Relationship Between HIV Coreceptor Tropism and Disease Progression in Persons With Untreated Chronic HIV Infection

Objective: To assess the effect of HIV coreceptor tropism (CRT) on the relative risk of progression to a composite outcome of CD4(+) Count <= 350 cells per microliter, treatment initiation, or death. Methods: CRT assays were performed after Study Closure in baseline samples obtained from enrollees in a prospectively monitored cohort of treatment-naive adults with >= 450 CD4(+) cells per microliter and >= 1000 HIV-1 RNA copies per milliliter. Results: Dual/mixed (D/M) and R5 CRT were detected in 32 and 282 patients, respectively. The baseline CD4(+) count (617 versus 694 cells/mu L-1 P = 0.05) differed in patients with D/M versus R5 CRT. Otherwise, baseline laboratory characteristics were similar. The relative risk of progression to the composite end point was 2.15 (P = 0.002) for D/M versus R5 CRT, 2.07 per 1.0 log(10) higher viral load (P < 0.001) and 0.87 per 50 cells per microliter higher CD4(+) cell count (P < 0.001). The effect of DIM CRT was also significant in separate analyses of time to initiation of antiretroviral therapy or CD4(+) cell count <= 350 cells per microliter. Conclusions: Untreated patients with D/M rather than R5 CRT had a faster rate of disease progression, whether assessed by a composite outcome of time to CD4(+) count <= 350 cells per microliter, treatment initiation, or death or by separate analyses of time to CD4(+) count <= 350 cells per microliter or treatment initiation.