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Current HIV Research

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ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

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Systematic Review Article

A Review of Current Strategies Towards the Elimination of Latent HIV-1 and Subsequent HIV-1 Cure

Author(s): Edward K. Maina*, Asma A. Adan, Haddison Mureithi, Joseph Muriuki and Raphael M. Lwembe

Volume 19, Issue 1, 2021

Published on: 19 August, 2020

Page: [14 - 26] Pages: 13

DOI: 10.2174/1570162X18999200819172009

open access plus

Abstract

Background: During the past 35 years, highly effective ART has saved the lives of millions of people worldwide by suppressing viruses to undetectable levels. However, this does not translate to the absence of viruses in the body as HIV persists in latent reservoirs. Indeed, rebounded HIV has been recently observed in the Mississippi and California infants previously thought to have been cured. Hence, much remains to be learned about HIV latency, and the search for the best strategy to eliminate the reservoir is the direction current research is taking. A systems-level approach that fully recapitulates the dynamics and complexity of HIV-1 latency In vivo and is applicable in human therapy is prudent for HIV eradication to be more feasible.

Objectives: The main barriers preventing the cure of HIV with antiretroviral therapy have been identified, progress has been made in the understanding of the therapeutic targets to which potentially eradicating drugs could be directed, integrative strategies have been proposed, and clinical trials with various alternatives are underway. The aim of this review is to provide an update on the main advances in HIV eradication, with particular emphasis on the obstacles and the different strategies proposed. The core challenges of each strategy are highlighted and the most promising strategy and new research avenues in HIV eradication strategies are proposed.

Methods: A systematic literature search of all English-language articles published between 2015 and 2019, was conducted using MEDLINE (PubMed) and Google scholar. Where available, medical subject headings (MeSH) were used as search terms and included: HIV, HIV latency, HIV reservoir, latency reactivation, and HIV cure. Additional search terms consisted of suppression, persistence, establishment, generation, and formation. A total of 250 articles were found using the above search terms. Out of these, 89 relevant articles related to HIV-1 latency establishment and eradication strategies were collected and reviewed, with no limitation of study design. Additional studies (commonly referenced and/or older and more recent articles of significance) were selected from bibliographies and references listed in the primary resources.

Results: In general, when exploring the literature, there are four main strategies heavily researched that provide promising strategies to the elimination of latent HIV: Haematopoietic Stem-Cell Transplantation, Shock and Kill Strategy, Gene-specific transcriptional activation using RNA-guided CRISPR-Cas9 system, and Block and Lock strategy. Most of the studies of these strategies are applicable in vitro, leaving many questions about the extent to which, or if any, these strategies are applicable to complex picture In vivo. However, the success of these strategies at least shows, in part, that HIV-1 can be cured, though some strategies are too invasive and expensive to become a standard of care for all HIV-infected patients.

Conclusion: Recent advances hold promise for the ultimate cure of HIV infection. A systems-level approach that fully recapitulates the dynamics and complexity of HIV-1 latency In vivo and applicable in human therapy is prudent for HIV eradication to be more feasible. Future studies aimed at achieving a prolonged HIV remission state are more likely to be successful if they focus on a combination strategy, including the block and kill, and stem cell approaches. These strategies propose a functional cure with minimal toxicity for patients. It is believed that the cure of HIV infection will be attained in the short term if a strategy based on purging the reservoirs is complemented with an aggressive HAART strategy.

Keywords: HIV-1 latency, latent reservoir, transplantation, shock and kill, block and lock, CRISPR-Cas9.

