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

Adriana Andrade, Susan L. Rosenkranz, Anthony R. Cillo, Darlene Lu, Eric S. Daar, Jeffrey M. Jacobson, Michael Lederman, Edward P. Acosta, Thomas Campbell, Judith Feinberg, Charles Flexner, John W. Mellors, Daniel R. Kuritzkes

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)884-891
Number of pages8
JournalJournal of Infectious Diseases
Volume208
Issue number6
DOIs
StatePublished - Sep 15 2013

Keywords

  • ACTG A5160s
  • ACTG A5166s
  • ACTG A5248
  • Roche ultrasensitive assay
  • raltegravir
  • single copy assay
  • viral decay

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Three distinct phases of HIV-1 RNA decay in treatment-naive patients receiving raltegravir-based antiretroviral therapy: ACTG A5248'. Together they form a unique fingerprint.

Cite this