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 ĝ‰Currency sign350 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 ĝ‰¥450 CD4 cells per microliter and ĝ‰¥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/μL; 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 log10 higher viral load (P < 0.001) and 0.87 per 50 cells per microliter higher CD4 cell count (P < 0.001). The effect of D/M CRT was also significant in separate analyses of time to initiation of antiretroviral therapy or CD4 cell count ĝ‰Currency sign350 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 ĝ‰Currency sign350 cells per microliter, treatment initiation, or death or by separate analyses of time to CD4 count ĝ‰Currency sign350 cells per microliter or treatment initiation.