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[1]
Søgaard OS, Graversen ME, Leth S, et al. The Depsipeptide Romidepsin Reverses HIV-1 Latency In vivo. PLoS Pathog 2015; 11(9): e1005142.
[http://dx.doi.org/10.1371/journal.ppat.1005142] [PMID: 26379282]
[2]
Elsheikh M M, Tang Y, Li D, Jiang G. Deep latency: A new insight into a functional HIV cure EBioMedicine 2019; 45: 624-9.
[http://dx.doi.org/10.1016/j.ebiom.2019.06.020]
[3]
Woodham AW, Skeate JG, Sanna AM, et al. Human immunodeficiency virus immune cell receptors, coreceptors, and cofactors: Implications for prevention and treatment. AIDS Patient Care STDS 2016; 30(7): 291-306.
[http://dx.doi.org/10.1089/apc.2016.0100] [PMID: 27410493]
[4]
Kulpa DA, Chomont N. HIV persistence in the setting of antiretroviral therapy: when, where and how does HIV hide? J virus Erad 2020; 1(2): 59-66.http://www.ncbi.nlm.nih.gov/pubmed/26448966
[5]
Chun T W, Moir S, Fauci A S. HIV reservoirs as obstacles and opportunities for an HIV cure Nature Immunology 2015; 16(6): 584-9.
[http://dx.doi.org/10.1038/ni.3152]
[6]
Shah A, Gangwani MR, Chaudhari NS, Glazyrin A, Bhat HK, Kumar A. Neurotoxicity in the Post-HAART Era: Caution for the Antiretroviral Therapeutics. Neurotox Res 2016; 30(4): 677-97.
[http://dx.doi.org/10.1007/s12640-016-9646-0] [PMID: 27364698]
[7]
Bertrand L, Velichkovska M, Toborek M. Cerebral Vascular Toxicity of Antiretroviral Therapy. J Neuroimmune Pharmacol 2019; LLC: 1-16.
[http://dx.doi.org/10.1007/s11481-019-09858-x] [PMID: 31209776]
[8]
Mouton J P, Cohen K, Maartens G. Key toxicity issues with the WHO-recommended first-line antiretroviral therapy regimen Expert Review of Clinical Pharmacology 2016; 9(11): 1493-503.
[http://dx.doi.org/10.1080/17512433.2016.1221760]
[9]
Casado JL, Santiuste C, Vazquez M, et al. Bone mineral density decline according to renal tubular dysfunction and phosphaturia in tenofovir-exposed HIV-infected patients. AIDS 2016; 30(9): 1423-31.
[http://dx.doi.org/10.1097/QAD.0000000000001067] [PMID: 26919733]
[10]
Gupta R K, et al. HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation Nature, Nature Publishing Group 2019; 568(7751): 244-8.
[http://dx.doi.org/10.1038/s41586-019-1027-4]
[11]
Sáez-Cirión A, Bacchus C, Hocqueloux L, et al. ANRS VISCONTI Study Group. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog 2013; 9(3): e1003211.
[http://dx.doi.org/10.1371/journal.ppat.1003211] [PMID: 23516360]
[12]
Shiau S, Kuhn L. Antiretroviral treatment in HIV-infected infants and young children: Novel issues raised by the Mississippi baby Expert Review of Anti-Infective Therapy 2014; 12(3): 307-18.
[http://dx.doi.org/10.1586/14787210.2014.888311]
[13]
Kim Y, Anderson J L, Lewin S R. Getting the ‘kill’ into ‘shock and kill’: Strategies to eliminate latent HIV cell host and microbe 2018; 23(1): 14-26.
[http://dx.doi.org/10.1016/j.chom.2017.12.004]
[14]
Saayman SM, Lazar DC, Scott TA, et al. Potent and targeted activation of latent HIV-1 using the CRISPR/dCas9 activator complex. Mol Ther 2016; 24(3): 488-98.
[http://dx.doi.org/10.1038/mt.2015.202] [PMID: 26581162]
[15]
Vanhamel J, Bruggemans A, Debyser Z. Establishment of latent HIV-1 reservoirs: what do we really know? J virus Erad 2019; 5(1): 3-9.http://www.ncbi.nlm.nih.gov/pubmed/30800420
[16]
Xiao Q, Guo D, Chen S. Application of CRISPR/Cas9-based gene editing in HIV-1/AIDS therapy Frontiers in Cellular and Infection Microbiology 2019; 9: 69.
[http://dx.doi.org/10.3389/fcimb.2019.00069]
[17]
Spivak AM, Planelles V. Novel Latency Reversal Agents for HIV-1 Cure. Annu Rev Med 2018; 69(1): 421-36.
[http://dx.doi.org/10.1146/annurev-med-052716-031710] [PMID: 29099677]
[18]
Barton K, Hiener B, Winckelmann A, et al. Broad activation of latent HIV-1 In vivo. Nat Commun 2016; 7(1): 12731.
[http://dx.doi.org/10.1038/ncomms12731] [PMID: 27605062]
