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The Influence of Vitamin A and Hormonal Contraception on HIV Transmission and Disease Progression in Women
J M Baeten*1, J K Kreiss, L Lavreys, R S McClelland, M Sagar, H M Martin, B A Richardson, B Chohan, D Panteleeff, S Emery, K Mandaliya, J O Ndinya-Achola, J J Bwayo, J Overbaugh
1Univ of Washington, Seattle; 2Fred Hutchinson Cancer Res Ctr, Seattle, WA; 3Univ of Nairobi, Kenya; 4Coast Provincial Gen Hosp, Mombasa, Kenya
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Background: Identification of modifiable factors that impact HIV-1 transmission and disease progression is needed, especially for resource-poor settings where options for treatment and prevention of HIV-1 are limited. Vitamin A deficiency and hormonal contraceptive use are common among women in developing countries, and studies have suggested that both factors may influence the natural history of HIV-1.
Methods: Since 1993, we have conducted studies of HIV-1 infectivity and natural history among HIV-1 infected and at-risk women in Mombasa, Kenya. The role of vitamin A deficiency in HIV-1 disease was assessed in a randomized clinical trial of daily oral vitamin A supplementation among 400 HIV-1 seropositive women. The effect of hormonal contraceptive use on HIV-1 natural history was examined in a prospective cohort study of ~1500 prostitutes followed from prior to HIV-1 acquisition. A total of 161 women who became infected with HIV-1 and whose date of infection could be accurately estimated were followed for a median of 34 months after the time of infection. For these studies, we used HIV-1 PCR of genital tract samples as a marker of infectivity, and HIV-1 plasma viral load and CD4 count as surrogates for disease progression. We also determined viral diversity in HIV-1 envelope sequences present during primary infection.
Results: In the vitamin A trial, there was no 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, and no effect of supplementation on plasma HIV-1 viral load or CD4 counts was observed. Further analysis suggested low vitamin A levels reflect more active HIV-1 infection and an acute phase response rather than true deficiency. In the longitudinal prostitute cohort, the use of oral contraceptive pills or the injectable contraceptive depot medroxyprogesterone acetate (DMPA) was associated with increased risk of HIV-1 acquisition. Among women who became infected with HIV-1, DMPA use at time of infection was associated with higher set point plasma viral load (+ 0.33 log10 copies/ml, p = 0.03). Multiple viral variants were detected in 57% of these women and were more common among those who used hormonal contraception at the time of HIV-1 acquisition (OR 2.7, p = 0.003). Viral diversity was associated with more rapid CD4 decline.
Conclusions: Vitamin A supplementation is unlikely to decrease the infectivity of women infected with HIV-1 or impact disease progression. The use of hormonal contraception may be associated with increased risk of HIV-1 infection, acquisition of a more complex virus population, higher HIV-1 plasma viral load, and faster disease progression.
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