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HIV-1 Subtype D Infection Is Associated with Faster Disease Progression than Subtype A, in Spite of Similar HIV-1 Plasma Viral Loads
Jared Baeten*1, B Chohan1, L Lavreys1, V Chohan2, R McClelland1,2, R McClelland1,2, L Certain1, K Mandaliya3, W Jaoko2, and J Overbaugh4
1Univ of Washington, Seattle, US; 2Univ of Nairobi, Kenya; 3Coast Provincial Gen Hosp, Mombasa, Kenya; and 4Fred Hutchinson Cancer Res Ctr, Seattle, WA, US
Background: Whether strain differences in HIV-1, including differences
in subtype, influence HIV-1 disease progression remains debatable. While some studies
have found that individuals infected with non-A subtypes, particularly subtype
D, appeared to progress faster than those infected with subtype A, others have not shown significant differences. One
limitation of previous studies is that most included seroprevalent
cases of HIV-1, for whom the dates of HIV-1 acquisition were unknown. We
investigated the effect of HIV-1 subtype on disease progression among 145
Kenyan women followed from the time of HIV-1 infection.
Methods: We used data from a prospective cohort study of initially
HIV-1 seronegative commercial sex workers from Mombasa, Kenya,
in which women were followed monthly. Those who seroconverted
to HIV-1 and who had well-defined dates of HIV-1 infection were included in
this analysis. HIV-1 subtype was determined by heteroduplex
mobility assay or sequence analysis of the V1-V3 region of envelope. Linear
mixed-effects analyses were used to assess the effect of HIV-1 subtype on HIV-1
plasma viral load and CD4 count, and Cox proportional hazards analysis was used
to assess the effect of subtype on mortality.
Results: Of 145 women, 114
had subtype A (78%), 10 had subtype C (7%), and 21 had subtype D (14%). Women
were followed for a median of 5.4 years after HIV-1 acquisition. Of 30 women who
died, 20 were infected with subtype A, 3 with subtype C, and 7 with subtype D. Compared
with those with subtype A, women infected with subtype D had higher mortality
(hazard ratio 2.3, 95% confidence interval 1.0 to 5.6) and a faster rate of CD4
decline (p = 0.003). The mortality
risk persisted after adjustment for HIV-1 plasma viral load (for subtype D vs subtype A, adjusted hazard ratio 2.7, 95% confidence
interval 1.0 to 7.2). There were no statistically significant differences by
HIV-1 subtype in HIV-1 plasma viral load during follow-up.
Conclusions: Among this cohort of Kenyan women followed from
the time of HIV-1 acquisition, infection with HIV-1 subtype D was associated
with a faster rate of CD4 decline and a >2-fold higher risk of death than
with subtype A infection, in spite of similar HIV-1 plasma viral loads.
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