Effect of human immunodeficiency virus Type 1 (HIV-1) subtype on disease progression in persons from Rakai, Uganda, with incident HIV-1 infection.
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 < or =250 cells/mm(3)) 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, 1.71-11.3] 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.
Kiwanuka
Noah
N
Uganda Virus Research Institute, Entebbe, Uganda. nkiwanuka@rhsp.org
Laeyendecker
Oliver
O
Robb
Merlin
M
Kigozi
Godfrey
G
Arroyo
Miguel
M
McCutchan
Francine
F
Eller
Leigh Anne
LA
Eller
Michael
M
Makumbi
Fred
F
Birx
Deborah
D
Wabwire-Mangen
Fred
F
Serwadda
David
D
Sewankambo
Nelson K
NK
Quinn
Thomas C
TC
Wawer
Maria
M
Gray
Ronald
R
D000328:Adult; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000145:classification / Q000401:mortality / Q000503:physiopathology*; D006679:HIV Seropositivity / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000472:pathogenicity*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load; D014774:Virulence