HIV Infection, Immunosuppression, and Age at Diagnosis of Non-AIDS-Defining Cancers.

Background: It is unclear whether immunosuppression leads to younger ages at cancer diagnosis among people living with human immunodeficiency virus (PLWH). A previous study found that most cancers are not diagnosed at a younger age in people with AIDS, with the exception of anal and lung cancers. This study extends prior work to include all PLWH and examines associations between AIDS, CD4 count, and age at cancer diagnosis. Methods: We compared the median age at cancer diagnosis between PLWH in the North American AIDS Cohort Collaboration on Research and Design and the general population using data from the Surveillance, Epidemiology and End Results Program. We used statistical weights to adjust for population differences. We also compared median age at cancer diagnosis by AIDS status and CD4 count. Results: After adjusting for population differences, younger ages at diagnosis (P < .05) were observed for PLWH compared with the general population for lung (difference in medians = 4 years), anal (difference = 4), oral cavity/pharynx (difference = 2), and kidney cancers (difference = 2) and myeloma (difference = 4). Among PLWH, having an AIDS-defining event was associated with a younger age at myeloma diagnosis (difference = 4; P = .01), and CD4 count <200 cells/µL (vs ≥500) was associated with a younger age at lung cancer diagnosis (difference = 4; P = .006). Conclusions: Among PLWH, most cancers are not diagnosed at younger ages. However, this study strengthens evidence that lung cancer, anal cancer, and myeloma are diagnosed at modestly younger ages, and also shows younger ages at diagnosis of oral cavity/pharynx and kidney cancers, possibly reflecting accelerated cancer progression, etiologic heterogeneity, or risk factor exposure in PLWH.

Risk of End-Stage Liver Disease in HIV-Viral Hepatitis Coinfected Persons in North America From the Early to Modern Antiretroviral Therapy Eras.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients coinfected with hepatitis B (HBV) and C (HCV) viruses are at increased risk of end-stage liver disease (ESLD). Whether modern antiretroviral therapy has reduced ESLD risk is unknown. METHODS: Twelve clinical cohorts in the United States and Canada participating in the North American AIDS Cohort Collaboration on Research and Design validated ESLD events from 1996 to 2010. ESLD incidence rates and rate ratios according to hepatitis status adjusted for age, sex, race, cohort, time-updated CD4 cell count and HIV RNA were estimated in calendar periods corresponding to major changes in antiretroviral therapy: early (1996-2000), middle (2001-2005), and modern (2006-2010) eras. RESULTS: Among 34 119 HIV-infected adults followed for 129 818 person-years, 380 incident ESLD outcomes occurred. ESLD incidence (per 1000 person-years) was highest in triply infected (11.57) followed by HBV- (8.72) and HCV- (6.10) coinfected vs 1.27 in HIV-monoinfected patients. Adjusted incidence rate ratios (95% confidence intervals) comparing the modern to the early antiretroviral era were 0.95 (.61-1.47) for HCV, 0.95 (.40-2.26) for HBV, and 1.52 (.46-5.02) for triply infected patients. Use of antiretrovirals dually activity against HBV increased over time. However, in the modern era, 35% of HBV-coinfected patients were not receiving tenofovir. There was little use of HCV therapy. CONCLUSIONS: Despite increasing use of antiretrovirals, no clear reduction in ESLD risk was observed over 15 years. Treatment with direct-acting antivirals for HCV and wider use of tenofovir-based regimens for HBV should be prioritized for coinfected patients.

Predictors of viral suppression and rebound among HIV-positive men who have sex with men in a large multi-site Canadian cohort.

