Objective: To evaluate the association between the Rhesus system RH2-blood group
expression and susceptibility to HIV infection, viral load, CD4þ count and rate of CD4þ
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 crosssectional
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 HIVpositive
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 CD4þ counts from a natural history
cohort study were also compared across categories of RH2. Kaplan–Meier plots were
generated for 4-year CD4þ-decline to 350 cells/ml.
Results: No RH2 homozygotes were found among HIV-positives. Moreover, RH2-
negatives were 1.37 times more likely to be HIV-positive than heterozygotes (P¼0.02)
AQ6 and 33 times more likely than RH2 homozygotes (P¼0.01). RH2-positive subjects
showed significantly higher mean CD4þ counts (P < 0.0001), lower viral load
(P¼0.024) and slower CD4þ decline (P¼0.038).
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.

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