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
. 2022 Sep 7;14(9):1980.
doi: 10.3390/v14091980.

Forging a Functional Cure for HIV: Transcription Regulators and Inhibitors

Sonia Mediouni  1 , Shuang Lyu  1 , Susan M Schader  2 , Susana T Valente  1
Affiliations
Review

Forging a Functional Cure for HIV: Transcription Regulators and Inhibitors

Sonia Mediouni et al. Viruses. .

Abstract

Current antiretroviral therapy (ART) increases the survival of HIV-infected individuals, yet it is not curative. The major barrier to finding a definitive cure for HIV is our inability to identify and eliminate long-lived cells containing the dormant provirus, termed viral reservoir. When ART is interrupted, the viral reservoir ensures heterogenous and stochastic HIV viral gene expression, which can reseed infection back to pre-ART levels. While strategies to permanently eradicate the virus have not yet provided significant success, recent work has focused on the management of this residual viral reservoir to effectively limit comorbidities associated with the ongoing viral transcription still observed during suppressive ART, as well as limit the need for daily ART. Our group has been at the forefront of exploring the viability of the block-and-lock remission approach, focused on the long-lasting epigenetic block of viral transcription such that without daily ART, there is no risk of viral rebound, transmission, or progression to AIDS. Numerous studies have reported inhibitors of both viral and host factors required for HIV transcriptional activation. Here, we highlight and review some of the latest HIV transcriptional inhibitor discoveries that may be leveraged for the clinical exploration of block-and-lock and revolutionize the way we treat HIV infections.

Keywords: HIV; block-and-lock; epigenetic modulation; functional cure; inhibitors; latency; transcription.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Basal, Boost and Viral stages of HIV transcription.
Figure 2
Figure 2
Tat inhibitors. (A) Schematic of Tat protein’s domains. (B) Inhibitors of HIV Tat protein activities.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Marconi V.C., Moser C., Gavegnano C., Deeks S.G., Lederman M.M., Overton E.T., Tsibris A., Hunt P.W., Kantor A., Sekaly R.P., et al. Randomized Trial of Ruxolitinib in Antiretroviral-Treated Adults with Human Immunodeficiency Virus. Clin. Infect. Dis. 2022;74:95–104. doi: 10.1093/cid/ciab212. - DOI - PMC - PubMed
    1. Llibre J.M., Hung C.C., Brinson C., Castelli F., Girard P.M., Kahl L.P., Blair E.A., Angelis K., Wynne B., Vandermeulen K., et al. Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: Phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies. Lancet. 2018;391:839–849. doi: 10.1016/S0140-6736(17)33095-7. - DOI - PubMed
    1. Gupta R.K., Abdul-Jawad S., McCoy L.E., Mok H.P., Peppa D., Salgado M., Martinez-Picado J., Nijhuis M., Wensing A.M.J., Lee H., et al. HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation. Nature. 2019;568:244–248. doi: 10.1038/s41586-019-1027-4. - DOI - PMC - PubMed
    1. Gupta R.K., Peppa D., Hill A.L., Gálvez C., Salgado M., Pace M., McCoy L.E., Griffith S.A., Thornhill J., Alrubayyi A., et al. Evidence for HIV-1 cure after CCR5Δ32/Δ32 allogeneic haemopoietic stem-cell transplantation 30 months post analytical treatment interruption: A case report. Lancet HIV. 2020;7:e340–e347. doi: 10.1016/S2352-3018(20)30069-2. - DOI - PMC - PubMed
    1. The Lancet Hiv Like London buses, two putative cure cases arrive at once. Lancet HIV. 2019;6:e205. doi: 10.1016/S2352-3018(19)30086-4. - DOI - PubMed

Publication types

Substances