[19]
Huang H, Liu S, Jean M, et al. A novel bromodomain inhibitor reverses HIV-1 latency through Specific binding with BRD4 to promote tat and P-TEFb association. Front Microbiol 2017; 8(JUN): 1035.
[http://dx.doi.org/10.3389/fmicb.2017.01035] [PMID: 28638377]
[20]
Marsden M D, Zack J A. HIV cure strategies: A complex approach for a complicated viral reservoir? Future Virology 2019; 14(1): 5-8.
[http://dx.doi.org/10.2217/fvl-2018-0205]
[21]
Duarte RF, Salgado M, Sánchez-Ortega I, et al. CCR5 Δ32 homozygous cord blood allogeneic transplantation in a patient with HIV: a case report. Lancet HIV 2015; 2(6): e236-42.
[http://dx.doi.org/10.1016/S2352-3018(15)00083-1] [PMID: 26423196]
[22]
Tebas P, Stein D, Tang WW, et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N Engl J Med 2014; 370(10): 901-10.
[http://dx.doi.org/10.1056/NEJMoa1300662] [PMID: 24597865]
[23]
Kessing CF, Nixon CC, Li C, et al. In Vivo suppression of HIV rebound by didehydro-cortistatin A, a “block-and-lock” strategy for HIV-1 treatment. Cell Rep 2017; 21(3): 600-11.
[http://dx.doi.org/10.1016/j.celrep.2017.09.080] [PMID: 29045830]
[24]
Deeks S G. HIV: Shock and kill. Nature 2012; 487(7408): 439-40.
[25]
Margolis D M, Garcia J V, Hazuda D J, Haynes B F. Latency reversal and viral clearance to cure HIV-1. Science 2016; 353 (6297): aaf6517.
[http://dx.doi.org/10.1126/science.aaf6517]
[26]
Kumar A, Darcis G, Van Lint C, Herbein G. Epigenetic control of HIV-1 post integration latency: Implications for therapy Clinical Epigenetics,Springer Verlag 2015; 7(1): 1-12.
[http://dx.doi.org/10.1186/s13148-015-0137-6]
[27]
Ellmeier W, Seiser C. Histone deacetylase function in CD4+ T cells Nature Reviews Immunology, Nature Publishing Group 2018; 18(10): 617-34.
[http://dx.doi.org/10.1038/s41577-018-0037-z]
[28]
Sung JA, Sholtis K, Kirchherr J, et al. Vorinostat renders the replication-competent latent reservoir of human immunodeficiency virus (HIV) vulnerable to clearance by CD8 T cells. EBioMedicine 2017; 23: 52-8.
[http://dx.doi.org/10.1016/j.ebiom.2017.07.019] [PMID: 28803740]
[29]
Wu G, Swanson M, Talla A, et al. HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal. JCI Insight 2017; 2(16): 92901.
[http://dx.doi.org/10.1172/jci.insight.92901] [PMID: 28814661]
[30]
Grau-Expósito J, Luque-Ballesteros L, Navarro J, et al. Latency reversal agents affect differently the latent reservoir present in distinct CD4+ T subpopulations. PLoS Pathog 2019; 15(8): e1007991.
[http://dx.doi.org/10.1371/journal.ppat.1007991] [PMID: 31425551]
[31]
Winckelmann A, Barton K, Hiener B, et al. Romidepsin-induced HIV-1 viremia during effective antiretroviral therapy contains identical viral sequences with few deleterious mutations. AIDS 2017; 31(6): 771-9.
[http://dx.doi.org/10.1097/QAD.0000000000001400] [PMID: 28272134]
[32]
Rasmussen TA, Tolstrup M, Brinkmann CR, et al. Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial. Lancet HIV 2014; 1(1): e13-21.
[http://dx.doi.org/10.1016/S2352-3018(14)70014-1] [PMID: 26423811]
[33]
Jamaluddin MS, Hu P-W, Jan Y, Siwak EB, Rice AP. Short communication: The broad-spectrum histone deacetylase inhibitors vorinostat and panobinostat activate latent HIV in CD4(+) T cells in part through phosphorylation of the T-loop of the CDK9 subunit of P-TEFb. AIDS Res Hum Retroviruses 2016; 32(2): 169-73.
[http://dx.doi.org/10.1089/aid.2015.0347] [PMID: 26727990]
[34]
Leth S, Schleimann MH, Nissen SK, et al. Combined effect of Vacc-4x, recombinant human granulocyte macrophage colony-stimulating factor vaccination, and romidepsin on the HIV-1 reservoir (REDUC): a single-arm, phase 1B/2A trial. Lancet HIV 2016; 3(10): e463-72.
[http://dx.doi.org/10.1016/S2352-3018(16)30055-8] [PMID: 27658863]
[35]
Elliott JH, McMahon JH, Chang CC, et al. Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. Lancet HIV 2015; 2(12): e520-9.
