HIV protease inhibitors

Current Opinion in Infectious Diseases

Volumn 10, Issue 6, 1997, Pages 491-495

  Molla, Akhteruzzaman ^a   Japour, Anthony ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; INDINAVIR; NELFINAVIR; PROTEINASE; PROTEINASE INHIBITOR; RITONAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; SAQUINAVIR; VIRUS ENZYME; VIRUS RNA; ZALCITABINE; ZIDOVUDINE;

DRUG EFFICACY; DRUG RESEARCH; DRUG RESISTANCE; GENE MUTATION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; ORAL DRUG ADMINISTRATION; SHORT SURVEY; VIRUS MUTANT;

EID: 0030776530     PISSN: 09517375     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001432-199712000-00015     Document Type: Short Survey

References (29)

1. Dubouck C: The HIV protease as a therapeutic target for AIDS. AIDS Res Hum Retrovir 1992, 8:153-160.
2. Kohl NE, Emini EA, Schleif WA, Davis LJ, Heimbach JC, Dixon RAF, Scolnick EM, Sigal IS: Active human immunodefiency virus protease is required for viral infectivity. Proc Natl Acad Sci USA 1988, 85:4686-4690.
3. Navia MA, Fitzgerald PMD, McKeever BM, Leu CT, Heimbach JC, Herber WK, Sigal IKS, Darke PL, Springer JP: Three dimensional structure of the aspartyl protease from human immunodefiency virus HIV-1. Nature 1989, 337:515-621.
4. Wlodawer A, Miller M, Jaskolski M, Sathyanarayana BK, Baldwin E, Weber IT, Selk LM, Clawson L, Schneider J, Kent SBH: Conserved folding in retroviral proteases: crystal structure of a synthetic HIV-a protease. Science 1989, 245:616-621.
5. + T-cell counts in HIV-infected patients. Ann Int Med 1996, 124:1039-1050.
6. Danner SA, Carr A, Leonard JM, Lehman LM, Gudiol F, Gonzales J, Raventos A, Rubio R, Bouza E, Pintado V et al.: A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease. N Engl J Med 1995, 333:1528-1533.
7. Markowitz M, Saag M, Powderly WG, Hurley AM, Hsu A, Valdes JM, Henry D, Sattler M, Marca AL, Leonard JM, Ho DD: A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection. N Engl J Med 1995, 333:1534-1539.
8. Stein DS, Fish DG, Bilello JA, Preston SL, Martineau GL, Drusano ??, A 24-week open-label phase I/II evaluation of the HIV protease inhibitor MK-639 (indinavir). AIDS 1996, 10:485-492.
9. Kempf DJ, Marsh KC, Kumar G, Rodrigues AD, Denissen JF, McDonald E, Kukulka MJ, Hsu A, Granneman GR, Baroldi PA et al.: Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir. Antimicrob Agent Chemother 1997, 41:654-660 Co-administration of other HIV protease inhibitors with ritonavir in rats and dogs produced an elevated and sustained plasma level of drugs (other inhibitors).
10. Molla A, Korneyeva M, Gao Q, Vasavanonda S, Schipper PJ, Mo H, Markowitz M, Chernyavskiy T, Niu P, Lyons N et al.: Ordered accumulation of mutations in HIV protease confers resistance to ritonavir. Nature Med 1996, 2:760-766 This study showed the significant phenotypic resistance developed during ritonavir therapy required multiple mutations in HIV protease, which emerged subsequently in an ordered, stepwise fashion and the appearance of resistance mutations was delayed in patients with higher plasma levels of ritonavir.
11. Condra JH, Schleif WA, Blahy OM, Gabryelski LJ, Graham DJ, Quintero JC, Rhodes A, Robbins HL, Roth E, Shivaprakash M et al.: In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors. Nature (Lond) 1995, 374:569-571.
12. Jacobsen H, Haenggi M, Ott M, Duncan IB, Vella S, Mous J et al.: In vivo resistance to HIV protease inhibitor saquinavir-an update. AIDS Res Hum Retrovir 1995, 11:S169.
13. Patick AK, Duran M, Cao Y, Ho T, Zhou P, Keller MR, Chapman S, Anderson R, Kuritzkes D, Shugarts D et al.: Genotypic analysis of HIV-1 variants isolated from patients treated with protease inhibitor nelfinavir, alone or in combination with d4T [abstract 10]. Program and Abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections, January 22-26. Washington; 1997.
14. Gulick R, Mellors J, Havlir D, Gonzalez C, McMahon D, Richman D, Valentine F, Jonas L, Meibohm A, Chiou R et al.: Potent and sustained antiretroviral activity of indinavir in combination with zidovudine and lamivudine [abstract LB7]. Program and Abstracts of the Third Conference on Retroviruses and Opportunistic Infections, January 28-February 1. Washington; 1996.
15. Chauvin J-P: Update on ritonavir/AZT/ddC triple therapy trial and on ritonavir compassionate use experience in France. Program and abstracts of the International Congress on Drug Therapy in HIV Infection, November 3-7. UK: Birmingham; 1996.
