Adverse drug reactions attributed to generic substitution of antiretroviral medications among HIV treatment and pre-exposure prophylaxis clients in British Columbia, Canada.

BACKGROUND: In British Columbia, antiretrovirals (ARVs) for HIV treatment (HIV-Tx) and pre-exposure prophylaxis (PrEP) are free-of-charge through publicly-funded Drug Treatment Programs (DTPs). When available, less costly generics are substituted for brand-name ARVs. We describe the incidence and type of product substitution issue (PSI) adverse drug reactions (ADRs) attributed to generic ARVs. METHODS: Cohorts included DTP clients ≥19 years who received generic ARVs for HIV-Tx (abacavir-lamivudine, emtricitabine-tenofovir DF, efavirenz-emtricitabine-tenofovir DF, atazanavir or darunavir between 01 Jun 2017 and 30 Jun 2022) or PrEP (emtricitabine-tenofovir DF, 01 Apr 2018 to 30 Jun 2022). Demographic, ARV and ADR data were extracted from DTP databases and summarized by descriptive statistics. PSI incidence was calculated for each product during the year following brand-to-generic and generic-to-generic transitions (first-year-post-rollout), and compared between generic versions using generalized estimating equations. For context, incidence of any ARV product-related ADR was calculated in the same 1-year periods. RESULTS: During first-year-post-rollout periods, 5339 HIV-Tx (83% male, median age 52 years) and 8095 PrEP (99% male, median 33 years) clients received generic ARVs, and reported 78 and 23 generic PSIs, respectively. PSI incidence was <1% for most generic ARVs, with mild-moderate symptoms including gastrointestinal upset, headache, dizziness, fatigue/malaise and skin rash. In HIV-Tx clients, the efavirenz-containing product had higher PSI incidence than other ARVs (2.2%, p = .004), due to more neuropsychiatric adverse reactions. Any ADR incidence was stable across measurement periods, and generic PSIs represented less than one third of all product-related ADRs. CONCLUSIONS: Generic substitution of antiretrovirals for HIV-Tx and PrEP was well tolerated, with ≤2% incidence of mild-moderate PSI ADRs.

Expert consensus statement on the science of HIV in the context of criminal law.

INTRODUCTION: Globally, prosecutions for non-disclosure, exposure or transmission of HIV frequently relate to sexual activity, biting, or spitting. This includes instances in which no harm was intended, HIV transmission did not occur, and HIV transmission was extremely unlikely or not possible. This suggests prosecutions are not always guided by the best available scientific and medical evidence. DISCUSSION: Twenty scientists from regions across the world developed this Expert Consensus Statement to address the use of HIV science by the criminal justice system. A detailed analysis of the best available scientific and medical research data on HIV transmission, treatment effectiveness and forensic phylogenetic evidence was performed and described so it may be better understood in criminal law contexts. Description of the possibility of HIV transmission was limited to acts most often at issue in criminal cases. The possibility of HIV transmission during a single, specific act was positioned along a continuum of risk, noting that the possibility of HIV transmission varies according to a range of intersecting factors including viral load, condom use, and other risk reduction practices. Current evidence suggests the possibility of HIV transmission during a single episode of sex, biting or spitting ranges from no possibility to low possibility. Further research considered the positive health impact of modern antiretroviral therapies that have improved the life expectancy of most people living with HIV to a point similar to their HIV-negative counterparts, transforming HIV infection into a chronic, manageable health condition. Lastly, consideration of the use of scientific evidence in court found that phylogenetic analysis alone cannot prove beyond reasonable doubt that one person infected another although it can be used to exonerate a defendant. CONCLUSIONS: The application of up-to-date scientific evidence in criminal cases has the potential to limit unjust prosecutions and convictions. The authors recommend that caution be exercised when considering prosecution, and encourage governments and those working in legal and judicial systems to pay close attention to the significant advances in HIV science that have occurred over the last three decades to ensure current scientific knowledge informs application of the law in cases related to HIV.

Trends in discharges from the HIV/AIDS ward at a tertiary Canadian Hospital from 2005 to 2014.

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.

Incidence of diabetes mellitus and factors associated with its development in HIV-positive patients over the age of 50.