[http://dx.doi.org/10.1016/S2352-3018(15)00226-X] [PMID: 26614966]
[36]
Knights HDJ. Corrigendum to “A critical review of the evidence concerning the HIV latency reversing effect of disulfiram, the possible explanations for its inability to reduce the size of the latent reservoir In vivo, and the caveats associated with its use in practice”. Aids Res Treat 2019; 2019: 4942573.
[http://dx.doi.org/10.1155/2019/4942573] [PMID: 31001433]
[37]
Boehm D, Ott M. Host methyltransferases and demethylases: Potential new epigenetic targets for HIV cure strategies and beyond AIDS research and human retroviruses, Mary Ann Liebert Inc 2017; 33(1): S8-S22.
[http://dx.doi.org/10.1089/aid.2017.0180]
[38]
Ne E, Palstra RJ, Mahmoudi T. “Transcription: Insights From the HIV-1 Promoter,” In International Review of Cell and Molecular Biology. Elsevier Inc. 2018; Vol. 335: pp. 191-243.
[39]
Mbonye U, Karn J. The Molecular Basis for Human Immunodeficiency Virus Latency. Annu Rev Virol 2017; 4(1): 261-85.
[http://dx.doi.org/10.1146/annurev-virology-101416-041646] [PMID: 28715973]
[40]
Khan S, Iqbal M, Tariq M, Baig S M, Abbas W. Epigenetic regulation of HIV-1 latency: Focus on polycomb group (PcG) proteins Clinical Epigenetics, BioMed Central Ltd 2018; 10(1): 1-19.
[http://dx.doi.org/10.1186/s13148-018-0441-z]
[41]
Tripathy MK, McManamy MEM, Burch BD, Archin NM, Margolis DM. H3K27 demethylation at the proviral promoter sensitizes latent HIV to the effects of vorinostat in ex vivo cultures of resting CD4+ T cells. J Virol 2015; 89(16): 8392-405.
[http://dx.doi.org/10.1128/JVI.00572-15] [PMID: 26041287]
[42]
Nixon CC, Mavigner M, Sampey GC, et al. Systemic HIV and SIV latency reversal via non-canonical NF-κB signalling In vivo. Nature 2020; 578(7793): 160-5.
[http://dx.doi.org/10.1038/s41586-020-1951-3] [PMID: 31969707]
[43]
McBrien JB, Mavigner M, Franchitti L, et al. Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8+ cells. Nature 2020; 578(7793): 154-9.
[http://dx.doi.org/10.1038/s41586-020-1946-0] [PMID: 31969705]
[44]
Jones RB, Mueller S, O’Connor R, et al. A subset of latency-reversing agents expose HIV-infected resting CD4+ T-cells to recognition by cytotoxic T-lymphocytes. PLoS Pathog 2016; 12(4): e1005545.
[http://dx.doi.org/10.1371/journal.ppat.1005545] [PMID: 27082643]
[45]
Mbondji-Wonje C, Dong M, Wang X, et al. Distinctive variation in the U3R region of the 5′ Long Terminal Repeat from diverse HIV-1 strains. PLoS One 2018; 13(4): e0195661.
[http://dx.doi.org/10.1371/journal.pone.0195661] [PMID: 29664930]
[46]
Laird GM, Bullen CK, Rosenbloom DI, et al. Ex vivo analysis identifies effective HIV-1 latency-reversing drug combinations. J Clin Invest 2015; 125(5): 1901-12.
[http://dx.doi.org/10.1172/JCI80142] [PMID: 25822022]
[47]
Jiang G, Dandekar S. Targeting NF-κB signaling with protein Kinase C agonists as an emerging strategy for combating HIV latency AIDS Research and Human Retroviruses, Mary Ann Liebert Inc 2015; 4-12.
[http://dx.doi.org/10.1089/aid.2014.0199]
[48]
Brogdon J, Ziani W, Wang X, Veazey RS, Xu H. In vitro effects of the small-molecule protein kinase C agonists on HIV latency reactivation. Sci Rep 2016; 6: 39032.
[http://dx.doi.org/10.1038/srep39032] [PMID: 27941949]
[49]
López-Huertas MR, Jiménez-Tormo L, Madrid-Elena N, et al. The CCR5-antagonist Maraviroc reverses HIV-1 latency in vitro alone or in combination with the PKC-agonist Bryostatin-1. Sci Rep 2017; 7(1): 2385.
[http://dx.doi.org/10.1038/s41598-017-02634-y] [PMID: 28539614]
[50]
Madrid-Elena N, García-Bermejo ML, Serrano-Villar S, et al. Maraviroc is associated with latent HIV-1 reactivation through NF-κB activation in resting CD4+ T cells from HIV-infected individuals on suppressive antiretroviral therapy. J Virol 2018; 92(9): e01931-17.
