Abstract
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/mm3 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.
Citations
Mar 31, 2004·European Journal of Medicinal Chemistry·Gülhan Turan-ZitouniMehmet Taha Yildiz
Mar 31, 2004·European Journal of Medicinal Chemistry·Ilkay Yildiz-OrenNejat Ucarturk
Sep 13, 2000·Il Farmaco·E A SenerN Altanlar
May 7, 2002·Il Farmaco·Ozlem Temiz ArpaciNurten Altanlar
Jul 29, 1998·Il Farmaco·O TemizN Uçartürk
May 13, 1999·Il Farmaco·E De Clercq
Nov 20, 1998·Journal of Virological Methods·L M DemeterA Japour
Oct 1, 1998·Antiviral Research·E De Clercq
May 20, 1999·Antiviral Research·H Rübsamen-WaigmannM A Wainberg
Mar 13, 1999·International Journal of Antimicrobial Agents·A M Been-TiktakJ C Borleffs
Feb 24, 2001·Bioorganic & Medicinal Chemistry Letters·J W CorbettS K Erickson-Viitanen
Oct 15, 2008·SAR and QSAR in Environmental Research·M ArisoyU Abbasoglu
Aug 1, 1996·Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association·R T SchooleyJ Kahn
Feb 1, 1997·Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association·L M DemeterR C Reichman
Oct 13, 1998·Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association·L M DemeterR C Reichman
Mar 1, 1995·Antimicrobial Agents and Chemotherapy·A M Been-TiktakJ C Borleffs
Aug 23, 2000·Journal of Virology·R H ArcherL M Demeter
May 24, 1997·Lancet·H Rübsamen-WaigmannA Shah
Jul 2, 2005·Expert Opinion on Emerging Drugs·M L AndreolaM Legraverend
Aug 16, 2001·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Lee T. Bacheler
Jun 7, 2014·SAR and QSAR in Environmental Research·S YilmazI Yalcin
Oct 19, 2006·Archiv der Pharmazie·Martin RichterAndreas Hilgeroth
Mar 15, 2005·Archiv der Pharmazie·Ozlem Temiz-ArpaciNurten Altanlar
Oct 23, 1997·Clinical Microbiology Reviews·E De Clercq
Nov 1, 1996·Antimicrobial Agents and Chemotherapy·A M Been-TiktakJ C Borleffs
Jul 1, 1996·Antimicrobial Agents and Chemotherapy·R T DaveyH C Lane
Nov 8, 2003·The Journal of Organic Chemistry·Alan R KatritzkyPeter J Steel