BACKGROUND: Gay, bisexual and other men who have sex with men (MSM) are disproportionately affected by HIV in Canada. Combination antiretroviral therapy has been shown to dramatically decrease progression to AIDS, premature death and HIV transmission. However, there are no comprehensive data regarding combination antiretroviral therapy outcomes among this population. We sought to identify socio-demographic and clinical correlates of viral suppression and rebound. METHODS: Our analysis included MSM participants in the Canadian Observational Cohort, a multi-site cohort of HIV-positive adults from Canada's three most populous provinces, aged ≥18 years who first initiated combination antiretroviral therapy between 2000 and 2011. We used accelerated failure time models to identify factors predicting time to suppression (2 measures <50 copies/mL ≥30 days apart) and subsequent rebound (2 measures >200 copies/mL ≥30 days apart). RESULTS: Of 2,858 participants, 2,448 (86 %) achieved viral suppression in a median time of 5 months (Q1-Q3: 3-7 months). Viral suppression was significantly associated with later calendar year of antiretroviral therapy initiation, no history of injection drug use, lower baseline viral load, being on an initial regimen consisting of non-nucleoside reverse-transcriptase inhibitors, and older age. Among those who suppressed, 295 (12 %) experienced viral rebound. This was associated with earlier calendar year of antiretroviral therapy initiation, injection drug use history, younger age, higher baseline CD4 cell count, and living in British Columbia. CONCLUSIONS: Further strategies are required to optimize combination antiretroviral therapy outcomes in men who have sex with men in Canada, specifically targeting younger MSM and those with a history of injection drug use.

Life expectancy of HIV-positive individuals on combination antiretroviral therapy in Canada.

BACKGROUND: We sought to evaluate life expectancy and mortality of HIV-positive individuals initiating combination antiretroviral therapy (ART) across Canada, and to consider the potential error introduced by participant loss to follow-up (LTFU). METHODS: Our study used data from the Canadian Observational Cohort (CANOC) collaboration, including HIV-positive individuals aged ≥18 years who initiated ART on or after January 1, 2000. The CANOC collaboration collates data from eight sites in British Columbia, Ontario, and Quebec. We computed abridged life-tables and remaining life expectancies at age 20 and compared outcomes by calendar period and patient characteristics at treatment initiation. To correct for potential underreporting of mortality due to participant LTFU, we conservatively estimated 30% mortality among participants lost to follow-up. RESULTS: 9997 individuals contributed 49,589 person-years and 830 deaths for a crude mortality rate of 16.7 [standard error (SE) 0.6] per 1000 person-years. When assigning death to 30% of participants lost to follow-up, we estimated 1170 deaths and a mortality rate of 23.6 [SE 0.7] per 1000 person-years. The crude overall life expectancy at age 20 was 45.2 [SE 0.7] and 37.5 [SE 0.6] years after adjusting for LTFU. In the LTFU-adjusted analysis, lower life expectancy at age 20 was observed for women compared to men (32.4 [SE 1.1] vs. 39.2 [SE 0.7] years), for participants with injection drug use (IDU) history compared to those without IDU history (23.9 [SE 1.0] vs. 52.3 [SE 0.8] years), for participants reporting Aboriginal ancestry compared to those with no Aboriginal ancestry (17.7 [SE 1.5] vs. 51.2 [SE 1.0] years), and for participants with CD4 count <350 cells/µL compared to CD4 count ≥350 cells/µL at treatment initiation (36.3 [SE 0.7] vs. 43.5 [SE 1.3] years). Life expectancy at age 20 in the calendar period 2000-2003 was lower than in periods 2004-2007 and 2008-2012 in the LTFU-adjusted analyses (30.8 [SE 0.9] vs. 38.6 [SE 1.0] and 54.2 [SE 1.4]). CONCLUSIONS: Life expectancy and mortality for HIV-positive individuals receiving ART differ by calendar period and patient characteristics at treatment initiation. Failure to consider LTFU may result in underestimation of mortality rates and overestimation of life expectancy.

U.S. trends in antiretroviral therapy use, HIV RNA plasma viral loads, and CD4 T-lymphocyte cell counts among HIV-infected persons, 2000 to 2008.

