Twenty patients were enrolled in a phase I clinical trial of atevirdine, a nonnucleoside reverse transcriptase inhibitor (NNRTI), given in combination with zidovudine for treatment of human immunodeficiency virus type 1 (HIV-1) infection. Fifteen patients had received no previous antiretroviral therapy. HIV-1 isolates obtained at 6-week intervals were tested for sensitivity to atevirdine and zidovudine. Two patients developed a rash within 2 weeks of enrollment, and 1 of these developed concomitant fever and hepatitis. No hematopoietic, neurologic, or pancreatic toxicities were observed. Atevirdine had considerable initial interpatient pharmacokinetic variability. Forty-seven percent of patients treated with atevirdine plus zidovudine had increased CD4 lymphocyte counts, and HIV isolates from 62% of patients remained sensitive to atevirdine after 24 weeks of therapy. Atevirdine plus zidovudine was well-tolerated. Additional studies should be done to determine the role of atevirdine in the therapy for HIV infection.
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Concentration-targeted phase I trials of atevirdine mesylate in patients with HIV infection: dosage requirements and pharmacokinetic studies. The ACTG 187 and 199 study teams.
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January 2000
Department of Pharmacy, State University of New York at Buffalo, Amherst 14260, USA.
Rationale: To determine the dosage requirements and pharmacokinetics of atevirdine, a non-nucleoside reverse transcriptase inhibitor and its N-dealkylated metabolite (N-ATV) during phase I studies in patients receiving atevirdine alone or in combination with zidovudine.
Design: Two open label, phase I studies conducted by the adult AIDS Clinical Trials Group (ACTG) in which atevirdine was administered every 8 h with weekly dosage adjustments to attain targeted trough plasma atevirdine concentrations.
Setting: Five Adult AIDS Clinical Trials Units.
Phase I study of atevirdine mesylate (U-87201E) monotherapy in HIV-1-infected patients.
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October 1998
Infectious Diseases Unit, University of Rochester School of Medicine and Dentistry, New York, USA.
The safety, tolerability, and antiviral activity of atevirdine (ATV), a nonnucleoside reverse transcriptase inhibitor, were studied in a phase I/II clinical trial (ACTG 187) of patients with CD4 counts < or =500/mm3. In all, 34 HIV-1-infected patients were randomized to receive ATV for 12 weeks in doses chosen to achieve one of three serum trough levels: 5 to 13 microM, 14 to 22 microM, or 23 to 31 microM. Rash was the most common adverse event, with a grade 3 or 4 rash occurring in 4 patients.
View Article and Find Full Text PDFCerebral perfusion scanning in treating AIDS dementia: a pilot study.
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February 1998
Department of Nuclear Medicine, Center for Immunology, St. Vincent's Hospital, Sydney, Australia.
Unlabelled: Acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) is a common effect of the AIDS virus. We studied the regional cerebral blood flow of patients with early ADC and its response to atevirdine mesylate.
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In-vitro selection of HIV-1 variants resistant to non-nucleoside reverse transcriptase inhibitors in monocyte-derived macrophages.
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Eijkman-Winkler Institute of Medical Microbiology, University of Utrecht, University Hospital, The Netherlands.
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AIDS
October 1996
National Centre in HIV Epidemiology and Clinical Research, Darlinghurst, Sydney, Australia.
Objectives: To determine the efficacy of the non-nucleoside reverse transcriptase inhibitor atevirdine in the treatment of AIDS dementia complex (ADC).
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