Progress Note 2024: Curing HIV; Not in My Lifetime or Just Around the Corner?

• Type of Material: Article
• Authors: Justin Harper, Emory University; Michael R. Betts, University of Pennsylvania; Mathias Lichterfeld, Brigham and Women's Hospital; Michaela Muller-Trutwin, Université Paris-Cité; David Margolis, University of North Carolina; Katharine J. Bar, University of Pennsylvania; Jonathan Z. Li, Brigham and Women's Hospital; Joseph M. McCune, Bill & Melinda Gates Foundation; Sharon R. Lewin, University of Melbourne; Deanna Kulpa, Emory University; Santiago Avila-Rios, Instituto Nacional de Enfermedades Respiratorias; Dazon Dixon Diallo, SisterLove, Inc; Michael M. Lederman, Case Western Reserve University; Mirko Paiardini, Emory University
• Language: English
• Date: 2024-03-01
• Publisher: Case Western Reserves University
• Publication Version: Final Published Version
• Copyright Statement: © 2024 Pathogens and Immunity
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.20411/pai.v8i2.696; https://www.paijournal.com/index.php/paijournal/article/view/665
• Title of Journal or Parent Work: Pathogens and Immunity
• Volume: 8
• Issue: 2
• Start Page: 115
• End Page: 179
• Grant/Funding Agency: National Institutes of Health
• Grant/Funding Information: JH and MP are supported by funding from the Enterprise for Research and Advocacy to Stop and Eradicate (ERASE) HIV Martin Delaney Collaboratory co-funded by National Heart, Lung, and Blood Institute; National Institute of Diabetes, Digestive, and Kidney Diseases; National Institute of Neurological Disorders and Stroke; National Institute on Drug Abuse; and the National Institute of Allergy and Infectious Diseases (UM1AI164562).
• Keywords: SIV; HIV; ART; reservoir; HIV control; persistence; HIV cure
• Research Categories: Virology

Abstract

Once a death sentence, HIV is now considered a manageable chronic disease due to the development of antiretroviral therapy (ART) regimens with minimal toxicity and a high barrier for genetic resistance. While highly effective in arresting AIDS progression and rendering the virus untransmissible in people living with HIV (PLWH) with undetectable viremia (U=U) [1, 2], ART alone is incapable of eradicating the “reservoir” of resting, latently infected CD4+ T cells from which virus recrudesces upon treatment cessation. As of 2022 estimates, there are 39 million PLWH, of whom 86% are aware of their status and 76% are receiving ART [3]. As of 2017, ART-treated PLWH exhibit near normalized life expectancies without adjustment for socioeconomic differences [4]. Furthermore, there is a global deceleration in the rate of new infections [3] driven by expanded access to pre-exposure prophylaxis (PrEP), HIV testing in vulnerable populations, and by ART treatment [5]. Therefore, despite outstanding issues pertaining to cost and access in developing countries, there is strong enthusiasm that aggressive testing, treatment, and effective viral suppression may be able to halt the ongoing HIV epidemic (ie, UNAIDS' 95-95-95 targets) [6–8]; especially as evidenced by recent encouraging observations in Sydney [9]. Despite these promising efforts to limit further viral transmission, for PLWH, a “cure” remains elusive; whether it be to completely eradicate the viral reservoir (ie, cure) or to induce long-term viral remission in the absence of ART (ie, control; Figure 1). In a previous salon hosted by Pathogens and Immunity in 2016 [10], some researchers were optimistic that a cure was a feasible, scalable goal, albeit with no clear consensus on the best route. So, how are these cure strategies panning out? In this commentary, 8 years later, we will provide a brief overview on recent advances and failures towards identifying determinants of viral persistence and developing a scalable cure for HIV. Based on these observations, and as in the earlier salon, we have asked several prominent HIV cure researchers for their perspectives.