Abstract
Cape Town, South Africa, has a seasonal pattern of UVB radiation and a predominantly dark-skinned urban population who suffer high HIV-1 prevalence. This coexistent environmental and phenotypic scenario puts residents at risk for vitamin D deficiency, which may potentiate HIV-1 disease progression. We conducted a longitudinal study in two ethnically distinct groups of healthy young adults in Cape Town, supplemented with vitamin D3 in winter, to determine whether vitamin D status modifies the response to HIV-1 infection and to identify the major determinants of vitamin D status (UVB exposure, diet, pigmentation, and genetics). Vitamin D deficiency was observed in the majority of subjects in winter and in a proportion of individuals in summer, was highly correlated with UVB exposure, and was associated with greater HIV-1 replication in peripheral blood cells. High-dosage oral vitamin D3 supplementation attenuated HIV-1 replication, increased circulating leukocytes, and reversed winter-associated anemia. Vitamin D3 therefore presents as a low-cost supplementation to improve HIV-associated immunity.
Highlights
Constitutive and facultative skin pigmentation regulates the penetration of UV radiation into the skin, because eumelanin competes with 7-DHC for UVB photons, controlling the availability of UVB for previtamin D3 production [4]
Each of these determinants is modified at a variety of levels: skin production by pigmentation, age, and the time, duration, and level of UVB exposure; dietary intake by vitamin D composition of foods; storage by body mass index (BMI) [7] and serum vitamin D-binding protein (DBP) [8]; and turnover by polymorphic variation in genes encoding metabolizing enzymes [cytochrome P450 (CYP) 2R1, CYP27B1, CYP24A1, 7-DHC reductase (DHCR7)], the vitamin D receptor (VDR) and DBP [9,10,11,12], age [13], infection [14, 15], serum calcium and parathyroid hormone concentrations [16], and smoking habit [17]
In an urban African location with seasonal UVB variability and high infectious disease prevalence, we found that personal UVB exposure habit is the most important determinant of vitamin D status in healthy adults with moderate to dark skin pigmentation
Summary
The Xhosa, who migrated as part of the geographic expansion of north and northwest African agriculturalists, are a significant proportion of the population Another major population group comprises people of self-identified Cape Mixed ancestry, who represent a complex admixture of Xhosa, Khoisan (the oldest inhabitants), European, South Asian, and Indonesian populations [18]. Given their exposure to seasonal UVB variation and high infectious disease risk, the peoples of the Cape are of particular importance in studying the determinants and immunological consequence of vitamin D status. We undertook a longitudinal study of healthy young adults in Cape Town to assess the relative contribution of pigmentation, seasonal UVB exposure, dietary vitamin D intake, Significance
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More From: Proceedings of the National Academy of Sciences of the United States of America
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