Meta-analysis of randomized controlled trials of simplified versus continued protease inhibitor-based antiretroviral therapy in HIV-1-infected patients

AIDS. 2003 Nov 21;17(17):2451-9. doi: 10.1097/00002030-200311210-00007.

Abstract

Objective: To evaluate the efficacy and safety of simplified maintenance therapy (SMT) compared with continued protease inhibitor (PI) therapy.

Design: Meta-analysis of nine randomized controlled trials in which 833 patients were switched to SMT (abacavir, efavirenz or nevirapine) and 616 continued PI, assessing virologic failure (primary outcome), discontinuation of therapy for reasons other than virologic failure, CD4 cell count, total plasma cholesterol and triglycerides.

Results: The risk ratio for virologic failure for SMT compared to continued PI was 1.06 [95% confidence interval (CI) 0.58-1.92; test for homogeneity P = 0.01] for SMT, 2.56, (95% CI, 1.17-5.64) for abacavir, 0.83 (95% CI, 0.36-1.91) for efavirenz and 0.54 (95% CI, 0.29-1.02) for nevirapine. The risk ratio for premature discontinuation of therapy with SMT was 0.61 (95% CI, 0.48-0.77; test for homogeneity P < 0.10). The difference in absolute mean cholesterol for SMT compared to continued PI was -0.15 mmol/l, (95% CI, -0.40 to 0.09; test for homogeneity P < 0.01) for SMT, -0.51 mmol/l (95% CI, -0.70 to -0.33) for abacavir, 0.22 mmol/l (95% CI, 0 to 0.43) for efavirenz and -0.19 mmol/l (95% CI, -0.48 to 0.09) for nevirapine.

Conclusions: Current evidence suggests that SMT with abacavir rather than continued PI increases the risk of virologic failure, this increased risk may be confined to patients with prior mono or dual therapy with reverse transcriptase inhibitors. There is not enough evidence on whether SMT with efavirenz and nevirapine influences the risk of virologic failure. SMT with any of the three drugs reduces the risk of discontinuation of therapy, and SMT with abacavir reduces plasma cholesterol.

Publication types

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

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active*
  • CD4 Lymphocyte Count
  • Cholesterol / blood
  • Dideoxynucleosides / therapeutic use
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV-1*
  • Humans
  • Male
  • Odds Ratio
  • Protease Inhibitors / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Treatment Outcome
  • Triglycerides / blood

Substances

  • Anti-HIV Agents
  • Dideoxynucleosides
  • Protease Inhibitors
  • Reverse Transcriptase Inhibitors
  • Triglycerides
  • Cholesterol
  • abacavir