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Introduction: In many resource-limited settings, combination antiretroviral therapy (cART) failure is diagnosed clinically or immunologically. As such, there is a high likelihood that patients may stay on a virologically failing regimen for a substantial period of time. Here, we compared the long-term impact of initiating non-nucleoside reverse transcriptase inhibitor (NNRTI)- versus boosted protease inhibitor (bPI)-based cART in British Columbia (BC), Canada., Methods: We followed prospectively 3925 ART-naïve patients who started NNRTIs (N=1963, 50%) or bPIs (N=1962; 50%) from 1 January 2000 until 30 June 2013 in BC. At six months, we assessed whether patients virologically failed therapy (a plasma viral load (pVL) >50 copies/mL), and we stratified them based on the pVL at the time of failure ≤500 versus >500 copies/mL. We then followed these patients for another six months and calculated their probability of achieving subsequent viral suppression (pVL <50 copies/mL twice consecutively) and of developing drug resistance. These probabilities were adjusted for fixed and time-varying factors, including cART adherence., Results: At six months, virologic failure rates were 9.5 and 14.3 cases per 100 person-months for NNRTI and bPI initiators, respectively. NNRTI initiators who failed with a pVL ≤500 copies/mL had a 16% higher probability of achieving subsequent suppression at 12 months than bPI initiators (0.81 (25th-75th percentile 0.75-0.83) vs. 0.72 (0.61-0.75)). However, if failing NNRTI initiators had a pVL >500 copies/mL, they had a 20% lower probability of suppressing at 12 months than pVL-matched bPI initiators (0.37 (0.29-0.45) vs. 0.46 (0.38-0.54)). In terms of evolving HIV drug resistance, those who failed on NNRTI performed worse than bPI in all scenarios, especially if they failed with a viral load >500 copies/mL., Conclusions: Our results show that patients who virologically failed at six months on NNRTI and continued on the same regimen had a lower probability of subsequently achieving viral suppression and a higher chance of evolving HIV drug resistance. These results suggest that improving access to regular virologic monitoring is critically important, especially if NNRTI-based cART is to remain a preferred choice for first-line therapy in resource-limited settings.

Objectives: The authors examined the impact of exposure to the 2010 Winter Olympics time period on outcomes measuring disruption of local sex work environments in Vancouver, Canada., Methods: The authors conducted a before-and-after study, using multivariable logistic regression, to assess the relationship between exposure to the Olympics period (19 January-14 March 2010) versus the post-Olympics period (1 April-1 July 2010) and outcomes., Results: This study included 207 youth (14+ years) and adult sex workers (SWs) (Olympics: n=107; post-Olympics: n=100). SWs in the two periods were statistically similar, with an overall median age of 33 years (IQR: 28-40), and 106 (51.2%) of indigenous ancestry or ethnic minority. In separate multivariable logistic regression models, the Olympics period remained statistically significantly associated with perceived heightened police harassment of SWs without arrest (adjusted ORs (AOR): 3.95, 95% CIs 1.92 to 8.14), decreased availability of clients (AOR: 1.97, 95% CIs 1.11 to 3.48) and increased difficulty meeting clients due to road closures/construction (AOR: 7.68, 95% CIs 2.46 to 23.98). There were no significantly increased odds in perceived reports of new (0.999), youth (0.536) or trafficked SWs (zero reports) in the Olympic period., Conclusions: To reduce potential adverse public health impacts of enhanced police harassment and displacement of local sex work markets, results suggest that evidence-based public health strategies need to be adopted for host cities of future events (eg, the London 2012 Olympic Games), such as the removal of criminal sanctions targeting sex work and the piloting and rigorous evaluation of safer indoor work spaces.

Objective: Tuberculosis (TB) is a leading cause of death in human immunodeficiency virus (HIV)-positive individuals. We sought to compare mortality rates in TB/HIV co-infected individuals globally and by country/territory., Design: We conducted a cross-national systematic assessment., Methods: TB mortality rates in HIV-positive and HIV-negative individuals were obtained from the World Health Organization (WHO) Stop TB department for 212 recognized countries/territories in the years 2006-2008. Multivariate linear regression determined the impact of health care resource and economic variables on our outcome variable, and TB mortality rates., Results: In 2008, an estimated 13 TB/HIV deaths occurred per 100,000 population globally with the African region having the highest death rate ([AFRH] ≥4% adult HIV-infection rate) at 86 per 100,000 individuals. The next highest rates were for the Eastern European Region (EEUR) and the Latin American Region (LAMR) at 4 and 3 respectively per 100,000 population. African countries' HIV-positive TB mortality rates were 29.9 times higher than non-African countries (95% confidence interval [CI]: 16.8-53.4). Every US$100 of government per capita health expenditure was associated with a 33% (95% CI: 24%-42%) decrease in TB/HIV mortality rates. The multivariate model also accounted for calendar year and did not include highly active antiretroviral therapy (HAART) coverage., Conclusions: Our results indicate that while the AFRH has the highest TB/HIV death rates, countries in EEUR and LAMR also have elevated mortality rates. Increasing health expenditure directed towards universal HAART access may reduce mortality from both diseases.

