Background:  The appropriate clinical use of HIV co-receptor inhibitors may require an understanding of the prevalence of CCR5- vs CXCR4-tropic strains in different populations and their relationship to treatment response. Here we present analyses of baseline tropism and treatment response for 724 treatment-experienced patients participating in enfuvirtide (ENF) phase 3 studies.

Methods:  Patients were triple-class experienced with a median of 12 prior antiretrovirals; baseline median viral load was 5.2 log₁₀ copies/mL, and CD4 count was 88 cells/mm³. Envelopes were tested using the Monogram Biosciences PhenoSense entry assay for all patients receiving ENF + Optimized Background (OB) and for a matched subset of patients receiving OB alone. Summary statistics and multivariable regression analysis were used to analyze tropism; HIV-1 RNA and CD4 changes were calculated as least squares means.

Results:  Of 724 patients at baseline, virus was CCR5 (R5)-tropic for 361 (50%), dual or mixed (D/M) for 347 (48%), and CXCR4 (X4)-tropic for 16 (2%). Patients with D/M strains were most prevalent (55%) in low, and least prevalent (40%) in high CD4 strata (115 of 210 for CD4 <25 vs 73 of 181 for CD4 >200). Regression analysis of R5 vs D/M strains identified a strong correlation between D/M and lower CD4 cell counts (p <0.001), but no significant difference was found in number of prior ART drugs, baseline PSS, or prior use of lopinavir (LPV) (p >0.5). During ENF + OB treatment (n = 627), patients with R5 and D/M + X4 virus populations had similar viral load decreases (–1.54 and –1.43 log₁₀ copies/mL, respectively; p = 0.2871) and CD4 cell increases (+98 and +96 cells/mm³, respectively; p = 0.855). Changes in co-receptor tropism from baseline to viral failure occurred for 20% of patients receiving ENF +OB and 13% of patients receiving OB alone. Changes from D/M to R5 were most common and occurred more frequently among ENF + OB patients (14%) than patients receiving OB alone (6%, p = 0.043).

Conclusions:  D/M tropism was observed in nearly half of this triple-class-experienced population, including 40% of patients with baseline CD4 >200. Virologic and immunologic responses to treatment with ENF did not differ according to baseline virus tropism. At the population level, a shift from D/M to R5 tropism in ENF + OB patients was observed; further studies will be needed to determine whether this effect was lasting or transient and whether it related specifically to ENF or to other factors including a generalized treatment response.