Modelling HIV-1 control and remission

Bekker, L. G. et al. HIV infection. Nat. Rev. Dis. Prim. 9, 42, https://doi.org/10.1038/s41572-023-00452-3 (2023).Article 
PubMed 

Google Scholar 
Deeks, S. G. et al. Research priorities for an HIV cure: International AIDS Society Global Scientific Strategy 2021. Nat. Med. 27, 2085–2098, https://doi.org/10.1038/s41591-021-01590-5 (2021).Article 
CAS 
PubMed 

Google Scholar 
Deeks, S. G. & Walker, B. D. Human immunodeficiency virus controllers: mechanisms of durable virus control in the absence of antiretroviral therapy. Immunity 27, 406–416, https://doi.org/10.1016/j.immuni.2007.08.010 (2007).Article 
CAS 
PubMed 

Google Scholar 
Saez-Cirion, 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, https://doi.org/10.1371/journal.ppat.1003211 (2013).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Li, J. Z. & Blankson, J. N. How elite controllers and posttreatment controllers inform our search for an HIV-1 cure. J. Clin. Invest. 131, e149414, https://doi.org/10.1172/JCI149414 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Siliciano, J. D. & Siliciano, R. F. In vivo dynamics of the latent reservoir for HIV-1: new insights and implications for cure. Annu Rev. Pathol. 17, 271–294, https://doi.org/10.1146/annurev-pathol-050520-112001 (2022).Article 
CAS 
PubMed 

Google Scholar 
Nishimura, Y. et al. Early antibody therapy can induce long-lasting immunity to SHIV. Nature 543, 559–563, https://doi.org/10.1038/nature21435 (2017).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Borducchi, E. N. et al. Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys. Nature 563, 360–364, https://doi.org/10.1038/s41586-018-0600-6 (2018).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Gaebler, C. et al. Prolonged viral suppression with anti-HIV-1 antibody therapy. Nature 606, 368–374, https://doi.org/10.1038/s41586-022-04597-1 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Doitsh, G. et al. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature 505, 509–514, https://doi.org/10.1038/nature12940 (2014).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
He, X. et al. Rapid loss of CD4 T cells by pyroptosis during acute SIV infection in rhesus macaques. J. Virol. 96, e0080822, https://doi.org/10.1128/jvi.00808-22 (2022).Article 
CAS 
PubMed 

Google Scholar 
Graw, F. & Perelson, A. S. Modeling viral spread. Annu. Rev. Virol. 3, 555–572, https://doi.org/10.1146/annurev-virology-110615-042249 (2016).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
McMyn, N. F. et al. The latent reservoir of inducible, infectious HIV-1 does not decrease despite decades of antiretroviral therapy. J. Clin. Invest. 133, e171554, https://doi.org/10.1172/JCI171554 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Yang, O. O., Cumberland, W. G., Escobar, R., Liao, D. & Chew, K. W. Demographics and natural history of HIV-1-infected spontaneous controllers of viremia. AIDS 31, 1091–1098, https://doi.org/10.1097/qad.0000000000001443 (2017).Article 
CAS 
PubMed 

Google Scholar 
Nguyen, S. et al. Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8+ T cells. Sci. Transl. Med. 11, eaax4077, https://doi.org/10.1126/scitranslmed.aax4077 (2019).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Collins, D. R. et al. Functional impairment of HIV-specific CD8+ T cells precedes aborted spontaneous control of viremia. Immunity 54, 2372–2384 e2377, https://doi.org/10.1016/j.immuni.2021.08.007 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Jiang, C. et al. Distinct viral reservoirs in individuals with spontaneous control of HIV-1. Nature 585, 261–267, https://doi.org/10.1038/s41586-020-2651-8 (2020).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Armani-Tourret, M. et al. Immune targeting of HIV-1 reservoir cells: a path to elimination strategies and cure. Nat. Rev. Microbiol. 22, 328–344, https://doi.org/10.1038/s41579-024-01010-8 (2024).Article 
CAS 
PubMed 

