HIV-1 protease inhibitors: A review

Infections in Medicine

Volumn 16, Issue 11, 1999, Pages 716-738

  Dietrich, Michael A ^a,b   Butts, John D ^a,c   Raasch, Ralph H ^a,c  

^a UNIVERSITY OF NORTH CAROLINA HOSPITALS   (United States)

^b UNIVERSITY OF NORTH CAROLINA   (United States)

^c Division of Pharmacotheraphy

Author keywords

AIDS; Antiretroviral therapy, combination; HIV; Pharmacotherapy; Protease inhibitors

Indexed keywords

AMPRENAVIR; ANALGESIC AGENT; ANTIARRHYTHMIC AGENT; ANTIHISTAMINIC AGENT; ANTIMYCOBACTERIAL AGENT; CALCIUM CHANNEL BLOCKING AGENT; CISAPRIDE; ERGOTAMINE; HYPNOTIC SEDATIVE AGENT; INDINAVIR; LOPINAVIR; NELFINAVIR; NEUROLEPTIC AGENT; ORAL CONTRACEPTIVE AGENT; PROTEINASE INHIBITOR; RITONAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; SAQUINAVIR;

DRUG BIOAVAILABILITY; DRUG CONTRAINDICATION; DRUG COST; DRUG EFFICACY; DRUG INDUCED DISEASE; DRUG MECHANISM; DRUG TOLERABILITY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; REVIEW;

EID: 0032700062     PISSN: 07496524     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (98)