OBJECTIVE: We sought to determine the incidence and factors associated with development of diabetes mellitus (DM) in older HIV-infected individuals. RESEARCH DESIGN AND METHODS: We analyzed data from people living with HIV (PLWH) ≥50 years of age enrolled in a large urban HIV outpatient clinic in Vancouver, British Columbia. Patients were categorized as having DM if they had random blood sugar ≥11.1 mmol/L, fasting blood sugar ≥7 mmol/L, HbA1C ≥6.5%, antidiabetic medication use during the follow-up period, or medical chart review confirming diagnosis of DM. We estimated the probability of developing DM, adjusting for demographic and clinical factors, using a logistic regression model. RESULTS: Among 1065 PLWH followed for a median of 13 years (25th and 75th percentile (Q1-Q3): 9-18), the incidence of DM was 1.61/100 person-years follow-up. In the analysis of factors associated with new-onset DM (n=703), 88% were male, 38% had a history of injection drug use, 43% were hepatitis C coinfected, and median body mass index was 24 kg/m2 (Q1-Q3: 21-27). Median age at antiretroviral therapy (ART) initiation was 48 years (Q1-Q3: 43-53) and at DM diagnosis was 55 years (Q1-Q3: 50-61). Patients who started ART in 1997-1999 and had a longer exposure to older ART were at the highest risk of developing DM. CONCLUSIONS: Among PLWH aged ≥50 years, the incidence of DM was 1.39 times higher than men in the general Canadian population of similar age. ART initiated in the early years of the epidemic and exposure to older ART appeared to be the main drivers of the development of DM.

Increases in CD4+ T-cell count at antiretroviral therapy initiation among HIV-positive illicit drug users during a treatment-as-prevention initiative in Canada.

BACKGROUND: Although treatment-as-prevention (TasP) efforts are a new cornerstone of efforts to respond to the HIV/AIDS pandemic, their effects among people who use drugs (PWUD) have not been fully evaluated. This study characterizes temporal trends in CD4+ T-cell (CD4) count at ART initiation and rates of virological response among HIV-positive PWUD during a TasP initiative. METHODS: We used data on individuals initiating ART within a prospective cohort of PWUD linked to comprehensive clinical records. Using multivariable linear regression, we evaluated the relationship between CD4 count prior to ART initiation and year of initiation and time to HIV-1 RNA viral load <50 copies/ml following initiation using Cox proportional hazards modelling. RESULTS: Among 355 individuals, CD4 count at initiation rose from 130 to 330 cells/ml from 2005 to 2013. In multivariable regression, initiation year was significantly associated with higher CD4 count (ß=29.5 cells per year, 95% CI 21.0, 37.9). Initiating ART at higher CD4 counts was significantly associated with optimal viral response (adjusted hazard ratio =1.13 per 100 cells/ml increase, 95% CI 1.05, 1.22). CONCLUSIONS: Increases in CD4 cell count at initiation over time was associated with superior virological response, consistent with the aims of the TasP initiative.

An Event-Level Analysis of Condom Use During Anal Intercourse Among Self-Reported Human Immunodeficiency Virus-Negative Gay and Bisexual Men in a Treatment as Prevention Environment.

BACKGROUND: We sought to identify factors associated with condom use during anal intercourse among self-identified human immunodeficiency virus-negative gay, bisexual, and other men who have sex with men (GBM) in Vancouver, Canada following "treatment as prevention" (TasP) scale-up in 2010. METHODS: Sexually active GBM were recruited using respondent-driven sampling from 2012 to 2014. We analyzed participants' most recent sexual encounter with up to their last 5 sexual partners within the past 6 months. In addition to individual- and event-level explanatory factors, we assessed potential associations with TasP awareness, TasP-related prevention practice (viral load sorting), and TasP-related attitudes (human immunodeficiency virus treatment optimism). Accounting for clustering at the respondent-driven sampling chain-level and participant-level, factors associated with event-level condom use versus nonuse were determined using a multivariable generalized linear mixed model built using backward selection and AIC minimization. RESULTS: Of 513 participants, 436 GBM (85%) reported a total of 1196 anal sex events with 56% condom use. The proportion of condom-protected sexual events decreased monthly over the study period (odds ratio [OR], 0.95 per month, 95% confidence interval [CI], 0.92-0.98). The TasP practices and attitudes were significantly associated with lower odds of condom use at the univariate level, but were no longer significant at multivariate level. In the multivariable model, event-level partner methamphetamine use (adjusted OR [aOR], 0.18; 95% CI, 0.06-0.58), frequency of recent anal intercourse with that partner (aOR, 0.97 per act; 95% CI, 0.95-0.98) and time since first sex with that partner (aOR, 0.97 per 6 months; 95% CI, 0.95-0.99) were associated with lower odds of condom use, whereas event-level participant alcohol use (aOR, 1.41; 95% CI, 1.01-1.98) and no planned future sex with that partner (aOR, 1.56; 95% CI, 1.08-2.27) were associated with greater odds of condom use. Event-level receptive-only (aOR, 2.10; 95% CI, 1.38-3.20) or insertive-only (aOR, 2.53; 95% CI, 1.64-3.90) sexual positions were associated with greater odds of condom use compared with reporting both positions. CONCLUSIONS: The TasP-related factors were not the most salient predictors of GBM's condom use. Health promotion must consider associations between condomless anal sex and substance use and relational factors.