Google Scholar 
Choudhary, S. K. et al. Low immune activation despite high levels of pathogenic human immunodeficiency virus type 1 results in long-term asymptomatic disease. J. Virol. 81, 8838–8842, https://doi.org/10.1128/JVI.02663-06 (2007).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
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, https://doi.org/10.1093/infdis/jiy479 (2018).Article 
PubMed 
PubMed Central 

Google Scholar 
Passaes, C. et al. Early antiretroviral therapy favors post-treatment SIV control associated with the expansion of enhanced memory CD8+ T-cells. Nat. Commun. 15, 178, https://doi.org/10.1038/s41467-023-44389-3 (2024).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Pinkevych, M. et al. Timing of initiation of anti-retroviral therapy predicts post-treatment control of SIV replication. PLoS Pathog. 19, e1011660, https://doi.org/10.1371/journal.ppat.1011660 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Sharaf, R. et al. HIV-1 proviral landscapes distinguish posttreatment controllers from noncontrollers. J. Clin. Invest. 128, 4074–4085, https://doi.org/10.1172/JCI120549 (2018).Article 
PubMed 
PubMed Central 

Google Scholar 
Etemad, B. et al. HIV post-treatment controllers have distinct immunological and virological features. Proc. Natl Acad. Sci. USA 120, e2218960120, https://doi.org/10.1073/pnas.2218960120 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Perelson, A. S. Modelling viral and immune system dynamics. Nat. Rev. Immunol. 2, 28–36, https://doi.org/10.1038/nri700 (2002).Article 
CAS 
PubMed 

Google Scholar 
Nowak, M. & May, R. M. Virus dynamics: mathematical principles of immunology and virology. (Oxford University Press, UK, 2000).Hill, A. L., Rosenbloom, D. I. S., Nowak, M. A. & Siliciano, R. F. Insight into treatment of HIV infection from viral dynamics models. Immunol. Rev. 285, 9–25, https://doi.org/10.1111/imr.12698 (2018).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Padmanabhan, P. & Dixit, N. M. in Quasispecies: From Theory to Experimental Systems (eds E. Domingo & P. Schuster) 277–302 (Springer International Publishing, 2016).Perelson, A. S. & Ribeiro, R. M. Modeling the within-host dynamics of HIV infection. BMC Biol. 11, 96, https://doi.org/10.1186/1741-7007-11-96 (2013).Article 
PubMed 
PubMed Central 

Google Scholar 
Wang, S., Hottz, P., Schechter, M. & Rong, L. Modeling the slow CD4+ T cell decline in HIV-infected individuals. PLoS Comput Biol. 11, e1004665, https://doi.org/10.1371/journal.pcbi.1004665 (2016).Article 
CAS 

Google Scholar 
Li, J. Z. et al. The size of the expressed HIV reservoir predicts timing of viral rebound after treatment interruption. AIDS 30, 343–353, https://doi.org/10.1097/qad.0000000000000953 (2016).Article 
CAS 
PubMed 

Google Scholar 
Goulder, P. & Deeks, S. G. HIV control: is getting there the same as staying there? PLoS Pathog. 14, e1007222, https://doi.org/10.1371/journal.ppat.1007222 (2018).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Conway, J. M. & Perelson, A. S. Post-treatment control of HIV infection. Proc. Natl Acad. Sci. USA 112, 5467–5472, https://doi.org/10.1073/pnas.1419162112 (2015).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Bonhoeffer, S., Rembiszewski, M., Ortiz, G. M. & Nixon, D. F. Risks and benefits of structured antiretroviral drug therapy interruptions in HIV-1 infection. AIDS 14, 2313–2322, https://doi.org/10.1097/00002030-200010200-00012 (2000).Article 
CAS 
PubMed 

Google Scholar 
Johnson, P. L. et al. Vaccination alters the balance between protective immunity, exhaustion, escape, and death in chronic infections. J. Virol. 85, 5565–5570, https://doi.org/10.1128/JVI.00166-11 (2011).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Hashimoto, M. et al. CD8 T cell exhaustion in chronic infection and cancer: opportunities for interventions. Annu. Rev. Med. 69, 301–318, https://doi.org/10.1146/annurev-med-012017-043208 (2018).Article 
CAS 
PubMed 

