Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Dec;576(7787):397-405.
doi: 10.1038/s41586-019-1841-8. Epub 2019 Dec 18.

Why and where an HIV cure is needed and how it might be achieved

Thumbi Ndung'u  1   2   3 , Joseph M McCune  4 , Steven G Deeks  5
Affiliations
Review

Why and where an HIV cure is needed and how it might be achieved

Thumbi Ndung'u et al. Nature. 2019 Dec.

Abstract

Despite considerable global investment, only 60% of people who live with HIV currently receive antiretroviral therapy. The sustainability of current programmes remains unknown and key incidence rates are declining only modestly. Given the complexities and expenses associated with lifelong medication, developing an effective curative intervention is now a global priority. Here we review why and where a cure is needed, and how it might be achieved. We argue for expanding these efforts from resource-rich regions to sub-Saharan Africa and elsewhere: for any intervention to have an effect, region-specific biological, therapeutic and implementation issues must be addressed.

PubMed Disclaimer

Conflict of interest statement

Competing interests S.G.D. receives grant support from Gilead, Merck and ViiV. He is a member of the scientific advisory boards for BryoLogyx and Enochian Biosciences and has consulted for AbbVie, Biotron and Eli Lilly. T.N. receives grant support from Gilead.

Figures

Fig. 1 |
Fig. 1 |. Pathways towards a cure.
There are two broadly defined pathways for a treatment-free period of virus control. a, Eradication. The ideal outcome for a curative intervention would be the complete eradication of all replication-competent virus; gene-editing, latency reversal and block-and-lock approaches are all aimed at reducing the reservoir size and, if fully effective, could lead to complete eradication of the virus within an individual. b, Remission. Given observations made in elite and post-treatment controllers, a more plausible strategy may be to reduce the reservoir to more manageable levels while also enhancing immune control. Multiple combination approaches are now being pursued. CTLs, cytotoxic T lymphocytes.
Fig. 2 |
Fig. 2 |. The cascade of treatment and control.
According to the most recent UNAIDS estimates, of the 37.9 million people living with HIV, only about 79% have been diagnosed and only about 53% are on effective therapy. It is estimated that about 1% are doing well in the absence of therapy (‘elite’ control and rarely ‘post-treatment control’). Only two individuals are believed to have been cured.
Fig. 3 |
Fig. 3 |. HIV remission pathway.
Many strategies that are currently in development are aimed at achieving durable control, rather than complete eradication. All interventions require individuals to first control HIV with ART. Interventions that are aimed at reducing the reservoir size (shock-and-kill, block-and-lock) are then initiated, followed by combination approaches to enhance immune control. ART is eventually interrupted, followed by an expected transient period of transient viraemia and eventually control of HIV. Post-ART monitoring of viral load may prove to be the most challenging and expensive component of this strategy.
See this image and copyright information in PMC

Comment in

References

    1. Hütter G et al. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N. Engl. J. Med 360, 692–698 (2009). - PubMed
    1. Gupta RK et al. HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation. Nature 568, 244–248 (2019). - PMC - PubMed

    2. Two HIV-infected adults, with haematological malignancies were apparently cured of HIV after an effective stem-cell transplant from an allogeneic donor whose T cells lacked CCR5, a key co-receptor for virus entry.

    1. Namazi G et al. The control of HIV after antiretroviral medication pause (CHAMP) study: posttreatment controllers identified from 14 clinical studies. J. Infect. Dis 218, 1954–1963 (2018). - PMC - PubMed
    1. Sáez-Cirión A et al. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog. 9, e1003211 (2013). - PMC - PubMed

    2. A subset of HIV-infected adults who start ART early and remain on therapy for a sustained period are able to effectively control HIV replication after treatment interruption; although the mechanism(s) at play remain unclear, these ‘post-treatment controllers’ provide strong evidence that the host–virus association can in some settings be slanted towards ART-free viral remission.

    1. Deeks SG et al. International AIDS Society global scientific strategy: towards an HIV cure 2016. Nat. Med 22, 839–850 (2016). - PMC - PubMed

Publication types