Abstract
HIV-1 protease inhibitors have had a dramatic impact on the management of HIV disease.1 As part of an aggressive three-drug combination, protease inhibitor therapy results in durable, potent suppression of viral replication. Recent data, however, indicates that a significant proportion of patients may not achieve long-term viral suppression.2,3,4 The prognostic implications of protease inhibitor drug failure, and its clinical management, remain unknown. This chapter will review the clinical characteristics and genotypic resistance patterns associated with each of the protease inhibitors, and then discuss the limited clinical data addressing drug failure and salvage therapy.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Deeks S, Smith M, Holodniy M, Kahn J. HIV-1 protease inhibitors: a review for clinicians. JAMA 1997; 277: 145–153.
Hirsch, M for the protocol 039 (indinavir) study group. Indinavir (IDV) in combination with zidovudine (ZDV) and lamivudine (3TC) in ZDV-experienced patients with CD4 cell counts <=50 cells/ mm3. In: Program and abstracts of the IV Conference on Retroviruses and Opportunistic Infections, Washington, DC, January 22-26, abstract LB7.
Hammer S, Demeter LM, Fischl MA, Squires KE, Bosch RJ, Hughes MD for the ACTG 320 Study and Virology Teams. Clinical, immunological and virological outcomes in ACTG 320, a randomized, placebo controlled trial of indinavir in combination with two nucleosides in HIV-1 infected persons with CD4+ cell/counts < 200 cells/mm3. In: Program and abstracts of the International Workshop on HIV Resistance, Treatment Strategies, and Eradication; St. Petersburgh FL, USA June 25–28, 1997 [abstract 67].
Deeks S, Loftus R, Cohen P, Chin S, Grant RM. Incidence and predictors of virologic failure to indinavir (IDV) or/and ritonavir (RTV) in an urban health clinic. In: Programs and abstracts of the 37th International Conference on Antimicrobial Agents and Chemotherapy. Toronto, Canada 1997 [Abstract LB-2].
Havlir DV, Richman DD. Viral dynamics of HIV: implications for drug development and therapeutic strategies. Ann Intern Med 1996; 124: 984–994.
Department of Health and Human Services, Panel on Clinical Practices for Treatment of HIV Infection. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. November 5, 1997 document.
Carpenter CC, Fischl M, Hammer SM, Hirsch MS, Jacobsen DM, Katzenstein DA, et al. Antiretroviral therapy for HIV infection in 1997: Updated recommendations of the International AIDS Society-USA Panel. JAMA 1997; 277: 1962–1969.
Collier AC, Coombs RW, Schoenfeld DA, et al. Treatment of human immunodeficiency virus infection with saquinavir, zidovudine and zalcitabine. N Eng J Med 1996; 334: 1011–1017.
Farthing C, Sension M, Churchill H, Chang H, Siemon-Hryczyk P, Pilson R, Fischer L. Soft gel capsule saquinavir (sgcSQV) in combination with AZT and 3TC in antiretroviral-naive HIV-1 infected patients. Program and abstracts of the Infectious Diseases Society of America 35th Annual Meeting, San Francisco, September 13–16, 1997. [Abstract 220].
Markowitz M, Saag M, Powderly WG, et al. A preliminary study of ritonavir, and inhibitor of HIV-1 protease, to treat HIV-1 infection. N Eng J Med 1995; 333: 1534–1539.
Gulick R, Mellowr, J, Havlir D, et al. Indinavir (IDV), zidovudine (ZDV) and lamivudine (3TC): concurrent or sequential therapy in ZDV-experienced patients. In: Programs and abstracts of the 37th International Conference on Antimicrobial Agents and Chemotherapy. Toronto, Canada 1997. [Abstract 1-89].
Saag M, Knowles M, Chang Y, et al. Combination use of ritonavir and saquinavir in HIV-infected patients: preliminary safety and activity data. In: Program and abstracts of the XI International Conference on AIDS, July 7–12, 1996; Vancouver, Canada. [Abstract I-101].
