The main finding of this study includes: a significant association of a low plasma 25 (OH)D3 level at baseline with TB-co-infection and HIV disease progression; efavirenz-based cART significantly reduces plasma 25 (OH)D3 levels and this effect is more pronounced when given alone than with rifampicin-based anti-TB therapy; low plasma cholesterol level, high CYP3A activity, and high plasma efavirenz concentration are predictors of early cART-induced low 25 (OH)D3 level. This evidence concerns the gene CYP3A4 and tuberculosis.