Dose-ranging, randomized, clinical trial of atazanavir with lamivudine and stavudine in antiretroviral-naive subjects 48-week results

• Published in: AIDS (London) Vol. 17; no. 18; pp. 2603 - 2614
• Main Authors: Murphy, Robert L, Sanne, Ian, Cahn, Pedro, Phanuphak, Praphan, Percival, Lisa, Kelleher, Thomas, Giordano, Michael
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 05.12.2003
• Subjects: Acidosis, Lactic - chemically induced; Adolescent; Adult; Aged; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral Therapy, Highly Active - methods; Antiviral agents; Atazanavir Sulfate; Biological and medical sciences; CD4 Lymphocyte Count; Cholesterol, LDL - blood; Disorders of blood lipids. Hyperlipoproteinemia; Female; HIV Infections - drug therapy; HIV Protease Inhibitors - adverse effects; HIV Protease Inhibitors - therapeutic use; HIV-1; Human immunodeficiency virus 1; Humans; Lamivudine - therapeutic use; Male; Medical sciences; Metabolic diseases; Middle Aged; Nelfinavir - adverse effects; Nelfinavir - therapeutic use; Oligopeptides - adverse effects; Oligopeptides - therapeutic use; Pharmacology. Drug treatments; Pyridines - adverse effects; Pyridines - therapeutic use; RNA, Viral - analysis; Stavudine - therapeutic use; Treatment Outcome; Triglycerides - blood; RNA; Cardiovascular disease; Vascular disease; Design; Efficiency; Immunological investigation; Reverse transcriptase inhibitor; T-Lymphocyte; Nelfinavir; highly active antiretroviral therapy; Intestinal disease; Antiviral; Hyperlipemia; Dyslipemia; Dose; Human; Enzyme inhibitor; Retroviridae; AIDS; Method; Lentivirus; Infection; Virus; Numeration; Peptidases; Nucleotidyltransferases; Chemotherapy; End; Nucleosidic analog; Human immunodeficiency virus; hyperlipidemia; RNA-directed DNA polymerase; HIV-1 virus; Lipids; Stavudine; protease inhibitors; Clinical trial; Pyrimidine nucleoside; Immunopathology; Drug combination; Atazanavir; Enzyme; Transferases; Metabolic diseases; Lamivudine; Immune deficiency; Dideoxynucleoside; Viral disease; Digestive diseases; Hydrolases; Protease inhibitor
• ISSN: 0269-9370
• DOI: 10.1097/00002030-200312050-00007

To compare the efficiency and safety of atazanavir and nelfinavir in antiretroviral-naive patients. Randomization to atazanavir 400 mg or 600 mg once daily; nelfinavir 1250 mg twice a day, plus lamivudine and stavudine. A blinded (to the atazanavir dose), 48-week trial in patients with HIV-1 RNA > or = 2000 copies/ml, CD4 cell count > or = 100 x 10(6) cells/l. Primary end-point: change in HIV-1 RNA from baseline at 48 weeks. Secondary end-point: subjects with HIV-1 RNA < 400, and < 50 copies/ml, CD4 cell count changes, adverse events. The 467 randomized subjects had comparable baseline characteristics across treatments. With atazanavir 400 mg, 600 mg and nelfinavir, respectively, mean changes in HIV-1 RNA (log10 copies/ml) from baseline to 48 weeks were -2.51, -2.58, -2.31; HIV-1 RNA < 400 copies/ml [intent-to-treat population (ITT), non-completion = failure (NC = F)], 64%, 67%, 53%; HIV-1 RNA < 50 copies/ml (ITT NC = F), 35%, 36%, 34%; mean CD4 cell count increased comparably at 48 weeks (234 x 10(6), 243 x 10(6), 211 x 10(6) cells/l). Adverse events were similar across treatments with the exception of diarrhea (more frequent with nelfinavir) and jaundice (more frequent with atazanavir). Mean changes from baseline to 48 weeks were: fasting low density lipoprotein cholesterol, +5.2%, +7.1% and +23.2% (at 56 weeks) and fasting triglycerides (48 weeks), +7.2%, +7.6% and +49.5%, in the atazanavir 400 mg, 600 mg, and nelfinavir groups, respectively (P < 0.01, atazanavir versus nelfinavir). Atazanavir is a potent, safe, well tolerated, and effective once-daily protease inhibitor with low pill burden (two capsules/day). Lipid changes with atazanavir were significantly less than with nelfinavir, however, clinical significance of these finding in terms of decreased cardiovascular risk is unknown.