Google Scholar 
Baral, S., Antia, R. & Dixit, N. M. A dynamical motif comprising the interactions between antigens and CD8 T cells may underlie the outcomes of viral infections. Proc. Natl Acad. Sci. USA 116, 17393–17398, https://doi.org/10.1073/pnas.1902178116 (2019).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Baral, S., Roy, R. & Dixit, N. M. Modeling how reversal of immune exhaustion elicits cure of chronic hepatitis C after the end of treatment with direct-acting antiviral agents. Immunol. Cell Biol. 96, 969–980, https://doi.org/10.1111/imcb.12161 (2018).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Chatterjee, B., Singh Sandhu, H. & Dixit, N. M. Modeling recapitulates the heterogeneous outcomes of SARS-CoV-2 infection and quantifies the differences in the innate immune and CD8 T-cell responses between patients experiencing mild and severe symptoms. PLoS Pathog. 18, e1010630, https://doi.org/10.1371/journal.ppat.1010630 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Desikan, R., Raja, R. & Dixit, N. M. Early exposure to broadly neutralizing antibodies may trigger a dynamical switch from progressive disease to lasting control of SHIV infection. PLoS Comput Biol. 16, e1008064, https://doi.org/10.1371/journal.pcbi.1008064 (2020).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Lu, L. L., Suscovich, T. J., Fortune, S. M. & Alter, G. Beyond binding: antibody effector functions in infectious diseases. Nat. Rev. Immunol. 18, 46–61, https://doi.org/10.1038/nri.2017.106 (2018).Article 
CAS 
PubMed 

Google Scholar 
Nishimura, Y. et al. Immunotherapy during the acute SHIV infection of macaques confers long-term suppression of viremia. J. Exp. Med. 218, e20201214, https://doi.org/10.1084/jem.20201214 (2021).Article 
CAS 
PubMed 

Google Scholar 
Borducchi, E. N. et al. Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys. Nature 540, 284–287, https://doi.org/10.1038/nature20583 (2016).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Walker-Sperling, V. E. K. et al. Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques. Nat. Commun. 13, 3463, https://doi.org/10.1038/s41467-022-31196-5 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Baral, S., Raja, R., Sen, P. & Dixit, N. M. Towards multiscale modeling of the CD8+ T cell response to viral infections. Wiley Interdiscip. Rev. Syst. Biol. Med. 11, e1446, https://doi.org/10.1002/wsbm.1446 (2019).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
McBrien, J. B., Kumar, N. A. & Silvestri, G. Mechanisms of CD8+ T cell-mediated suppression of HIV/SIV replication. Eur. J. Immunol. 48, 898–914, https://doi.org/10.1002/eji.201747172 (2018).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Seich Al Basatena, N. K. et al. Can non-lytic CD8+ T cells drive HIV-1 escape? PLoS Pathog. 9, e1003656, https://doi.org/10.1371/journal.ppat.1003656 (2013).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Klatt, N. R. et al. CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells. PLoS Pathog. 6, e1000747, https://doi.org/10.1371/journal.ppat.1000747 (2010).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Wong, J. K. et al. In vivo CD8+ T-cell suppression of SIV viremia is not mediated by CTL clearance of productively infected cells. PLoS Pathog. 6, e1000748, https://doi.org/10.1371/journal.ppat.1000748 (2010).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Gadhamsetty, S., Coorens, T. & de Boer, R. J. Notwithstanding circumstantial alibis, cytotoxic T cells can be major killers of HIV-1-infected cells. J. Virol. 90, 7066–7083, https://doi.org/10.1128/JVI.00306-16 (2016).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Cao, Y., Cartwright, E. K., Silvestri, G. & Perelson, A. S. CD8+ lymphocyte control of SIV infection during antiretroviral therapy. PLoS Pathog. 14, e1007350, https://doi.org/10.1371/journal.ppat.1007350 (2018).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Policicchio, B. B. et al. CD8+ T cells control SIV infection using both cytolytic effects and non-cytolytic suppression of virus production. Nat. Commun. 14, 6657, https://doi.org/10.1038/s41467-023-42435-8 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
De Boer, R. J. & Perelson, A. S. Quantifying T lymphocyte turnover. J. Theor. Biol. 327, 45–87, https://doi.org/10.1016/j.jtbi.2012.12.025 (2013).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Migueles, S. A. et al. HIV vaccines induce CD8+ T cells with low antigen receptor sensitivity. Science 382, 1270–1276, https://doi.org/10.1126/science.adg0514 (2023).Article 
CAS 
PubMed 

