HIV replication capacity is an independent predictor of disease progression in persons with untreated chronic HIV infection.

OBJECTIVE: To assess the effect of pol replication capacity (RC) on the hazard ratio of progression to a composite endpoint of time to progression to <350 CD4+ cells per microliter, initiation of therapy, or death. METHODS: pol RC assays were performed after study closure in baseline samples obtained from 316 enrollees in a prospectively monitored cohort of treatment-naive adults with >or=450 CD4+ cells per microliter and >or=1000 HIV-1 RNA copies per milliliter. RESULTS: The median RC was 79%. Patients with a lower RC had a lower median viral load (4.0 vs 4.2 Log HIV-1 RNA copies/mL, P = 0.026) and a lower rate of protease inhibitor resistance 2% vs 8%, P = 0.03). Otherwise, baseline demographic and laboratory characteristics were similar. The hazard ratio of progression to the composite endpoint was 0.73 (P = 0.041) for persons with lower RC, 2.07 per 1.0 log10 higher viral load (P < 0.001), and 0.86 per 50 cells per microliter higher CD4+ cell count (P < 0.001). The effect of lower RC was also significant in a separate analysis of time to initiation of therapy (P = 0.04). CONCLUSIONS: These results show that untreated patients with lower vs higher RC had a slower rate of progression as assessed by a composite outcome of time to CD4+ count

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 < or =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 > or =450 CD4 cells per microliter and > or =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/microL; 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 < or =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 < or =350 cells per microliter, treatment initiation, or death or by separate analyses of time to CD4 count < or =350 cells per microliter or treatment initiation.