Long-term effectiveness of initiating non-nucleoside reverse transcriptase inhibitor- versus ritonavir-boosted protease inhibitor-based antiretroviral therapy: implications for first-line therapy choice in resource-limited settings.

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.

Factors associated with the frequency of monitoring of liver enzymes, renal function and lipid laboratory markers among individuals initiating combination antiretroviral therapy: a cohort study.

BACKGROUND: As the average age of the HIV-positive population increases, there is increasing need to monitor patients for the development of comorbidities as well as for drug toxicities. METHODS: We examined factors associated with the frequency of measurement of liver enzymes, renal function tests, and lipid levels among participants of the Canadian Observational Cohort (CANOC) collaboration which follows people who initiated HIV antiretroviral therapy in 2000 or later. We used zero-inflated negative binomial regression models to examine the associations of demographic and clinical characteristics with the rates of measurement during follow-up. Generalized estimating equations with a logit link were used to examine factors associated with gaps of 12 months or more between measurements. RESULTS: Electronic laboratory data were available for 3940 of 7718 CANOC participants. The median duration of electronic follow-up was 3.5 years. The median (interquartile) rates of tests per year were 2.76 (1.60, 3.73), 2.55 (1.44, 3.38) and 1.42 (0.50, 2.52) for liver, renal and lipid parameters, respectively. In multivariable zero-inflated negative binomial regression models, individuals infected through injection drug use (IDU) were significantly less likely to have any measurements. Among participants with at least one measurement, rates of measurement of liver, renal and lipid tests were significantly lower for younger individuals and Aboriginal Peoples. Hepatitis C co-infected individuals with a history of IDU had lower rates of measurement and were at greater risk of having 12 month gaps between measurements. CONCLUSIONS: Hepatitis C co-infected participants infected through IDU were at increased risk of gaps in testing, despite publicly funded health care and increased risk of comorbid conditions. This should be taken into consideration in analyses examining factors associated with outcomes based on laboratory parameters.

Gay and bisexual men's awareness and knowledge of treatment as prevention: findings from the Momentum Health Study in Vancouver, Canada.

INTRODUCTION: Awareness and knowledge of treatment as prevention (TasP) was assessed among HIV-positive and HIV-negative gay, bisexual and other men who have sex with men (GBMSM) in Vancouver, Canada. METHODS: Baseline cross-sectional survey data were analyzed for GBMSM enrolled, via respondent-driven sampling (RDS), in the Momentum Health Study. TasP awareness was defined as ever versus never heard of the term "TasP." Multivariable logistic regression identified covariates of TasP awareness. Among those aware of TasP, men's level of knowledge of TasP was explored through an examination of self-perceived knowledge levels, risk perceptions and short-answer definitions of TasP which were coded as "complete" if three TasP-related components were identified (i.e. HIV treatment, viral suppression and prevention of transmission). Information source was also assessed. Analyses were stratified by HIV status and RDS adjusted. RESULTS: Of 719 participants, 23% were HIV-positive, 68% Caucasian and median age was 33 (Interquartile range (IQR) 26,47). Overall, 46% heard of TasP with differences by HIV status [69% HIV-positive vs. 41% HIV-negative GBMSM (p<0.0001)]. In adjusted models: HIV-positive GBMSM were more likely to have heard of TasP if they were Canadian born, unemployed, not using party drugs and had higher CD4 counts; HIV-negative GBMSM were more likely to have heard of TasP if they were Caucasian (vs. Aboriginal), students, had higher education, a regular partner and multiple sexual partners. Among those aware of TasP 91% of HIV-positive and 69% of HIV-negative GBMSM (p<0.0001) felt they knew "a lot" or "a bit in general" about TasP; 64 and 41% (p=0.002) felt HIV treatment made the risk of transmission "a lot lower"; and 21 and 13% (p<0.0001) demonstrated "complete" TasP definitions. The leading information source was doctors (44%) for HIV-positive GBMSM and community agencies (38%) for HIV-negative GBMSM, followed by gay media for both populations (34%). CONCLUSIONS: Nearly half of GBMSM in this study reported having heard of TasP, yet only 14% demonstrated complete understanding of the concept. Variations in TasP awareness and knowledge by HIV status, and key socio-demographic, behavioural and clinical factors, highlight a need for health communication strategies relevant to diverse communities of GBMSM in order to advance overall TasP health literacy.

