Methods: The effect of HIV-1 subtypes on HIV transmission and disease progression was investigated using data from community-based cohort studies in Rakai district, Uganda. HIV-1 subtype was determined by genomic sequencing of the gag and gp41 viral regions and by the Multi-region Hybridization Assay (MHA). HIV viral loads were determined by Roche Amplicor v1.5, and CD4+ T cell counts by BD Facscalibur system. Adjusted measures of association were estimated using Poisson regression model, linear mixed effects model, and Cox proportional hazards model.

Results: Adjusting for age, viral load, and genital ulcers (GUD), HIV transmission was higher for subtype A relative subtype D (Rate ratio, 1.98; 95% CI, 1.17 - 3.34). Age (<30 years) of the positive partner (RR, 3.98; 95%CI, 1.90 - 8.35), GUD (RR, 1.83; 95% CI, 1.16 - 2.89), and viral load (RR, 2.17; 95% CI, 1.60 - 2.94) were significant risk factors for HIV transmission. Regardless of subtype, the rate of CD4+ T cell loss (cells/µL per year) was -31.6 (95%CI; -44.6, -18.6), adjusted for age, baseline CD4 counts, and viral load. Adjusted rate of CD4+ cell loss was -8.8 (95%CI; -35.1, 17.4) for subtype A, -34.3 (95%CI; -64.0, -4.6) for R, -37.5 (95%CI; -54.1, -20.8) for subtype D, and -77.5 (95%CI; -136.6, -18.4) for M. The median time from seroconversion to AIDS was shorter for subtypes D, R and M (6.5, 5.6, and 5.8 years, respectively), compared with A (8.0 years; p =0.022). Relative to subtype A, adjusted hazard ratios (95% CI) of progression to AIDS were 2.13 (1.10 - 4.11) for subtype D, 2.16 (1.05 - 4.45) for recombinants, and 4.40 (1.71-11.3) for infection with multiple HIV strains.

Conclusions: In Rakai, subtype A has a higher rate of HIV transmission than subtype D or inter-subtype recombinants. However, subtype A has a slower rate of progression to AIDS compared to subtype D, recombinants, and multiple HIV strains. Determination of HIV-1 subtype may be important in trials of preventive and therapeutic HIV-1 vaccines and in the management of HIV infected individuals.