HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression

Richard T. Davey, Niranjan Bhat, Christian Yoder, Tae Wook Chun, Julia A. Metcalf, Robin Dewar, Ven Natarajan, Richard A. Lempicki, Joseph W. Adelsberger, Kirk D. Miller, Joseph A. Kovacs, Michael A. Polis, Robert E. Walker, Judith Falloon, Henry Masur, Dennis Gee, Michael Baseler, Dimiter S. Dimitrov, Anthony S. Fauci, H. Clifford Lane

Research output: Contribution to journalArticlepeer-review

Abstract

Identifying the immunologic and virologic consequences of discontinuing antiretroviral therapy in HIV-infected patients is of major importance in developing long-term treatment strategies for patients with HIV-1 infection. We designed a trial to characterize these parameters after interruption of highly active antiretroviral therapy (HAART) in patients who had maintained prolonged viral suppression on antiretroviral drugs. Eighteen patients with CD4+ T cell counts ≥ 350 cells/μl and viral load below the limits of detection for ≥1 year while on HAART were enrolled prospectively in a trial in which HAART was discontinued. Twelve of these patients had received prior IL-2 therapy and had low frequencies of resting, latently infected CD4 cells. Viral load relapse to >50 copies/ml occurred in all 18 patients independent of prior IL-2 treatment, beginning most commonly during weeks 2-3 after cessation of HAART. The mean relapse rate constant was 0.45 (0.20 log10 copies) day-1, which was very similar to the mean viral clearance rate constant after drug resumption of 0.35 (0.15 log10 copies) day-1 (P = 0.28). One patient experienced a relapse delay to week 7. All patients except one experienced a relapse burden to >5,000 RNA copies/ml. Ex vivo labeling with BrdUrd showed that CD4 and CD8 cell turnover increased after withdrawal of HAART and correlated with viral load whereas lymphocyte turnover decreased after reinitiation of drug treatment. Virologic relapse occurs rapidly in patients who discontinue suppressive drug therapy, even in patients with a markedly diminished pool of resting, latently infected CD4+ T cells.

Original languageEnglish (US)
Pages (from-to)15109-15114
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number26
DOIs
StatePublished - Dec 21 1999

Keywords

  • Antiretroviral drugs
  • CD4
  • HIV-1 infection
  • Relapse
  • Viral load

ASJC Scopus subject areas

  • General

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