Person:

Sudfeld, Christopher

Background: There is growing evidence of an association between low vitamin D and HIV disease progression; however, no prospective studies have been conducted among adults receiving antiretroviral therapy (ART) in sub-Saharan Africa. Methods Serum 25-hydroxyvitamin D (25(OH)D) levels were assessed at ART initiation for a randomly selected cohort of HIV-infected adults enrolled in a trial of multivitamins (not including vitamin D) in Tanzania during 2006–2010. Participants were prospectively followed at monthly clinic visits for a median of 20.6 months. CD4 T-cell measurements were obtained every 4 months. Proportional hazard models were utilized for mortality analyses while generalized estimating equations were used for CD4 T-cell counts. Results: Serum 25(OH)D was measured in 1103 adults 9.2% were classified as vitamin D deficient (<20 ng/ml), 43.6% insufficient (20–30 ng/mL), and 47.2% as sufficient (>30 ng/mL). After multivariate adjustment, vitamin D deficiency was significantly associated with increased mortality as compared to vitamin D sufficiency (HR: 2.00; 95% CI: 1.19–3.37; p = 0.009), whereas no significant association was found for vitamin D insufficiency (HR: 1.24; 95% CI: 0.87–1.78; p = 0.24). No effect modification by ART regimen or change in the associations over time was detected. Vitamin D status was not associated with change in CD4 T-cell count after ART initiation. Conclusions: Deficient vitamin D levels may lead to increased mortality in individuals receiving ART and this relationship does not appear to be due to impaired CD4 T-cell reconstitution. Randomized controlled trials are needed to determine the safety and efficacy of vitamin D supplementation for individuals receiving ART.

Background: HIV-infected adults initiating antiretroviral therapy (ART) in sub-Saharan Africa continue to experience high rates of morbidity and mortality during the initial months of treatment. Observational studies in high-income and resource-limited settings indicate that HIV-infected adults with low vitamin D levels may be at increased risk of mortality, HIV disease progression, and incidence of pulmonary tuberculosis (TB). As a result, vitamin D3 supplementation may improve survival and treatment outcomes for HIV-infected adults initiating ART. Methods/Design The Trial of Vitamins-4 (ToV4) is an individually randomized, double-blind, placebo-controlled trial of vitamin D3 (cholecalciferol) supplementation conducted among 4000 HIV-infected adults with low vitamin D levels [25-hydroxyvitamin D (25(OH)D) <30 ng/mL] initiating ART in Dar es Salaam, Tanzania. The two primary aims of the trial are to determine the effect of a vitamin D3 supplementation regimen on incidence of (1) mortality and (2) pulmonary TB as compared to a matching placebo regimen. The primary safety outcome of the study is incident hypercalcemia. The investigational vitamin D3 regimen consists of oral supplements containing 50,000 IU vitamin D3 taken under direct observation at randomization and once a week for 3 weeks (four doses) followed by daily oral supplements containing 2000 IU vitamin D3 taken at home from the fourth week until trial discharge at 1 year post ART initiation. Trial participants are followed up at weekly clinic visits during the first month of ART and at monthly clinic visits thereafter until trial discharge at 1 year post ART initiation. Secondary aims of the trial are to examine the effect of the vitamin D3 regimen on CD4 T cell reconstitution, incidence of non-TB comorbidities, body mass index (BMI), depression and anxiety, physical activity, bone health, and immunologic biomarkers. Discussion The ToV4 will provide causal evidence on the effect of vitamin D3 supplementation on incidence of pulmonary TB and mortality among HIV-infected Tanzanian adults initiating ART. The trial will also give insight to whether vitamin D3 supplementation trials for the prevention of pulmonary TB should be pursued in HIV-uninfected populations. Trial registration ClinicalTrials.gov, NCT01798680. Registered on 21 February 2013. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1819-5) contains supplementary material, which is available to authorized users.

Objective

Selenium supplementation for HIV-infected women may increase genital shedding of HIV-1, but no studies have examined the effect on viral shedding in breast milk.

Research Methods and Procedures

HIV-infected pregnant women enrolled at 12–27 weeks gestation in a randomized, double-blind, placebo-controlled trial of daily selenium (200 μg as selenomethionine) had cell-free HIV-1 RNA quantified in breast milk at 4–9 weeks postpartum. All participants received high dose multivitamins containing vitamin B-complex, C, and E as standard of care.

Results

The proportion of women with detectable (>50 copies/mL) HIV-1 RNA in breast milk appeared to be increased in the selenium group (36.4%) as compared to the placebo (27.5%) among the total cohort (n=420), but results were borderline statistically significant (RR: 1.32; 95% CI: 1.00–1.76; p=0.05). In secondary analyses, the proportion of women with detectable HIV-1 RNA in breast milk was significantly greater in the selenium group (37.8%) as compared to placebo (27.5%) among women who did not receive HAART (RR: 1.37; 95% CI: 1.03–1.82; p=0.03). This relationship was primarily due to a significant effect of selenium among primiparous women (RR: 2.24; 95% CI: 1.30–3.86; p<0.01), but not multiparous women (RR: 1.14; 95% CI: 0.81–1.59; p=0.54) (p-value for interaction=0.02). Too few women received HAART in this study (n=12) to establish the effect of selenium supplementation.

Conclusions

Selenium supplementation appears to increase HIV-1 RNA detection in breast milk among primiparous women not receiving HAART. Safety studies among pregnant women on HAART need to be conducted before providing selenium containing supplements.