Transmitted HIV-1 is more pathogenic in heterosexual individuals than homosexual men

Transmission bottlenecks introduce selection pressures on HIV-1 that vary substantially with the mode of transmission. Recent studies on small cohorts have suggested that stronger selection pressures lead to fitter transmitted/founder (T/F) strains. Manifestations of this selection bias at the population level have remained elusive. Here, we analysed early CD4 cell count measurements reported from ∼340,000 infected heterosexual individuals (HSX) and men-who-have-sex-with-men (MSM), across geographies, ethnicities and calendar years and found them to be consistently lower in HSX than MSM (P<0.05). The corresponding average reduction in CD4 counts relative to healthy adults was 86.5% in HSX and 67.8% in MSM (P<10 −4 ). This difference could not be attributed to differences in age, HIV-1 subtype, viral load, gender, ethnicity, time of transmission, or diagnosis delay across the groups. We concluded that the different selection pressures arising from the different predominant transmission modes have resulted in more pathogenic T/F strains in HSX than MSM.