Clinical Efficacy of Combination Therapy Based on Protease Inhibitors or the NNRTIs Nevirapine and Delavirdine: An Indirect Comparison

The aim of the current study was to compare the clinical efficacy of triple antiretroviral regimens based on protease inhibitors and non-nucleoside analogue reverse transcriptase inhibitors (NNRTIs) in adults positive for antibodies to HIV-1.

The investigators employed a systematic review and meta-analysis using indirect comparisons of clinical trials comparing three drug regimens based on two nucleoside reverse transcriptase inhibitors (NRTIs) and either a protease inhibitor or an NNRTI with two drug regimens (two NRTIs).

Participants had no previous exposure to protease inhibitors or NNRTIs. Data sources included Medline, the Cochrane controlled trials register, Aidstrials, Aidsdrugs, conference proceedings, and trial registers.

The main outcome measure was progression to AIDS or death.

Results

14 trials, totaling 6785 patients, were identified. Most patients had been exposed to an NRTI and had advanced immunodeficiency at baseline; 1096 progressed to AIDS or died.

Seven trials assessed protease inhibitors based triple regimens and seven assessed NNRTI-based triple regimens nevirapine [Viramune] or delavirdine [Resciptor]).

Triple therapy was more effective than dual therapy. The effect was pronounced for protease inhibitor-based regimens but non-significant for NNRTI-based regimens. Indirect comparison of the two regimens gave an odds ratio of 0.54 in favour of protease inhibitor-based treatments.

Increases in CD4 cell counts were smaller and suppression of viral replication less with NNRTI-based regimens.

According to the authors, “Indirect evidence shows that protease inhibitor-based triple regimens are superior to regimens based on the NNRTIs nevirapine and delavirdine in patients with advanced immunodeficiency who have been exposed to NRTIs. Large trials with clinical end points are required.”

Service Universitaire des Maladies Infectieuses et du Voyageur, Centre Hospitalier de Tourcoing, Faculte de Medecine de Lille, BP 619, F 59208 Tourcoing, France.

Editor’s Note: Interestingly, efavirenz (Sustiva)-based regimens were not evaluated in this study.

02/04/04