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

NWCS 445: Novel Biomarkers to Shorten TB Treatment

Objectives: Primary: To develop a highly predictive algorithm that identifies TB patients who will be cured by treatment...

Read More

A5308: A Prospective, Single-Arm, Open-Label Study to...

This study is being done with people who are infected with HIV, but do not show any signs of having HIV. They are also feeling...

Read More

A5288: MULTIOCTAVE, Management Using the Latest Technologies...

The study is being done to: test a strategy of using a resistance test to choose anti-HIV drugs. Resistance tests look at the...

Read More

A5274: REMEMBER, Reducing Early Mortality and Early...

This study is being done in people who are starting HIV treatment and who live in areas where the TB infection rate is high. The...

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