Eliminating the Latent HIV Reservoir by Reactivation Strategies: Advancing to Clinical Trials

Overview

Journal Hum Vaccin Immunother

Specialty Allergy & Immunology

Date 2013 Apr 9

PMID 23563519

Citations 30

Authors

Thomas A Rasmussen

Martin Tolstrup

Anni Winckelmann

Lars Ostergaard

Ole S Sogaard

Affiliations

Soon will be listed here.

Abstract

Combination antiretroviral therapy (cART) has transformed HIV from a deadly to a chronic disease, but HIV patients are still burdened with excess morbidity and mortality, long-term toxicities from cART, stigmatization, and insufficient access to cART worldwide. Thus, a cure for HIV would have enormous impact on society as well as the individual. As the complexity and mechanisms of HIV persistence during therapy are being unraveled, new therapeutic targets for HIV eradication are discovered. Substances that activate HIV production in the latently infected cells have recently received much attention. By turning on expression of latent HIV proviruses, reactivation strategies could contribute to the eradication HIV infection. Compounds that are currently being or soon to be tested in clinical trials are emphasized. The results from these trials will provide important clues as to whether or not reactivating strategies could become significant components of a cure for HIV.

Citing Articles

The role of genetic diversity, epigenetic regulation, and sex-based differences in HIV cure research: a comprehensive review.

Letchumanan P, Das K Epigenetics Chromatin. 2025; 18(1):1.

PMID: 39754177 PMC: 11697457. DOI: 10.1186/s13072-024-00564-4.

Targeting Viral Transcription for HIV Cure Strategies.

Izquierdo-Pujol J, Puertas M, Martinez-Picado J, Moron-Lopez S Microorganisms. 2024; 12(4).

PMID: 38674696 PMC: 11052381. DOI: 10.3390/microorganisms12040752.

Identifying the dynamic gene regulatory network during latent HIV-1 reactivation using high-dimensional ordinary differential equations.

Song J, Carey M, Zhu H, Miao H, Ramirez J, Wu H Int J Comput Biol Drug Des. 2021; 11(1-2):135-153.

PMID: 34531927 PMC: 8442249. DOI: 10.1504/ijcbdd.2018.10011910.

Attacking Latent HIV with convertibleCAR-T Cells, a Highly Adaptable Killing Platform.

Herzig E, Kim K, Packard T, Vardi N, Schwarzer R, Gramatica A Cell. 2019; 179(4):880-894.e10.

PMID: 31668804 PMC: 6922308. DOI: 10.1016/j.cell.2019.10.002.

Polyanionic carbosilane dendrimers as a new adjuvant in combination with latency reversal agents for HIV treatment.

Relano-Rodriguez I, Juarez-Sanchez R, Pavicic C, Munoz E, Munoz-Fernandez M J Nanobiotechnology. 2019; 17(1):69.

PMID: 31113488 PMC: 6529996. DOI: 10.1186/s12951-019-0500-4.

References

Andreeff M, Stone R, Michaeli J, Young C, Tong W, Sogoloff H . Hexamethylene bisacetamide in myelodysplastic syndrome and acute myelogenous leukemia: a phase II clinical trial with a differentiation-inducing agent. Blood. 1992; 80(10):2604-9. View

Rullas J, Bermejo M, Garcia-Perez J, Beltan M, Gonzalez N, Hezareh M . Prostratin induces HIV activation and downregulates HIV receptors in peripheral blood lymphocytes. Antivir Ther. 2004; 9(4):545-54. View

Imamichi H, DeGray G, Asmuth D, Fischl M, Landay A, Lederman M . HIV-1 viruses detected during episodic blips following interleukin-7 administration are similar to the viruses present before and after interleukin-7 therapy. AIDS. 2010; 25(2):159-64. PMC: 3074174. DOI: 10.1097/QAD.0b013e328340a270. View

Neuhaus J, Jacobs Jr D, Baker J, Calmy A, Duprez D, La Rosa A . Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection. J Infect Dis. 2010; 201(12):1788-95. PMC: 2872049. DOI: 10.1086/652749. View

