We aimed to evaluate whether the HLA-G 14-base pair (bp) polymorphism (rs16375) has an impact on human immunodeficiency virus HIV progression and survival in an antiretroviral therapy-naive Zimbabwean cohort (n = 312). Rs16375 was genotyped using a competitive allele-specific polymerase chain reaction system; CD4 cell counts and HIV RNA were measured with flow cytometry and commercially available polymerase chain reaction; survival was followed up for 4.3 years. The homozygous HLA-G -14-bp genotype is associated with higher viral load (P = .004), lower CD4 cell count (P = .01), and increased mortality (hazard ratio, 1.9; 95% confidence interval, 1.033-3.522; P = .04) compared with HLA-G +14-bp carriers.