Effectiveness and safety of didanosine, lamivudine and efavirenz versus zidovudine, lamivudine and efavirenz for the initial treatment of HIV-infected patients from the Spanish VACH cohort

• Published in: Journal of antimicrobial chemotherapy Vol. 63; no. 1; pp. 189 - 196
• Main Authors: Crespo, Manuel, Ribera, Esteban, Suárez-Lozano, Ignacio, Domingo, Pere, Pedrol, Enric, López-Aldeguer, José, Muñoz, Agustín, Viladés, Consuelo, Sánchez, Trinitario, Viciana, Pompeyo, Teira, Ramón, García-Alcalde, María Luisa, Vergara, Antonio, Lozano, Fernándo, Galindo, María José, Cosin, Jaime, Roca, Bernardino, Terrón, Alberto, Geijo, Paloma, Vidal, Francesc, Garrido, Myriam
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.01.2009; Oxford Publishing Limited (England)
• Subjects: Adult; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Benzoxazines - administration & dosage; Benzoxazines - adverse effects; Benzoxazines - therapeutic use; Biological and medical sciences; Clinical trials; Cohort Studies; Comparative studies; Didanosine - administration & dosage; Didanosine - adverse effects; Didanosine - therapeutic use; Effectiveness; Female; HIV; HIV Infections - drug therapy; HIV-1 - drug effects; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Lamivudine - administration & dosage; Lamivudine - adverse effects; Lamivudine - therapeutic use; Male; Medical sciences; naive patients; nucleoside reverse transcriptase inhibitors; observational cohort study; once-a-day regimen; Patient safety; Pharmacology. Drug treatments; Prospective Studies; Spain; Treatment Outcome; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Europe; Spain; observational cohort study; nucleoside reverse transcriptase inhibitors; naive patients; once-a-day regimen; Purine nucleoside; Antiretroviral agent; Benzoxazine derivatives; RNA-directed DNA polymerase; Acetylenic compound; Toxicity; Non nucleoside compound; Efavirenz; Efficiency; Cohort study; Reverse transcriptase inhibitor; Nucleoside analog; Antiviral; Single daily dose; Nucleoside; Safety; Pyrimidine nucleoside; Public health; Human; Immunopathology; Enzyme; Transferases; Enzyme inhibitor; Lamivudine; Patient; AIDS; Immune deficiency; Infection; Allosteric inhibitor; Nucleotidyltransferases; Treatment; Dideoxynucleoside; Viral disease; Didanosine; Therapeutic protocol; Zidovudine; Comparative study
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkn450

Background Preliminary data suggest that a once-daily combination of lamivudine, didanosine and efavirenz is an effective alternative regimen for antiretroviral-naive HIV-1-infected patients. However, data from randomized trials comparing this combination versus standard first-line regimens are not available yet. In an observational study, we analyse the efficacy and tolerability of didanosine plus lamivudine and efavirenz versus zidovudine plus lamivudine and efavirenz in a cohort of therapy naive patients. Methods We performed an observational study on prospectively collected data from patients participating in a multicentre Spanish treatment-naive cohort (VACH cohort). Efficacy was assessed comparing time to therapeutic failure and CD4 cell recovery. Safety was analysed comparing the proportion of patients who discontinued therapy for toxicity or any other reason. Results Overall, 219 patients treated with once-daily didanosine/lamivudine/efavirenz and 409 patients receiving twice-daily zidovudine/lamivudine (Combivir®) plus efavirenz were evaluated. By intent-to treat analysis (non-completers and therapeutic change = failure), time to treatment failure was similar in both groups of treatment: 40.0 months (95% CI 23.3–56.8 months) among patients on didanosine/lamivudine/efavirenz and 33.3 months (95% CI 25.6–41.1 months) in patients treated with zidovudine/lamivudine/efavirenz (P = 0.253). The risk of failure due to treatment change was almost double among patients treated with zidovudine/lamivudine/efavirenz compared with those who received didanosine/lamivudine/efavirenz. Conclusions Our data suggest that didanosine/lamivudine/efavirenz is a combination with an efficacy comparable to zidovudine/lamivudine/efavirenz as first-line therapy for HIV infection. The risk of treatment change was significantly higher among patients treated with zidovudine/lamivudine/efavirenz than in those starting therapy with didanosine/lamivudine/efavirenz.