Background: Food insufficiency is often associated with health risks and adverse outcomes among marginalized populations. However, little is known about correlates of food insufficiency among injection drug users (IDU)., Methods: We conducted a cross-sectional study to examine the prevalence and correlates of self-reported hunger in a large cohort of IDU in Vancouver, Canada. Food insufficiency was defined as reporting "I am hungry, but don't eat because I can't afford enough food". Logistic regression was used to determine independent socio-demographic and drug-use characteristics associated with food insufficiency., Results: Among 1,053 participants, 681 (64.7%) reported being hungry and unable to afford enough food. Self-reported hunger was independently associated with: unstable housing (adjusted odds ratio [AOR]: 1.68, 95% confidence interval [CI]: 1.20 - 2.36, spending ≥ $50/day on drugs (AOR: 1.43, 95% CI: 1.06 - 1.91), and symptoms of depression (AOR: 3.32, 95% CI: 2.45 - 4.48)., Conclusion: These findings suggest that IDU in this setting would likely benefit from interventions that work to improve access to food and social support services, including addiction treatment programs which may reduce the adverse effect of ongoing drug use on hunger.

Sustained combination of HIV prevention strategies is essential to curb the spread of the HIV/AIDS epidemic. The use of highly active antiretroviral therapy (HAART) decreases morbidity and mortality, as well as HIV transmission, among treated individuals. The concept of 'treatment as prevention' is dependent on HAART's ability to sustain HIV-1 RNA virological suppression at the individual and population levels, and has been demonstrated in studies evaluating transmission in mother-to-child, sero-discordant couples and large treated populations. The worldwide expansion of maximally effective antiretroviral drug regimens has been coupled with concerns regarding the magnitude of the financial investment required. However, HAART's compounding effect on reduced morbidity, mortality and transmission makes the expansion of HAART coverage highly cost-averting. Building on a mathematical model that evaluated the impact of expanded HAART access on viral load in a Canadian setting, we demonstrate that an investment of CA$249 million over the lifetime of treated individuals would result in a net gain of CA$2.1 billion over 30 years. This provides a powerful economic incentive to rapidly scale up HAART access worldwide.

Objectives: To examine the long-term impact of adherence on virologic, immunologic, and dual response stratified by type of HAART regimen in treatment-naive patients starting HAART in British Columbia, Canada; and to assess the degree of virologic and immunologic response associated with emergence of drug resistance, progression to AIDS, and mortality., Methods: Eligible participants initiated HAART between 1 January 2000 and 30 November 2004, were followed until 30 November 2005, and had at least 2 years of follow-up. Virologic and immunologic responses were dichotomized at their median values. Virologic response was defined as at least 65% of follow-up time with plasma viral load (pVL) of less than 50 copies/ml. Immunologic response was defined as a CD4 cell count increase of at least 145 cells/microl. Adherence measures were based on prescription refill compliance. Proportional odds models and logistic regression were used to address our objectives., Results: The distribution of patient responses was 394 (44.9%) for CD4+/pVL+ (best), 350 (39.9%) for CD4-/pVL+ or CD4+/pVL- (incomplete), and 134 (15.3%) for CD4-/pVL- (worst). We found a positive correlation between adherence and virologic and immunologic responses (P < 0.01). Having worst compared with best response (reference group) was associated with higher odds of mortality (odds ratio: 6.09; 95% confidence interval: 2.57-14.42) and emergence of drug resistance (odds ratio: 10.56; 95% confidence interval: 5.93-18.81) even after adjusting for adherence and HAART regimen., Conclusion: Patients not attaining the best virologic and immunologic responses are at a high risk for emergence of drug resistance and mortality, and these responses are highly dependent on the adherence level and initial HAART regimen. Patients on protease inhibitor-single did worse no matter the adherence level.

Objectives: To assess the use of the Biojector B2000 needle-free gas-powered injection system for subcutaneous administration of enfuvirtide in HIV-infected patients and to compare this system with standard needles and syringes with respect to ease of use, severity of injection site reactions (ISR), and enfuvirtide plasma levels., Design: An observational study among 32 treatment-experienced HIV clinic patients receiving enfuvirtide., Methods: Adult patients were assessed before and after switching from standard needles to the Biojector for enfuvirtide administration. Patients used the Biojector for up to 24 weeks and rated ease of use from 0 (easy) to 3 (difficult). ISR were graded from 0 to 31 for signs and symptoms (erythema, induration, pruritus, nodules/cysts, ecchymosis), duration of individual lesions, and number of lesions. Plasma was collected pre-dose and 1 h post-dose for enfuvirtide measurement. The high-pressure liquid chromatography with tandem mass spectrometry method used was specific for enfuvirtide over its known plasma metabolite. Wilcoxon rank sum tests were used to compare needle-based and Biojector outcomes., Results: The Biojector was rated as being significantly easier to use (P < 0.001) and reduced the occurrence of ISR compared with standard needles (P < 0.001). Enfuvirtide plasma levels were not statistically different between the two administration methods at either pre-dose trough (P = 0.41) or 1 h post-dose (P = 0.74)., Conclusions: The Biojector needle-free injection system was easy to use for enfuvirtide administration and was associated with a decreased severity of ISR. Plasma enfuvirtide levels pre-dose and 1 h post-dose were comparable when injecting with standard needles or the Biojector.