Minucci S, Pelicci P . Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer. 2006; 6(1):38-51. DOI: 10.1038/nrc1779. View

van Praag R, Prins J, Roos M, Schellekens P, ten Berge I, Yong S . OKT3 and IL-2 treatment for purging of the latent HIV-1 reservoir in vivo results in selective long-lasting CD4+ T cell depletion. J Clin Immunol. 2001; 21(3):218-26. DOI: 10.1023/a:1011091300321. View

Kuller L, Tracy R, Belloso W, De Wit S, Drummond F, Lane H . Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008; 5(10):e203. PMC: 2570418. DOI: 10.1371/journal.pmed.0050203. View

Doyon G, Zerbato J, Mellors J, Sluis-Cremer N . Disulfiram reactivates latent HIV-1 expression through depletion of the phosphatase and tensin homolog. AIDS. 2012; 27(2):F7-F11. DOI: 10.1097/QAD.0b013e3283570620. View

Levy Y, Sereti I, Tambussi G, Routy J, Lelievre J, Delfraissy J . Effects of recombinant human interleukin 7 on T-cell recovery and thymic output in HIV-infected patients receiving antiretroviral therapy: results of a phase I/IIa randomized, placebo-controlled, multicenter study. Clin Infect Dis. 2012; 55(2):291-300. PMC: 3381639. DOI: 10.1093/cid/cis383. View

10.

Routy J, Tremblay C, Angel J, Trottier B, Rouleau D, Baril J . Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study. HIV Med. 2012; 13(5):291-6. DOI: 10.1111/j.1468-1293.2011.00975.x. View

11.

Akimova T, Beier U, Liu Y, Wang L, Hancock W . Histone/protein deacetylases and T-cell immune responses. Blood. 2012; 119(11):2443-51. PMC: 3311271. DOI: 10.1182/blood-2011-10-292003. View

12.

Hutter G, Nowak D, Mossner M, Ganepola S, Mussig A, Allers K . Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med. 2009; 360(7):692-8. DOI: 10.1056/NEJMoa0802905. View

13.

Contreras X, Schweneker M, Chen C, McCune J, Deeks S, Martin J . Suberoylanilide hydroxamic acid reactivates HIV from latently infected cells. J Biol Chem. 2009; 284(11):6782-9. PMC: 2652322. DOI: 10.1074/jbc.M807898200. View

14.

Bouchat S, Gatot J, Kabeya K, Cardona C, Colin L, Herbein G . Histone methyltransferase inhibitors induce HIV-1 recovery in resting CD4(+) T cells from HIV-1-infected HAART-treated patients. AIDS. 2012; 26(12):1473-82. DOI: 10.1097/QAD.0b013e32835535f5. View

15.

Levy Y, Lacabaratz C, Weiss L, Viard J, Goujard C, Lelievre J . Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment. J Clin Invest. 2009; 119(4):997-1007. PMC: 2662568. DOI: 10.1172/JCI38052. View

16.

Shan L, Deng K, Shroff N, Durand C, Rabi S, Yang H . Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity. 2012; 36(3):491-501. PMC: 3501645. DOI: 10.1016/j.immuni.2012.01.014. View

17.

Schlaepfer E, Speck R . TLR8 activates HIV from latently infected cells of myeloid-monocytic origin directly via the MAPK pathway and from latently infected CD4+ T cells indirectly via TNF-α. J Immunol. 2011; 186(7):4314-24. DOI: 10.4049/jimmunol.1003174. View

18.

Kovochich M, Marsden M, Zack J . Activation of latent HIV using drug-loaded nanoparticles. PLoS One. 2011; 6(4):e18270. PMC: 3071729. DOI: 10.1371/journal.pone.0018270. View

19.

Persaud D, Luzuriaga K, Ziemniak C, Muresan P, Greenough T, Fenton T . Effect of therapeutic HIV recombinant poxvirus vaccines on the size of the resting CD4+ T-cell latent HIV reservoir. AIDS. 2011; 25(18):2227-34. PMC: 3314338. DOI: 10.1097/QAD.0b013e32834cdaba. View

20.

Margolis D . Eradication therapies for HIV Infection: time to begin again. AIDS Res Hum Retroviruses. 2011; 27(4):347-53. PMC: 3065332. DOI: 10.1089/AID.2011.0017. View