Title: Early HIV RNA decay during raltegravir-containing regimens exhibits two distinct subphases (1a and 1b)

Abstract

Background: In this work, we analyzed the early kinetics with integrase inhibitor treatment to gain new insights into viral dynamics. Methodology: We analyzed data from 39 HIV-1 infected, treatment-naive, participants: 28 treated with raltegravir (RAL; multiple doses) monotherapy for 9 days, and 11 with RAL 400 mg twice daily and emtricitabine (200 mg daily)/tenofovir disoproxil fumarate (300 mg daily). Plasma HIV-1 RNA was measured frequently; the data was fitted using a mathematical model of viral dynamics distinguishing between infected cells with unintegrated HIV DNA and productively infected cells. Parameters were estimated using mixed-effect models. Results: RAL treatment led to a biphasic viral decline with a rapid first phase (1a) lasting approximately 5 days followed by a slower phase (1b). Phase 1a is attributed to the rapid elimination of productively infected cells. Phase 1b reflects the loss of infected cells with nonintegrated provirus due to cell loss and integration of HIV DNA. The half-lives of productively infected cells and of infected cells that had completed reverse transcription but had not yet integrated HIV DNA were approximately 19 h and between 3.6 and 5.8 days, respectively. The effectiveness of RAL in preventing proviral integration was 94% and 99.7%, for the combination therapymore » and monotherapy groups, respectively. Conclusion: We found that the first phase of viral decay with RAL therapy was composed of two subphases corresponding to the half-lives of infected cells with integrated proviruses and with unintegrated HIV-DNA.« less

Authors:

Andrade, Adriana ^[1]; Guedj, Jeremie ^[2]; Rosenkranz, Susan L. ^[3]; Lu, Darlene ^[3]; Mellors, John ^[4]; Kuritzkes, Daniel R. ^[5]; Perelson, Alan S.  ^[6];

• Search DOE PAGES for author "Perelson, Alan S."
• Search DOE PAGES for ORCID "0000-0002-2455-0002"

Ribeiro, Ruy Miguel  ^[6]

• Search DOE PAGES for author "Ribeiro, Ruy Miguel"
• Search DOE PAGES for ORCID "0000-0002-3988-8241"

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+ Show Author Affiliations

1. Johns Hopkins Univ., Baltimore, MD (United States)
2. University Paris-Diderot (France); National Centre for Scientific Research-Mixed Organizations (CNRS-UMR), Paris (France)
3. Harvard Univ., Boston, MA (United States)
4. Univ. of Pittsburgh, PA (United States)
5. Brigham and Women's Hospital (Harvard Medical School), Boston, MA (United States)
6. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

Publication Date:

Sat Nov 28 00:00:00 EST 2015

Research Org.:

Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Org.:

USDOE; National Institutes of Health (NIH)

OSTI Identifier:

1825425

Report Number(s):

LA-UR-14-29591
Journal ID: ISSN 0269-9370

Grant/Contract Number:  

89233218CNA000001; AC52-06NA25396; R01-AI104373; R01-AI028433; R01-OD011095; UM1 AI068636; UM1 AI068634

Resource Type:

Accepted Manuscript

Journal Name:

AIDS

Additional Journal Information:

Journal Volume: 29; Journal Issue: 18; Journal ID: ISSN 0269-9370

Publisher:

Wolters Kluwer Health, Inc.

Country of Publication:

United States

Language:

English

Subject:

60 APPLIED LIFE SCIENCES; Biological Science