HIV-1 rebound during interruption of highly active antiretroviral therapy has no deleterious effect on reinitiated treatment. Comet Study Group.
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 T1/2 of 1.5 days, and during days 7-28 with T1/2 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 (T1/2 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.
Laboratoire d'Immunologie Cellulaire, URA CNRS 625, Paris, France.
A U
AU
Neumann
R
R
Tubiana
V
V
Calvez
C
C
Robert
T S
TS
Li
H
H
Agut
B
B
Autran
C
C
Katlama
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir