HIV-1 shedding in women: trial of vitamin A

Abstract

Vitamin A deficiency has been associated with increased vaginal shedding of HIV-1 infected cells among pregnant and non-pregnant HIV-1 infected women, as well as with increased mother-to-child HIV-1 transmission, suggesting that deficiency may increase infectivity of women with HIV-1. We conducted a randomized, double-blind, placebo-controlled trial of 6 weeks of daily oral vitamin A (10,000 IU retinyl palmitate) among 400 HIV-1 infected non-pregnant women in Mombasa, Kenya. The primary aim was to assess the effect of supplementation on vaginal shedding of HIV-1 and HIV-1 infected cells. At follow-up, we found no statistically significant difference in the prevalence of HIV-1 DNA (18% vs. 21%, p = 0.4) or the quantity of HIV-1 RNA (3.12 vs. 3.00 log10 copies/swab, p = 1.0) in vaginal secretions of women receiving vitamin A compared to women receiving placebo. No effect of supplementation on plasma HIV-1 viral load or CD4 or CD8 counts was observed, and no effect was seen among women who were vitamin A deficient at baseline.To better understand the disparity between the earlier observational studies and the results of our randomized trial, we conducted a cross-sectional study using data from the 400 HIV-1 infected trial participants as well as 200 HIV-1 uninfected women who did not participate in the randomized trial because of their HIV-1 status. The objective was to examine the relationships between vitamin A deficiency and HIV-1 status, HIV-1 disease stage, and the acute phase response. Vitamin A deficiency was independently associated with HIV-1 infection (OR 2.7, 95% CI 1.9--4.0) and the acute phase response (OR 2.8, 95% CI 1.9--4.1). Among HIV-1 infected women, vitamin A deficiency and the acute phase response were both independently associated with higher HIV-1 plasma viral load and lower CD4 count. After supplementation as part of the randomized trial, HIV-1 infected women having an acute phase response had no increase in serum vitamin A levels. Thus, among HIV-1 infected individuals, low serum vitamin A concentrations are associated with more active infection and the acute phase response, and may not reflect true deficiency.Our results suggest that vitamin A supplementation may be ineffective for treating or preventing HIV-1 infection.