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 (2015).
Bloch, M. T. et al. The role of hydroxyurea in enhancing the virologic control achieved through structured treatment interruption in primary HIV infection: final results from a randomized clinical trial (Pulse). J. Acquir. Immune Def. Syndr. 42, 192–202 (2006).
Henrich, T. J. et al. Antiretroviral-rree HIV-1 remission and viral rebound after allogeneic stem cell transplantation. Ann. Intern. Med. 161, 319 (2014).
Luzuriaga, K. et al. Viremic relapse after HIV-1 remission in a perinatally infected child. N. Engl. J. Med. 372, 786–788 (2015).
Lisziewicz, J. et al. Control of HIV despite the discontinuation of antiretroviral therapy. N. Engl. J. Med. 340, 1683–1683 (1999).
Cromer, D. et al. Modeling of antilatency treatment in HIV: what is the optimal duration of antiretroviral therapy-free HIV remission? J. Virol. 91, e01395-17 (2017).
Henrich, T. J. et al. HIV-1 persistence following extremely early initiation of antiretroviral therapy (ART) during acute HIV-1 infection: an observational study. PLOS Med. 14, e1002417 (2017).
Colby, D. J. et al. Rapid HIV RNA rebound after antiretroviral treatment interruption in persons durably suppressed in Fiebig I acute HIV infection. Nat. Med. 24, 923–926 (2018).
Deeks, S. G. Shock and kill. Nature 487, 439 (2012).
Elliott, J. H. et al. Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy. PLOS Pathog. 10, e1004473 (2014).
Sogaard, O. S. et al. The depsipeptide romidepsin reverses HIV-1 latency in vivo. PLOS Pathog. 11, e1005142 (2015).
Rasmussen, T. A. 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 1, e13–e21 (2014).
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 (2017).
Hiener, B. et al. Identification of genetically intact HIV-1 proviruses in specific CD4+ T cells from effectively treated participants. Cell Rep 21, 813–822 (2017).
Kaminski, R. et al. Excision of HIV-1 DNA by gene editing: a proof-of-concept in vivo study. Gene Ther. 23, 690–695 (2016).
Kaminski, R. et al. Elimination of HIV-1 genomes from human T-lymphoid cells by CRISPR/Cas9 gene editing. Sci. Rep. 6, 22555 (2016).
Wang, G., Zhao, N., Berkhout, B. & Das, A. T. CRISPR-Cas9 can inhibit HIV-1 replication but NHEJ repair facilitates virus escape. Mol. Ther. 24, 522–526 (2016).
Zhu, W. et al. The CRISPR/Cas9 system inactivates latent HIV-1 proviral DNA. Retrovirology 12, 22 (2015).
Tebas, P. et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N. Engl. J. Med. 370, 901–910 (2014).
Hütter, G. et al. CCR5 targeted cell therapy for HIV and prevention of viral escape. Viruses 7, 4186–4203 (2015).
Nowak, M. & May, R. M. in Virus Dynamics: Mathematical Principles of Immunology and Virology (Oxford Univ. Press, 2000).
Ribeiro, R. M. et al. Estimation of the initial viral growth rate and basic reproductive number during acute HIV-1 infection. J. Virol. 84, 6096–6102 (2010).
Matrajt, L., Younan, P. M., Kiem, H. P. & Schiffer, J. T. The majority of CD4+ T-cell depletion during acute simian-human immunodeficiency virus SHIV89.6P infection occurs in uninfected cells. J. Virol. 88, 3202–3212 (2014).
Perez, E. E. et al. Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat. Biotechnol. 26, 808 (2008).
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).
Sneller, M. C. et al. A randomized controlled safety/efficacy trial of therapeutic vaccination in HIV-infected individuals who initiated antiretroviral therapy early in infection. Sci. Transl Med. 9, eaan8848 (2017).
Saez-Cirion, A., Jacquelin, B., Barré-Sinoussi, F. & Müller-Trutwin, M. Immune responses during spontaneous control of HIV and AIDS: what is the hope for a cure? Phil. Trans. R. Soc. Lond, B, Biol. Sci. 369, 20130436 (2014).
Conway, J. M. & Perelson, A. S. Post-treatment control of HIV infection. Proc. Natl Acad. Sci. USA 112, 5467–5472 (2015).
Gianella, S., Anderson, C. M., Richman, D. D., Smith, D. M. & Little, S. J. No evidence of post treatment control after early initiation of antiretroviral therapy in the San Diego primary infection cohort. AIDS 29, 2093–2097 (2015).
Calin, R. et al. Treatment interruption in chronically HIV-infected patients with an ultralow HIV reservoir. AIDS 30, 761–769 (2016).
de Souza, M. S. et al. Initiation of antiretroviral therapy during acute HIV-1 infection leads to a high rate of nonreactive HIV serology. Clin. Infect. Dis. 63, 555–561 (2016).
