Pre-Human Immunodeficiency Virus (HIV) α4β7hi CD4+ T Cells and HIV Risk Among Heterosexual Individuals in Africa.

BACKGROUND

CD4+ T cells expressing α4β7 are optimal targets for human immunodeficiency virus (HIV) infections, with higher pre-HIV α4β7hi expression linked to increased HIV acquisition and progression in South African women. However, similar associations were not observed in men who have sex with men or people who inject drugs in the Americas, indicating need for further research.

METHODS

This retrospective case-control study enrolled heterosexual men and women from South Africa (HIV Vaccine Trials Network [HVTN] 503) and East Africa (Partners Preexposure Prophylaxis/Couples' Observational Study [PP/COS]), quantifying α4β7 expression on CD4+ T cells as a predictor of subsequent HIV risk using flow cytometry analyses.

RESULTS

Associations between α4β7hi expression and HIV acquisition varied across cohorts. In HVTN 503, women had a higher risk estimate compared to men, but this was not significant. In PP/COS, α4β7hi expression was generally protective, particularly in Ugandans. Additionally, α4β7hi expression inversely correlated with peak viral load in PP/COS but not in HVTN 503; in the latter cohort, α4β7hi expression was inversely correlated with the CD4/CD8 ratio and predicted rapid CD4+ T-cell decline, similar to what was observed previously in South Africa.

CONCLUSIONS

These findings suggest that α4β7hi expression on CD4+ T cells may not predict HIV acquisition and progression in all contexts, which may be due to cohort effects, modes of transmission, viral clade, or other factors.