Vitamin A supplementation does not reduce the genital shedding of herpes simplex virus-2 (HSV-2) in HIV-positive women, according to the results of a randomised placebo controlled trial published in the April 15th edition of the Journal of Infectious Diseases. The investigators also found genital shedding of HSV was strongly associated with the secretion of HIV in the genitals and recommend that aciclovir therapy should be provided as a way of preventing the transmission of both HSV and HIV.
Between 1998 and 2000, 376 HIV-positive women were recruited to a randomised, double blind, placebo controlled trial to determine the impact of vitamin A supplementation of the shedding of HSV-2. The investigators conducted this study after an earlier cross-sectional study showed a strong association between low serum concentrations of vitamin A and genital shedding of HSV-2 in HIV-positive women. Further, randomised placebo controlled trials have also shown that vitamin A supplementation can reduce the burden of infectious disease. In addition, HSV-2 has been shown in several studies to play an important role in facilitating transmission of HIV, therefore an intervention that decreases HSV-2 shedding could have the potential to reduce the transmission of both HSV-2 and HIV.
A total of 192 women were randomised to receive daily vitamin A supplementation at a dose of 10,000 IU per day, and 184 were randomised to receive a placebo. All the women were HIV-positive and infected with HSV-2, and were aged between 18 and 45 years. None of the women were pregnant, taking any other vitamin supplements, or taking oral contraceptives.
At baseline, the women in the two arms of the study had comparable CD4 cell counts and HIV viral loads. Furthermore, 44% of women enrolled in the study showed a high degree of immune damage with a CD4 cell count below 200 cells/mm3 (comparable across both arms), and 58% of individuals were vitamin A deficient (again, comparable in both arms).
Six weeks’ supply of study medication was provided, and 330 women (88%) returned for follow-up. The investigators found no significant difference in the prevalence of HSV-2 genital shedding between women receiving vitamin A supplementation and those receiving the placebo (40% versus 44%, p=0.5), nor did the quantity of HSV-2 shed differ between the two arms of the study, and there was no difference in the amount of HSV-2 related genital ulceration seen in the two arms (20 women in the supplementation arm, versus 19 women in the placebo arm, p=1.0).
Given the high rates of advanced immune suppression present in the study population, the investigators repeated their analysis, restricting it to individuals with a CD4 cell count above 200 cells/mm3. Once again they found that there was no difference in the prevalence of HSV-2 shedding (35% versus 34%), or in the amount of HSV-2 being shed (p=0.8). Further analysis excluded women taking DMPA or Norplant contraception, again with the same results.
The investigators did, however, find that women who shed HSV had higher HIV viral loads in both their plasma (p<0.001) and vaginal secretions (p=0.007) than women who were not shedding HSV-2. This association remained statistically significant after adjusting for CD4 cell count (p=0.001) and HIV viral load (p=0.04).
The investigators comment, “in this… randomised trial, we found that vitamin A supplementation had no statistically significant effect on the prevalence or quantity of HSV DNA shed in the genital tract of women coinfected with HSV-2 and HIV-1, even among women whose serum concentrations of vitamin A suggested vitamin A deficiency.” They add, “Supplementation with vitamin A is unlikely to be widely effective in reducing shedding and transmission of HSV.”
They also said that the association found in their earlier cross-sectional study of an association between vitamin A deficiency and shedding of HSV was spurious.
In conclusion, the investigators note that a strong correlation was found between the shedding of HIV and HSV in the genital tract and recommend that “interventions to decrease HSV reactivation, such as HSV suppressive therapy with aciclovir, should be pursued as potential strategies to decrease shedding and transmission of HIV.”
Further information on this website
Herpes simplex - overview
Herpes - factsheet
Baeten JM et al. Vitamin A supplementation and genital shedding of herpes simplex virus among HIV-infected women: a randomized controlled trial. Journal of Infectious Diseases, 189: 1466-1471, 2004.