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

Adriana Andrade, Jeremie Guedj, Susan L. Rosenkranz, Darlene Lu, John Mellors, Daniel R. Kuritzkes, Alan S. Perelson, Ruy M. Ribeiro

Research output: Contribution to journalArticlepeer-review

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 400mg twice daily and emtricitabine (200mg daily)/tenofovir disoproxil fumarate (300mg 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 19h 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.

Original languageEnglish (US)
Pages (from-to)2419-2426
Number of pages8
JournalAIDS
Volume29
Issue number18
DOIs
StatePublished - Nov 2015

Keywords

  • ACTG 5248 study
  • ACTG 5249 substudy
  • Emtricitabine
  • Integrase inhibitor
  • Mathematical model
  • Plasma HIV RNA
  • Raltegravir
  • Tenofovir disoproxil fumarate
  • Viral decay
  • Viral dynamics
  • Viral kinetics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Early HIV RNA decay during raltegravir-containing regimens exhibits two distinct subphases (1a and 1b)'. Together they form a unique fingerprint.

Cite this