Vitamin A Supplementation and Genital Shedding of Herpes Simplex Virus among HIV‐1–Infected Women: A Randomized Clinical Trial

Department of Laboratory Medicine, University of Washington Seattle, Seattle, Washington, United States
The Journal of Infectious Diseases (Impact Factor: 6). 05/2004; 189(8):1466-71. DOI: 10.1086/383049
Source: PubMed


Cross-sectional analyses have associated vitamin A deficiency with genital shedding of herpes simplex virus (HSV) among human
immunodeficiency virus type 1 (HIV-1)-infected women. A randomized clinical trial of vitamin A supplementation given daily
for 6 weeks was conducted among 376 women in Mombasa, Kenya, who were coinfected with HSV-2 and HIV-1. At follow-up, there
was no significant difference in the detection of genital HSV DNA between women receiving vitamin A supplementation and women
receiving placebo (40% vs. 44%, respectively; P = .5) Among women shedding HSV, there was no significant difference in the mean HSV DNA quantity between the group that received
vitamin A supplementation and the group that received placebo (4.51 vs. 4.67 log10 copies/swab; P = .6). HSV shedding was associated with significantly higher vaginal and cervical HIV-1 shedding, even after controlling
for the plasma HIV-1 load and the CD4 count. Vitamin A supplementation is unlikely to decrease HSV shedding and infectivity.

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    • "HSV2, in turn, has a strong impact on HIV transmission and acquisition, and may also affect the natural history of HIV infection [3,5–10]. A meta-analysis of longitudinal studies found HSV2 seropositivity to be associated with a risk ratio of HIV acquisition of 2.7 (95% confidence interval (CI) = 1.9– 3.9) in men and 3.1 (95% CI = 1.7–5.6) in women [11] and most cross-sectional studies have found a correlation between HSV2 and frequency and/or quantity of HIV mucosal shedding [12] [13] [14]. HSV2 prevalence and the estimated proportion of HIV infections attributable to HSV2 (population attributable fraction, PAF) are very high in sub-Saharan Africa (Africa) and therefore HSV2 control could have a substantial population-level impact on the HIV epidemic © 2009 Elsevier Ltd. ⁎Corresponding author. "
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    ABSTRACT: Herpes simplex virus type-2 (HSV2) infection increases HIV transmission. We explore the impact of a potential prophylactic HSV2 vaccination on HIV incidence in Africa using STDSIM an individual-based model. A campaign that achieved 70% coverage over 5 years with a vaccine that reduced susceptibility to HSV2 acquisition and HSV2 reactivation by 75% for 10 years, reduced HIV incidence by 30-40% after 20 years (range 4-66%). Over 20 years, in most scenarios fewer than 100 vaccinations were required to avert one HIV infection. HSV2 vaccines could have a substantial impact on HIV incidence. Intensified efforts are needed to develop an effective HSV2 vaccine.
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    • "Sexual transmission of HIV-1 is suspected to be increased when HSV-2 is shed in the genital tract of dually HIV-1- and HSV-2-infected individuals [19,20]. HSV-2 may increase the infectiousness of HIV-infected subjects, by increasing genital HIV load during an HSV-2 genital recurrence [5-8] through the transactivation of HIV-1 LTR by interaction with HSV proteins (ICPO, ICP4) or the production of pro-inflammatory chemokines known to enhance HIV-1 replication [9,10]. The recruitment of activated CD4+ cells [12]that markedly upregulate HIV replication in HSV-infected lesions [13] may also account for the high titer of HIV in genital HSV lesions. "
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    ABSTRACT: Herpes simplex virus type 2 (HSV-2) is a major cofactor of human immunodeficiency virus type 1 (HIV-1) sexual acquisition and transmission. In the present study, we investigated whether HIV-1 and HSV-2 may interact at the cellular level by forming HIV-1 hybrid virions pseudotyped with HSV-2 envelope glycoproteins, as was previously reported for HSV type 1. We evaluated in vitro the production of HSV-2/HIV-1 pseudotypes in mononuclear CEM cells and epithelial HT29 and P4P cells. We analyzed the incorporation into the HIV-1 membrane of HSV-2 gB and gD, two major HSV-2 glycoproteins required for HSV-2 fusion with the cell membrane, in co-infected cells and in HIV-1-infected P4P cells transfected by plasmids coding for gB or gD. We show that HSV-2 and HIV-1 co-replicated in dually infected cells, and gB and gD were co-localized with gp160. However, HIV-1 particles, produced in HIV-1-infected cells expressing gB or gD after transfection or HSV-2 superinfection, did not incorporate either gB or gD in the viral membrane, and did not have the capacity to infect cells normally non-permissive for HIV-1, such as epithelial cells. Our results do not support the hypothesis of HSV-2/HIV-1 pseudotype formation and involvement in the synergistic genital interactions between HIV-1 and HSV-2.
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    ABSTRACT: Vitamin A supplementation to preschool children is known to decrease the risks of mortality and morbidity from some forms of diarrhea, measles, human immunodeficiency virus (HIV) infection, and malaria. These effects are likely to be the result of the actions of vitamin A on immunity. Some of the immunomodulatory mechanisms of vitamin A have been described in clinical trials and can be correlated with clinical outcomes of supplementation. The effects on morbidity from measles are related to enhanced antibody production and lymphocyte proliferation. Benefits for severe diarrhea could be attributable to the functions of vitamin A in sustaining the integrity of mucosal epithelia in the gut, whereas positive effects among HIV-infected children could also be related to increased T-cell lymphopoiesis. There is no conclusive evidence for a direct effect of vitamin A supplementation on cytokine production or lymphocyte activation. Under certain circumstances, vitamin A supplementation to infants has the potential to improve the antibody response to some vaccines, including tetanus and diphtheria toxoids and measles. There is limited research on the effects of vitamin A supplementation to adults and the elderly on their immune function; currently available data provide no consistent evidence for beneficial effects. Additional studies with these age groups are needed.
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