1. Conner EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. N Engl J Med. 1994; 331:1173-1180.
2. Sperling RS, Shapiro DE, Coombs R, et al. Maternal plasma HIV-1 RNA and the success of zidovudine (ZDV) in the prevention of mother-child transmission. In: Program and abstracts of the 3rd Conference on Retroviruses and Opportunistic Infections; January 28-February 1, 1996; Washington, DC. Abstract LB1.
3. Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, Panel on Clinical Practices for Treatment of HIV Infection; Department of Health and Human Services and the Henry J. Kaiser Family Foundation, December 1998.
4. Navia M, Fitzgerald PMD, McKeever BM, et al. Three-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-1. Nature. 1989;337:615-620.
5. Kohl NE, Emini EA, Schleif WA, et al. Active human immunodeficiency virus protease is required for viral infectivity. Proc Natl Acad Sci U S A. 1988;85:4686-4690.
6. Robins T, Plattner J. HIV protease inhibitors: their anti-HIV activity and potential role in treatment. J Acquir Immune Defic Syndr. 1993; 6:162-170.
7. Leonard JM. Perspectives in HIV protease inhibitors. Antiviral Chemother. 1996;4:319-325.
8. Craig JC, Duncan IB, Hockley D, et al. Antiviral properties of RO 31-8959, an inhibitor of human immunodeficiency virus proteinase. Antiviral Res. 1991;16:295-305.
9. Flexner C. HIV-protease inhibitors. N Engl J Med. 1998;338:1281-1292.
10. Barry M, Gibbons S, Back D, et al. Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations. Clin Pharmacokinet. 1997;32:194-209.
11. Invirase (saquinavir mesylate) package insert. Nutley, NJ: Roche Laboratories, Hoffman-LaRoche Inc.
12. Fortovase (saquinavir mesylate) package insert. Nutley, NJ; Roche Laboratories, Hoffman-LaRoche Inc.
13. Norvir (ritonavir) package insert. Abbott Park, Ill: Abbott Pharmaceuticals.
14. Crixivan (indinavir sulfate) package insert. West Point, Pa: Merck and Company Inc.
15. Viracept (nelfinavir mesylate) package insert. LaJolla, Calif: Agouron Pharmaceuticals Inc.
16. Keruly JC, Chaisson RE, Moore RD. Diabetes and hyperglycemia in patients receiving protease inhibitors. In Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections; February 1-5, 1998; Chicago. Abstract 415.
17. Dong BJ, Gruta C, Leeg L, et al. Diabetes and the use of protease inhibitors. In Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections; February 1-5, 1998; Chicago. Abstract 416.
18. Protease inhibitor class labeling warning for diabetes, hyperglycemia. FDC Report, June 16, 1997. T&G-5.
19. Dube MP, Johnson DLJ, Currier JSC, et al. Protease inhibitor-associated hyperglycemia: results of switching from indinavir to nelfinavir. In: Program and abstracts of the 12th World AIDS Conference; June 28-July 3, 1998; Geneva. Abstract 32172.
20. Walli RK, Herfort O, Michl GM, et al. Peripheral insulin resistance leading to impaired glucose tolerance in HIV-1 infected patients treated with protease inhibitors. In: Program and abstracts of the 12th World AIDS Conference; June 28-July 3, 1998; Geneva. Abstract 41177.
21. Rodo MS, Pena RC, Cervantes M, et al. Hyperglycemia associated with protease inhibitor therapy. In: Program and abstracts of the 12th World AIDS Conference; June 28-July 3, 1998; Geneva. Abstract 12387.
22. Hengel RL, Geary JA, Vuchetich MA, et al. Multiple symmetrical lipomatosis associated with protease inhibitor therapy. In: Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections; February 1-5, 1998; Chicago. Abstract 407.
23. Rosenberg HE, Mulder J, Sepkowitz KA, et al. 'Protease paunch' in HIV+ persons receiving protease inhibitor therapy: incidence, risk and endocrinologic evaluation. In: Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections; February 1-5, 1998; Chicago. Abstract 408.
24. Carr A, Samaras K, Burton S, et al. A syndrome of peripheral lipodystrophy (LD), hyperlipidemia and insulin resistance due to HIV protease inhibitors (PIs). In: Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections; February 1-5, 1998; Chicago. Abstract 410.
25. Roth VR, Angel JB, Kravcik S. Development of a cervical fat pad following treatment with HIV-1 protease inhibitors. In Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections; February 1-5, 1998; Chicago. Abstract 411.
26. Mann M, Piazza-Hepp T, Koller E, et al. Abnormal fat distribution following protease inhibitor therapy: FDA summary. In: Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections; February 1-5, 1998; Chicago. Abstract 412.
27. Ruane PJ. Atypical accumulation of fatty tissue. In: Program and abstracts of the 37th ICAAC; September 28-October 1, 1997; Toronto. Abstract I-185.
28. Carr A, Samaras K, Chisolm DJ, et al. Pathogenesis of HIV-1 protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet. 1998;351:1881-1883.
29. Doung M, Sgro C, Grappin M, et al. Renal failure after treatment with ritonavir. Lancet. 1996;48:693-694.
30. Chugh S, Bird R, Alexander E. Ritonavir and renal failure. N Engl J Med. 1997;336:138.