Google Scholar 
Asquith, B., Edwards, C. T., Lipsitch, M. & McLean, A. R. Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. PLoS Biol. 4, e90, https://doi.org/10.1371/journal.pbio.0040090 (2006).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Ganusov, V. V. et al. Fitness costs and diversity of the cytotoxic T lymphocyte (CTL) response determine the rate of CTL escape during acute and chronic phases of HIV infection. J. Virol. 85, 10518–10528, https://doi.org/10.1128/JVI.00655-11 (2011).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Love, T. M., Thurston, S. W., Keefer, M. C., Dewhurst, S. & Lee, H. Y. Mathematical modeling of ultradeep sequencing data reveals that acute CD8+ T-lymphocyte responses exert strong selective pressure in simian immunodeficiency virus-infected macaques but still fail to clear founder epitope sequences. J. Virol. 84, 5802–5814, https://doi.org/10.1128/JVI.00117-10 (2010).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Swan, D. A., Rolland, M., Herbeck, J. T., Schiffer, J. T. & Reeves, D. B. Evolution during primary HIV infection does not require adaptive immune selection. Proc. Natl Acad. Sci. USA 119, e2109172119, https://doi.org/10.1073/pnas.2109172119 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Roberts, H. E. et al. Structured observations reveal slow HIV-1 CTL escape. PLoS Genet. 11, e1004914, https://doi.org/10.1371/journal.pgen.1004914 (2015).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Nagaraja, P., Alexander, H. K., Bonhoeffer, S. & Dixit, N. M. Influence of recombination on acquisition and reversion of immune escape and compensatory mutations in HIV-1. Epidemics 14, 11–25, https://doi.org/10.1016/j.epidem.2015.09.001 (2016).Article 
PubMed 

Google Scholar 
Pandit, A. & de Boer, R. J. Reliable reconstruction of HIV-1 whole genome haplotypes reveals clonal interference and genetic hitchhiking among immune escape variants. Retrovirology 11, 56, https://doi.org/10.1186/1742-4690-11-56 (2014).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Barton, J. P. et al. Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable. Nat. Commun. 7, 11660, https://doi.org/10.1038/ncomms11660 (2016).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Rosenbloom, D. I., Hill, A. L., Rabi, S. A., Siliciano, R. F. & Nowak, M. A. Antiretroviral dynamics determines HIV evolution and predicts therapy outcome. Nat. Med 18, 1378–1385, https://doi.org/10.1038/nm.2892 (2012).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Ribeiro, R. M. & Bonhoeffer, S. Production of resistant HIV mutants during antiretroviral therapy. Proc. Natl Acad. Sci. USA 97, 7681–7686, https://doi.org/10.1073/pnas.97.14.7681 (2000).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Arora, P. & Dixit, N. M. Timing the emergence of resistance to anti-HIV drugs with large genetic barriers. PLoS Comput. Biol. 5, e1000305, https://doi.org/10.1371/journal.pcbi.1000305 (2009).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Gaiha, G. D. et al. Structural topology defines protective CD8+ T cell epitopes in the HIV proteome. Science 364, 480–484, https://doi.org/10.1126/science.aav5095 (2019).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Lu, C. L. et al. Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo. Science 352, 1001–1004, https://doi.org/10.1126/science.aaf1279 (2016).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Cardozo-Ojeda, E. F. & Perelson, A. S. Modeling HIV-1 within-host dynamics after passive infusion of the broadly neutralizing antibody VRC01. Front. Immunol. 12, 710012, https://doi.org/10.3389/fimmu.2021.710012 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Gardner, M. R. et al. AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges. Nature 519, 87–91, https://doi.org/10.1038/nature14264 (2015).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Goyal, A. et al. Estimation of the in vivo neutralization potency of eCD4Ig and conditions for AAV-mediated production for SHIV long-term remission. Sci. Adv. 8, eabj5666, https://doi.org/10.1126/sciadv.abj5666 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Lynch, R. M. et al. Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection. Sci. Transl. Med. 7, 319ra206, https://doi.org/10.1126/scitranslmed.aad5752 (2015).Article 
CAS 
PubMed 

