Relationship between HIV coreceptor tropism and disease progression in persons with untreated chronic HIV infection

Abstract

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.

Figure 1

Rate of progression to composite endpoint of CD4⁺ ≤350, initiation of antiretroviral therapy or death for patients with R5 or D/M-tropic virus at baseline. Results are stratified for tertile of baseline CD4⁺ (≤ 547, 548–733 and ≥ 734 cells/μL).