31. Rublein J, Eron J, Butts J, Raasch R. Discontinuation rates for protease inhibitor regimens containing ritonavir 600 mg versus ritonavir 400 mg + saquinavir 400 mg. Ann Pharmacother. In press.
32. Kopp JB, Miller KD, Mican AM, et al. Crystalluria and urinary tract abnormalities associated with indinavir. Ann Intern Med. 1997; 127:119-125.
33. Tashima KT, Horowitz JD, Rosen S. Indinavir nephropathy. N Engl J Med. 1997;36:138-140.
34. Kovach DA, Smead J. Increased incidence of indinavir-associated nephrolithiasis in warm climate. In: Program and abstracts of the 38th ICAAC; September 24-27, 1998; San Diego. Abstract I-59.
35. Brau N, Leaf H, Wieczorek R, et al. Severe hepatitis in three AIDS patients treated with indinavir. Lancet. 1997;349:924-925.
36. Stein DS, Dunn H, Drusano GL. Acute thrombocytopenia secondary to the administration of the peptidomimetic HIV protease inhibitor MK-639 (L735524). AIDS. 1996;10:678-679.
37. Sheety BV, Kosa MB, Khalil DA, et al. Preclinical pharmacokinetics and distribution to tissue of AG1343, an inhibitor of human immunodeficiency virus type 1 protease. Antimicrob Agents Chemother. 1996;40:110-114.
38. Hawkins T. Nelfinavir-associated diarrhea is manageable with nonprescription medications. In: Program and abstracts of the 12th World AIDS Conference; June 28-July 3, 1998; Geneva. Abstract 12401.
39. Razzeca K, Odenheimer S, Davis M, et al. The treatment of nelfinavir-induced diarrhea. In: Program and abstracts of the 12th World AIDS Conference; June 28-July 3, 1998; Geneva. Abstract 12383.
40. Murphy R, El-Sader W, Cheung T, et al. Impact of protease inhibitor containing regimens on the risk of developing opportunistic infections and mortality in the CPCRA 034/ACTG 277 study. In: Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections; February 1-5, 1998; Chicago. Abstract 181.
41. Moore RD, Keruly JC, Chaisson RE. Decline in CMV and other opportunistic diseases with combination antiretroviral therapy. In: Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections; February 1-5, 1998; Chicago. Abstract 184.
42. McCollum M, Klaus B, La Rue R, et al. HAART reduced overall costs of HIV care at DVAMC. In: Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections; February 1-5, 1998; Chicago. Abstract 200.
43. Keisher P, Kvanh M, Turner D, et al. Decreased hospital utilization and costs are associated with protease inhibitor therapy but not nudeoside therapy. In: Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections; February 1-5, 1998; Chicago. Abstract 204.
44. Paul S, Ziecheck W, Gilgert HM, et al. Impact of HAART on rates and types of hospitalization at a New York City hospital. In: Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections; February 1-5, 1998; Chicago. Abstract 205.
45. Bermudes RA, Toemer JG, Mathews WC, et al. The effect initiating protease inhibitor therapy on hospitalization rates and the quality of life in HIV+ patients. In: Program and abstracts of the 37th ICAAC; September 28-October 1, 1997; Toronto. Abstract I-182.
46. Hogg RS, Heath KV, Yip B, et al. Improved survival among HIV-infected individuals: the potential impact of newer antiretroviral therapy strategies. In: Program and abstracts of the 37th ICAAC; September 28-October 1, 1997; Toronto. Abstract I-198.
47. Palella FJ, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998; 338:853-860.
48. Sherer R, Pulvirenti J, Cohen M, et al. Six-year improvement in HIV hospital outcomes at Cook County Hospital, Chicago: impact of AIDS care units and HAART. In: Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections; February 1-5, 1998; Chicago. Abstract 206.
49. Farthing C, Sension M, Pilson R, et al. Fortovase (saquinavir) soft-gel capsule in combination with AZT 3TC in antiretroviral-naïve HIV-1 infected patients. In: Program and abstracts of the 12th World AIDS Conference; June 28-July 3, 1998; Geneva. Abstract 12301.
50. Collier AC, Coombs RW, et al. Treatment of human immunodeficiency virus infection with saquinavir, zidovudine, and zalcitabine. N Engl J Med. 1996;334:1011-1017.
51. Salgo M, Beattie D, Bragman K, et al. Saquinavir vs Hivid vs combination as treatment for advanced HIV infection in patients discontinuing/unable to take Retrovir. In: Program and abstracts of the XI International Conference on AIDS; July 7-12, 1996; Vancouver, British Columbia. Abstract Mo.B.410.
52. Katlama C, Calves V, Pellegrin JL, et al. MIKADO: saquinavir soft-gel capsule (SGC) in combination with D4T/DDC. In: Program and abstracts of the 12th World AIDS Conference; June 28-July 3, 1998; Geneva. Abstract 12244.
53. Hoen B, Harzic M, Fleury HF, et al. ARNS053 trial of zidovudine (ZDV), lamivudine (3TC), and ritonavir combination in patients with symptomatic primary HIV-1 infection: preliminary results. In: Program and abstracts of the 4th Conference on Retroviruses and Opportunistic Infections; January 22-26, 1997; Washington, DC. Abstract 232.
