TY - JOUR
T1 - Plasma viremia as a sensitive indicator of the antiretroviral activity of L-697,661
AU - Davey, R. T.
AU - Dewar, R. L.
AU - Reed, G. F.
AU - Vasudevachari, M. B.
AU - Polis, M. A.
AU - Kovacs, J. A.
AU - Falloon, J.
AU - Walker, R. E.
AU - Masur, H.
AU - Haneiwich, S. E.
AU - O'Neill, D. G.
AU - Decker, M. R.
AU - Metcalf, J. A.
AU - Deloria, M. A.
AU - Laskin, O. L.
AU - Salzman, N.
AU - Lane, H. C.
PY - 1993
Y1 - 1993
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0027194963&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027194963&partnerID=8YFLogxK
U2 - 10.1073/pnas.90.12.5608
DO - 10.1073/pnas.90.12.5608
M3 - Article
C2 - 8516307
AN - SCOPUS:0027194963
SN - 0027-8424
VL - 90
SP - 5608
EP - 5612
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 12
ER -