HIV-1 coreceptor use in triple-class treatment-experienced patients: baseline prevalence, correlates, and relationship to enfuvirtide response.

ABSTRACT

OBJECTIVE: We wished to assess, in heavily treatment-experienced patients, the prevalence of and baseline characteristics associated with HIV-1 coreceptor use and their relationship to responses to enfuvirtide treatment. METHODS: Samples were obtained from participants in phase 3 studies of enfuvirtide. Multiple logistic regression and analysis of covariance were performed on data for baseline coreceptor use, virological and immunological response, and changes in coreceptor use during treatment. RESULTS: Baseline envelopes were phenotyped for 724 patients; 50% harbored R5 strains, 48% harbored dual/mixed (D/M) strains, and 2% harbored X4 strains. D/M strains were associated with significantly lower CD4(+) cell counts but comparable viral loads, compared with R5 strains (P=.0005). Virological and immunological responses to enfuvirtide-based treatment showed no correlation with baseline coreceptor use. Changes in virus tropism from D/M to R5 strains during treatment were common, particularly in patients who received enfuvirtide (27%, vs. 14% who received no enfuvirtide; P<.05). CONCLUSION: At baseline, D/M strains were associated with lower CD4(+) cell counts but similar viral loads, compared with R5 strains, and were common across CD4(+) cell count strata. The comparable virological and immunological responses and bias toward shifts from D/M to R5 strains in patients who received enfuvirtide support its use in triple-class treatment-experienced patients and its study as a therapeutic partner for coreceptor-binding inhibitors.