54. Saimot AG, Landman R, Damond F, et al. Ritonavir, stavudine (d4T), didanosine (ddI) as triple combination treatment in antiretroviral-naïve patients. In: Program and abstracts of the 4th Conference on Retroviruses and Opportunistic Infections; January 22-26, 1997; Washington, DC Abstract 246.
55. Markowitz M, Saag M, Powderly WG, et al. Preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection. N Engl J Med. 1995;28:1534-1539.
56. Danner SA, Carr A, Leonard JM, 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;28: 1528-1533.
57. Mathez D, de Truchis P, Gorin I, et al. Ritonavir, AZT, ddC, as a triple combination in AIDS patients. In: Program and abstracts of the 4th Conference on Retroviruses and Opportunistic Infections; January 22-26, 1997; Washington, DC. Abstract 285.
58. Notermans DW, de Wolf F, Foidraine NA, et al. The effects of an antiretroviral triple combination with ritonavir, AZT, and 3TC. In: Program and abstracts of the 3rd International Congress on Drug Therapy in HIV Infection; November 3-7, 1996; Birmingham, UK. Abstract OP8.2.
59. Gulick R, Mellors J, Havlir D, et al. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infections and prior antiretroviral therapy. N Engl J Med. 1997;337:734-739.
60. Steigbigel RT, Berry P, Tepler H, et al. Extended follow-up of patients in a study of indinavir at 800mg q8h (2.4g/d), 1000mg q8h (3g/d), and 800mg q6h (3.2g/d). In: Program and abstracts of the XI International Conference on AIDS; July 7-12, 1996; Vancouver, British Columbia. Abstract Mo.B.412.
61. 3. In: Program and abstracts of the XI International Conference on AIDS; July 7-12, 1996; Vancouver, British Columbia. Abstract LB.B.6017.
62. 3. In: Program and abstracts of the XI International Conference on AIDS; July 7-12, 1996; Vancouver, British Columbia. Abstract Th.B.931.
63. 3. In: Program and abstracts of the 4th Conference on Retroviruses and Opportunistic Infections; January 22-26, 1997; Washington, DC. Abstract LB7.
64. Hammer SM, Squires KE, Hughes MD, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. N Engl J Med. 1997;337:725-733.
65. Stein D, Drusano G, Steigbigel R, et al. Two year follow-up of patients treated with indinavir 800mg q8h. In: Program and abstracts of the 4th Conference on Retroviruses and Opportunistic Infections; January 22-26, 1997; Washington, DC. Abstract 195.
66. Saag M, Knowles M, Chang Y, et al. Durable effect of Viracept (nelfinavir mesylate, NFV) in triple combination therapy. In: Program and abstracts of the 37th ICAAC; September 28-October 1, 1997; Toronto. Abstract I-101.
67. Gathe J Jr, Burkhardt B, Hawley P, et al. A randomized phase II study of Viracept, a novel HIV protease inhibitor, used in combination with stavudine (d4T) vs stavudine (d4T) alone. In: Program and abstracts of the XI International Conference on AIDS; July 7-12, 1996; Vancouver, British Columbia. Abstract Mo.B.413.
68. Pedneault L, Elion R, Adler M, et al. Stavudine (d4T), didanosine (ddI), and nelfinavir combination therapy in HIV-infected subjects: Antiviral effect and safety in an ongoing pilot study. In: Program and abstracts of the 4th Conference on Retroviruses and Opportunistic Infections; January 22-26, 1997; Washington, DC. Abstract 241.
69. Conant M, Markowitz M, Hurley A, et al. A randomized phase II dose range-finding study of the HIV protease inhibitor Viracept as monotherapy in HIV-positive patients. In: Program and abstracts of the XI International Conference on AIDS; July 7-12, 1996; Vancouver, British Columbia. Abstract Tu.B.2129.
70. Markowitz M, Cao Y, Hurley A, et al. Triple therapy with AZT an 3TC in combination with nelfinavir mesylate in 12 antiretroviral-naïve subjects chronically infected with HIV-1. In: Program and abstracts of the XI International Conference on AIDS; July 7-12, 1996; Vancouver, British Columbia. Abstract LB.B.6031.
71. Powderly W, Sension M, Conant M, et al. The efficacy of Viracept in pivotal phase II/III double-blind, randomized, controlled trials as monotherapy and in combination with d4T or AZT/3TC. In: Program and abstracts of the 4th Conference on Retroviruses and Opportunistic Infections; January 22-26, 1997; Washington, DC. Abstract 370.
72. Condra JH, Schleif WA, Blahy OM, et al. In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors. Nature. 1995;374: 569-571.
73. Eberle J, Bechowsky B, Rose D, et al. Resistance of HIV type 1 protease inhibitor Ro 31-8959. AIDS Res Hum Retroviruses. 1995; 11:671-676.
74. Molla A, Komeyeva M, Gao Q, et al. Ordered accumulation of mutations in HIV-1 protease confers resistance to ritonavir. Nat Med. 1996; 2:760-766.
75. Jacobsen H, Yasargil IC, Winslow DL, et al. Characterization of human immunodeficiency virus type 1 mutants with decreased sensitivity to proteinase inhibitor Ro 31-8959. Virology. 1995;206:527-534.
76. Murihead GJ, Shaw T, Williams PEO, et al. Pharmacokinetics of the HIV-proteinase inhibitor, Ro 318959, after single and multiple oral doses in healthy volunteers. Br J Clin Pharmacol. 1992;34(suppl):170P-171P.
