Introduction: Long-term natural history cohorts of HIV-1 in the absence of treatment provide the best measure of virulence by different viral subtypes. Methods: Newly HIV infected Ugandan and Zimbabwean women (N = 303) were recruited and monitored for clinical, social, behavioral, immunological and viral parameters for 3 to 9.5 years. Results: Ugandan and Zimbabwean women infected with HIV-1 subtype C had 2.5-fold slower rates of CD4 T-cell declines and higher frequencies of long-term non-progression than those infected with subtype A or D (GEE model, P A > C (P < 0.001, ANOVA). Discussion: HIV-1 subtype C was less virulent than either A or D in humans; the latter being the most virulent. Longer periods of asymptomatic HIV-1 subtype C could explain the continued expansion and dominance of subtype C in the global epidemic.
