Investigational drugs for HIV: trends, opportunities and key players

ABSTRACT

Introduction

Since the first antiretroviral drug was described, the field of HIV treatment and prevention has undergone two drug-based revolutions: the first one, enabled by the virtually concomitant discovery of non-nucleoside reverse transcriptase and protease inhibitors, was the inception of combined antiretroviral therapy. The second followed the creation of integrase strand-transfer inhibitors with improved safety, potency, and resistance profiles. Long-acting antiretroviral drugs, including broadly neutralizing antibodies, now offer the opportunity for a third transformational change in HIV management.

Areas covered

Our review focused on HIV treatment and prevention with investigational drugs that offer the potential for infrequent dosing, including drugs not yet approved for clinical use. We also discussed approved drugs for which administration modalities or formulations are being optimized. We performed a literature search in published manuscripts, conference communications, and registered clinical trials.

Expert opinion

While the field focuses on extending dosing intervals, we identify drug tissue penetration as an understudied opportunity to improve HIV care. We repeat that self-administration remains an essential milestone to reach the full potential of long-acting drugs. Treatments and prevention strategies based on broadly neutralizing antibodies require a deeper understanding of their antiretroviral properties.

KEYWORDS:

• Broadly neutralizing antibodies
• cabotegravir
• fostemsavir
• HIV
• lenacapavir
• pre-exposure prophylaxis
• prevention
• treatment

Article highlights

• Treatment with the integrase strand transfer inhibitors dolutegravir or bictegravir achieves an optimal virological outcome

• Since virological suppression is as good as it gets, areas for improvement include less frequent drug intake

• Investigational drugs include long-acting injectable antiretroviral compounds such as the clinically approved lenacapavir and cabotegravir

• It is unclear how broadly neutralizing antibodies can benefit patients until they are better characterized and less susceptible to resistance

• Self-administration of long-acting injectable drugs is a critical milestone for optimal prevention and, to a lesser extent, treatment

• Long-acting injectables do not guarantee treatment adherence, nor are they immune to drug-drug interactions and absorption issues

This box summarizes key points contained in the article.

Declaration of interests

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.