BACKGROUND: The U.S. National HIV/AIDS Strategy targets for 2015 include "increasing access to care and improving health outcomes for persons living with HIV in the United States" (PLWH-US). OBJECTIVE: To demonstrate the utility of the NA-ACCORD (North American AIDS Cohort Collaboration on Research and Design) for monitoring trends in the HIV epidemic in the United States and to present trends in HIV treatment and related health outcomes. DESIGN: Trends from annual cross-sectional analyses comparing patients from pooled, multicenter, prospective, clinical HIV cohort studies with PLWH-US, as reported to national surveillance systems in 40 states. SETTING: U.S. HIV outpatient clinics. PATIENTS: HIV-infected adults with 1 or more HIV RNA plasma viral load (HIV VL) or CD4 T-lymphocyte (CD4) cell count measured in any calendar year from 1 January 2000 to 31 December 2008. MEASUREMENTS: Annual rates of antiretroviral therapy use, HIV VL, and CD4 cell count at death. RESULTS: 45 529 HIV-infected persons received care in an NA-ACCORD-participating U.S. clinical cohort from 2000 to 2008. In 2008, the 26 030 NA-ACCORD participants in care and the 655 966 PLWH-US had qualitatively similar demographic characteristics. From 2000 to 2008, the proportion of participants prescribed highly active antiretroviral therapy increased by 9 percentage points to 83% (P < 0.001), whereas the proportion with suppressed HIV VL (≤2.7 log10 copies/mL) increased by 26 percentage points to 72% (P < 0.001). Median CD4 cell count at death more than tripled to 0.209 × 109 cells/L (P < 0.001). LIMITATION: The usual limitations of observational data apply. CONCLUSION: The NA-ACCORD is the largest cohort of HIV-infected adults in clinical care in the United States that is demographically similar to PLWH-US in 2008. From 2000 to 2008, increases were observed in the percentage of prescribed HAART, the percentage who achieved a suppressed HIV VL, and the median CD4 cell count at death. PRIMARY FUNDING SOURCE: National Institutes of Health; Centers for Disease Control and Prevention; Canadian Institutes of Health Research; Canadian HIV Trials Network; and the government of British Columbia, Canada.

Conversations with mothers: exploring reasons for prevention of mother-to-child transmission (PMTCT) failures in the era of programmatic scale-up in Soweto, South Africa.

Reasons for incident cases of vertical HIV transmission in the era of free access to PMTCT in South Africa were investigated. This mixed-methods study was conducted in Soweto, South Africa from June-August, 2009. Birthmothers of HIV-infected infants born after 1 December 2008 were eligible. All participants completed an interviewer-administered questionnaire. Women also participated in a focus group (n = 10) or individual structured interview (n = 35). Mean age of participants (n = 45) was 28.7 years (SD = 5.4). Major findings are: (i) failure of per-guideline prescription of ARV strategies for infants (31%) and/or mothers (57%); (ii) maternal refusal of treatment (n = 5); (iii) preterm delivery (31%); (iv) delayed ANC attendance because of facility-related barriers and maternal apprehension around HIV testing; (v) fear of stigma; (vi) maternal difficulty with administering infant AZT (n = 9) and (vii) maternal confusion about infant feeding. A variety of individual, social, and structural factors must be addressed to optimize PMTCT service delivery in South Africa.

Women and vulnerability to HAART non-adherence: a literature review of treatment adherence by gender from 2000 to 2011.

A literature review of original research articles on adherence to antiretroviral therapy (ART) in developed countries, covering January 2000 to June 2011, was conducted to determine if gender differences exist in the prevalence of nonadherence to ART. Of the 1,255 articles reviewed, only 189 included data on the proportion of the study population that was adherent and only 57 (30.2%) of these reported proportional adherence values by gender. While comparing articles was challenging because of varied reporting strategies, women generally exhibit poorer adherence than men. Thirty of the 44 articles (68.2%) that reported comparative data on adherence by gender found women to be less adherent than men. Ten articles (17.5%) reported significant differences in proportional adherence by gender, nine of which showed women to be less adherent than men. These findings suggest that in multiple studies from developed countries, female gender often predicts lower adherence. The unique circumstances of HIV-positive women require specialized care to increase adherence to ART.

Cohort profile: the Comparative Outcomes And Service Utilization Trends (COAST) Study among people living with and without HIV in British Columbia, Canada.

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

HAART slows progression to anal cancer in HIV-infected MSM.

