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

TitleEarly HIV RNA decay during raltegravir-containing regimens exhibits two distinct subphases (1a and 1b).
Publication TypeJournal Article
Year of Publication2015
AuthorsAndrade A, Guedj J, Rosenkranz SL, Lu D, Mellors J, Kuritzkes DR, Perelson AS, Ribeiro RM
Corporate AuthorsACTG A5249s protocol team
JournalAIDS
Volume29
Issue18
Pagination2419-26
Date Published2015 Nov 28
ISSN1473-5571
Abstract

BACKGROUND: 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 therapy 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.

DOI10.1097/QAD.0000000000000843
Alternate JournalAIDS
PubMed ID26558541
PubMed Central IDPMC4646723
Grant ListR01 AI028433 / AI / NIAID NIH HHS / United States
R01 AI104373 / AI / NIAID NIH HHS / United States
R01 OD011095 / OD / NIH HHS / United States
R01-AI028433 / AI / NIAID NIH HHS / United States
R01-AI104373 / AI / NIAID NIH HHS / United States
R01-OD011095 / OD / NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States