Cameron W, Sun E, Markowitz M, et al. Combination use of ritonavir and saquinavir in HIV-infected patients: preliminary safety and activity data. In: Program and abstracts of the XI International Conference on AIDS, July 7-12, 1996: Vancouver, Canada. [Abstract TH.B.934].
Jacobsen H, Hanggi M, Ott M, Duncan IB, Owen S, Andreoni M, Vella S, Mous J. In vivo resistance to a human immunodeficiency virus type 1 protease inhibitor: mutations, kinetics, and frequencies. J Inf Dis 1996; 173: 1379–1387.
Condra JH, Holder DJ, Schlief WA, et al. Genetic correlates of in vivo viral resistance to indinavir, a human immunodeficiency virus type 1 protease inhibitor. J Virology 1996; 70: 8270–8276.
Molla A, Korneyeva M, Gao Q, et al. Ordered accumulation of mutations to an HIV-1 protease confers resistance to ritonavir. Nature Med 1996; 2: 760–766.
Patick AK, Kuritzkes D, Johnson VA, et al. Genotypic and phenotypic analyses of HIV-1 variants isolated from patients treated with nelfinavir and other HIV-1 protease inhibitors. In: Program and abstracts of the International Workshop on HIV Resistance, Treatment Strategies, and Eradication; St. Petersburgh FL, USA June 25–28, 1997. [Abstract 18].
Para MF, Collier A, Coombs R, et al. for the ACTG 333 Study Team. ACTG 333: antiviral effects of switching from saquinavir hard capsule (SQVhc) to saquinavir soft gelatin capsule (SQVsgc) vs. switching to indinavir (IDV) after prior saquinavir. In: Program and Abstracts of the Infectious Diseases Society of America 35th Annual Meeting, San Francisco, September 13–16, 1997. [Abstract 21 ].
Dulioust A, Paulous S, Guillemot L, Boue F, Galanaud P, Clavel F. Selection of saquinavir-resistant mutants following a switch from saquinavir. In: Program and abstracts of the International Workshop on HIV Resistance, Treatment Strategies, and Eradication; St. Petersburgh FL, USA June 25–28, 1997. [Abstract 16].
Deeks S, Grant RM, Horton C, Simmonds N, Follansbee S, Eastman S. Virologic effect on ritonavir (RTV) plus saquinavir (SQV) in subjects who have failed indinavir (IDV). In: Programs and abstracts of the 37th International Conference on Antimicrobial Agents and Chemotherapy. Toronto, Canada 1997. [Abstract 1205].
Gallant JE, Hall C, Barnett S, Raines C. Ritonavir/saquinavir (RTV/SQV) as Salvage Therapy after Failure of Initial Protease Inhibitor (PI) Regimen. In: Program Abstracts of the 5th Conference on Retroviruses and Opportunistic Infections, Chicago, Illinois, February 1-5, 1998 (abstract 427).
Deeks SG, Grant RM, Symmonds W, Becker M, Hellmann NS, Chesney M, Volberding PA. Pilot study of nelfinavir, saquinavir-soft gel capsule, abacavir with and without nevirapine in patients who have failed an indinavir-containing regimen. In: Program and abstracts of the 2nd International Workshop on HIV Drug Resistance and Treatment Strategies; Lake Maggiore, Italy, June 24-27, 1998.
Henry K, Kane E, Melrome H, Simpson J, Patick A, Winslow D. Experience with ritonavir/saquinavir based regimen for the treatment of HIV-infection in subjects developing increased viral loads while receiving nelfinavir. In: Programs and abstracts of the 37th International Conference on Antimicrobial Agents and Chemotherapy. Toronto, Canada 1997. [Abstract I-204].
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer Science+Business Media New York
About this chapter
Cite this chapter
Deeks, S.G. (1999). Failure of HIV-1 Protease Inhibitors to Fully Suppress Viral Replication. In: Mills, J., Volberding, P.A., Corey, L. (eds) Antiviral Chemotherapy 5. Advances in Experimental Medicine and Biology, vol 458. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4743-3_17
Download citation
DOI: https://doi.org/10.1007/978-1-4615-4743-3_17
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7150-2
Online ISBN: 978-1-4615-4743-3
eBook Packages: Springer Book Archive