OBJECTIVE: Antiretrovirals do not prevent anal intraepithelial neoplasia. However, the influence of antiretrovirals in the natural history of invasive anal cancer is less clear. The objective is to investigate the impact of antiretrovirals in the time to the development of anal cancer in HIV-positive MSM. DESIGN: A retrospective analysis of cases of anal cancer in a cohort of HIV-positive MSM receiving antiretrovirals between 1988 and 2008. METHODS: Time from first CD4 cell count or HIV RNA viral load test to anal cancer diagnosis was analysed using Cox regression and Kaplan-Meier curves. Anal cancer cases treated in the era prior to HAART (<1996) were compared with those treated later (1996-2008). RESULTS: Anal cancer cases (n = 37) were compared with a cohort of 1654 HIV-positive MSM on antiretrovirals. Antiretrovirals were started in the pre-HAART era by 70% of cancer cases, and median CD4 cell count nadir was 70 cells/µl (10-130). Time to development of anal cancer was shorter for cases treated during the pre-HAART era [adjusted hazard ratio (AHR) 3.04, 95% confidence interval (95% CI) 1.48-6.24, P = 0.002], with a CD4 cell count nadir less than 100 cells/µl (AHR 2.21, 95% CI 1.06-4.62, P = 0.035) and longer duration of CD4 cell count less than 100 cells/µl (AHR 1.33, 95% CI 1.11-1.58, P = 0.002). CONCLUSION: Results show that severe immunosuppression and starting therapy pre-HAART are associated with an increased risk of anal cancer. HIV-positive MSM initiating antiretrovirals during the HAART era (1996-2008) had a longer time to the development of anal cancer than those treated pre-HAART. Our results suggest that early use of HAART may delay progression to anal cancer.

Cohort Profile: HAART Observational Medical Evaluation and Research (HOMER) cohort.

Since 1986, antiretroviral therapy (ART) has been available free of charge to individuals living with HIV in British Columbia (BC), Canada, through the BC Centre of Excellence in HIV/AIDS (BC-CfE) Drug Treatment Program (DTP). The Highly Active Antiretroviral Therapy (HAART) Observational Medical Evaluation and Research (HOMER) cohort was established in 1996 to maintain a prospective record of clinical measurements and medication profiles of a subset of DTP participants initiating HAART in BC. This unique cohort provides a comprehensive data source to investigate mortality, prognostic factors and treatment response among people living with HIV in BC from the inception of HAART. Currently over 5000 individuals are enrolled in the HOMER cohort. Data captured include socio-demographic characteristics (e.g. sex, age, ethnicity, health authority), clinical variables (e.g. CD4 cell count, plasma HIV viral load, AIDS-defining illness, hepatitis C co-infection, mortality) and treatment variables (e.g. HAART regimens, date of treatment initiation, treatment interruptions, adherence data, resistance testing). Research findings from the HOMER cohort have featured in numerous high-impact peer-reviewed journals. The HOMER cohort collaborates with other HIV cohorts on both national and international scales to answer complex HIV-specific research questions, and welcomes input from external investigators regarding potential research proposals or future collaborations. For further information please contact the principal investigator, Dr Robert Hogg (robert_hogg@sfu.ca).

Late initiation of combination antiretroviral therapy in Canada: a call for a national public health strategy to improve engagement in HIV care.

INTRODUCTION: Combination antiretroviral therapy (ART) significantly decreases morbidity, mortality and HIV transmission. We aimed to characterize the timing of ART initiation based on CD4 cell count from 2000 to 2012 and identify factors associated with late initiation of treatment. METHODS: Participants from the Canadian Observational Cohort (CANOC), a multi-site cohort of HIV-positive adults initiating ART naively after 1 January 2000, in three Canadian provinces (British Columbia, Ontario and Québec) were included. Late initiation was defined as a CD4 count <200 cells/mm(3) or an AIDS-defining illness before ART initiation (baseline). Temporal trends were assessed using the Cochran-Armitage test, and independent correlates of late initiation were identified using logistic regression. RESULTS: In total, 8942 participants (18% female) of median age 40 years (Q1-Q3 33-47) were included. The median baseline CD4 count increased from 190 cells/mm(3) (Q1-Q3 80-320) in 2000 to 360 cells/mm(3) (Q1-Q3 220-490) in 2012 (p<0.001). Overall, 4274 participants (48%) initiated ART with a CD4 count <200 cells/mm(3) or AIDS-defining illness. Late initiation was more common among women, non-MSM, older individuals, participants from Ontario and BC (vs. Québec), persons with injection drug use (IDU) history and individuals starting ART in earlier calendar years. In sub-analysis exploring recent (2008 to 2012) predictors using an updated CD4 criterion (<350 cells/mm(3)), IDU and residence in BC (vs. Québec) were no longer significant correlates of late initiation. CONCLUSIONS: This analysis documents increasing baseline CD4 counts over time among Canadians initiating ART. However, CD4 counts at ART initiation remain below contemporary treatment guidelines, highlighting the need for strategies to improve earlier engagement in HIV care.

