Investigational protease inhibitors as antiretroviral therapies

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:

• Protease inhibitors
• HIV
• pharmacoenhancers
• antiretroviral therapy
• drug delivery
• nanocarriers

Article highlights

• Novel investigational PIs are under development that have better side effect profiles, and may be able to treat resistant strains effectively.

• Novel experimental darunavir-based PIs are under development, and have potential to treat resistant virus strains.

• Known and new pharmacoenhancers are being investigated for the development of new regimens that are relatively more effective than the current regimens.

• Several nanocarriers are being developed to deliver PIs into the CNS to treat infected brain macrophages and microglia.

• These novel drugs and drug delivery systems are likely to help treat neuroAIDS.

This box summarizes key points contained in the article.

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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The authors acknowledge financial support from the National Institute of Health grant 1R01AA022063-01A1.