A Short-Term Study of the Safety, Pharmacokinetics, and Efficacy of Ritonavir, an Inhibitor of HIV-1 Protease
Year: 1995
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: BACKGROUND: Reverse-transcriptase inhibitors have only moderate clinical efficacy against the human immunodeficiency virus type 1 (HIV-1). Ritonavir is an inhibitor of HIV-1 protease with potent in vitro anti-HIV properties and good oral bioavailability. METHODS: We evaluated the antiviral activity and safety of ritonavir in a double-blind, randomized, placebo-controlled phase 1 and 2 study of 84 HIV-positive patients with 50 or more CD4+ lymphocytes per cubic millimeter. The patients were randomly assigned to one of four regimens of ritonavir therapy, or to placebo for four weeks and then (by random assignment) to one of the ritonavir regimens. RESULTS: During the first 4 weeks, increases in CD4+ lymphocyte counts and reductions in the log number of copies of HIV-1 RNA per milliliter of plasma were similar among the four dosage groups, but in the three lower-dosage groups there was a return to base-line levels by 16 weeks. After 32 weeks, in the seven patients in the highest-dosage group (600 mg of ritonavir every 12 hours), the median increase from base line in the CD4+ lymphocyte count was 230 cells per cubic millimeter, and the mean decrease in the plasma concentration of HIV-1 RNA (as measured by a branched-DNA assay) was 0.81 log (95 percent confidence interval, 0.40 to 1.22). In a subgroup of 17 patients in the two higher-dosage groups, RNA was also measured with an assay based on the polymerase chain reaction, and after eight weeks of treatment there was a mean maximal decrease in viral RNA of 1.94 log (95 percent confidence interval, 1.37 to 2.51). Adverse events included nausea, circumoral paresthesia, elevated hepatic aminotransferase levels, and elevated triglyceride levels. Ten withdrawals from the study were judged to be related to ritonavir treatment. CONCLUSIONS: In this short-term study, ritonavir was well tolerated and had potent activity against HIV-1, but its clinical benefits remain to be established.
Source: New England Journal of Medicine
Authors: Sven A. Danner, Andrew Carr, John M. Leonard, Leah M. Lehman, Francesc Gudiol, Juan Gonzales, Antonio Raventos, Rafael Rubio, Emilio Bouza, Vicente Pintado, Antonio Gil Aguado, Juan Garcia de Lomas, Rafael Delgado, Jan C.C. Borleffs, Ann Hsu, Joaquin M. Valdes, Charles A.B. Boucher, David A. Cooper
Institutions: Amsterdam UMC Location University of Amsterdam, St Vincent's Hospital Sydney, Bellvitge University Hospital, Hospital Universitario La Paz, Hospital Universitari Germans Trias i Pujol, Hospital Universitario 12 De Octubre, Hospital General Universitario Gregorio Marañón, Hospital Universitario Ramón y Cajal, Hospital Clínico Universitario de Valencia, University Medical Center Utrecht
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2339057709