[http://dx.doi.org/10.1128/JVI.01931-17] [PMID: 29444937]
[51]
Donninelli G, Gessani S, Del Cornò M. Interplay between HIV-1 and Toll-like receptors in human myeloid cells: friend or foe in HIV-1 pathogenesis? J Leukoc Biol 2016; 99(1): 97-105.
[http://dx.doi.org/10.1189/jlb.4VMR0415-160R] [PMID: 26307548]
[52]
Tsai A, Irrinki A, Kaur J, et al. Toll-like receptor 7 agonist GS-9620 induces HIV expression and HIV-specific immunity in cells from HIV-infected individuals on suppressive antiretroviral therapy. J Virol 2017; 91(8): e02166-16.
[http://dx.doi.org/10.1128/JVI.02166-16] [PMID: 28179531]
[53]
Offersen R, Nissen SK, Rasmussen TA, et al. A novel toll-like receptor 9 agonist, MGN1703, enhances HIV-1 transcription and NK cell-mediated inhibition of HIV-1-infected autologous CD4+ T cells. J Virol 2016; 90(9): 4441-53.
[http://dx.doi.org/10.1128/JVI.00222-16] [PMID: 26889036]
[54]
Macedo AB, Novis CL, De Assis CM, et al. Dual TLR2 and TLR7 agonists as HIV latency-reversing agents. JCI Insight 2018; 3(19): 122673.
[http://dx.doi.org/10.1172/jci.insight.122673] [PMID: 30282829]
[55]
Cheng L, Wang Q, Li G, et al. TLR3 agonist and CD40-targeting vaccination induces immune responses and reduces HIV-1 reservoirs. J Clin Invest 2018; 128(10): 4387-96.
[http://dx.doi.org/10.1172/JCI99005] [PMID: 30148455]
[56]
Rochat MA, Schlaepfer E, Speck RF. Promising role of toll-like receptor 8 agonist in concert with prostratin for activation of silent HIV. J Virol 2017; 91(4): e02084-16.
[http://dx.doi.org/10.1128/JVI.02084-16] [PMID: 27928016]
[57]
Hattori SI, Matsuda K, Tsuchiya K, et al. Combination of a latency-reversing agent with a smac mimetic minimizes secondary HIV-1 infection in vitro. Front Microbiol 2018; 9(SEP): 2022.
[http://dx.doi.org/10.3389/fmicb.2018.02022] [PMID: 30283406]
[58]
Sampey GC, et al. The SMAC mimetic AZD5582 is a potent HIV latency reversing agent. bioRxiv 2018; (May): 312447.
[http://dx.doi.org/10.1101/312447]
[59]
Asamitsu K, Fujinaga K, Okamoto T. HIV Tat/P-TEFb interaction: a potential target for novel anti-HIV therapies. Molecules 2018; 23(4): 933.
[http://dx.doi.org/10.3390/molecules23040933] [PMID: 29673219]
[60]
Alqahtani A, Choucair K, Ashraf M, et al. Bromodomain and extra-terminal motif inhibitors: a review of preclinical and clinical advances in cancer therapy. Future Sci OA 2019; 5(3): FSO372.
[http://dx.doi.org/10.4155/fsoa-2018-0115] [PMID: 30906568]
[61]
Khoury G, Mota TM, Li S, et al. HIV latency reversing agents act through Tat post translational modifications. Retrovirology 2018; 15(1): 36.
[http://dx.doi.org/10.1186/s12977-018-0421-6] [PMID: 29751762]
[62]
Conrad RJ, Fozouni P, Thomas S, et al. The short isoform of BRD4 promotes HIV-1 latency by engaging repressive SWI/SNF chromatin-remodeling complexes. Mol Cell 2017; 67(6): 1001-1012.e6.
[http://dx.doi.org/10.1016/j.molcel.2017.07.025] [PMID: 28844864]
[63]
Lu P, Qu X, Shen Y, et al. The BET inhibitor OTX015 reactivates latent HIV-1 through P-TEFb. Sci Rep 2016; 6: 24100.
[http://dx.doi.org/10.1038/srep24100] [PMID: 27067814]
[64]
Darcis G, Kula A, Bouchat S, et al. An in-depth comparison of latency-reversing agent combinations in various in vitro and ex vivo HIV-1 latency models identified bryostatin-1+JQ1 and ingenol-B+JQ1 to potently reactivate viral gene expression. PLoS Pathog 2015; 11(7): e1005063.
[http://dx.doi.org/10.1371/journal.ppat.1005063] [PMID: 26225566]
[65]
Dahabieh MS, Battivelli E, Verdin E. Understanding HIV latency: the road to an HIV cure. Annu Rev Med 2015; 66(1): 407-21.
[http://dx.doi.org/10.1146/annurev-med-092112-152941] [PMID: 25587657]
[66]
Ross TM. Using death to one ’ s advantage : HIV modulation of apoptosis. 2001; pp. 332-41.
[67]
Pham H T, Mesplède T. The latest evidence for possible HIV-1 curative strategies. Drugs in Context 2018. 7: 212522.
