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Review
. 2016 Oct;25(10):1189-200.
doi: 10.1080/13543784.2016.1212837. Epub 2016 Aug 2.

Investigational protease inhibitors as antiretroviral therapies

Narasimha M Midde  1 , Benjamin J Patters  1 , Pss Rao  2 , Theodore J Cory  3 , Santosh Kumar  1
Affiliations
Review

Investigational protease inhibitors as antiretroviral therapies

Narasimha M Midde et al. Expert Opin Investig Drugs. 2016 Oct.

Abstract

Introduction: Highly Active Antiretroviral Therapy (HAART) has tremendously improved the life expectancy of the HIV-infected population over the past three decades. Protease inhibitors have been one of the major classes of drugs in HAART regimens that are effective in treating HIV. However, the emergence of resistance and cross-resistance against protease inhibitors encourages researchers to develop new PIs with broad-spectrum activity, as well as novel means of enhancing the efficacy of existing PIs.

Areas covered: In this article we discuss recent advances in HIV protease inhibitor (PI) development, focusing on both investigational and experimental agents. We also include a section on pharmacokinetic booster drugs for improved bioavailability of protease inhibitors. Further, we discuss novel drug delivery systems using a variety of nanocarriers for the delivery of PIs across the blood-brain barrier to treat the HIV in the brain.

Expert opinion: We discuss our opinion on the promises and challenges on the development of novel investigational and experimental PIs that are less toxic and more effective in combating drug-resistance. Further, we discuss the future of novel nanocarriers that have been developed to deliver PIs to the brain cells. Although these are promising findings, many challenges need to be overcome prior to making them a viable option.

Keywords: HIV; Protease inhibitors; antiretroviral therapy; drug delivery; nanocarriers; pharmacoenhancers.

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Conflict of interest statement

Declaration of interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Figures

Figure 1
Figure 1
Investigational protease inhibitors under different clinical developmental phases.
Figure 2
Figure 2
Experimental PIs that are developed based on the structure of darunavir.
Figure 3
Figure 3
Non-darunavir-based experimental protease inhibitors.
See this image and copyright information in PMC

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