Lack of RH2 gene expression may have influenced the HIV pandemic in sub-Saharan Africa.

OBJECTIVE: To evaluate the association between the Rhesus system RH2-blood group expression and susceptibility to HIV infection, viral load, CD4+ cell count and rate of CD4+ decline. We also aimed to determine if a country's HIV prevalence may be predicted from its RH2 relative frequency. DESIGN: Our previous studies did not find any HIV-infected RH2 homozygotes. Therefore, the current cross-sectional study analysed a larger sample to determine whether HIV-infection also occurs in homozygotes. We also conducted a cross-sectional analysis of RH2 expression in an HIV natural history cohort in Botswana. Lastly, we analysed published data from 60 countries around the world to interrogate the link between RH2 frequency and HIV prevalence. METHODS: One thousand and six hundred anticoagulated blood samples (800 HIV-positive and 800 HIV-negative) were phenotyped for RH2 using serological methods. The proportion of RH2-positive samples was compared across categories of HIV status and odds ratios calculated. Mean viral load and CD4+ cell counts from a natural history cohort study were also compared across categories of RH2. Kaplan--Meier plots were generated for 4-year CD4+-decline to 350 cells/µl. RESULTS: No RH2 homozygotes were found among HIV-positives. Moreover, RH2-negatives were 1.37 times more likely to be HIV-positive than heterozygotes (P = 0.02) and 33 times more likely than RH2 homozygotes (P = 0.01). RH2-positive patients showed significantly higher mean CD4+ cell counts (P < 0.0001), lower viral load (P = 0.024) and slower CD4+ decline (P = 0.038). CONCLUSION: RH2 is potentially a critical host genetic factor determining susceptibility of any population to HIV infection, and probably transcends most other factors in importance for HIV risk of infection.