[http://dx.doi.org/10.7573/dic.212522]
[68]
De Crignis E, Mahmoudi T. “The multifaceted contributions of chromatin to HIV-1 integration, transcription, and latency,” In international review of cell and molecular biology. Elsevier Inc. 2017; Vol. 328: pp. 197-252.
[69]
Kuzmina A, Krasnopolsky S, Taube R. Super elongation complex promotes early HIV transcription and its function is modulated by P-TEFb. Transcription 2017; 8(3): 133-49.
[http://dx.doi.org/10.1080/21541264.2017.1295831] [PMID: 28340332]
[70]
Geng G, Liu B, Chen C, et al. Development of an attenuated tat protein as a highly-effective agent to specifically activate HIV-1 latency. Mol Ther 2016; 24(9): 1528-37.
[http://dx.doi.org/10.1038/mt.2016.117] [PMID: 27434587]
[71]
Tang X, Lu H, Dooner M, Chapman S, Quesenberry PJ, Ramratnam B. Exosomal Tat protein activates latent HIV-1 in primary, resting CD4+ T lymphocytes. JCI Insight 2018; 3(7): 95676.
[http://dx.doi.org/10.1172/jci.insight.95676] [PMID: 29618654]
[72]
Sgadari C, Monini P, Tripiciano A, et al. Continued decay of HIV proviral DNA upon vaccination with HIV-1 tat of subjects on long-term ART: an 8-year follow-up study. Front Immunol 2019; 10(FEB): 233.
[http://dx.doi.org/10.3389/fimmu.2019.00233] [PMID: 30815001]
[73]
Olesen R, et al. Immune checkpoints and the HIV-1 reservoir: proceed with caution J virus Erad 2020; 2(3): 183-6. http://www.ncbi.nlm.nih.gov/pubmed/27482460
[74]
Wykes M N, Lewin S R. Immune checkpoint blockade in infectious diseases Nature Reviews Immunology,Nature Publishing Group 2018; 18(2): 91-104.
[http://dx.doi.org/10.1038/nri.2017.112]
[75]
Evans VA, van der Sluis RM, Solomon A, et al. Programmed cell death-1 contributes to the establishment and maintenance of HIV-1 latency. AIDS 2018; 32(11): 1491-7.
[http://dx.doi.org/10.1097/QAD.0000000000001849] [PMID: 29746296]
[76]
Bui JK, Cyktor JC, Fyne E, Campellone S, Mason SW, Mellors JW. Blockade of the PD-1 axis alone is not sufficient to activate HIV-1 virion production from CD4+ T cells of individuals on suppressive ART. PLoS One 2019; 14(1): e0211112.
[http://dx.doi.org/10.1371/journal.pone.0211112] [PMID: 30682108]
[77]
Sperk M, Domselaar RV, Neogi U. Immune Checkpoints as the Immune System Regulators and Potential Biomarkers in HIV-1 Infection. Int J Mol Sci 2018; 19(7): 2000.
[http://dx.doi.org/10.3390/ijms19072000] [PMID: 29987244]
[78]
Sarracino A, Gharu L, Kula A, et al. Posttranscriptional regulation of HIV-1 gene expression during replication and reactivation from latency by nuclear matrix protein MATR3. MBio 2018; 9(6): e02158-18.
[http://dx.doi.org/10.1128/mBio.02158-18] [PMID: 30425153]
[79]
Baxter A E, O’Doherty U, Kaufmann D E. Beyond the replication-competent HIV reservoir: Transcription and translation-competent reservoirs Retrovirology,BioMed Central Ltd 2018; 15(1): 1-15.
[http://dx.doi.org/10.1186/s12977-018-0392-7]
[80]
Rao S, Amorim R, Niu M, Temzi A, Mouland AJ. The RNA surveillance proteins UPF1, UPF2 and SMG6 affect HIV-1 reactivation at a post-transcriptional level. Retrovirology 2018; 15(1): 42.
[http://dx.doi.org/10.1186/s12977-018-0425-2] [PMID: 29954456]
[81]
Archin NM, Kirchherr JL, Sung JA, et al. Interval dosing with the HDAC inhibitor vorinostat effectively reverses HIV latency. J Clin Invest 2017; 127(8): 3126-35.
[http://dx.doi.org/10.1172/JCI92684] [PMID: 28714868]
[82]
Siliciano RF, Greene WC. HIV latency. Cold Spring Harb Perspect Med 2011; 1(1): a007096.
[http://dx.doi.org/10.1101/cshperspect.a007096] [PMID: 22229121]
[83]
Tian X, Zhang A, Qiu C, et al. The upregulation of LAG-3 on T cells defines a subpopulation with functional exhaustion and correlates with disease progression in HIV-infected subjects. J Immunol 2015; 194(8): 3873-82.
[http://dx.doi.org/10.4049/jimmunol.1402176] [PMID: 25780040]
