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Clinical trials of HIV antiretroviral therapy: Protease inhibitors

Author
Paul E Sax, MD
Section Editor
John G Bartlett, MD
Deputy Editor
Jennifer Mitty, MD, MPH

INTRODUCTION

The widespread use of combination antiretroviral therapy using nucleoside reverse transcriptase inhibitors (NRTIs) and a protease inhibitor (PI) dramatically improved the prognosis for people living with HIV [1]. With the potent PIs ritonavir and indinavir, clinical trials demonstrated survival advantages for use of these drugs compared with regimens that consisted only of NRTIs [2,3]. Since the FDA approval in 1995 of saquinavir, many additional protease inhibitors have been developed with varying efficacy and adverse event profiles.

This topic will review the major clinical trials comparing protease inhibitors currently in common use: saquinavir, nelfinavir, lopinavir, atazanavir, fosamprenavir, tipranavir, and darunavir. As neither indinavir nor full dose ritonavir are presently preferred options for therapy in any clinical setting, studies evaluating their efficacy, safety, and tolerability will not be reviewed further here.

A discussion of the relative advantages and disadvantages of the different drugs and the clinical context where they may be best utilized is presented elsewhere. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient" and "Overview of antiretroviral agents used to treat HIV".)

Details about pharmacology, dosing and side effect profiles, as well as "pharmacokinetic boosting" with ritonavir are discussed elsewhere (see "Overview of antiretroviral agents used to treat HIV", section on 'Protease inhibitors (PIs)'). Clinical trial information regarding other classes of HIV drugs is addressed within their respective topics.

GENERAL PRINCIPLES

Antiretroviral therapy (ART) generally consists of at least three active antiretroviral medications. In treatment-naïve patients, this consists of two NRTIs (sometimes referred to as the "backbone") and a third drug, either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor. The selection of specific antiretroviral regimens is discussed elsewhere. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient".)

                  

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Literature review current through: Nov 2016. | This topic last updated: Tue Oct 14 00:00:00 GMT+00:00 2014.
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References
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