The future of long-acting agents for preexposure prophylaxis

Abstract

Purpose of reviewThe main reason for the failure of oral preexposure prophylaxis (PrEP) regimens for HIV is poor adherence. Intramuscular cabotegravir was recently approved for PrEP, and a number of other long-acting antiretroviral formulations and products are currently in clinical development. This includes subcutaneous and intravenous injections, implants, and microarray (microneedle) patches, as well as extended duration oral drugs. The success and future uptake of these products will depend on a variety of factors. Recent findingsLong-acting delivery of antiretroviral agents for PrEP confers significant advantages over short-acting oral delivery. This is exemplified by the superior efficacy of intramuscular cabotegravir given every eight weeks as compared to daily oral co-formulated tenofovir disoproxil fumarate and emtricitabine. There is also evidence for PrEP efficacy for a broadly neutralizing monoclonal antibody given intravenously every eight weeks. One of the leading candidates for long-acting PrEP, islatravir, was being studied as a monthly oral drug or a nonerodable subcutaneous implant inserted for up to 12 months. However, clinical studies of this agent were put on hold in late 2021 because of unanticipated lymphopenia.

The importance of the “how”: the case for differentiated service delivery of long‐acting and extended delivery regimens for HIV prevention and treatment

“…1 HIV Programmes and Advocacy, IAS -the International AIDS Society, Cape Town, South Africa; 2 Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa; 3 Wits RHI, University of the Witwatersrand, Johannesburg, South Africa; 4 Global Health, Bill & Melinda Gates Foundation, Seattle, Washington, USA; 5 Primary Health Care, PATH, Seattle, Washington, USA; 6 Primary Health Care, PATH, Hanoi, Vietnam; 7 Lean on Me Foundation, Nairobi, Kenya; 8 School of Public Health, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya; 9 Department of Global Health, University of Washington, Seattle, Washington, USA; 10 National Empowerment Network of People Living with HIV/AIDS in Kenya (NEPHAK), Nairobi, Kenya; 11 The Thai Red Cross AIDS Research Centre -PREVENTION, Bangkok, Thailand; 12 Global Network of People Living with HIV (GNP+), Cape Town, South Africa; 13 Global HIV, Hepatitis, and Sexually Transmitted Infections Programmes, World Health Organization, Geneva, Switzerland; 14 IAS -International AIDS Society, Geneva, Switzerland…”

Women for science and science for women: Gaps, challenges and opportunities towards optimizing pre-exposure prophylaxis for HIV-1 prevention

“…The lymphocytopenia was transient and normalized once the islatravir was discontinued, however the risk of depleted lymphocytes predisposes to increased risk for infections. Under early stage clinical evaluation is also an annual TAF implant and an elvitegravir (EVG)/TAF vaginal insert ( 35 , 82 , 83 ). Preclinical proof-of-concept for preventing vaginal transmission of simian human immunodeficiency virus (SHIV) in non-human primates has been demonstrated for this product ( 35 ).…”

The path to equitable HIV prevention

“…Nevertheless, they will be insufficient to reach the population-level epidemic dynamics if not successfully implemented. Long-acting PrEP is a potential game-changer for populations whose social vulnerabilities contribute to poorer PrEP outcome 16 . Hopefully access barriers will not hinder the benefits for those most in need.…”