Dual protease inhibitor therapy in the management of the HIV-1.
Throughout the first 20 years of the HIV-1 epidemic, there have been tremendous advances in the development of antiretroviral therapy (ART). In 1995, the availability of protease inhibitors (PI) as part of triple drug regimens resulted in durable viral suppression with an associated decline in HIV-1-related morbidity and mortality. Despite this early success, limitations of therapy have become apparent. In particular, the need for highly potent antiviral regimens, the importance of outstanding adherence to therapy, drug-related toxicity and the increasing problem of drug-drug and drug-food interactions. Dual PI therapy has been investigated with the hope of overcoming these problems. Select PI combinations may result in synergistic antiviral activity with enhanced viral suppression. Moreover, the ability of select agents to inhibit the cytochrome P450 (CYP450) system results in pharmacologic enhancement that allows for dosing with fewer pills on a less frequent basis, both of which can enhance drug adherence. Furthermore, these pharmacologic interactions can overcome drug-drug and drug-food interactions. Finally, the ability to increase drug levels using certain PI combinations may allow for drug concentrations to exceed those needed to inhibit resistant strains of HIV-1. The rationale for using dual PI therapy, along with the results of clinical trials using various PI combinations in treatment-naïve and experienced patients, is reviewed in this article.
Cedars-Sinai Burns & Allen Research Institute, Division of Infectious Diseases, Department of Medicine, Los Angeles, CA, USA.
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D004338:Drug Combinations; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans
D004338:Drug Combinations; D017320:HIV Protease Inhibitors