FIRST- LINE ANTIRETROVIRAL TREATMENT FAILURE IN EAST AFRICAN CHILDREN.

Objectives: To describe the incidence of antiretroviral treatment failure and associated factors in a pediatric clinical cohort within the East African International epidemiology Databases to Evaluate AIDS (EA-IeDEA) consortium. Design: A retrospective cohort study. Clinical treatment failure was defined as advancement in clinical WHO stage, or CDC class at least 24 weeks after initiation of treatment. Immunological failure was defined as developing or returning to the following age-related immunological thresholds after at least 24 weeks on treatment; CD4 count of <200 or CD4%<10% for children aged 2-5 years and CD4 count of < 100 for a child aged > 5years. Setting: The study utilized the electronic medical records of HIV-infected pediatric patients enrolled into the EA-IeDEA consortium clinics from January 2005 to August 2012. Results: A total of 5927 children were included in the analysis. The estimated cumulative incidence of clinical ART treatment failure at one year and four years post ART initiation was11.5% and 31% respectively, while that of immunological treatment failure was at 3% and 22.5% respectively. The main factors associated with clinical failure were advanced clinical stage at ART-initiation, year started ART and residing in a rural area. Factors associated with immunological failure were male gender and age of the child at ART-initiation. Only 6% of those identified as having clinical treatment failure were switched to second line treatment during the four years of follow-up. Conclusion: The probability of clinical and immunologic failure was relatively high and increased with time.

Antiretroviral prophylaxis for HIV prevention in heterosexual men and women.

BACKGROUND: Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations. METHODS: We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1-seronegative partner in each couple was randomly assigned to one of three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly for up to 36 months. At enrollment, the HIV-1-seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services. RESULTS: We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF-FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1-seronegative partner was male. Among HIV-1-seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different (P=0.23), and both study medications significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline, and among these eight, antiretroviral resistance developed in two during the study. CONCLUSIONS: Oral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women. (Funded by the Bill and Melinda Gates Foundation; Partners PrEP ClinicalTrials.gov number, NCT00557245.).

Low correlation between household carbon monoxide and particulate matter concentrations from biomass-related pollution in three resource-poor settings.

Household air pollution from the burning of biomass fuels is recognized as the third greatest contributor to the global burden of disease. Incomplete combustion of biomass fuels releases a complex mixture of carbon monoxide (CO), particulate matter (PM) and other toxins into the household environment. Some investigators have used indoor CO concentrations as a reliable surrogate of indoor PM concentrations; however, the assumption that indoor CO concentration is a reasonable proxy of indoor PM concentration has been a subject of controversy. We sought to describe the relationship between indoor PM2.5 and CO concentrations in 128 households across three resource-poor settings in Peru, Nepal, and Kenya. We simultaneously collected minute-to-minute PM2.5 and CO concentrations within a meter of the open-fire stove for approximately 24h using the EasyLog-USB-CO data logger (Lascar Electronics, Erie, PA) and the personal DataRAM-1000AN (Thermo Fisher Scientific Inc., Waltham, MA), respectively. We also collected information regarding household construction characteristics, and cooking practices of the primary cook. Average 24h indoor PM2.5 and CO concentrations ranged between 615 and 1440 µg/m(3), and between 9.1 and 35.1 ppm, respectively. Minute-to-minute indoor PM2.5 concentrations were in a safe range (<25 µg/m(3)) between 17% and 65% of the time, and exceeded 1000 µg/m(3) between 8% and 21% of the time, whereas indoor CO concentrations were in a safe range (<7 ppm) between 46% and 79% of the time and exceeded 50 ppm between 4%, and 20% of the time. Overall correlations between indoor PM2.5 and CO concentrations were low to moderate (Spearman ρ between 0.59 and 0.83). There was also poor agreement and evidence of proportional bias between observed indoor PM2.5 concentrations vs. those estimated based on indoor CO concentrations, with greater discordance at lower concentrations. Our analysis does not support the notion that indoor CO concentration is a surrogate marker for indoor PM2.5 concentration across all settings. Both are important markers of household air pollution with different health and environmental implications and should therefore be independently measured.

Patient perceptions of facilitators and barriers to reducing hazardous alcohol use among people living with HIV in East Africa.

BACKGROUND: Hazardous alcohol use among people living with HIV is associated with poor outcomes and increased morbidity and mortality. Understanding the hazardous drinking experiences of people living with HIV is needed to reduce their alcohol use. METHODS: We conducted 60 interviews among people living with HIV in East Africa with hazardous drinking histories. Interviews and Alcohol Use Disorder Identification Test (AUDIT) scores were conducted 41 - 60 months after their baseline assessment of alcohol use to identify facilitators and barriers to reduced alcohol use over time. RESULTS: People living with HIV who stopped or reduced hazardous drinking were primarily motivated by their HIV condition and desire for longevity. Facilitators of reduced drinking included health care workers' recommendations to reduce drinking (despite little counseling and no referrals) and social support. In those continuing to drink at hazardous levels, barriers to reduced drinking were stress, social environment, alcohol accessibility and alcohol dependency. CONCLUSIONS: Interventions that capacity-build professional and lay health care workers with the skills and resources to decrease problematic alcohol use, along with alcohol cessation in peer support structures, should be explored.