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

TitleThree distinct phases of HIV-1 RNA decay in treatment-naive patients receiving raltegravir-based antiretroviral therapy: ACTG A5248.
Publication TypeJournal Article
Year of Publication2013
AuthorsAndrade A, Rosenkranz SL, Cillo AR, Lu D, Daar ES, Jacobson JM, Lederman M, Acosta EP, Campbell T, Feinberg J, Flexner C, Mellors JW, Kuritzkes DR
Corporate AuthorsAIDS Clinical Trials Group A5248 Team
JournalJ Infect Dis
Volume208
Issue6
Pagination884-91
Date Published2013 Sep
ISSN1537-6613
KeywordsAdenine, Adult, Anti-HIV Agents, Benzoxazines, Female, HIV Infections, HIV-1, Humans, Lopinavir, Male, Middle Aged, Organophosphonates, Pilot Projects, Prospective Studies, Pyrrolidinones, Raltegravir Potassium, Ritonavir, RNA Stability, RNA, Viral, Tenofovir, Viral Load
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.

DOI10.1093/infdis/jit272
Alternate JournalJ. Infect. Dis.
PubMed ID23801609
PubMed Central IDPMC3749011
Grant ListAI069465 / AI / NIAID NIH HHS / United States
AI069472 / AI / NIAID NIH HHS / United States
AI069494 / AI / NIAID NIH HHS / United States
AI68634 / AI / NIAID NIH HHS / United States
AI69450 / AI / NIAID NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
RR025780 / RR / NCRR NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UL1 RR 025005 / RR / NCRR NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UM1 AI069494 / AI / NIAID NIH HHS / United States
UM1 AI069534 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States