77. Condra JH, Holder DJ, Schleif WA, et al. Genetic correlates of in vivo viral resistance to indinavir, a human immunodeficiency virus type 1 protease inhibitor. J Virol. 1996;70:8270-8276.
78. Mellors JW, McMahon DK, Chodakewitz JA, et al. Correlation between genotypic evidence of HIV-1 resistance to the protease inhibitor MK-639 and loss of antiretroviral effect in treated patients. In: Program and abstracts of the Fourth International Workshop on HIV Drug Resistance; July 6-9, 1995; Sardinia, Italy. Abstract 71.
79. Mellors J, Japour AJ, Leonard J, et al. Ritonavir-saquinavir in protease inhibitor naïve patients after 72 weeks. In: Program and abstracts of the 12th World AIDS Conference; June 28-July 3, 1998; Geneva. Abstract 12295.
80. Gerard Y, Valette M, Ajana F, et al. Efficacy of proteinase inhibitors (PI) in combination with reverse transcriptase inhibitors (RTI): study in 177 HIV-1 infected patients in the north France AIDS reference center. In: Program and abstracts of the 4th Conference on Retroviruses and Opportunistic Infections; January 22-26, 1997; Washington, DC. Abstract 243.
81. Steinhart CR, George SA, et al. Salvage therapy using the combination of ritonavir and saquinavir in patients with advanced HIV infection. In: Program and abstracts of the 4th Conference on Retroviruses and Opportunistic Infections; January 22-26, 1997; Washington, DC. Abstract 199.
82. Barbour II, Clayton O. Efficacy and safety of quadruple combination therapy in treatment-experienced HIV/AIDS patient. In: Program and abstracts of the 4th Conference on Retroviruses and Opportunistic Infections; January 22-26, 1997; Washington, DC. Abstract 245.
83. Gisolf EH, deWolf F, Pelgrom J, et al. Treatment of ritonavir/saquinavir versus RTN/SQV/stavudine (the Prometheus study): preliminary results. In: Program and abstracts of the 12th World AIDS Conference, June 28-July 3, 1998; Geneva. Abstract 12274.
84. Markowitz M, Mo H, Kempf D, et al. Selection and analysis of human immunodeficiency virus type 1 variants with increased resistance to ABT-538, a novel protease inhibitor. J Virol. 1995;69:701-706.
85. Data on file, Abbott Laboratories.
86. FDC Reports ('The Pink Sheet'), March 17, 1997, T&G-2&3.
87. Eron J, Haubrich R, Richman D, et al. Pulmonary assessment of 141W94 in combination with other protease inhibitors. In: Program and abstracts of the 5th Conference on Retroviral and Opportunistic Infections; February 1-5, 1998; Chicago. Abstract 6.
88. Haubrich R. Phase 2 study of amprenavir, a novel protease inhibitor, in combination with zidovudine/3TC. In: Program and abstracts of the 12th World AIDS Conference; June 28-July 3, 1998; Geneva. Abstract 12321.
89. Bart PA, Rizzardi GP, Gallant S, et al. Combination abacavir (1592, ABC)/amprenavir (141W94) therapy in HIV-1 infected antiretroviral naïve subjects with CD4+ counts >00cell/μ1 and viral load >000 copies/ml. In: Program and abstracts of the 12th World AIDS Conference; June 28-July 3, 1998; Geneva. Abstract 12204.
90. Sham H, Kempf D, Molla A, et al. Design, synthesis and biological properties of ABT-378, a highly potent HIV protease inhibitor. In: Program and abstracts of the 4th Conference on Retroviruses and Opportunistic Infections; January 22-26, 1997; Washington, DC. Abstract 14.
91. Korneyeva M, Chernyvskiy D, Norbeck H, et al. Virological evaluation of ritonavir-resistant HIV to the HIV protease inhibitor ABT-378. In: Program and abstracts of the 4th Conference on Retroviruses and Opportunistic Infections; January 22-26, 1997; Washington, DC. Abstract 212.
92. Kumar GN, Jayanti V, Johnson MK, et al. Increased bioavailability and plasma levels of the HIV-1 protease inhibitor ABT-378 in rats due to inhibition of the in vitro metabolism by ritonavir. In: Program and abstracts of the 4th Conference on Retroviruses and Opportunistic Infections; January 22-26, 1997; Washington, DC. Abstract 207.
93. Markowitz M, Cao Y, Vesanen M, et al. Recent HIV infection treated with AZT, 3TC and a potent protease inhibitor. In: Program and abstracts of the 4th Conference on Retroviruses and Opportunistic Infections; January 22-26, 1997; Washington, DC. Abstract LB-8.
94. Perelson AS, Essunger P, Markowitz M, et al. How long should treatment be given if we use an antiretroviral regimen that completely blocks HIV replication. In: Program and abstracts of the VI International Conference on AIDS; July 7-12, 1996; Vancouver, British Columbia. Abstract Th.B.390.
95. Chun TW, Carruth L, Finzi D, et al. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature. 1997;387(6629):123-124.
96. Carpenter CC, Fischel MA, Hammer SM, et al. Antiretroviral therapy for HIV infection in 1996: recommendations of an international panel. JAMA. 1996;276:146-154.
97. Ho DD. Time to hit HIV: early and hard. N Engl J Med. 1995;33:450-451.
98. Carpenter CCJ, Fischel MA, Hammer SM, et al. Antiretroviral therapy for HIV infection in 1997: updated recommendations of an international AIDS society - USA panel. JAMA. 1997;277:1962-1969.