[84]
Soppe J A, Lebbink R J. Antiviral goes viral: Harnessing CRISPR/Cas9 to combat viruses in humans trends in microbiology 2017; 25(10): 833-50.
[http://dx.doi.org/10.1016/j.tim.2017.04.005]
[85]
Shang H T, Ding J W, Yu S Y, Wu T, Zhang Q L, Liang F J. Progress and challenges in the use of latent HIV-1 reactivating agents Acta Pharmacologica Sinica,Nature Publishing Group 2015; 36(8): 908-16.
[http://dx.doi.org/10.1038/aps.2015.22]
[86]
Wang Q, Liu S, Liu Z, et al. Genome scale screening identification of SaCas9/gRNAs for targeting HIV-1 provirus and suppression of HIV-1 infection. Virus Res 2018; 250: 21-30.
[http://dx.doi.org/10.1016/j.virusres.2018.04.002] [PMID: 29625148]
[87]
Lee SA, Elliott JH, McMahon J, et al. Population Pharmacokinetics and Pharmacodynamics of Disulfiram on Inducing Latent HIV-1 Transcription in a Phase IIb Trial. Clin Pharmacol Ther 2019; 105(3): 692-702.
[http://dx.doi.org/10.1002/cpt.1220] [PMID: 30137649]
[88]
Méndez C, Ledger S, Petoumenos K, Ahlenstiel C, Kelleher AD. RNA-induced epigenetic silencing inhibits HIV-1 reactivation from latency. Retrovirology 2018; 15(1): 67.
[http://dx.doi.org/10.1186/s12977-018-0451-0] [PMID: 30286764]
[89]
Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, Anderson AC. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med 2010; 207(10): 2187-94.
[http://dx.doi.org/10.1084/jem.20100643] [PMID: 20819927]
[90]
Jiang G, Mendes EA, Kaiser P, et al. Synergistic reactivation of latent HIV expression by ingenol-3-angelate, PEP005, targeted NF-kB signaling in combination with JQ1 induced p-TEFb activation. PLoS Pathog 2015; 11(7): e1005066.
[http://dx.doi.org/10.1371/journal.ppat.1005066] [PMID: 26225771]
[91]
Bouchat S, Delacourt N, Kula A, et al. Sequential treatment with 5-aza-2′-deoxycytidine and deacetylase inhibitors reactivates HIV-1. EMBO Mol Med 2016; 8(2): 117-38.
[http://dx.doi.org/10.15252/emmm.201505557] [PMID: 26681773]
[92]
Kim Y, Anderson J L, Lewin S R. Getting the ‘kill’ into ‘shock and kill’: strategies to eliminate latent HIV cell host and microbe, cell press 2018; 23(1): 14-26.
[http://dx.doi.org/10.1016/j.chom.2017.12.004]
[93]
Jin S, Liao Q, Chen J, et al. TSC1 and DEPDC5 regulate HIV-1 latency through the mTOR signaling pathway. Emerg Microbes Infect 2018; 7(1): 138.
[http://dx.doi.org/10.1038/s41426-018-0139-5] [PMID: 30087333]
[94]
Pache L, Dutra MS, Spivak AM, et al. BIRC2/cIAP1 is a negative regulator of HIV-1 transcription and can Be targeted by smac mimetics to promote reversal of viral latency. Cell Host Microbe 2015; 18(3): 345-53.
[http://dx.doi.org/10.1016/j.chom.2015.08.009] [PMID: 26355217]
[95]
Salgado M, Kwon M, Gálvez C, et al. IciStem Consortium. Mechanisms that contribute to a profound reduction of the HIV-1 reservoir after allogeneic stem cell transplant. Ann Intern Med 2018; 169(10): 674-83.
[http://dx.doi.org/10.7326/M18-0759] [PMID: 30326031]
[96]
Ahlenstiel C, Mendez C, Lim ST, et al. Novel RNA duplex locks HIV-1 in a latent state via chromatin-mediated transcriptional silencing. Mol Ther Nucleic Acids 2015; 4(10): e261.
[http://dx.doi.org/10.1038/mtna.2015.31] [PMID: 26506039]
[97]
Mousseau G, Kessing CF, Fromentin R, Trautmann L, Chomont N, Valente ST. The tat inhibitor didehydro-cortistatin a prevents HIV-1 reactivation from latency. MBio 2015; 6(4): e00465.
[http://dx.doi.org/10.1128/mBio.00465-15] [PMID: 26152583]
[98]
Kyei GB, Meng S, Ramani R, et al. Splicing factor 3B subunit 1 interacts with HIV tat and plays a role in viral transcription and reactivation from latency. MBio 2018; 9(6): e01423-18.
[http://dx.doi.org/10.1128/mBio.01423-18] [PMID: 30401776]
[99]
Balachandran A, Wong R, Stoilov P, et al. Identification of small molecule modulators of HIV-1 Tat and Rev protein accumulation. Retrovirology 2017; 14(1): 7.
