Association of HIV-1 replication capacity with treatment outcomes in patients with virologic treatment failure

BACKGROUND: The extent to which HIV-1 replication capacity (RC) influences the response to therapy remains to be established. METHODS: Phenotypic susceptibility and RC of baseline isolates (n = 139) from patients enrolled in the ARGENTA trial were measured and correlated to treatment outcomes over 36 months. RESULTS: RC in baseline isolates correlated with the number of phenotypically active drugs (R = 0.34, P < 0.001). Crude viral RC did not predict treatment outcomes. When viral RC was adjusted by baseline CD4 cell counts, HIV-1 RNA levels, and phenotypic susceptibility to the rescue regimen, it showed significant association with the immunologic outcome (per log10 RC higher, mean difference in 36 months' time-averaged change from baseline CD4 count = -68 cells/microL; P = 0.020). In the subgroup of patients with 3 or more phenotypically active drugs in the salvage regimen (n = 35, median RC = 65%), subjects carrying isolates with RC < or =65% as compared to those with RC >65% had better time-averaged HIV-1 RNA responses (mean: -1.04 vs. -0.32 log10 copies/mL; P = 0.012) and CD4 cell responses (mean: 132 vs. -7 cells/microL; P = 0.006). Among patients with HIV-1 RNA levels persistently >500 copies/mL (n = 61), RC, on a log10 basis, was inversely associated with time-averaged 36-month CD4 cell responses (beta = -0.26; P = 0.046). CONCLUSION: After normalizing for viral susceptibility to the employed regimen or in patient subsets with suboptimal virologic response, higher viral RC may predict worse subsequent treatment outcomes.