Effect of Human Immunodeficiency Virus Type 1 (H1V-1) Subtype on Disease Progression in Persons from Rakai, Uganda, with Incident HIV-1 Infection

Kiwanuka, Noah; Laeyendecker, Oliver; Robb, Merlin; Kigozi, Godfrey; Arroyo, Miguel; McCutchan, Francine; Eller, Leigh Anne; Eller, Michael; Makumbi, Fred; Birx, Deborah; Wabwire-Mangen, Fred; Serwadda, David; Sewankambo, Nelson K.; Quinn, Thomas C.; Wawer, Maria; Gray, Ronald
March 2008
Journal of Infectious Diseases;3/1/2008, Vol. 197 Issue 5, p707
Academic Journal
Background. Human immunodeficiency virus type 1 (HIV-1) subtypes differ in biological characteristics that may affect pathogenicity. Methods. We determined the HIV-1 subtype-specific rates of disease progression among 350 HIV-1 seroconverters. Subtype, viral load, and CD4+ cell count were determined. Cox proportional hazards regression modeling was used to estimate adjusted hazard ratios (HRs) of progression to acquired immunodeficiency syndrome (AIDS) (defined as a CD4+ cell count of ⩽250 cells/mm³) and to AIDS-associated death. Results. A total of 59.1% of study subjects had subtype D strains, 15.1% had subtype A, 21.1% had intersubtype recombinant subtypes, 4.3% had multiple subtypes, and 0.3% had subtype C. Of the 350 subjects, 129 (37%) progressed to AIDS, and 68 (19.5%) died of AIDS. The median time to AIDS onset was shorter for persons with subtype D (6.5 years), recombinant subtypes (5.6 years), or multiple subtypes (5.8 years), compared with persons with subtype A (8.0 years; P = .022). Relative to subtype A, adjusted HRs of progression to AIDS were 2.13 [95% confidence interval {CI}, 1.10-4.11] for subtype D, 2.16 [95% CI, 1.05-4.45] for recombinant subtypes, and 4.40 [95% CI, 1.71-11.31 for multiple subtypes. The risk of progression to death was significantly higher for subtype D (adjusted HR, 5.65; 95% CI, 1.37-23.4), recombinant subtypes (adjusted HR, 6.70; 95% CI, 1.56-28.8), and multiple subtypes (adjusted HR, 7.67; 95% CI, 1.27-46.3), compared with subtype A. Conclusions. HIV disease progression is affected by HIV-1 subtype. This finding may impact decisions on when to initiate antiretroviral therapy and may have implications for future trials of HIV-1 vaccines aimed at slowing disease progression.


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