Phase I study of atevirdine mesylate (U-87201E) monotherapy in HIV-1-infected patients

Lisa M. Demeter, Patricia M. Meehan, Gene Morse, Margaret A. Fischl, Michael Para, William Powderly, John Leedom, Jeanne Holden-Wiltse, Carol Greisberger, Kenneth Wood, Joseph Timpone, Lynne K. Wathen, Thomas Nevin, Lionel Resnick, Donald H. Batts, Richard C. Reichman

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


The safety, tolerability, and antiviral activity of atevirdine (ATV), a non-nucleoside reverse transcriptase inhibitor, were studied in a phase I/II clinical trial (ACTG 187) of patients with CD4 counts ≤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 μM, 14 to 22 μM, or 23 to 31 μM. Rash was the most common adverse event, with a grade 3 or 4 rash occurring in 4 patients. No significant change from baseline in HIV-1 plasma RNA mean copy number was detected at week 4 (+0.09 log10 copies/ml; p = .30). However, some evidence indicated moderate antiviral activity at week 4, based on median changes in CD4 count (+23/mm3; p = .05), and viral peripheral blood mononuclear cell (PBMC) titer (-0.68 log10 copies/ml; p = .03). In addition, 2 of 4 patients with detectable baseline serum p24 antigen showed declines of >50%. HIV-1 resistance to ATV was detected in 41% of patients and was most commonly associated with RT mutations K103N and Y181C. In contrast, the Y181C mutation was not detected in ATV-resistant isolates obtained from patients enrolled in ACTG 199, a study of ATV given in combination with zidovudine. Under the conditions of this study, ATV failed to demonstrate significant antiretroviral activity. However, transient in vivo activity might have been obscured by rapid development of resistance coupled with inadequate sampling at early time points following initiation of ATV therapy.

Original languageEnglish
Pages (from-to)135-144
Number of pages10
JournalJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology
Issue number2
StatePublished - Oct 1 1998


  • Atevirdine
  • Drug resistance
  • HIV-1 infection
  • Nonnucleoside reverse transcriptase inhibitors
  • Phase I/II clinical trial


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