Canadian consensus statement on HIV and its transmission in the context of criminal law.

INTRODUCTION: A poor appreciation of the science related to HIV contributes to an overly broad use of the criminal law against individuals living with HIV in cases of HIV nondisclosure. METHOD: To promote an evidence-informed application of the law in Canada, a team of six Canadian medical experts on HIV and transmission led the development of a consensus statement on HIV sexual transmission, HIV transmission associated with biting and spitting, and the natural history of HIV infection. The statement is based on a literature review of the most recent and relevant scientific evidence (current as of December 2013) regarding HIV and its transmission. It has been endorsed by >70 additional Canadian HIV experts and the Association of Medical Microbiology and Infectious Disease Canada. RESULTS: Scientific and medical evidence clearly indicate that HIV is difficult to transmit during sex. For the purpose of informing the justice system, the per-act possibility of HIV transmission through sex, biting or spitting is described along a continuum from low possibility, to negligible possibility, to no possibility of transmission. This possibility takes into account the impact of factors such as the type of sexual acts, condom use, antiretroviral therapy and viral load. Dramatic advances in HIV therapy have transformed HIV infection into a chronic manageable condition. DISCUSSION: HIV physicians and scientists have a professional and ethical responsibility to assist those in the criminal justice system to understand and interpret the science regarding HIV. This is critical to prevent miscarriage of justice and to remove unnecessary barriers to evidence-based HIV prevention strategies.

INTRODUCTION: En raison, entre autres, d'une mauvaise appréciation des données scientifiques liées au VIH, la justice criminelle est beaucoup trop mise à contribution contre les personnes qui vivent avec le VIH et ne divulguent pas leur séropositivité. MÉTHODOLOGIE: Afin de promouvoir une application de la loi canadienne fondée sur des données probantes, une équipe de six experts médicaux canadiens du VIH et de sa transmission a élaboré un énoncé de consensus sur la transmission sexuelle du VIH, sa transmission par les morsures ou les crachats et son évolution naturelle. Cet énoncé repose sur une analyse bibliographique des données scientifiques les plus récentes et les plus pertinentes (en décembre 2013) au sujet du VIH et de sa transmission. Il est appuyé par plus de 70 autres experts du VIH au Canada et par l'Association pour la microbiologie médicale et l'infectiologie Canada. RÉSULTATS: Les données scientifiques et médicales établissent clairement que le VIH est difficile à transmettre pendant les relations sexuelles. Afin d'informer le système judiciaire, la possibilité réelle de transmission lors d'une relation sexuelle, d'une morsure ou d'un crachat est décrite le long d'un continuum de faible possibilité, de possibilité négligeable et d'aucune possibilité de transmission. Ce continuum tient compte des effets de facteurs comme le type d'acte sexuel, l'utilisation de condoms, la thérapie antirétrovirale et la charge virale. Les progrès considérables en matière de traitement du VIH ont transformé l'infection par le VIH en une maladie chronique gérable. EXPOSÉ: Les médecins et les chercheurs spécialisés en VIH ont la responsabilité professionnelle et éthique d'aider les acteurs du système de justice criminelle à comprendre et interpréter la recherche sur le VIH. C'est essentiel pour éviter les erreurs judiciaires et pour écarter tout obstacle inutile aux stratégies de prévention du VIH fondées sur des données probantes.

Cohort profile: Seek and treat for the optimal prevention of HIV/AIDS in British Columbia (STOP HIV/AIDS BC).

The Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) cohort is a census of all identified HIV-positive individuals in the province of British Columbia. It was formed through the linkage of nine provincial treatment, surveillance and administrative databases. This open cohort allows for bidirectional analyses from 1996 onward and is refreshed annually. Extensive data collection for cohort members includes demographic information, detailed clinical and laboratory data, complete prescription drug use including antiretroviral agents, and information on health service utilization encompassing inpatient and outpatient care, addictions treatment and palliative care. This cohort provides an unprecedented opportunity to evaluate, over an extended time period, patterns and determinants of key outcomes including engagement in the cascade of HIV care from diagnosis to treatment to viral suppression as well as monitoring trends in medical costs, health outcomes and other key healthcare delivery indicators at a population level with wide-ranging, high-quality data. The overall purpose of these activities is to enable the development and implementation of strategically targeted interventions to improve access to testing, care and treatment for all HIV-positive individuals living in British Columbia.

Cohort Profile: Longitudinal Investigations into Supportive and Ancillary health services.