Risk of cardiovascular disease associated with HCV and HBV coinfection among antiretroviral-treated HIV-infected individuals.

BACKGROUND: The increased risk for cardiovascular disease (CVD) in HIV is well established. Despite high prevalence of viral hepatitis coinfection with HIV, there are few studies on the risk of CVD amongst antiretroviral therapy (ART)-treated coinfected patients. METHODS: Ontario HIV Treatment Network Cohort Study participants who initiated ART without prior CVD events were analysed. HBV and HCV coinfection were identified by serology and RNA test results. CVD was defined as any of: coronary artery disease including atherosclerosis, chronic ischaemic heart disease and arteriosclerotic vascular disease; myocardial infarction; congestive heart failure; cerebrovascular accident or stroke; coronary bypass; angioplasty; and sudden cardiac death. The impact of HBV and HCV coinfection on time to CVD was assessed using multivariable competing risk models accounting for left truncation between ART initiation and study enrolment. RESULTS: A total of 3,416 HIV-monoinfected, 432 HIV-HBV- and 736 HIV-HCV-coinfected individuals were followed for a median (IQR) of 2.32 years (1.36-8.02). Over the study period, 167 CVD events and 613 deaths were documented. After adjustment for age, gender, race, year initiating ART, weight and smoking status, HBV was not associated with time to CVD onset (aHR=1.05, 95% CI [0.63, 1.74]; P=0.86). There was an elevated risk of CVD for HCV-coinfected individuals, which approached statistical significance (aHR=1.44, 95% CI [0.97, 2.13]; P=0.07). CONCLUSIONS: Our results are consistent with a moderate increase of CVD among individuals with HIV-HCV coinfection relative to those with HIV infection alone, lending support to consideration of initiation of HCV antiviral treatment.

Trends in plasma HIV-RNA suppression and antiretroviral resistance in British Columbia, 1997-2010.

OBJECTIVES: To examine temporal trends in plasma viral load (pVL) suppression and antiretroviral resistance from 1997 to 2010 in British Columbia (BC), Canada, and determine characteristics, pVL ranges, and resistance profiles of HIV-positive individuals with unsuppressed pVL in 2010. METHODS: HIV-positive individuals ≥19 years old in the provincial database at the BC Centre for Excellence in HIV/AIDS were included. Virological suppression was defined as 2 consecutive pVL <500 copies per milliliter within each calendar year. Temporal trends were evaluated using the Cochran-Armitage test. Persons with suppressed vs. unsuppressed pVL in 2010 were compared using the Pearson χ² or Fisher exact test (categorical variables) and the Wilcoxon rank-sum test (quantitative variables), including unsuppressed individuals only if they were on antiretroviral therapy (ART) in 2010 or their baseline CD4 count was <350 cells per cubic millimeter or <500 cells per cubic millimeter, in separate analyses. RESULTS: The proportion of individuals with suppressed pVL increased from 24% to 80% (P < 0.001). In comparative analyses, individuals with unsuppressed pVL (877 of 6142) were more likely to be female (30% vs. 16%), younger (median, 43 vs. 48 years), have injection drug use history (38% vs. 30%), report Aboriginal ancestry (30% vs. 16%), and have hepatitis C coinfection (57% vs. 34%) (all P < 0.001). Similar patterns were observed using the <500 cells per cubic millimeter CD4 cutoff. The median pVL of all unsuppressed individuals in 2010 was 12,896 copies per milliliter (interquartile range, 1495-47,763). CONCLUSIONS: The proportion of individuals achieving pVL suppression in BC has increased markedly since 1997; however, further efforts are needed to maximize the individual and societal benefits of modern antiretroviral therapy.

Significant differences in clinical outcomes between HIV-hepatitis C virus coinfected individuals with and without injection drug use history.

