Plasma viremia as a sensitive indicator of the antiretroviral activity of L-697,661

R. T. Davey, R. L. Dewar, G. F. Reed, M. B. Vasudevachari, M. A. Polis, J. A. Kovacs, J. Falloon, R. E. Walker, H. Masur, S. E. Haneiwich, D. G. O'Neill, M. R. Decker, J. A. Metcalf, M. A. Deloria, O. L. Laskin, N. Salzman, H. C. Lane

Research output: Contribution to journalArticlepeer-review

Abstract

L-697,661 is a non-nucleoside analogue with potent, selective inhibitory activity against the reverse transcriptase of human immunodeficiency virus type 1 (HIV-1). The present study evaluated the potential role of this compound in the treatment of HIV-1-infected patients in a double-blinded, placebo- and zidovudine-controlled trial using plasma viremia as a marker of antiviral activity and real-time phenotypic evaluation of viral isolates for the emergence of resistance. Participants received 12 weeks of either placebo, 25 mg twice a day, 100 mg three times a day, or 500 mg twice a day of L-697,661, or zidovudine, 100 mg five times a day. Mean logarithmic reciprocal titers of plasma virus in patients taking either L-697,661 or zidovudine decreased by week 4 of therapy; for L-697,661 recipients these changes were dose-dependent and, at the highest dose tested, were comparable in magnitude to those seen with zidovudine. Viral suppression induced by L- 697,661 persisted through 8 weeks of treatment but decreased by week 12. This rebound paralleled emergence of viral isolates showing resistance to L- 697,661. We conclude that although L-697,661 has potent antiretroviral activity in vivo, its utility may be compromised by rapid emergence of L- 697,661-resistant virus. Plasma viremia is a highly sensitive technique affording considerable utility in the early testing of such agents.

Original languageEnglish (US)
Pages (from-to)5608-5612
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number12
DOIs
StatePublished - 1993
Externally publishedYes

ASJC Scopus subject areas

  • General

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