Journal article
Three Distinct Phases of HIV-1 RNA Decay in Treatment-Naive Patients Receiving Raltegravir-Based Antiretroviral Therapy: ACTG A5248
The Journal of infectious diseases, v 208(6), pp 884-891
24 Jun 2013
PMID: 23801609
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 (
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.
Clinical Trials Registration.
NCT00660972.
Metrics
Details
- Title
- Three Distinct Phases of HIV-1 RNA Decay in Treatment-Naive Patients Receiving Raltegravir-Based Antiretroviral Therapy: ACTG A5248
- Creators
- Adriana Andrade - Johns Hopkins UniversitySusan L. Rosenkranz - Harvard UniversityAnthony R. Cillo - 3University of Pittsburg Medical Center, PennsylvaniaDarlene Lu - Harvard UniversityEric S. Daar - The Lundquist InstituteJeffrey M. Jacobson - Drexel UniversityMichael Lederman - Case Western Reserve UniversityEdward P. Acosta - University of Alabama at BirminghamThomas Campbell - University of Colorado HospitalJudith Feinberg - University of CincinnatiCharles Flexner - Johns Hopkins UniversityJohn W. Mellors - 3University of Pittsburg Medical Center, PennsylvaniaDaniel R. Kuritzkes - Brigham and Women's HospitalAIDS Clinical Trials Grp A5248 Tea
- Publication Details
- The Journal of infectious diseases, v 208(6), pp 884-891
- Publisher
- Oxford University Press
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000324510200003
- Scopus ID
- 2-s2.0-84883206439
- Other Identifier
- 991019335322904721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology
- Infectious Diseases
- Microbiology