A randomized, controlled, trial of short cycle intermittent compared to continuous antiretroviral therapy for the treatment of HIV infection in Uganda

PLoS One. 2010 Apr 22;5(4):e10307. doi: 10.1371/journal.pone.0010307.

Abstract

Background: Short cycle treatment interruption could reduce toxicity and drug costs and contribute to further expansion of antiretroviral therapy (ART) programs.

Methods: A 72 week, non-inferiority trial enrolled one hundred forty six HIV positive persons receiving ART (CD4+ cell count > or =125 cells/mm(3) and HIV RNA plasma levels <50 copies/ml) in one of three arms: continuous, 7 days on/7 days off and 5 days on/2 days off treatment. Primary endpoint was ART treatment failure determined by plasma HIV RNA level, CD4+ cell count decrease, death attributed to study participation, or opportunistic infection.

Results: Following enrollment of 32 participants, the 7 days on/7 days off arm was closed because of a failure rate of 31%. Six of 52 (11.5%) participants in the 5 days on/2 days off arm failed. Five had virologic failure and one participant had immunologic failure. Eleven of 51 (21.6%) participants in the continuous treatment arm failed. Nine had virologic failure with 1 death (lactic acidosis) and 1 clinical failure (extra-pulmonary TB). The upper 97.5% confidence boundary for the difference between the percent of non-failures in the 5 days on/2 days off arm (88.5% non-failure) compared to continuous treatment (78.4% non failure) was 4.8% which is well within the preset non-inferiority margin of 15%. No significant difference was found in time to failure in the 2 study arms (p = 0.39).

Conclusions: Short cycle 5 days on/2 days off intermittent ART was at least as effective as continuous therapy.

Trial registration: ClinicalTrials.gov NCT00339456.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Anti-Retroviral Agents / administration & dosage*
  • CD4 Lymphocyte Count
  • Drug Administration Schedule
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / mortality
  • Humans
  • Male
  • Middle Aged
  • Opportunistic Infections
  • RNA, Viral / blood
  • Treatment Failure
  • Treatment Outcome
  • Uganda
  • Viral Load / drug effects
  • Viral Load / methods

Substances

  • Anti-Retroviral Agents
  • RNA, Viral

Associated data

  • ClinicalTrials.gov/NCT00339456