The Longitudinal Investigations into Supportive and Ancillary health services (LISA) study is a cohort of people living with HIV/AIDS who have ever accessed anti-retroviral therapy (ART) in British Columbia, Canada. The LISA study was developed to better understand the outcomes of people living with HIV with respect to supportive services use, socio-demographic factors and quality of life. Between July 2007 and January 2010, 1000 participants completed an interviewer-administered questionnaire that included questions concerning medical history, substance use, social and medical support services, food and housing security and other social determinants of health characteristics. Of the 1000 participants, 917 were successfully linked to longitudinal clinical data through the provincial Drug Treatment Program. Within the LISA cohort, 27% of the participants are female, the median age is 39 years and 32% identify as Aboriginal. Knowledge translation activities for LISA include the creation of plain language summaries, internet resources and arts-based engagement activities such as Photovoice.

Sex work and the public health impacts of the 2010 Olympic Games.

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.

Estimating the impact of expanded access to antiretroviral therapy on maternal, paternal and double orphans in sub-Saharan Africa, 2009-2020.

BACKGROUND: HIV/AIDS has orphaned 11.6 million children in sub-Saharan Africa. Expanded antiretroviral therapy (ART) use may reduce AIDS orphanhood by decreasing adult mortality and population-level HIV transmission. METHODS: We modeled two scenarios to measure the impact of adult ART use on the incidence of orphanhood in 10 sub-Saharan African countries, from 2009 to 2020. Demographic model data inputs were obtained from cohort studies, UNAIDS, UN Population Division, WHO and the US Census Bureau. RESULTS: Compared to current rates of ART uptake, universal ART access averted 4.37 million more AIDS orphans by year 2020, including 3.15 million maternal, 1.89 million paternal and 0.75 million double orphans. The number of AIDS orphans averted was highest in South Africa (901.71 thousand) and Nigeria (839.01 thousand), and lowest in Zimbabwe (86.96 thousand) and Côte d'Ivoire (109.12 thousand). CONCLUSION: Universal ART use may significantly reduce orphanhood in sub-Saharan Africa.

Tuberculosis mortality in HIV-infected individuals: a cross-national systematic assessment.

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.

Hunger and associated harms among injection drug users in an urban Canadian setting.

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.

Expanded Highly Active Antiretroviral Therapy Coverage - A Powerful Strategy to Curb Progression to AIDS, Death and New Infections.

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.

Differential impact of adherence on long-term treatment response among naive HIV-infected individuals.

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.

Enfuvirtide plasma levels and injection site reactions using a needle-free gas-powered injection system (Biojector).

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.

The prevalence and incidence of sexually transmitted infections in a prospective cohort of injection drug users in Vancouver, British Columbia.

BACKGROUND: While several studies have reported on sexual risk behaviours and the prevalence of sexually transmitted infections (STIs) among injection drug users (IDUs), there are fewer prospective studies that have been able to examine populations of IDUs with no history of STIs. Therefore, the authors examined prevalence, correlates and factors associated with time to first STI infection in a prospective cohort of IDUs in Vancouver, British Columbia. METHODS: The authors examined the prevalence and correlates of STIs among IDUs at the time of recruitment into a prospective cohort study. The authors also evaluated the cumulative rate of time to first STI among IDUs with no history of STIs at baseline using the Kaplan-Meier method, and modelled factors independently associated with first STI using Cox regression. RESULTS: Between May 1996 and November 2003, 1560 individuals were recruited into the cohort; of these individuals, 745 reported a history of STI at baseline. Among the 815 who did not report an STI at baseline, 671 (82%) had at least one follow-up visit and were eligible for the analysis of time to first STI. After 36 months of follow-up, the cumulative rate of first STI was 8.2% for men and 15.9% for women (log-rank P<0.001), whereas the cumulative rate of first STI was 8.0% for IDUs who did not report sex trade involvement versus 19.8% for IDUs who reported sex trade involvement (log-rank P<0.001). In multivariate analyses, the risk of first STI remained independently associated with unprotected sex with regular partners (relative hazard=2.04, 95% CI 1.29 to 3.23; P=0.001) and unprotected sex with sex trade clients (relative hazard=2.36, 95% CI 1.46 to 3.82; P=0.005). CONCLUSIONS: In the present study, the authors found that STIs were associated with both regular sex partnerships and sex trade involvement. These findings are of particular concern because both unprotected sex with regular partners and sex trade involvement is common among IDUs. Interventions to encourage condom use among IDUs, particularly those with regular sex partners and those involved in the sex trade, should be further developed.