No treatment versus 24 or 60 weeks of antiretroviral treatment during primary HIV infection: the randomized Primo-SHM trial

PLoS Med. 2012;9(3):e1001196. doi: 10.1371/journal.pmed.1001196. Epub 2012 Mar 27.

Abstract

Background: The objective of this study was to assess the benefit of temporary combination antiretroviral therapy (cART) during primary HIV infection (PHI).

Methods and findings: Adult patients with laboratory evidence of PHI were recruited in 13 HIV treatment centers in the Netherlands and randomly assigned to receive no treatment or 24 or 60 wk of cART (allocation in a 1∶1∶1 ratio); if therapy was clinically indicated, participants were randomized over the two treatment arms (allocation in a 1∶1 ratio). Primary end points were (1) viral set point, defined as the plasma viral load 36 wk after randomization in the no treatment arm and 36 wk after treatment interruption in the treatment arms, and (2) the total time that patients were off therapy, defined as the time between randomization and start of cART in the no treatment arm, and the time between treatment interruption and restart of cART in the treatment arms. cART was (re)started in case of confirmed CD4 cell count < 350 cells/mm(3) or symptomatic HIV disease. In total, 173 participants were randomized. The modified intention-to-treat analysis comprised 168 patients: 115 were randomized over the three study arms, and 53 randomized over the two treatment arms. Of the 115 patients randomized over the three study arms, mean viral set point was 4.8 (standard deviation 0.6) log(10) copies/ml in the no treatment arm, and 4.0 (1.0) and 4.3 (0.9) log(10) copies/ml in the 24- and 60-wk treatment arms (between groups: p < 0.001). The median total time off therapy in the no treatment arm was 0.7 (95% CI 0.0-1.8) y compared to 3.0 (1.9-4.2) and 1.8 (0.5-3.0) y in the 24- and 60-wk treatment arms (log rank test, p < 0.001). In the adjusted Cox analysis, both 24 wk (hazard ratio 0.42 [95% CI 0.25-0.73]) and 60 wk of early treatment (hazard ratio 0.55 [0.32-0.95]) were associated with time to (re)start of cART.

Conclusions: In this trial, temporary cART during PHI was found to transiently lower the viral set point and defer the restart of cART during chronic HIV infection.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • Drug Administration Schedule
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • Humans
  • Male
  • Middle Aged
  • Viral Load

Substances

  • Anti-Retroviral Agents

Associated data

  • ISRCTN/ISRCTN59497461