Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis

• Published in: PloS one Vol. 6; no. 7; p. e22003
• Main Authors: Mathis, Sandra, Khanlari, Bettina, Pulido, Federico, Schechter, Mauro, Negredo, Eugenia, Nelson, Mark, Vernazza, Pietro, Cahn, Pedro, Meynard, Jean-Luc, Arribas, Jose, Bucher, Heiner C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.07.2011; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Care and treatment; Clinical trials; Clinical Trials as Topic; DNA polymerases; Drug Therapy, Combination; Drugs; Failure analysis; Follow-Up Studies; Heterogeneity; Highly active antiretroviral therapy; HIV; HIV Infections - drug therapy; HIV Infections - virology; HIV patients; HIV Protease Inhibitors - therapeutic use; Human immunodeficiency virus; Humans; Inhibitors; Intention to Treat Analysis; Maintenance Chemotherapy; Medicine; Meta-analysis; Motivation; Patients; Protease; Protease inhibitors; Proteases; Randomization; Reintroduction; Risk; Risk Factors; Ritonavir; RNA-directed DNA polymerase; Side effects; Therapy; Treatment Outcome; Brazil; Rio de Janeiro Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0022003

The unparalleled success of combination antiretroviral therapy (cART) is based on the combination of three drugs from two classes. There is insufficient evidence whether simplification to ritonavir boosted protease inhibitor (PI/r) monotherapy in virologically suppressed HIV-infected patients is effective and safe to reduce cART side effects and costs. We systematically searched Medline, Embase, the Cochrane Library, conference proceedings and trial registries to identify all randomised controlled trials comparing PI/r monotherapy to cART in suppressed patients. We calculated in an intention to treat (loss-of follow-up, discontinuation of assigned drugs equals failure) and per-protocol analysis (exclusion of protocol violators following randomisation) and based on three different definitions for virological failure pooled risk ratios for remaining virologically suppressed. We identified 10 trials comparing 3 different PIs with cART based on a PI/r plus 2 reverse transcriptase inhibitors in 1189 patients. With the most conservative approach (viral load <50 copies/ml on two consecutive measurements), the risk ratios for viral suppression at 48 weeks of PI/r monotherapy compared to cART were in the ITT analysis 0.94 8 (95% CI 0.89 to 1.00) p = 0.06; risk difference -0.06 (95%CI -0.11 to 0) p = 0.05, p for heterogeneity  = 0.08, I(2) = 43.1%) and in the PP analysis 0.93 ((95%CI 0.90 to 0.97) p<0.001; risk difference -0.07 (95%CI -0.10 to -0.03) p<0.001, p for heterogeneity  = 0.44, I(2) = 0%). Reintroduction of cART in 44 patients with virological failure led in 93% to de-novo viral suppression. Virologically well suppressed HIV-infected patients have a lower chance to maintain viral suppression when switching from cART to PI/r monotherapy. Failing patients achieve high rates of de-novo viral suppression following reintroduction of reverse transcriptase inhibitors.