Dong, K. L. et al. Detection and treatment of Fiebig stage I HIV-1 infection in young at-risk women in South Africa: a prospective cohort study. Lancet HIV 5, e35–e44 (2018).
Day, C. L. et al. PD-1 expression on HIV-specific T cells is associated with T cell exhaustion and disease progression. Nature 443, 350 (2006).
Mattapallil, J. J. et al. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 434, 1093–1097 (2005).
Douek, D. C. et al. HIV preferentially infects HIV-specific CD4+ T cells. Nature 417, 95–98 (2002).
Deng, K. et al. Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature 517, 381–385 (2015).
Borducchi, E. N. et al. Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys. Nature 540, 284–287 (2016).
Barouch, D. H. et al. Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature 503, 224–228 (2014).
Burton, S. L. et al. Breakthrough of SIV strain smE660 challenge in SIV strain mac239-vaccinated rhesus macaques despite potent autologous neutralizing antibody responses. Proc. Natl Acad. Sci. USA 112, 10780–10785 (2015).
Rerks-Ngarm, S. et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N. Engl. J. Med. 361, 2209–2220 (2009).
Hessell, A. J. et al. Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques. Nat. Med. 15, 951–954 (2009).
Gautam, R. et al. A single injection of crystallizable fragment domain-modified antibodies elicits durable protection from SHIV infection. Nat. Med. 24, 610–616 (2018).
Bar, K. J., Sneller, M. & Harrison, L. J. Effect of HIV-specific antibody VRC01 on viral rebound after treatment interruption. N. Engl. J. Med. 375, 2037–2050 (2016).
Scheid, J. F. et al. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature 535, 556–560 (2016).
Nishimura, Y. et al. Early antibody therapy can induce long-lasting immunity to SHIV. Nature 543, 559–563 (2017).
Byrareddy, S. N. et al. Sustained virologic control in SIV+macaques after antiretroviral and α4β7 antibody therapy. Science 354, 197–202 (2016).
Grijsen, M. L. et al. No treatment versus 24 or 60 weeks of antiretroviral treatment during primary HIV infection: the randomized Primo-SHM trial. PLOS Med. 9, e1001196 (2012).
Davenport, M. P., Loh, L., Petravic, J. & Kent, S. J. Rates of HIV immune escape and reversion: implications for vaccination. Trends Microbiol. 16, 561–566 (2008).
Namazi, G. et al. The control of HIV after antiretroviral medication pause (CHAMP) study: post-treatment controllers identified from 14 clinical studies. J. Infect. Dis. https://doi.org/10.1093/infdis/jiy479 (2018).
Bernal, E. et al. Low-level viremia is associated with clinical progression in HIV-infected patients receiving antiretroviral treatment. J. Acquir. Immune Def. Syndr. 78, 329–337 (2018).
Bavinton, B. R. et al. Viral suppression and HIV transmission in serodiscordant male couples: an international, prospective, observational, cohort study. Lancet HIV 5, e438–e447 (2018).
Rodger, A. J. et al. Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy. JAMA 316, 171–181 (2016).
Hill, A. L., Rosenbloom, D. I. S., 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 (2014).
Rong, L. & Perelson, A. S. Modeling HIV persistence, the latent reservoir, and viral blips. J. Theor. Biol. 260, 308–331 (2009).
Michor, F. & Beal, K. Improving cancer treatment via mathematical modeling: surmounting the challenges is worth the effort. Cell 163, 1059–1063 (2015).
Bozic, I. et al. Evolutionary dynamics of cancer in response to targeted combination therapy. eLife 2, e00747 (2013).
Sharaf, R. R. & Li, J. Z. The alphabet soup of HIV reservoir markers. Curr. HIV/AIDS Rep. 14, 72–81 (2017).
Eriksson, S. et al. Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies. PLOS Pathog. 9, e1003174 (2013).
Williams, J. P. et al. HIV-1 DNA predicts disease progression and post-treatment virological control. eLife 3, e03821 (2014).
Li, J. Z. et al. The size of the expressed HIV reservoir predicts timing of viral rebound after treatment interruption. AIDS 30, 343–353 (2016).
Reeves, D. B. et al. Anti-proliferative therapy for HIV cure: a compound interest approach. Sci. Rep. 7, 4011 (2017).
Fennessey, C. M. et al. Genetically-barcoded SIV facilitates enumeration of rebound variants and estimation of reactivation rates in nonhuman primates following interruption of suppressive antiretroviral therapy. PLOS Pathog. 13, e1006359 (2017).
Pennings, P. S. Standing genetic variation and the evolution of drug resistance in HIV. PLOS Comput. Biol. 8, e1002527 (2012).
Pinkevych, M. et al. Modeling of experimental data supports HIV reactivation from latency after treatment interruption on average once every 5–8 days. PLOS Pathog. 12, e1005740 (2016).