Abstract

A variety of interventions to induce a functional cure of HIV are being explored, with the aim being to allow patients to cease antiretroviral therapy (ART) for prolonged periods of time or for life. These interventions share the goal of inducing ART-free remission from HIV pathogenesis and disease progression but achieve this in quite different ways, by reducing the size of the latent reservoir (for example, small-molecule stimulation of latently infected cells), reducing the number of target cells available for the virus (for example, gene therapy) or improving immune responses (for example, active or passive immunotherapy). Here, we consider a number of these alternative strategies for inducing post-treatment control of HIV and use mathematical modelling to predict the scale of the challenge inherent in these different approaches. For many approaches, over 99.9% efficacy will likely be required to induce durable ART-free remissions. The efficacy of individual approaches is currently far below what we predict will be necessary, and new technologies to achieve lifelong functional cure are needed.

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Acknowledgements

The authors receive funding support in the form of research grants and fellowships from the National Health and Medical Research Council (NHMRC) of Australia, the Australian Research Council and the National Institutes of Health (NIH). S.R.L. receives additional research funding support from The American Foundation for AIDS Research (amFAR).

Competing interests

The authors declare potential competing interests: S.R.L. receives investigator-initiated grant funding from ViiV, Merck and Gilead Sciences. She has provided paid consultancies to AbbVie and received honoraria for chairing meetings from Gilead, ViiV, Merck and BMS. A.D.K. receives non-financial support from Merck and Cytognos for the conduct of clinical trials outside this work and grants from Calimmune and Celgene. S.J.K. reports grants and personal fees from ViiV HealthCare and Gilead Sciences and grants from Johnson and Johnson and Sanofi Pasteur. M.P.D., D.S.K. and D.C. declare no competing interests.

Author information

Affiliations

  1. Kirby Institute for Infection and Immunity, UNSW Australia, Sydney, New South Wales, Australia

    • Miles P. Davenport
    • , David S. Khoury
    • , Deborah Cromer
    •  & Anthony D. Kelleher
  2. The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Victoria, Australia

    • Sharon R. Lewin
    •  & Stephen J. Kent
  3. Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Victoria, Australia

    • Sharon R. Lewin
    •  & Stephen J. Kent
  4. Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia

    • Stephen J. Kent
  5. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, Victoria, Australia

    • Stephen J. Kent

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Contributions

M.P.D., D.S.K. and D.C. researched data for the article. M.P.D., D.S.K., D.C., S.R.L., A.D.K. and S.J.K. reviewed and edited the manuscript before submission, made substantial contributions to the discussion of content and wrote the manuscript.

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Nature Reviews Immunology thanks N. Goonetilleke and other anonymous reviewer(s) for their contribution to the peer review of this work.

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Correspondence to Miles P. Davenport.

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https://doi.org/10.1038/s41577-018-0085-4