High-dose vitamin D₃ reduces deficiency caused by low UVB exposure and limits HIV-1 replication in urban Southern Africans

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.