Meeting Summary for Keystone Symposia on HIV Cure: Antiretroviral Therapy (ART)-Free Control of HIV Infection in Durban, South Africa, 2025

Kiho Tanaka¹, Tatenda Jimmy Blessing Chikowore^{2

3}, Steven G Deeks⁴, Jacob D Estes⁵, Ya-Chi Ho⁶, Sizun Jiang⁷, Ming Jie Lee⁸, Chang Li⁹, Albert Machinda¹⁰, Mauricio Martins¹¹, Patrick Mdletshe¹², Zaza M Ndhlovu^{2

13

14}, Ujjwal Neogi¹⁵, Melanie M Ott^{16

4}, Thomas A Rasmussen^{1

17}, Kavidha Reddy², Rachel L Rutishauser⁴, Anna Farrell-Sherman^{18

19}, Caroline T Tiemessen²⁰, James E Voss²¹, Cissy Kityo²², Sharon R Lewin^{1

23

24}, Thumbi Ndung'u^{2

3

21

25}, Joseph M McCune²⁶

Affiliations

¹ Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
² Africa Health Research Institute, Durban, South Africa.
³ University College London, London, United Kingdom.
⁴ Department of Medicine, University of California, San Francisco, San Francisco, California.
⁵ Vaccine & Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon.
⁶ Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut.
⁷ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
⁸ Department of Infectious Disease, Imperial College London, London, United Kingdom.
⁹ University of Washington, Department of Medicine, Division of Medical Genetics, Seattle, Washington.
¹⁰ The Africa HIV Cure Consortium (AHCC) and CIDRZ, Zambia.
¹¹ Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, Florida.
¹² Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.
¹³ School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
¹⁴ Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, Massachusetts.
¹⁵ Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.
¹⁶ Gladstone Institute of Virology, University of California, San Francisco, San Francisco, California.
¹⁷ Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
¹⁸ Fred Hutchinson Cancer Center, Vaccine and Infectious Disease Division, Seattle, Washington.
¹⁹ Molecular and Cellular Biology PhD Program, University of Washington, Seattle, Washington.
²⁰ Centre for HIV and STIs, National Institutes of Communicable Diseases, a division of the National Health Laboratory Service, and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
²¹ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California.
²² Joint Clinical Research Centre (JCRC), Kampala, Uganda.
²³ Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
²⁴ Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia.
²⁵ HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
²⁶ HIV Frontiers, Global Health Accelerator, Gates Foundation, Seattle, Washington.

PMID: 41143136
PMCID: PMC12553517
DOI: 10.20411/pai.v10i2.885

Meeting Summary for Keystone Symposia on HIV Cure: Antiretroviral Therapy (ART)-Free Control of HIV Infection in Durban, South Africa, 2025

Kiho Tanaka et al. Pathog Immun. 2025.

. 2025 Oct 18;10(2):196-229.

doi: 10.20411/pai.v10i2.885. eCollection 2025.

Authors

Affiliations

¹ Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
² Africa Health Research Institute, Durban, South Africa.
³ University College London, London, United Kingdom.
⁴ Department of Medicine, University of California, San Francisco, San Francisco, California.
⁵ Vaccine & Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon.
⁶ Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut.
⁷ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
⁸ Department of Infectious Disease, Imperial College London, London, United Kingdom.
⁹ University of Washington, Department of Medicine, Division of Medical Genetics, Seattle, Washington.
¹⁰ The Africa HIV Cure Consortium (AHCC) and CIDRZ, Zambia.
¹¹ Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, Florida.
¹² Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.
¹³ School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
¹⁴ Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, Massachusetts.
¹⁵ Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.
¹⁶ Gladstone Institute of Virology, University of California, San Francisco, San Francisco, California.
¹⁷ Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
¹⁸ Fred Hutchinson Cancer Center, Vaccine and Infectious Disease Division, Seattle, Washington.
¹⁹ Molecular and Cellular Biology PhD Program, University of Washington, Seattle, Washington.
²⁰ Centre for HIV and STIs, National Institutes of Communicable Diseases, a division of the National Health Laboratory Service, and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
²¹ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California.
²² Joint Clinical Research Centre (JCRC), Kampala, Uganda.
²³ Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
²⁴ Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia.
²⁵ HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
²⁶ HIV Frontiers, Global Health Accelerator, Gates Foundation, Seattle, Washington.

