Combination therapy with zidovudine prevents selection of human immunodeficiency virus type 1 variants expressing high-level resistance to L-697,661, a nonnucleoside reverse transcriptase inhibitor
| Autor: | W. Stille, J. L. Ryan, C. Kreisl, V W Byrnes, C. S. Hildebrand, William A. Schleif, S. Durr, F. E. Massari, V. I. Taylor, C L Schneider, H. von Briesen, Emilio A. Emini, S. Staszewski, Gary B. Calandra, R. Göhler, K. K. Bakshi, B. Hoffstedt, H. Rübsamen-Waigmann, K. W. Anderson, A. Kober, J. A. Waterbury |
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| Rok vydání: | 1995 |
| Předmět: |
Adult
Male Combination therapy Pyridones medicine.medical_treatment Molecular Sequence Data HIV Infections Biology Antiviral Agents Virus Zidovudine Double-Blind Method medicine Immunology and Allergy Humans Chemotherapy Benzoxazoles Reverse-transcriptase inhibitor Base Sequence Drug Resistance Microbial RNA-Directed DNA Polymerase Sequence Analysis DNA Virology Reverse transcriptase HIV Reverse Transcriptase CD4 Lymphocyte Count Infectious Diseases Tolerability Mutation HIV-1 Reverse Transcriptase Inhibitors Drug Therapy Combination Female Viral disease medicine.drug |
| Zdroj: | The Journal of infectious diseases. 171(5) |
| ISSN: | 0022-1899 |
| Popis: | L-697,661 is a human immunodeficiency virus type 1 (HIV-1)-specific nonnucleoside reverse transcriptase (RT) inhibitor. Its tolerability and activity in combination with zidovudine were evaluated in a 48-week double-blind study. One hundred nineteen zidovudine-naive HIV-1-infected patients with CD4 cell counts of 200-500/mm 3 received either combination therapy, L-697,661 alone, or zidovudine alone. Activity was assessed by CD4 cell count changes. Selection for L-697,661-resistant virus was monitored by susceptibility testing of RT expressed by circulating viral RNA. Therapy was generally well tolerated. All groups receiving zidovudine exhibited transient increases in CD4 cell counts, while the L-697,661 monotherapy group showed a significant decline and yielded RT >100-fold resistant to L-697,661 and associated with substitutions at RT residue 181. The RT from patients receiving combination therapy was maximally 15-fold less susceptible to L-697,661. Hence, cotreatment with zidovudine prevents selection of HIV-1 variants that are highly resistant to L-697,661 in patients naive to both compounds |
| Databáze: | OpenAIRE |
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