Association of vitamin D with HIV infected individuals, TB infected individuals, and HIV-TB co-infected individuals: a systematic review and meta-analysis

Systematic review and meta-analysis of adults with HIV infection, active tuberculosis, or HIV-TB co-infection, drawing on cohort, cross-sectional, and randomized trials from multiple countries. The supplementation evidence came from 5 active vitamin D trials across HIV, TB, and HIV-TB populations.

Included randomized trials evaluated vitamin D supplementation in several regimens: cholecalciferol 100,000 IU at inclusion and again at 5 and 8 months in HIV-TB participants; 50,000 IU at randomization, 2000 IU at week 4, then once weekly in HIV participants; four doses of 2.5 mg at weeks 0, 2, 4, and 6 in one TB trial; ergocalciferol 5 mg on day 1, then 2.5 mg on day 28 and day 56 in another TB trial; and 60,000 IU weekly for 2 months, then fortnightly for 4 months, then monthly for 18 months in a TB trial.

Vitamin D supplementation did not show clear clinical benefit for HIV-, TB-, or HIV-TB-related outcomes. In HIV, CD4 count and HIV viral load did not improve significantly; in TB, time to sputum smear conversion, time to culture conversion, relapse, and death were not significantly different. In HIV-TB, mortality was not significantly reduced (OR 0.78; 95% CI 0.34-1.67; p = 0.52; I2 = 60%). Across the observational comparisons, vitamin D levels were not significantly different among HIV, TB, and HIV-TB groups, although vitamin D deficiency was more common in the HIV-TB group than in the HIV group.

The evidence base was heterogeneous, combining observational studies and randomized trials across different countries, populations, assays, and supplementation schedules. Several outcomes were inconsistently reported or not fully extractable at arm level, limiting quantitative synthesis. Some analyses were underpowered and showed moderate heterogeneity, including the mortality analysis in HIV-TB (I2 = 60%).