Resumen de Effect of Micronutrient Supplementation on Disease Progression in Asymptomatic, Antiretroviral-Naive, HIV-Infected Adults in Botswana: A Randomized Clinical Trial
Marianna K. Baum, Adriana Campa, Shenghan Lai, Sabrina Sales Martinez, Patricia Burns, Lesedi Tsalaile, Mansour Farahani, Yinghui Li, Erik Van Widenfelt, John Bryan Page, Hermann Bussmann, Wafaie W. Fawzi, Sikhulele Moyo, Joseph Makhema, Ibou Thior, Myron Essex, Richard Marlink
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/?L 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/?L until May 2008; after this date, reaching a CD4 cell count of 250/?L 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/?L 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/?L, 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.
Botswana, in sub-Saharan Africa, reports one of the highest rates of human immunodeficiency virus (HIV) infection in the world, with an estimated 23.4% of individuals aged 15 to 49 years having HIV infection in 2011.1 Moreover, HIV subtype C, the subtype most prevalent in Botswana, has been associated with more prolonged early viremia and a higher set point than other HIV subtypes, with more adverse health consequences.2,3 Amid discussion on when to initiate antiretroviral therapy (ART) in Africa, Botswana is one of the first resource-limited countries involved in a large-scale effort to provide ART.4 Persons with HIV infection who have a CD4 cell count of 350/?L or less have started receiving ART as of April 2012. Although most countries have provided ART to HIV-infected patients in the last decade, and the World Health Organization (WHO) has recently revised their treatment guidelines, many challenges remain in providing treatment in the early stages of the disease.4- 6 Alternative strategies to slow progression early in HIV disease and delay an appreciable number of individuals from developing AIDS in the near future would allow additional time to prepare health care systems in resource-limited countries and allot needed resources for timely HIV interventions.7 Micronutrient deficiencies, known to influence immune function, are prevalent even before the development of symptoms of HIV disease and are associated with accelerated HIV disease progression.8,9 Micronutrient supplementation has improved markers of HIV disease progression (CD4 cell count, HIV viral load) and mortality in clinical trials; however, these studies were conducted either in the late stages of HIV disease10- 12 or in pregnant women.13 To our knowledge, there are no studies testing the effect of long-term micronutrient supplementation in early stages of HIV disease in ART-naive adults.
The B vitamins, vitamins C and E, and the trace element selenium are essential nutrients necessary for maintaining a responsive immune system.14 Selenium may also have an important role in preventing HIV replication.9,15,16 The objective of this randomized, double-blind, placebo-controlled clinical trial was to determine whether specific supplemental micronutrients enhance the immune system and slow HIV disease progression during the early stages of the disease in ART-naive adults.