OBJECTIVE: Studies focusing on HIV-hepatitis C virus (HCV) coinfected individuals without a history of IDU are limited. It is plausible that poorer clinical outcomes in HIV-HCV coinfection are due to factors associated with IDU, not from HCV itself. This study compares HIV treatment outcomes and survival between HIV-HCV coinfected individuals with and without IDU history. DESIGN: Observational cohort study. METHODS: We analyzed data from a multisite Canadian cohort study of HIV-positive individuals initiating combination antiretroviral therapy (ART) after 1 January 2000. This analysis was restricted to 1254 participants with HCV coinfection and known IDU history. Cox proportional hazards regression was used to evaluate time from ART initiation to virologic suppression (two consecutive measures <250 copies/ml) and CD4 cell count recovery (+100 cells/µl). In order to account for loss to follow-up (LTFU), competing risk analysis was used to evaluate time to death. RESULTS: A total of 1254 participants (31% women) were included. During a median follow-up time of 3.8 years (interquartile range = 2.1-6.2), 217 deaths were reported and 148 participants were LTFU. In adjusted multivariable analysis, individuals with IDU history were significantly less likely to achieve virologic suppression [adjusted hazard ratio (AHR) = 0.78, 95% confidence interval (CI) = 0.64-0.95]; marginally less likely to have CD4 cell count recovery (AHR = 0.82, 95% CI = 0.66-1.00); and had a significantly higher risk of death (AHR = 2.15, 95% CI = 1.25-3.70). CONCLUSION: IDU history independently elevates risk for poorer clinical outcomes, separate from HCV coinfection. HIV-HCV coinfected persons are not homogeneous in characteristics or outcomes, suggesting care should be taken during statistical analyses if attributing poorer HIV-specific outcomes solely to HCV coinfection.

Factors associated with late initiation of highly active antiretroviral therapy among young HIV-positive men and women aged 18 to 29 years in Canada.

Initiating highly active antiretroviral therapy (HAART) with low CD4 counts or AIDS-defining illnesses (ADIs) increases risk of treatment failure and death. We examined factors associated with late initiation among 18- to 29-year-olds within the Canadian Observational Cohort (CANOC) collaboration, a multi-site study of HIV-positive persons who initiated HAART after 2000. Late initiation was defined as beginning HAART with a CD4 count <200 cells/mm(3) and/or having a baseline ADI. Multivariable logistic regression was used to identify independent correlates of late initiation. In total, 1026 individuals (422 from British Columbia, 400 from Ontario, and 204 from Quebec) met our age criteria. At HAART initiation, median age was 27 years (interquartile range, 24, 28 years). A total of 412 individuals (40%) identified as late initiators. Late initiation was associated with female gender, age >25 years at initiation, initiating treatment in earlier years, and having higher baseline viral load. The high number of young adults in our cohort starting HAART late indicates important target populations for specialized services, increased testing, and linkages to care.

Immunodeficiency at the start of combination antiretroviral therapy in low-, middle-, and high-income countries.

OBJECTIVE: To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries. METHODS: Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were adjusted for age, gender, and calendar year; missing CD4 counts were imputed. RESULTS: In total, 379,865 patients from 9 LIC, 4 LMIC, 4 UMIC, and 6 HIC were included. In LIC, the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/µL between 2002 and 2009. Corresponding increases in LMIC, UMIC, and HIC were from 87 to 155 cells/µL (76% increase), 88 to 135 cells/µL (53%), and 209 to 274 cells/µL (31%). In 2009, compared with LIC, median counts were 13 cells/µL [95% confidence interval (CI): -56 to +30] lower in LMIC, 22 cells/µL (-62 to +18) lower in UMIC, and 112 cells/µL (+75 to +149) higher in HIC. They were 23 cells/µL (95% CI: +18 to +28 cells/µL) higher in women than men. Median counts were 88 cells/µL (95% CI: +35 to +141 cells/µL) higher in countries with an estimated national cART coverage >80%, compared with countries with <40% coverage. CONCLUSIONS: Median CD4 cell counts at the start of cART increased 2000-2009 but remained below 200 cells/µL in LIC and MIC and below 300 cells/µL in HIC. Earlier start of cART will require substantial efforts and resources globally.

Adolescent experiences of HIV and sexual health communication with parents and caregivers in Soweto, South Africa.

