Effect of HIV-1 subtypes on disease progression in rural Uganda: a prospective clinical cohort study.
OBJECTIVE
We examined the association of HIV-1 subtypes with disease progression based on three viral gene regions.


METHODS
A prospective HIV-1 clinical cohort study in rural Uganda.


METHODS
Partial gag, env and pol genes were sequenced. Cox proportional hazard regression modelling was used to estimate adjusted hazard ratios (aHRs) of progression to: CD4≤250, AIDS onset and death, adjusted for sex, age and CD4 count at enrolment.


RESULTS
Between 1990 and 2010, 292 incident cases were subtyped: 25% had subtype A, 45% had D, 26% had A/D recombinants, 1% had C and 4% were other recombinant forms. Of the 278 incident cases included in the disease progression analysis, 62% progressed to CD4≤250, 32% to AIDS, and 34% died with a higher proportion being among subtype D cases. The proportions of individuals progressing to the three endpoints were significantly higher among individuals infected with subtype D. Throughout the study period, individuals infected with subtype D progressed faster to CD4≤250, adjusted HR (aHR), (95% CI) = 1.72 (1.16-2.54), but this was mainly due to events in the period before antiretroviral therapy (ART) introduction, when individuals infected with subtype D significantly progressed faster to CD4≤250 than subtype A cases; aHR (95% CI) = 1.78 (1.01-3.14).


CONCLUSIONS
In this population, HIV-1 subtype D was the most prevalent and was associated with faster HIV-1 disease progression than subtype A. Further studies are needed to examine the effect of HIV-1 subtypes on disease progression in the ART period and their effect on the virological and immunological ART outcomes.
Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS, Entebbe, Uganda.
Deogratius
D
Ssemwanga
Rebecca N
RN
Nsubuga
Billy N
BN
Mayanja
Frederick
F
Lyagoba
Brian
B
Magambo
Dave
D
Yirrell
Lieve
L
Van der Paal
Heiner
H
Grosskurth
Pontiano
P
Kaleebu
D000293:Adolescent; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D011446:Prospective Studies; D012424:Rural Population; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load; D055815:Young Adult