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 antiretrolviral 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 (d(1))-, second (d(2))-, and, third (d(3))-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 d(1) with ultrasensitive data was 0.563/day (interquartile range [IQR], 0.501-0.610/day), significantly slower than d(1) for EFV-based regimens [P < .001]). The median duration of d(1). was 15.1 days, transitioning to d(2) at an HIV-1 RNA of 91 copies/mL, indicating a longer duration of d(1) and a d(2) 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 d(1), 0.070/day (IQR, 0.042-0.079) for d(2), and 0.0016/day (IQR, 0.0005-0.0022) for d(3); the median d(1) duration was 16.1 days, transitioning to d(2) at 69 copies/mL. d(3) 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.