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.
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
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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.