16. Cameron DW, Heath-Chiozzi M, Kravick S, Mills R, Potthoff A, Henry D for the Advanced HIV Ritonavir Study Group: Prolongation of life and prevention of AIDS complications in advanced HIV immunodeficiecy with ritonavir-update [abstract MOB411]. Program and Abstracts of the Eleventh International Conference on Aids, July 5-12. Vancouver, BC; 1996.
17. Gomez-Caro WH, Feregnno-Goyos M, Alvarado-Diez R, Mireles-Vieyra MP, Torras-Giner V: Saquinavir plus 3TC+AZT or ddC+AZT in advanced HIV/AIDS patients. Progam and Abstracts of the International Congress on Drug Therapy in HIV Infection, November 3-7. UK: Birmingham, 1996:33.
18. Emini EA, Holder DJ, Schleif WA, Danovich RM, Graham DJ, Laird DT, Shivaprakash M, Chodakewitz JA, Condra JH: Evidence for the prevention of new HIV-1 infection cycles in patients treated with indinavir plus zidovudine plus lamivudine [abstract 128]. Program and Abstracts of the International Workshop on HIV Drug Resistance, Treatment Strategies and Eradication, June 25-28. USA: Florida; 1997.
19. Markiwitz M, Cao Y, Hurley A, O'Donovan R, Peterkin J, Anderson B, Smiley L, Keller A, Johnson D, Ho DD: Triple therapy with AZT, 3TC in combination with nelfinavir mesylate in 12 antiretroviral naive subjects chronically infected with HIV [abstract LB.B.6031]. Program and Abstracts of the Eleventh International Conference on Aids, July 5-12. Vancouver, BC; 1996.
20. Markowitz M, Cao Y, Hurley A, O'Donovan R, Heath-Chiozzi M, Leonard JM, Smiley L, Keller A, Johnson P, Ho DD: Triple therapy with AZT, 3TC, and ritonavir in 12 subjects newly infected with HIV-1 [abstract Th. B. 433]. Program and Abstracts of the Eleventh International Conference on AIDS, July 5-12. Vancouver, BC; 1996.
21. Danner SA: Immediate versus delayed triple therapy with ritonavir, AZT and 3TC. Program and Abstracts of the International Congress on Drug Therapy in HIV Infection, November 3-7. UK: Birmingham; 1996.
22. Molla A, Korneyeva M, Chernyavskiy T, Colgrove R, Chung PH, Japour A, Mellors J, Xu Y, Rode R, Hsu A, and the M96-462 Study Group: Characterization of HIV-1 protease mutations, compliance and drug concentrations in patients who have an HIV RNA rebound on ritonavir-saquinavir [abstract 83]. Program and Abstracts of the International Workshop on HIV Drug Resistance, Treatment Strategies and Eradication, June 25-28. USA: Florida; 1997.
23. Mansky LM, Temin HR: Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase. J Virol 1995, 69:5087-5094.
24. Coffin JM: HIV population dynamics in vivo: implication for genetic variation, pathogenesis and therapy. Science 1995, 267:483-489.
25. Eberle J, Bechowsky B, Rose D, Hauser U, Von Der Helm K, Gurtler L, Nitschko H: Resistance of HIV type 1 to proteinase inhibitor Ro31-8959. AIDS Res Hum Retrovir 1995, 11:671-675.
26. Hanggi M, Ott M, Duncan IB, Owen S, Andreoni M, Vella S, Mous J: In vivo resistance to a human immunodeficiency virus type 1 proteinase inhibitor: mutations, kinetics and frequencies. J Infect Dis 1996, 173:1379-1387.
27. Patick AK, Kuritzkes D, Johnson VA, Shugarts D, Bakhtiari M, Potts KE, Farnsworth A, Anderson R, Koel JL, Hazelwood JD et al.: Genotypic and phenotypic analyses of HIV-1 variants isolated from patients treated with nelfinavir and other HIV-1 protease inhibitors [abstract 18]. Program and Abstracts of the International Workshop on HIV Drug Resistance, Treatment Strategies and Eradication, June 25-28. USA: Florida; 1997.
28. Erickso JW: The not-so-great escape. Nat Struct Biol 1995, 2:523-529.
29. Zhang YM, Imamichi H, Imamichi T, Lane HC, Falloon J, Vasudevachari MB, Salzman NP: Drug resistance during indinavir therapy is caused by mutations in the protease gene and in its gag substrate cleavage sites. J Virol 1997, 71:6662-6670 Sequence analysis of the protease gene during the course of indinavir therapy revealed that there was a sequential acquisition of protease mutations which confer resistance to indinavir. There was also mutation in the protease cleavage sites. This is the first report of the emergence of mutations in the gag p7/p1 protease cleavage sites in patients receiving protease inhibitor therapy, and identifies this change as an important determinant of HIV-1 resistance to protease inhibitors in patient populations.