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Functional cure of HIV: the scale of the challenge

Nature Reviews Immunology volume 19, pages 45–54 (2019)Cite this article

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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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Fig. 1: Potential effects of interventions to control latency.
Fig. 2: Predicting the effects of reducing the reservoir or the frequency of reactivation on the duration of remission.
Fig. 3: Modelling the impact of gene therapy on HIV remission.
Fig. 4: Effects of immune therapies on HIV remission.
Fig. 5: Predicting synergies from combination therapy.
Fig. 6: Predicting the potency of different latency interventions.

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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.

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Authors and 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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  1. Miles P. Davenport
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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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Correspondence to Miles P. Davenport.

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Davenport, M.P., Khoury, D.S., Cromer, D. et al. Functional cure of HIV: the scale of the challenge. Nat Rev Immunol 19, 45–54 (2019). https://doi.org/10.1038/s41577-018-0085-4

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