16th International AIDS Conference Toronto, Canada - August 13 - 18, 2006

INFECTION WITH SUBTYPE C HIV-1 OF LOWER REPLICATIVE FITNESS AS COMPARED TO SUBTYPES A AND D LEADS TO SLOWER DISEASE PROGRESSION IN ZIMBABWEAN AND UGANDAN WOMEN

Int Conf AIDS. 2006 Aug 13-18;16 Abstract No. TuAa0204

E. Arts¹, K. Demers¹, I. Nankya², F. Kyeyune², P. Mugyenyi², T. Chipato³, N. Padian⁴, B. van der Pol⁵, C. Morrison⁶, R. Salata^1
1 Case Western Reserve University, Medicine, Cleveland, United States, ² Joint Clinical Research Centre, Kampala, Uganda, ³ University of Zimbabwe, Harare, Zimbabwe, ⁴ University of California, San Francisco, United States, ⁵ Indiana University-Purdue University, Indianapolis, United States, ⁶ Family Health International, Research Triangle, United States

BACKGROUND: HIV-1 subtype C and derived recombinant forms are responsible for 60% of infections worldwide. However, HIV-1 group M-C viruses are at least 100-fold less fit than any HIV-1 isolate of M-A, -B, -D, -F, CRF01_AE, CRF02_AG, and CRF12_BF. Replicative HIV-1 fitness is a significant, strong correlate of disease progression. Thus, we investigated if infection with less fit subtype C in Zimbabwe (ZIM) as compared to subtype A and D HIV-1 isolates in Uganda (UG) resulted in slower disease progression in a natural history cohort.

METHODS: Analyses were performed on a subset of blood and endocervical samples collected every 3 months following infection of 158 ZM and 98 UG women. CD4 cell counts were performed on whole blood and viral RNA load (VL) was measured in plasma and endocervical samples. HIV-1 isolates were propagated from blood of the enrollment visit and classified into subtypes. Replicative fitness was determined using a competitive dual infection assay in PBMCs.

RESULTS: Slope of CD4 cell decline per week (over a range of 12 to 51 months) was calculated for each patient and the mean revealed a significantly faster decline in the UG (–1.4380 ± 0.6952 cells/week; n=54) than in the ZIM (–0.6375 ± 0.2707; n=91) cohorts (p<0.008). These differences appeared related to subtype responsible for infection, i.e. A or D infections in UG as compared to subtype C in ZIM, but were not attributable to incidences of malaria or TB. VL in blood or endocervix was not different by country within the first year of infection. The subtype C HIV-1 isolates of ZIM women are at least 100-fold less fit than subtype A and D HIV-1 isolates infecting the UG women.

CONCLUSIONS: When compared to subtype A and D, reduced replicative fitness of subtype C may be linked to slower disease progression.

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2006-08-13
TuAa0204

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