First-line antiretroviral therapy with efavirenz or lopinavir/ritonavir plus two nucleoside analogues: the SUSKA study, a non-randomized comparison from the VACH cohort

• Published in: Journal of antimicrobial chemotherapy Vol. 61; no. 6; pp. 1348 - 1358
• Main Authors: Domingo, Pere, Suárez-Lozano, Ignacio, Torres, Ferran, Teira, Ramón, Lopez-Aldeguer, José, Vidal, Francesc, Muñoz, Agustín, Viciana, Pompeyo, Lozano, Fernando, Vergara, Antonio, Roca, Bernadino, García Alcalde, Ma Luisa, Cosín, Jaime, Terrón, Alberto, Galindo, Ma José, Geijo, Paloma, Ribera, Esteban, Gonzalez, Juan, Sanchez, Trinitario, Lacalle, Juan Ramón, Garrido, Myriam
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.06.2008; Oxford Publishing Limited (England)
• Subjects: Adult; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Benzoxazines - adverse effects; Benzoxazines - therapeutic use; Biological and medical sciences; boosted protease inhibitors; CD4 Lymphocyte Count; Clinical outcomes; Comparative studies; Female; HIV; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - mortality; HIV Infections - virology; HIV-1 - isolation & purification; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Humans; Hypertriglyceridemia - chemically induced; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Kaplan-Meier Estimate; Longitudinal Studies; Lopinavir; Male; Medical sciences; naive patients; non-nucleoside reverse transcriptase inhibitors; observational study; Pharmacology. Drug treatments; Pyrimidinones - adverse effects; Pyrimidinones - therapeutic use; Regression analysis; Retrospective Studies; Ritonavir - adverse effects; Ritonavir - therapeutic use; RNA, Viral - blood; Survival analysis; Toxicity; Treatment Outcome; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Withholding Treatment; naive patients; boosted protease inhibitors; non-nucleoside reverse transcriptase inhibitors; observational study; Potentiation; Antiretroviral agent; Benzoxazine derivatives; RNA-directed DNA polymerase; Acetylenic compound; Ritonavir; Non nucleoside compound; Efavirenz; Randomization; Cohort study; Reverse transcriptase inhibitor; Nucleoside analog; Antiviral; Public health; Human; Immunopathology; Drug combination; Enzyme; Transferases; Lopinavir; Enzyme inhibitor; AIDS; Immune deficiency; First line treatment; Infection; Allosteric inhibitor; Peptidases; Nucleotidyltransferases; Viral disease; Hydrolases; Comparative study; Protease inhibitor
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkn121

Background Efavirenz and lopinavir/ritonavir are both recommended antiretroviral agents for combination first-line therapy, although information on direct comparisons between them is scarce. A retrospective longitudinal study from the VACH cohort comparing both regimens was performed. Methods Efficacy was examined comparing time to virological failure, CD4 recovery and clinical progression. Tolerability was examined comparing time to treatment discontinuation for any reason and for toxicity. Survival analysis was conducted using the Kaplan–Meier method, and standard and weighted Cox regression models. Results A total of 1550 antiretroviral-naive patients starting a two-nucleoside reverse transcriptase inhibitor regimen plus either efavirenz (n = 1159) or lopinavir/ritonavir (n = 391) were included in the study. At baseline, patients starting lopinavir/ritonavir had higher HIV-1 RNA and lower CD4+ cell counts. There was no difference in the adjusted hazards of virological failure [efavirenz versus lopinavir/ritonavir hazard ratio (HR) = 0.93, 95% confidence interval (CI): 0.77–1.12, P = 0.43], CD4 recovery (HR = 1.11, 95% CI: 0.95–1.30, P = 0.19) and clinical progression (HR = 0.71, 95% CI: 0.39–1.31, P = 0.27). There was an increased risk of discontinuation for any reason or for toxicity for lopinavir/ritonavir (HR = 2.10, 95% CI: 1.40–3.15, P = 0.0003). CD4 recovery with both drugs was also similar in the lowest CD4 strata. A higher risk of early hypertriglyceridaemia was associated with lopinavir/ritonavir-based regimens. Conclusions Our study suggests similar virological efficacy for efavirenz- or lopinavir/ritonavir-based first-line antiretroviral regimens, but an increased risk of discontinuation because of toxicity in case of lopinavir/ritonavir-based therapy. Immunological outcome appeared similar with both regimens.