Long-acting HIV pre-exposure prophylaxis (PrEP) approaches: recent advances, emerging technologies, and development challenges

ABSTRACT

Introduction

Poor or inconsistent adherence to daily oral pre-exposure prophylaxis (PrEP) has emerged as a key barrier to effective HIV prevention. The advent of potent long-acting (LA) antiretrovirals (ARVs) in conjunction with advances in controlled release technologies has enabled LA ARV drug delivery systems (DDS) capable of providing extended dosing intervals and overcome the challenge of suboptimal drug adherence with daily oral dosing.

Areas covered

This review discusses the current state of the LA PrEP field, recent advances, and emerging technologies, including ARV prodrug modifications and new DDS. Technological challenges, knowledge gaps, preclinical testing considerations, and future directions important in the context of clinical translation and implementation of LA HIV PrEP are discussed.

Expert opinion

The HIV prevention field is evolving faster than ever and the bar for developing next-generation LA HIV prevention options continues to rise. The requirements for viable LA PrEP products to be implemented in resource-limited settings are challenging, necessitating proactive consideration and product modifications during the design and testing of promising new candidates. If successfully translated, next-generation LA PrEP that are safe, affordable, highly effective, and accepted by both end-users and key stakeholders will offer significant potential to curb the HIV pandemic.

KEYWORDS:

• Adherence
• antiretroviral
• HIV prevention
• implants
• injectable
• long-acting
• microbicide
• prodrug
• nanoformulations
• drug delivery system

Article highlights

• State of the current HIV PrEP field and the need for the development of next-generation LA PrEP approaches

• Review of approaches enhancing the LA potential of existing ARVs through chemical modification

• Novel drug delivery strategies for LA HIV prophylaxis

• Technical challenges and knowledge gaps in LA HIV prevention products development and clinical advancements

This box summarizes key points contained in the article.

Acknowledgments

The contents are the responsibility of the authors and do not necessarily reflect the views of USAID, NIH, NIAID, or the United States Government. The authors would also like to thank USAID for their support in organizing a one-day Technology Innovation Workshop on ‘Current Challenges & Emerging Approaches in Long Acting HIV Prevention,’ on 8 November 2018 (hosted by CONRAD in Arlington, VA, USA) and the workshop attendees. The meeting discussions inspired the field landscaping that culminated with this review.

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.

Reviewer disclosures

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

Additional information

Funding

This review was made possible by the generous support of the American people through the United States Agency for International Development (USAID) through cooperative agreement number AID-OAA-A-17-00014 and the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) under award number R33AI142685.