Plasma viremia as a sensitive indicator of the antiretroviral activity of L-697,661.
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.[1]References
- Plasma viremia as a sensitive indicator of the antiretroviral activity of L-697,661. Davey, R.T., Dewar, R.L., Reed, G.F., Vasudevachari, M.B., Polis, M.A., Kovacs, J.A., Falloon, J., Walker, R.E., Masur, H., Haneiwich, S.E. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
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