Antiviral activity of the human immunodeficiency virus type 1-specific nonnucleoside reverse transcriptase inhibitor HBY 097 alone and in combination with zidovudine in a phase II study

Journal of Infectious Diseases

Volumn 179, Issue 3, 1999, Pages 709-713

  Kleim, Jörg Peter ^a,b,c,d,e   Winters, Mark ^a,b,c,d   Dunkler, Anke ^a,b,c,d   Suarez, José Ramon ^a,b,c,d   Rieß, Günther ^a,b,c,d   Winkler, Irvin ^a,b,c,d   Balzarini, Jan ^a,b,c,d   Oette, Dagmar ^a,b,c,d   Merigan, Thomas C ^a,b,c,d   Gulick, Roy ^f   Kumar, Princy ^g   Occhipinti, Donna ^h   Rodrigue, Daniel ^b   Leedom, John ^b   Schrader, Shannon ⁱ  

^a Central Biotechnology   (Germany)

^b STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c Hoechst Marion Roussel   (United States)

^d REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^e GLAXOSMITHKLINE   (United Kingdom)

^f GEORGETOWN UNIVERSITY   (United States)

^g MEDICAL COLLEGE OF GEORGIA   (United States)

^h LAC USC MEDICAL CENTER   (United States)

ⁱ NONE

Author keywords

[No Author keywords available]

Indexed keywords

RNA DIRECTED DNA POLYMERASE INHIBITOR; TALVIRALINE; ZIDOVUDINE;

ADULT; ANTIVIRAL ACTIVITY; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; FEMALE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MALE; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; VIRUS LOAD; VIRUS MUTATION;

ADULT; ANTI-HIV AGENTS; ANTIVIRAL AGENTS; CD4 LYMPHOCYTE COUNT; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; FEMALE; HIV INFECTIONS; HIV-1; HIV-1 REVERSE TRANSCRIPTASE; HUMANS; MALE; QUINOXALINES; REVERSE TRANSCRIPTASE INHIBITORS; RNA, VIRAL; TIME FACTORS; VIRAL LOAD; ZIDOVUDINE;

EID: 18744428228     PISSN: 00221899     EISSN: None     Source Type: Journal    
DOI: 10.1086/314633     Document Type: Article

References (15)

1. 1. Kleim JP, Bender R, Billhardt UM, et al. Activity of a novel quinoxaline derivative against human immunodeficiency virus type 1 reverse transcriptase and viral replication. Antimicrob Agents Chemother 1993;37: 1659-64.
2. 2. Kleim JP, Bender R, Kirsch R, et al. Preclinical evaluation of HBY 097, a new nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 replication. Antimicrob Agents Chemother 1995;39: 2253-7.
3. 3. Kleim JP, Rösner M, Winkler I, et al. Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor specific (RT Leu-74→Val or Ile and Val-75→ Leu or Ile) HIV-1 mutants. Proc Natl Acad Sci USA 1996;93:34-8.
4. 4. Kleim JP, Winkler I, Rösner M, et al. In vitro selection of different mutational patterns in the HIV-1 reverse transcriptase using high and low selective pressure of the nonnucleoside reverse transcriptase inhibitor HBY 097. Virology 1997;231:112-8.
5. 5. Rübsamen-Waigmann H, Huguencl E, Paessens A, et al. Second-generation non-nucleosidic reverse transcriptase inhibitor HBY 097 and HIV-1 viral load. Lancet 1997;349:1517.
6. 6. Winters MA, Tan LB, Katzenstein DA, Merigan TC. Biological variation and quality control of plasma human immunodeficiency virus type 1 RNA quantitation by reverse transcriptase polymerase chain reaction. J Clin Microbiol 1993;31:2960-6.
7. 7. Saag MS, Emini EA, Laskin OL, et al. A short term clinical evaluation of L-697,661, a non-nucleoside inhibitor of HIV-1 reverse transcriptase. N Engl J Med 1993;329:1065-72.
8. 8. Hsiou Y, Ding J, Das K, et al. Novel mechanism of drug resistance due to Lys103Asn mutation suggested by crystal structures of unliganded and inhibitor-bound Lys103Asn HIV-1 RT [abstract 13]. In; Program and abstracts: International Workshop on HIV Drug Resistance, Treatment Strategies, and Eradication (St. Petersburg, Florida), 1997.
9. 9. Balzarini J, Pelemans H, Riess G, et al. An AZT-resistant HIV-1 strain sub-cultured ìn the combined presence of quinoxaline HBY 097 and 2′,3′-dideoxy-3′-thiacytidine lamivudine), retains marked sensitívity to HBY 097. Biochem Pharmacol 1998;55:617-25.
10. 10. Nájera I, Holguin A, Quiñones-Mateu ME, et al. pol gene quasispecies of human immunodeficiency virus: mutations associated with drug resistance in virus from patients undergoing no drug therapy. J Virol 1995;69:23-31.
11. 11. Pelemans H, Esnouf R, Dunkler A, et al. Characteristics of the Pro225His mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase that appears under selective pressure of dose-escalating quinoxaline treatment of HIV-1. J Virol 1997;71:8195-203.
12. 12. Staszewski S, Miller V, Kober A, et al. Evaluation of the efficacy and tolerance of R018893, R089439 (loviride), and placebo in asymptomatic HIV-1-infected patients. Antiviral Ther 1996;1:42-50.
13. 13. De Jong MD, Vella S, Carr A, et al. High-dose nevirapine in previously untreated human immunodeficiency virus type 1 infected persons does not result in sustained suppression of viral replication. J Infect Dis 1997;175:966-70.
14. 14. Moxham CP, Banke-Bochita J, Fuder H, et al. A dose ranging study to evaluate the efficacy and safety of MKC-442 in HIV-infected patients [abstract 331]. In: Program and abstracts: Sixth European Conference on Clinical Aspects and Treatment of HIV (Hamburg), 1998.
15. 15. Murphy RL, Montaner J. Nevirapine: a review of its development, pharmacological profile, and potential for clinical use. Exp Opin Invest Drugs 1996;5:1183-99.