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

Citation: Andrade A1, Rosenkranz SL, Cillo AR, Lu D, Daar ES, Jacobson JM, Lederman M, Acosta EP, Campbell T, Feinberg J, Flexner C, Mellors JW, Kuritzkes DR; AIDS Clinical Trials Group A5248 Team. Three distinct phases of HIV-1 RNA decay in treatment-naive patients receiving raltegravir-based antiretroviral therapy: ACTG A5248. J Infect Dis. 2013 Sep;208(6):884-91. doi: 10.1093/infdis/jit272. Epub 2013 Jun 24.

Access full article:

https://www.ncbi.nlm.nih.gov/pubmed/23801609

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.

Categories

CRS
Topics

Clinical Trials

HPTN 078: Enhancing Recruitment, Linkage to Care and...

The purpose of this study is to develop and assess the efficacy of an integrated strategy that includes feasible and scalable...

Read More

A5346: Sitagliptin for Reducing Inflammation and Immune...

The purpose of the study is to evaluate whether sitagliptin (Januvia is the brand name for sitagliptin)...

Read More

A5349: Rifapentine-containing treatment shortening regimens...

The purpose of this study is to determine whether one or two four-month regimens of tuberculosis treatment are as effective as a...

Read More

A5321: Decay of HIV-1 Reservoirs in Patients on Long-Term...

The study is being done to try to determine which factors contribute to the persistence of HIV (how long the virus remains) in...

Read More

A5342: Evaluating the Safety, Tolerability, and Effect of a...

The purpose of this study is to evaluate the safety, tolerability, and effect of an experimental human monoclonal antibody...

Read More