Communication about sexual health between parents and adolescents has been shown to have a protective influence on behaviours that reduce the risk of HIV transmission. This study explored experiences of HIV and sexual health (HSH) communication between parents and/or caregivers and adolescents in an urban HIV-endemic community in Southern Africa. Adolescents (aged 14-19 years) were recruited from the Kganya Motsha Adolescent Centre and the Kliptown community between June and August 2009. Qualitative data were collected through focus group discussions (n=10 adolescents) and semi-structured interviews (n=31 adolescents). In total, 41 adolescents (56% female, 44% male, mean age=17.2) participated in the study. Adolescent participants identified emotional, physical and sociocultural barriers to initiating HSH communication with parents and caregivers including fear of verbal warnings, threats and physical assault. Adolescents also expressed a desire for mentorship around HSH communication beyond abstinence and peer-based information. Public health interventions need to support adolescents' access to bi-directional HSH information from adult mentors that address the lived realities of adolescents beyond expectations of abstinence.

Women-specific HIV/AIDS services: identifying and defining the components of holistic service delivery for women living with HIV/AIDS.

INTRODUCTION: The increasing proportion of women living with HIV has evoked calls for tailored services that respond to women's specific needs. The objective of this investigation was to explore the concept of women-specific HIV/AIDS services to identify and define what key elements underlie this approach to care. METHODS: A comprehensive review was conducted using online databases (CSA Social Service Abstracts, OvidSP, Proquest, Psycinfo, PubMed, CINAHL), augmented with a search for grey literature. In total, 84 articles were retrieved and 30 were included for a full review. Of these 30, 15 were specific to HIV/AIDS, 11 for mental health and addictions and four stemmed from other disciplines. RESULTS AND DISCUSSION: The review demonstrated the absence of a consensual definition of women-specific HIV/AIDS services in the literature. We distilled this concept into its defining features and 12 additional dimensions (1) creating an atmosphere of safety, respect and acceptance; (2) facilitating communication and interaction among peers; (3) involving women in the planning, delivery and evaluation of services; (4) providing self-determination opportunities; (5) providing tailored programming for women; (6) facilitating meaningful access to care through the provision of social and supportive services; (7) facilitating access to women-specific and culturally sensitive information; (8) considering family as the unit of intervention; (9) providing multidisciplinary integration and coordination of a comprehensive array of services; (10) meeting women "where they are"; (11) providing gender-, culture- and HIV-sensitive training to health and social care providers; and (12) conducting gendered HIV/AIDS research. CONCLUSIONS: This review highlights that the concept of women-specific HIV/AIDS services is a complex and multidimensional one that has been shaped by diverse theoretical perspectives. Further research is needed to better understand this emerging concept and ultimately assess the effectiveness of women-specific services on HIV-positive women's health outcomes.

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.

Gender differences in clinical outcomes among HIV-positive individuals on antiretroviral therapy in Canada: a multisite cohort study.

BACKGROUND: Cohort data examining differences by gender in clinical responses to combination antiretroviral therapy (ART) remain inconsistent and have yet to be explored in a multi-province Canadian setting. This study investigates gender differences by injection drug use (IDU) history in virologic responses to ART and mortality. METHODS: Data from the Canadian Observational Cohort (CANOC) collaboration, a multisite cohort study of HIV-positive individuals initiating ART after January 1, 2000, were included. This analysis was restricted to participants with a follow-up HIV-RNA plasma viral load measure and known IDU history. Weibull hazard regression evaluated time to virologic suppression (2 consecutive measures <50 copies/mL), rebound (>1000 copies/mL after suppression), and all-cause mortality. Sensitivity analyses explored the impact of presumed ART use in pregnancy on virologic outcomes. RESULTS: At baseline, women (1120 of 5442 participants) were younger (median 36 vs. 41 years) and more frequently reported IDU history (43.5% vs. 28.8%) (both p<0.001). Irrespective of IDU history, in adjusted multivariable analyses women were significantly less likely to virologically suppress after ART initiation and were at increased risk of viral load rebound. In adjusted time to death analysis, no differences by gender were noted. After adjusting for presumed ART use in pregnancy, observed gender differences in time to virologic suppression for non-IDU, and time to virologic rebound for IDU, became insignificant. CONCLUSIONS: HIV-positive women in CANOC are at heightened risk for poor clinical outcomes. Further understanding of the intersections between gender and other factors augmenting risk is needed to maximize the benefits of ART.