HIV-1 rebound during interruption of highly active antiretroviral therapy has no deleterious effect on reinitiated treatment

Avidan U. Neumann, Roland Tubiana, Vincent Calvez, Catherine Robert, Tai Sheng Li, Henri Agut, Brigitte Autran, Christine Katlama

Research output: Contribution to journalArticlepeer-review

155 Scopus citations


Background: Potent antiretroviral therapy (ART) with a protease inhibitor-based regimen is commonly used to treat HIV-1-infected patients. Transient treatment interruptions because of drug intolerance or other reasons are not uncommon. HIV-1 dynamics during therapy interruption and its consequences for the subsequent reinitiation of therapy have not been properly studied. Methods: Ten antiretroviral-naive, HIV-1-infected subjects (mean baseline CD4 cell count of 414 cells/mm3 and plasma viral load of 4.8 log10 copies/ml) were treated with the triple drug ART regimen indinavir/zidovudine/lamivudine for 28 days. Therapy was then interrupted for 28 days, after which the same ART regimen was re-started. Results: HIV-1 in plasma declined during the first 7 days of therapy with T(1/2) of 1.5 days, and during days 7-28 with T(1/2) of 8.9 days. Once therapy was interrupted, a delay of 4-7 days was observed in all subjects, preceding a rapid viral rebound with a mean doubling time of 1.6 days. Mean viral load after 28 days of interruption was 96% of baseline. Upon reinitiation of the same ART regimen, viral load declined at rates similar to those observed during the initial therapy (T(1/2) of 1.6 and 8.0 days, respectively). No resistance-conferring mutations were observed in the HIV-1 reverse transcriptase (RT) and protease regions after the interruption of therapy. Plasma viral loads were maintained below 200 copies/ml in subjects continuing therapy for 4 (n = 9) to 12 (n = 5) months, with a mean CD4 cell count increase of 145 cells/mm3. Conclusions: The reintroduction of efficient ART therapy after a 1 month interruption shows viral kinetics similar to that of naive patients, and is not associated with the development of resistance. No deleterious effect on the reinitiated therapy was observed in patients who temporarily discontinued ART therapy. Nevertheless, because viral load rebounds back to baseline during treatment interruption, viral suppression is in effect put off by that period of time.

Original languageEnglish
Pages (from-to)677-683
Number of pages7
Issue number6
StatePublished - 16 Apr 1999
Externally publishedYes


  • Anti-HIV agents/therapeutic use
  • Biological models
  • CD4 lymphocyte count
  • HIV-1 infection/virology/drug therapy
  • HIV-1 viral dynamics
  • Regression analysis


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