PMID: 41143136
PMCID: PMC12553517
DOI: 10.20411/pai.v10i2.885

Abstract

Antiretroviral therapy (ART) can effectively control human immunodeficiency virus (HIV) replication; however, lifelong treatment is required due to viral reservoirs, which fuel viral rebound. This necessitates curative interventions that can achieve either eradication of the reservoir or durable remission off ART. Advances in technology have fostered development of multi-omic techniques encompassing molecular tools, proteomic analyses, imaging, and artificial intelligence (AI)-driven data analysis to understand HIV reservoir biology and persistence. These have informed the investigation of therapeutic interventions such as broadly neutralizing antibodies, latency reversal, immune cell augmentation, antivirals, and gene therapy. From April 7-10, 2025, experts in the field convened at the Keystone Symposia conference, HIV Cure: Antiretroviral Therapy (ART)-Free Control of HIV Infection in Durban, South Africa, to discuss novel strategies for eradication and/or durable ART-free control of HIV.

Keywords: Africa; Animal Models; Antiretroviral Therapy-free Control; Antiretrovirals; Artificial Intelligence; Broadly Neutralizing Antibodies; Clinical Trials; Community; Cure; Gene Therapy; HIV; Imaging; Immune Cells; LMIC; Latency Reversal; Molecular; Multi-omics; Persistence; Proteomics; Reservoir; Therapeutics.

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Conflict of interest statement

The authors report no additional conflicts of interest.

Figures

**Figure 1.**
**Therapeutic approaches for ART-free control of HIV**. Many approaches have been investigated to achieve ART-free control of HIV, including those using broadly neutralizing antibodies, strategies to improve anti-HIV cellular responses, and other interventions such as Tat-based therapeutics, targeting metabolic pathways and apoptosis induction by the BCL-2 inhibitor, venetoclax. Of note, many strategies involved gene editing approaches, such as AAV delivery of broadly neutralising monoclonal antibodies, CAR moieties, CCR5 knockdown, and the use of CRISPR to induce or silence transcription of latent HIV and to genetically reprogram B cells.

See this image and copyright information in PMC

References

1. Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, Chaisson RE, Quinn TC, Chadwick K, Margolick J, Brookmeyer R, Gallant J, Markowitz M, Ho DD, Richman DD, Siliciano RF.. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science. 1997;278(5341):1295-300. doi: 10.1126/science.278.5341.1295. PubMed PMID: . - DOI - PubMed
1. Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JA, Baseler M, Lloyd AL, Nowak MA, Fauci AS.. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A. 1997;94(24):13193-7. doi: 10.1073/pnas.94.24.13193. PubMed PMID: ; PMCID: . - DOI - PMC - PubMed
1. Wong JK, Hezareh M, Gunthard HF, Havlir DV, Ignacio CC, Spina CA, Richman DD.. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science. 1997;278(5341):1291-5. doi: 10.1126/science.278.5341.1291. PubMed PMID: . - DOI - PubMed
1. Chawla A, Wang C, Patton C, Murray M, Punekar Y, de Ruiter A, Steinhart C.. A Review of Long-Term Toxicity of Antiretroviral Treatment Regimens and Implications for an Aging Population. Infect Dis Ther. 2018;7(2):183-95. doi: 10.1007/s40121-018-0201-6. PubMed PMID: ; PMCID: . - DOI - PMC - PubMed
1. Rosenberg NE, Shook-Sa BE, Liu M, Stranix-Chibanda L, Yotebieng M, Sam-Agudu NA, Hudgens MG, Phiri SJ, Mutale W, Bekker LG, Moyo S, Zuma K, Charurat ME, Justman J, Chi BH.. Adult HIV-1 incidence across 15 high-burden countries in sub-Saharan Africa from 2015 to 2019: a pooled analysis of nationally representative data. Lancet HIV. 2023;10(3):e175-e85. doi: 10.1016/S2352-3018(22)00328-9. PubMed PMID: ; PMCID: . - DOI - PMC - PubMed

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Meeting Summary for Keystone Symposia on HIV Cure: Antiretroviral Therapy (ART)-Free Control of HIV Infection in Durban, South Africa, 2025

Affiliations

Meeting Summary for Keystone Symposia on HIV Cure: Antiretroviral Therapy (ART)-Free Control of HIV Infection in Durban, South Africa, 2025

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources

Miscellaneous