Is there a higher risk of CNS adverse events for PI monotherapy versus triple therapy? A review of results from randomized clinical trials

HIV Clin Trials. 2014 May-Jun;15(3):79-86. doi: 10.1310/hct1503-79.

Abstract

Background: Protease inhibitor (PI) monotherapy for treatment could avoid the adverse events, drug resistance, and additional costs associated with other antiretrovirals that are normally used, particularly the nucleoside analogues. PI monotherapy has mainly been compared with standard triple therapy in randomized clinical trials of patients who have HIV RNA suppression at screening and no history of virological failure.

Methods: This review included 11 randomized clinical trials of darunavir/ritonavir (DRV/r) or lopinavir/ritonavir (LPV/r) monotherapy versus triple therapy in 1,267 patients with HIV RNA suppression at baseline who were studied between 48 and 144 weeks.

Results: There was no clear difference in the risk of central nervous system (CNS) adverse events between PI monotherapy (either DRV/r or LPV/r) and standard triple drug treatment. There were 2 clinical trials - MONOI (DRV/r) and MOST (LPV/r) - that showed CNS symptoms and detectable HIV RNA levels in the cerebrospinal fluid in a small number of individuals taking PI monotherapy.

Conclusions: There was no consistent evidence from the randomized trials currently available for an additional risk of HIV CNS disease during monotherapy with either LPV/r or DRV/r versus standard triple drug therapy. However, the information on CNS adverse events has not been reported using standardized definitions in the studies. In addition, few randomized studies included detailed analysis of neurocognitive function or detection of HIV RNA in the cerebrospinal fluid.

Keywords: HIV RNA; adverse events; central nervous system; cerebrospinal fluid; darunavir; lopinavir; nucleoside analogues.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Central Nervous System Diseases / chemically induced*
  • Cognition / drug effects
  • Drug Therapy, Combination
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / adverse effects
  • Humans
  • Lopinavir / adverse effects
  • RNA, Viral / blood
  • Randomized Controlled Trials as Topic*
  • Ritonavir / adverse effects

Substances

  • HIV Protease Inhibitors
  • RNA, Viral
  • Lopinavir
  • Ritonavir