Micronutrient supplement increases vaginal shedding of HIV, finds study

Micronutrient supplementation increases the genital shedding of HIV in women, according to a study published in the December 15^th 2004 edition of the Journal of Acquired Immune Deficiency Syndromes. In particular, the study found that women with normal selenium levels at baseline were more likely to shed HIV in vaginal fluid after supplementation. The study’s investigators believe that their findings raise “challenging questions” about the benefits and risks of micronutrient use by HIV-positive individuals.

Studies have previously demonstrated an association between micronutrient deficiencies and HIV disease progression and mortality and the use of a cheap multivitamin and mineral pill has been shown to improve survival in HIV-positive people who do not have access to antiretroviral therapy.

Given the interest in the use of micronutrients by HIV-positive people, investigators wished to gain a better understanding of the effect of micronutrient supplementation on HIV infectivity. Accordingly they designed a double-blind, randomised, placebo controlled study with the primary objective of determining the effects of micronutrient supplementation on genital and cervical shedding of HIV. A secondary objective of the study was to determine the effect of micronutrients on immune function and viral load.

Between 1998 and 2000 women attending outpatient clinics in Mombasa, Kenya were offered voluntary HIV testing and counselling. Women aged between 18 and 45 years testing HIV-positive were given an opportunity to join this study. In total 400 women were enrolled to the study and were randomly allocated on an equal basis to receive micronutrients or a placebo.

At baseline and then after six weeks women provided a medical history, underwent a physical examination, provided blood samples and vaginal and cervical secretions were obtained. Blood samples were used to monitor CD4 cell count, HIV viral load, and levels of selenium. Vaginal and cervical secretions were analysed for the shedding of HIV.

In total, 179 women randomised to receive the micronutrients returned after six weeks, as did a comparable number of women who took the placebo. At baseline, women in the two arms of the study were broadly similar, however CD4 cell count was slightly higher amongst women randomised to receive micronutrients (294 cells/mm³ versus 262 cells/mm³). At baseline, women randomised to receive micronutrients had a higher prevalence of HIV-infected vaginal cells, but a lower prevalence of HIV-infected cells shed by the cervix.

After six weeks, vaginal shedding of HIV was significantly higher amongst women who received micronutrients than among women who received the placebo (p = 0.002). The quantity of HIV shed by women receiving micronutrients was also greater than that shed by women receiving the placebo (median 1250 copies/ml versus 800 copies/ml). However, there was no significant difference in the cervical shedding of HIV between the two arms of the study.

Investigators then adjusted their data for baseline differences between the two arms of the study. Even after these adjustments, micronutrient supplementation resulted in a 2.5-fold greater likelihood of detection of HIV-infected vaginal secretions (p = 0.001) than those obtained from women taking the placebo, and in a significantly higher vaginal HIV viral load than that seen in women randomised to take the placebo (p = 0.004).

The investigators then restricted their analysis to women who were not shedding HIV in their vaginal secretions at baseline. After six weeks, shedding was detected in 23% of women taking supplementation and 9% of women taking the placebo (p = 0.001).

It was theorised by the investigators that the effect of supplementation might vary according to women’s baseline nutritional status. The investigators found that amongst women who had normal selenium status at baseline, supplementation was associated with increased prevalence of HIV-infected cells shed by the vagina (p = 0.002) and with a higher viral load in vaginal secretions (p

Micronutrient supplementation significantly increased CD4 cell count (p = 0.03), CD8 cell count (p = 0.005), but did not affect HIV viral load (p = 0.8).

“Multivitamin plus selenium supplementation may increase HIV infectivity in women”, write the investigators. They conclude that their findings “raise challenging questions about the relative risk versus benefits of supplementation in HIV-positive women…with widespread use of nutritional supplements, even a modest increase in infectivity could have important public health benefits.”