Google Scholar 
Bar, K. J. et al. Effect of HIV antibody VRC01 on viral rebound after treatment interruption. N. Engl. J. Med. 375, 2037–2050, https://doi.org/10.1056/NEJMoa1608243 (2016).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Crowell, T. A. et al. Safety and efficacy of VRC01 broadly neutralising antibodies in adults with acutely treated HIV (RV397): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet HIV 6, e297–e306, https://doi.org/10.1016/S2352-3018(19)30053-0 (2019).Article 
PubMed 
PubMed Central 

Google Scholar 
Saha, A. & Dixit, N. M. Pre-existing resistance in the latent reservoir can compromise VRC01 therapy during chronic HIV-1 infection. PLoS Comput. Biol. 16, e1008434, https://doi.org/10.1371/journal.pcbi.1008434 (2020).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
LaMont, C. et al. Design of an optimal combination therapy with broadly neutralizing antibodies to suppress HIV-1. Elife 11, e76004, https://doi.org/10.7554/eLife.76004 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Tripathi, K., Balagam, R., Vishnoi, N. K. & Dixit, N. M. Stochastic simulations suggest that HIV-1 survives close to its error threshold. PLoS Comput. Biol. 8, e1002684, https://doi.org/10.1371/journal.pcbi.1002684 (2012).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Gadhamsetty, S. & Dixit, N. M. Estimating frequencies of minority nevirapine-resistant strains in chronically HIV-1-infected individuals naive to nevirapine by using stochastic simulations and a mathematical model. J. Virol. 84, 10230–10240, https://doi.org/10.1128/JVI.01010-10 (2010).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Pennings, P. S. Standing genetic variation and the evolution of drug resistance in HIV. PLoS Comput. Biol. 8, e1002527, https://doi.org/10.1371/journal.pcbi.1002527 (2012).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Schoofs, T. et al. HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1. Science 352, 997–1001, https://doi.org/10.1126/science.aaf0972 (2016).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Thomas, P. et al. High-affinity mAb infusion can enhance maximum affinity maturation during HIV Env immunization. iScience 27, 109495, https://doi.org/10.1016/j.isci.2024.109495 (2024).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Garg, A. K., Desikan, R. & Dixit, N. M. Preferential presentation of high-affinity immune complexes in germinal centers can explain how passive immunization improves the humoral response. Cell Rep. 29, 3946–3957 e3945, https://doi.org/10.1016/j.celrep.2019.11.030 (2019).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Zhang, Y. et al. Germinal center B cells govern their own fate via antibody feedback. J. Exp. Med. 210, 457–464, https://doi.org/10.1084/jem.20120150 (2013).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Victora, G. D. & Nussenzweig, M. C. Germinal centers. Annu Rev. Immunol. 40, 413–442, https://doi.org/10.1146/annurev-immunol-120419-022408 (2022).Article 
CAS 
PubMed 

Google Scholar 
Wang, S. et al. Manipulating the selection forces during affinity maturation to generate cross-reactive HIV antibodies. Cell 160, 785–797, https://doi.org/10.1016/j.cell.2015.01.027 (2015).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Luo, S. & Perelson, A. S. Competitive exclusion by autologous antibodies can prevent broad HIV-1 antibodies from arising. Proc. Natl Acad. Sci. USA 112, 11654–11659, https://doi.org/10.1073/pnas.1505207112 (2015).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Tam, H. H. et al. Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination. Proc. Natl Acad. Sci. USA 113, E6639–E6648, https://doi.org/10.1073/pnas.1606050113 (2016).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Liao, H.-X. et al. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature 496, 469–476, https://doi.org/10.1038/nature12053 (2013).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Haynes, B. F. et al. Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies. Nat. Rev. Immunol. 23, 142–158, https://doi.org/10.1038/s41577-022-00753-w (2023).Article 
CAS 
PubMed 

