS-defining illness prior to their TI more likely to restart therapy. Higher CD4 cell counts at the time of TI and unknown hepatitis C status were associated with a reduced likelihood of restarting ART. CONCLUSION: Treatment interruptions were associated with younger, less ill, female and IDU participants. Most participants with interruptions eventually restarted therapy. Interruptions occurred less frequently in recent years.

Community-associated methicillin-resistant Staphylococcus aureus is prevalent in wounds of community-based injection drug users.

Injection drug users (IDUs) have an elevated risk for carriage of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). Cutaneous injection-related infections are common in IDUs but detailed studies are few. Based on a subsample of 218 individuals from a community-recruited cohort of IDUs at a supervised injection facility, we investigated the microbiology and related antibiotic susceptibility profiles of isolates from 59 wounds. Twenty-seven percent of subjects had at least one wound and 25 (43%) were culture positive for S. aureus alone [14 MRSA and 11 (19%) methicillin-susceptible (MSSA) isolates]. Sixteen of 18 MRSA isolates were classified as community associated (CA) by the presence of genes encoding for PVL. MRSA and MSSA occurred in mixed infection with other organisms on three and six occasions, respectively. All CA-MRSA isolates were susceptible to tetracycline, vancomycin and linezolid but only 13% were susceptible to clindamycin compared to 63% of MSSA isolates. The frequency of CA-MRSA is a cause for concern in wound infection in the IDU setting.