Effect of micronutrient supplementation on disease progression in asymptomatic, antiretroviral-naive, HIV-infected adults in Botswana: a randomized clinical trial.

IMPORTANCE: Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive. OBJECTIVE: To investigate whether long-term micronutrient supplementation is effective and safe in delaying disease progression when implemented early in adults infected with HIV subtype C who are ART-naive. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of supplementation with either daily multivitamins (B vitamins and vitamins C and E), selenium alone, or multivitamins with selenium vs placebo in a factorial design for 24 months. The study was conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/µL who were not receiving ART at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009. INTERVENTIONS: Daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo. MAIN OUTCOMES AND MEASURES: Reaching a CD4 cell count less than 200/µL until May 2008; after this date, reaching a CD4 cell count of 250/µL or less, consistent with the standard of care in Botswana for initiation of ART at the time of the study. RESULTS: There were 878 participants enrolled and randomized into the study. All participants were ART-naive throughout the study. In intent-to-treat analysis, participants receiving the combined supplement of multivitamins plus selenium had a significantly lower risk vs placebo of reaching CD4 cell count 250/µL or less (adjusted hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01; absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17 events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events). Multivitamins plus selenium in a single supplement, vs placebo, also reduced the risk of secondary events of combined outcomes for disease progression (CD4 cell count ≤250/µL, AIDS-defining conditions, or AIDS-related death, whichever occurred earlier [adjusted HR, 0.56; 95% CI, 0.33-0.95; P = .03; AER, 6.48/100 person-years; censoring rate, 0.90; 23 events]). There was no effect of supplementation on HIV viral load. Multivitamins alone and selenium supplementation alone were not statistically different from placebo for any end point. Reported adverse events were adjudicated as unlikely to be related to the intervention, and there were no notable differences in incidence of HIV-related and health-related events among study groups. CONCLUSIONS AND RELEVANCE: In ART-naive HIV-infected adults, 24-month supplementation with a single supplement containing multivitamins and selenium was safe and significantly reduced the risk of immune decline and morbidity. Micronutrient supplementation may be effective when started in the early stages of HIV disease.

Short Communication: Low False Recent Rate of Limiting Antigen-Avidity Assay Combined with HIV-1 RNA Data in Botswana.

Cross-sectional estimation of HIV incidence could misclassify some established or chronic HIV infections as recent. Usually long-term nonprogressors, elite and viremic controllers, and individuals on ART contribute to misclassification. Local data on the false recent rate (FRR) could minimize misclassification during estimation of HIV incidence. To improve monitoring of HIV incidence, we estimated local FRR in Botswana. A total of 1,036 specimens from individuals infected for at least 1.5-2 years were sampled between 2004 and 2009 and tested using the limiting antigen (LAg)-avidity assay using a cutoff of 1.5 normalized optical density units. The FRR was 0.97% (10/1,036; 95% confidence interval [CI] 0.46-1.77). Four samples had HIV-1 RNA >1,000 cps/ml, giving an adjusted FRR of 0.39% (4/1,036; 95% CI 0.11-0.99). A combination of LAg and HIV-1 RNA load data resulted in FRR below 1% in the Botswana population.

Recruitment, Follow-Up and Characteristics of HIV Infected Adults who Use Illicit Drugs in Southern Africa.

BACKGROUND: With one of the worst HIV prevalence rates in the world, Botswana has made great strides in addressing AIDS. Nevertheless, to fully contain the epidemic, outreach to marginalized groups, including illicit drug users, is critical. OBJECTIVE: To conduct targeted outreach within an intervention trial to recruit HIV-infected drug users and assess HIV disease and nutritional status. METHOD: Recruitment strategies included safeguarding confidentiality, involving ocal health-care professionals, advertising, and participation incentives. Urine toxicology, CD4 cell count, HIV viral load, blood chemistry, plasma micronutrients, dietary history, drug use and morbidity were assessed for two years. RESULTS: Targeted outreach identified 138 HIV-infected persons who used marijuana; 18.1% had CD4 cell counts ≤ 350 cells/µL and 39.9% had low BMI. Eligible marijuana users (N=52) had significantly lower BMI (21.8 3.7 vs. 24.3 ± 5.3 kg/m2, P=0.001), higher HIV viral load (4.36 ± 0.89 vs. 4.09 ± 0.89 log10, P=0.018), and higher kilocalorie intake (1924 ± 1055 vs. 1620 ± 926 Kcalories, P=0.025) than those who did not use marijuana (N=748) with similar CD4 cell count. Marijuana users ≥ 40 years old had more opportunistic diseases (P=0.020) than non-users of the same age. Benzodiazepine use was detected among 57 participants and they had higher BMI than marijuana users (24.4 ± 6.8 vs. 21.8 ± 3.7 kg/m2, P= 0.017). CONCLUSION: A population stigmatized by illicit drug use and HIV-infection can be brought into a clinical research setting in Africa. HIV-infected marijuana users were at a risk for higher HIV viral load, lower BMI and more comorbidities than nonusers. Outreach to this marginalized group is important for containing the HIV epidemic.