Google Scholar 
Shaffer, J. S., Moore, P. L., Kardar, M. & Chakraborty, A. K. Optimal immunization cocktails can promote induction of broadly neutralizing Abs against highly mutable pathogens. Proc. Natl Acad. Sci. USA 113, E7039–E7048, https://doi.org/10.1073/pnas.1614940113 (2016).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Garg, A. K., Mitra, T., Schips, M., Bandyopadhyay, A. & Meyer-Hermann, M. Amount of antigen, T follicular helper cells and affinity of founder cells shape the diversity of germinal center B cells: a computational study. Front. Immunol. 14, 1080853, https://doi.org/10.3389/fimmu.2023.1080853 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Hill, A. L., Rosenbloom, D. I., Fu, F., Nowak, M. A. & Siliciano, R. F. Predicting the outcomes of treatment to eradicate the latent reservoir for HIV-1. Proc. Natl Acad. Sci. USA 111, 13475–13480, https://doi.org/10.1073/pnas.1406663111 (2014).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Pinkevych, M. et al. HIV Reactivation from latency after treatment interruption occurs on average every 5–8 days-implications for HIV remission. PLoS Pathog. 11, e1005000, https://doi.org/10.1371/journal.ppat.1005000 (2015).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Ke, R., Lewin, S. R., Elliott, J. H. & Perelson, A. S. Modeling the effects of vorinostat in vivo reveals both transient and delayed HIV transcriptional activation and minimal killing of latently infected cells. PLoS Pathog. 11, e1005237, https://doi.org/10.1371/journal.ppat.1005237 (2015).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Petravic, J., Rasmussen, T. A., Lewin, S. R., Kent, S. J. & Davenport, M. P. Relationship between measures of HIV reactivation and decline of the latent reservoir under latency-reversing agents. J. Virol. 91, e02092–16, https://doi.org/10.1128/jvi.02092-02016 (2017).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Gupta, V. & Dixit, N. M. Trade-off between synergy and efficacy in combinations of HIV-1 latency-reversing agents. PLoS Comput. Biol. 14, e1006004, https://doi.org/10.1371/journal.pcbi.1006004 (2018).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Cao, Y., Lei, X., Ribeiro, R. M., Perelson, A. S. & Liang, J. Probabilistic control of HIV latency and transactivation by the Tat gene circuit. Proc. Natl Acad. Sci. USA 115, 12453–12458, https://doi.org/10.1073/pnas.1811195115 (2018).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Conway, J. M. & Coombs, D. A stochastic model of latently infected cell reactivation and viral blip generation in treated HIV patients. PLoS Comput. Biol. 7, e1002033, https://doi.org/10.1371/journal.pcbi.1002033 (2011).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Rodari, A., Darcis, G. & Van Lint, C. M. The current status of latency reversing agents for HIV-1 remission. Annu Rev. Virol. 8, 491–514, https://doi.org/10.1146/annurev-virology-091919-103029 (2021).Article 
CAS 
PubMed 

Google Scholar 
Cummins, N. W. 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. 14, e1002461, https://doi.org/10.1371/journal.pmed.1002461 (2017).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Henrich, T. J. et al. Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases. Ann. Intern. Med. 161, 319–327, https://doi.org/10.7326/M14-1027 (2014).Article 
PubMed 
PubMed Central 

Google Scholar 
Siliciano, J. D. & Siliciano, R. F. HIV cure: the daunting scale of the problem. Science 383, 703–705, https://doi.org/10.1126/science.adk1831 (2024).Article 
CAS 
PubMed 

