Three distinct phases of HIV-1 RNA decay in treatment-naive patients receiving raltegravir-based antiretroviral therapy: ACTG A5248

Objective. The goal of this study was to define viral kinetics after initiation of raltegravir (RAL)-based antiretroviral therapy (ART).Methods. ART-naive patients received RAL, tenofovir disoproxil fumarate, and emtricitabine for 72 weeks. Human immunodeficiency virus type 1 (HIV-1) RNA were measured by ultrasensitive and single-copy assays, and first (d₁)-, second (d₂)-, and, third (d₃)-phase decay rates were estimated by mixed-effects models. Decay data were compared to historical estimates for efavirenz (EFV)-and ritonavir/lopinavir (LPV/r)-based regimens.Results. Bi-and tri-exponential models for ultrasensitive assay (n = 38) and single-copy assay (n = 8) data, respectively, provided the best fits over 8 and 72 weeks. The median d₁ with ultrasensitive data was 0.563/day (interquartile range [IQR], 0.501-0.610/day), significantly slower than d₁ for EFV-based regimens [P <. 001]). The median duration of d₁ was 15.1 days, transitioning to d₂ at an HIV-1 RNA of 91 copies/mL, indicating a longer duration of d₁ and a d₂ transition at lower viremia levels than with EFV. Median patient-specific decay estimates with the single-copy assay were 0.607/day (IQR, 0.582-0.653) for d₁, 0.070/day (IQR, 0.042-0.079) for d₂, and 0.0016/day (IQR, 0.0005-0.0022) for d₃; the median d₁ duration was 16.1 days, transitioning to d₂ at 69 copies/mL. d₃ transition occurred at 110 days, at 2.6 copies/mL, similar to values for LPV/r-based regimens.Conclusions. Models using single-copy assay data revealed 3 phases of decay with RAL-containing ART, with a longer duration of first-phase decay consistent with RAL-mediated blockade of productive infection from preintegration complexes.Clinical Trials Registration. NCT00660972.