A randomized trial to study first-line combination therapy with or without a protease inhibitor in HIV-1-infected patients

• Published in: AIDS (London) Vol. 17; no. 7; pp. 987 - 999
• Main Authors: VAN LEEUWEN, Remko, KATLAMA, Christine, MORONI, Mauro, PAVIA, Andrew T, SCHMIDT, Reinhold E, GONZALEZ-LAHOZ, Juan, MONTANER, Julio, ANTUNES, Francisco, GULICK, Robert, BANHEGYI, Dénes, VAN DER VALK, Marc, REISS, Peter, MURPHY, Robert L, VAN WEERT, Liesbeth, VAN LETH, Frank, JOHNSON, Victoria A, SOMMADOSSI, Jean-Pierre, LANGE, Joep M. A, SQUIRES, Kathleen, GATELL, José, HORBAN, Andrej, CLOTET, Bonaventura, STASZEWSKI, Shlomo, VAN EEDEN, Arne, CLUMECK, Nathan
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 02-05-2003
• Subjects: Adolescent; Adult; Aged; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral Therapy, Highly Active; Antiviral agents; Biological and medical sciences; CD4 Lymphocyte Count; Female; HIV Infections - blood; HIV Infections - drug therapy; HIV Protease Inhibitors - adverse effects; HIV Protease Inhibitors - therapeutic use; HIV-1; Human viral diseases; Humans; Indinavir - adverse effects; Indinavir - therapeutic use; Infectious diseases; Lamivudine - adverse effects; Lamivudine - therapeutic use; Lipids - blood; Male; Medical sciences; Middle Aged; Nevirapine - adverse effects; Nevirapine - therapeutic use; Pharmacology. Drug treatments; Treatment Outcome; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Human; Immunopathology; Drug combination; Treatment efficiency; AIDS; Immune deficiency; Infection; Chemotherapy; Treatment; Viral disease; protease inhibitors; Antiviral; combination therapy; Therapeutic protocol; Atlantic; Comparative study; Protease inhibitor
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/00002030-200305020-00007

To compare one protease inhibitor (PI)-based and two PI-sparing antiretroviral therapy regimens.
International, open label, randomized study of antiretroviral drug-naive patients, with CD4 lymphocyte counts >/= 200 x 106 cells/l and plasma HIV-1 RNA levels > 500 copies/ml. Treatment assignment to stavudine and didanosine plus indinavir or nevirapine or lamivudine. Primary study endpoint was the percentage of patients with plasma HIV-1 RNA levels < 500 copies/ml after 48 weeks in the intention-to-treat analysis (ITT).
In total, 298 patients were enrolled. After 48 weeks, the percentage of patients in the indinavir, nevirapine and lamivudine arms with HIV-1 RNA < 500 copies/ml was 57.0%, 58.4% and 58.7%, respectively, in an ITT analysis. After 96 weeks of follow-up, these percentages were 50.0%, 59.6% and 45.0%, respectively. The percentage of patients with HIV-1 RNA < 50 copies/ml was significantly less for those allocated to lamivudine in an on-treatment analysis after 48 and 96 weeks of follow-up. Patients in the nevirapine arm experienced a smaller increase in the absolute number of CD4 T lymphocytes. There were no significant differences in the incidence of serious adverse events.
A comparable virological response can be achieved with first-line PI-base and PI-sparing regimens. The triple nucleoside regimen utilized may be less likely to result in viral suppression to < 50 copies/ml, while the nevirapine-based regimen is associated with a lower increase in CD4 T lymphocytes.