Google Scholar 
Lim, S. Y. et al. TLR7 agonists induce transient viremia and reduce the viral reservoir in SIV-infected rhesus macaques on antiretroviral therapy. Sci. Transl. Med. 10, eaao4521, https://doi.org/10.1126/scitranslmed.aao4521 (2018).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Kim, J. T. et al. Latency reversal plus natural killer cells diminish HIV reservoir in vivo. Nat. Commun. 13, 121, https://doi.org/10.1038/s41467-021-27647-0 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Turk, G. et al. A possible sterilizing cure of HIV-1 infection without stem cell transplantation. Ann. Intern. Med. 175, 95–100, https://doi.org/10.7326/L21-0297 (2021).Article 
PubMed 
PubMed Central 

Google Scholar 
Hutter, G. et al. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N. Engl. J. Med. 360, 692–698, https://doi.org/10.1056/NEJMoa0802905 (2009).Article 
PubMed 

Google Scholar 
Gupta, R. K. et al. Evidence for HIV-1 cure after CCR5Delta32/Delta32 allogeneic haemopoietic stem-cell transplantation 30 months post analytical treatment interruption: a case report. Lancet HIV 7, e340–e347, https://doi.org/10.1016/S2352-3018(20)30069-2 (2020).Article 
PubMed 
PubMed Central 

Google Scholar 
Zhang, Z., Hou, W. & Chen, S. Updates on CRISPR-based gene editing in HIV-1/AIDS therapy. Virol. Sin. 37, 1–10, https://doi.org/10.1016/j.virs.2022.01.017 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Tebas, P. et al. CCR5-edited CD4+ T cells augment HIV-specific immunity to enable post-rebound control of HIV replication. J. Clin. Invest. 131, e144486, https://doi.org/10.1172/JCI144486 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Fromentin, R. & Chomont, N. HIV persistence in subsets of CD4+ T cells: 50 shades of reservoirs. Semin Immunol. 51, 101438, https://doi.org/10.1016/j.smim.2020.101438 (2021).Article 
CAS 
PubMed 

Google Scholar 
Baxter, A. E. et al. Single-cell characterization of viral translation-competent reservoirs in HIV-infected individuals. Cell Host Microbe 20, 368–380, https://doi.org/10.1016/j.chom.2016.07.015 (2016).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Grau-Exposito, J. et al. Latency reversal agents affect differently the latent reservoir present in distinct CD4+ T subpopulations. PLoS Pathog. 15, e1007991, https://doi.org/10.1371/journal.ppat.1007991 (2019).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Fletcher, C. V. et al. Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc. Natl Acad. Sci. USA 111, 2307–2312, https://doi.org/10.1073/pnas.1318249111 (2014).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Moreno-Gamez, S. et al. Imperfect drug penetration leads to spatial monotherapy and rapid evolution of multidrug resistance. Proc. Natl Acad. Sci. USA 112, E2874–E2883, https://doi.org/10.1073/pnas.1424184112 (2015).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Feder, A. F., Harper, K. N., Brumme, C. J. & Pennings, P. S. Understanding patterns of HIV multi-drug resistance through models of temporal and spatial drug heterogeneity. Elife 10, e69032, https://doi.org/10.7554/eLife.69032 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Rabezanahary, H. et al. Despite early antiretroviral therapy effector memory and follicular helper CD4 T cells are major reservoirs in visceral lymphoid tissues of SIV-infected macaques. Mucosal Immunol. 13, 149–160, https://doi.org/10.1038/s41385-019-0221-x (2020).Article 
CAS 
PubMed 