[http://dx.doi.org/10.1186/s12977-017-0330-0] [PMID: 28122580]
[100]
Campos N, Myburgh R, Garcel A, et al. Long lasting control of viral rebound with a new drug ABX464 targeting Rev - mediated viral RNA biogenesis. Retrovirology 2015; 12(1): 30.
[http://dx.doi.org/10.1186/s12977-015-0159-3] [PMID: 25889234]
[101]
Lopalco L. CCR5: From natural resistance to a new anti-HIV strategy. Viruses 2010; 2(2): 574-600.
[http://dx.doi.org/10.3390/v2020574] [PMID: 21994649]
[102]
Hütter G, Nowak D, Mossner M, et al. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med 2009; 360(7): 692-8.
[http://dx.doi.org/10.1056/NEJMoa0802905] [PMID: 19213682]
[103]
Gupta RK, Peppa D, Hill AL, 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(5): e340-7.
[http://dx.doi.org/10.1016/S2352-3018(20)30069-2] [PMID: 32169158]
[104]
Hütter G, Thiel E. Allogeneic transplantation of CCR5-deficient progenitor cells in a patient with HIV infection: an update after 3 years and the search for patient no. 2. AIDS 2011; 25(2): 273-4.
[http://dx.doi.org/10.1097/QAD.0b013e328340fe28] [PMID: 21173593]
[105]
Almeida MJ, Matos A. Designer Nucleases: Gene-Editing Therapies using CCR5 as an Emerging Target in HIV. Curr HIV Res 2019; 17(5): 306-23.
[http://dx.doi.org/10.2174/1570162X17666191025112918] [PMID: 31652113]
[106]
Cummins NW, Rizza S, Litzow MR, et al. Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study. PLoS Med 2017; 14(11): e1002461.
[http://dx.doi.org/10.1371/journal.pmed.1002461] [PMID: 29182633]
[107]
Verheyen J, Thielen A, Lübke N, et al. Rapid rebound of a preexisting CXCR4-tropic human immunodeficiency virus variant after allogeneic transplantation with CCR5 Δ32 homozygous stem cells. Clin Infect Dis 2019; 68(4): 684-7.
[http://dx.doi.org/10.1093/cid/ciy565] [PMID: 30020413]
[108]
Peluso M J, Deeks S G, McCune J M. HIV ‘cure’: A shot in the arm? EBioMedicine,Elsevier BV 2019; 42: 3-5.
[http://dx.doi.org/10.1016/j.ebiom.2019.04.011]
[109]
Liu Z, Chen S, Jin X, et al. Genome editing of the HIV co-receptors CCR5 and CXCR4 by CRISPR-Cas9 protects CD4+ T cells from HIV-1 infection. Cell Biosci 2017; 7(1): 47.
[http://dx.doi.org/10.1186/s13578-017-0174-2] [PMID: 28904745]
[110]
Limsirichai P, Gaj T, Schaffer DV. CRISPR-mediated activation of latent HIV-1 expression. Mol Ther 2016; 24(3): 499-507.
[http://dx.doi.org/10.1038/mt.2015.213] [PMID: 26607397]
[111]
Liao HK, Gu Y, Diaz A, et al. Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells. Nat Commun 2015; 6(1): 6413.
[http://dx.doi.org/10.1038/ncomms7413] [PMID: 25752527]
[112]
Zhu W, Lei R, Le Duff Y, et al. The CRISPR/Cas9 system inactivates latent HIV-1 proviral DNA. Retrovirology 2015; 12(1): 22.
[http://dx.doi.org/10.1186/s12977-015-0150-z] [PMID: 25808449]
[113]
Bobbin ML, Burnett JC, Rossi JJ. RNA interference approaches for treatment of HIV-1 infection. Genome Med 2015; 7(1): 50.
[http://dx.doi.org/10.1186/s13073-015-0174-y] [PMID: 26019725]
[114]
Mediouni S, Chinthalapudi K, Ekka MK, et al. Didehydro-cortistatin a inhibits HIV-1 by specifically binding to the unstructured basic region of tat. MBio 2019; 10(1): e02662-18.
[http://dx.doi.org/10.1128/mBio.02662-18] [PMID: 30723126]
[115]
Besnard E, Hakre S, Kampmann M, et al. The mTOR Complex Controls HIV Latency. Cell Host Microbe 2016; 20(6): 785-97.
[http://dx.doi.org/10.1016/j.chom.2016.11.001] [PMID: 27978436]
[116]
Valenti M T, Serena M, Carbonare L D, Zipeto D. CRISPR/Cas system: An emerging technology in stem cell research World Journal of Stem Cells 2019; 11(11): 937-56.
[http://dx.doi.org/10.4252/wjsc.v11.i11.937]
[117]
O’Geen H, Yu A S, Segal D J. How specific is CRISPR/Cas9 really? Current Opinion in Chemical Biology, Elsevier Ltd 2015; 29: 72-8.
[http://dx.doi.org/10.1016/j.cbpa.2015.10.001]

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