Google Scholar 
Estes, J. D. et al. Defining total-body AIDS-virus burden with implications for curative strategies. Nat. Med. 23, 1271–1276, https://doi.org/10.1038/nm.4411 (2017).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Reeves, D. B. et al. A majority of HIV persistence during antiretroviral therapy is due to infected cell proliferation. Nat. Commun. 9, 4811, https://doi.org/10.1038/s41467-018-06843-5 (2018).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Reeves, D. B. et al. Estimating the contribution of CD4 T cell subset proliferation and differentiation to HIV persistence. Nat. Commun. 14, 6145, https://doi.org/10.1038/s41467-023-41521-1 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Reeves, D. B. et al. Anti-proliferative therapy for HIV cure: a compound interest approach. Sci. Rep. 7, 4011, https://doi.org/10.1038/s41598-017-04160-3 (2017).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Kufera, J. T. et al. CD4+ T cells with latent HIV-1 have reduced proliferative responses to T cell receptor stimulation. J. Exp. Med. 221, e20231511, https://doi.org/10.1084/jem.20231511 (2024).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Kosmrlj, A. et al. Effects of thymic selection of the T-cell repertoire on HLA class I-associated control of HIV infection. Nature 465, 350–354, https://doi.org/10.1038/nature08997 (2010).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Mora-Bitria, L. & Asquith, B. Innate receptors modulating adaptive T cell responses: KIR-HLA interactions and T cell-mediated control of chronic viral infections. Immunogenetics 75, 269–282, https://doi.org/10.1007/s00251-023-01293-w (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Boelen, L. et al. Inhibitory killer cell immunoglobulin-like receptors strengthen CD8(+) T cell-mediated control of HIV-1, HCV, and HTLV-1. Sci. Immunol. 3, eaao2892, https://doi.org/10.1126/sciimmunol.aao2892 (2018).Article 
PubMed 
PubMed Central 

Google Scholar 
Viard, M. et al. Impact of HLA class I functional divergence on HIV control. Science 383, 319–325, https://doi.org/10.1126/science.adk0777 (2024).Article 
CAS 
PubMed 

Google Scholar 
Vemparala, B. et al. Antiviral capacity of the early CD8 T-cell response is predictive of natural control of SIV infection. https://doi.org/10.1101/2023.10.13.562306 (2023).Passaes, C. et al. Optimal maturation of the SIV-specific CD8+ T cell response after primary infection is associated with natural control of SIV: ANRS SIC study. Cell Rep. 32, 108174, https://doi.org/10.1016/j.celrep.2020.108174 (2020).Article 
CAS 
PubMed 

Google Scholar 
Sen, P., Saha, A. & Dixit, N. M. You cannot have your synergy and efficacy too. Trends Pharm. Sci. 40, 811–817, https://doi.org/10.1016/j.tips.2019.08.008 (2019).Article 
CAS 
PubMed 

Google Scholar 
Desikan, R., Antia, R. & Dixit, N. M. Physical ‘strength’ of the multi-protein chain connecting immune cells: does the weakest link limit antibody affinity maturation? BioEssays 43, 2000159, https://doi.org/10.1002/bies.202000159 (2021).Article 
CAS 

Google Scholar 
Gubser, C., Chiu, C., Lewin, S. R. & Rasmussen, T. A. Immune checkpoint blockade in HIV. EBioMedicine 76, 103840, https://doi.org/10.1016/j.ebiom.2022.103840 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Caskey, M. Broadly neutralizing antibodies for the treatment and prevention of HIV infection. Curr. Opin. HIV AIDS 15, 49–55, https://doi.org/10.1097/COH.0000000000000600 (2020).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Chen, Z. & Julg, B. Therapeutic vaccines for the treatment of HIV. Transl. Res. 223, 61–75, https://doi.org/10.1016/j.trsl.2020.04.008 (2020).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Board, N. L., Moskovljevic, M., Wu, F., Siliciano, R. F. & Siliciano, J. D. Engaging innate immunity in HIV-1 cure strategies. Nat. Rev. Immunol. 22, 499–512, https://doi.org/10.1038/s41577-021-00649-1 (2022).Article 
CAS 
PubMed 

Google Scholar 
Wensing, A. M. J., Chabannon, C. & Kuball, J. The connected worlds of stem cell transplantation and HIV. Lancet HIV 7, e594–e595, https://doi.org/10.1016/S2352-3018(20)30170-3 (2020).Article 
PubMed 

Google Scholar 
Mu, W., Carrillo, M. A. & Kitchen, S. G. Engineering CAR T cells to target the HIV reservoir. Front. Cell Infect. Microbiol. 10, 410, https://doi.org/10.3389/fcimb.2020.00410 (2020).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 

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