1. Chun, T.-W. et al. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc. Natl Acad. Sci. USA 94, 13193–13197 (1997).

2. Finzi, D. et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278, 1295–1300 (1997).

3. Wong, J. K. et al. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 278, 1291–1295 (1997).

4. Siliciano, J. D. et al. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat. Med. 9, 727–728 (2003).

5. UNAIDS. UNAIDS Data 2017. (2017).

6. The International AIDS Society Scientific Working Group on HIV Cure. Towards an HIV cure: a global scientific strategy. Nat. Rev. Immunol. 12, 607–614 (2012).

7. Archin, N. M. et al. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature 487, 482–485 (2012).

8. Archin, N. M. et al. HIV-1 expression within resting CD4+ T cells after multiple doses of vorinostat. J. Infect. Dis. 210, 728–735 (2014).

9. 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).

10. Søgaard, O. S. et al. The depsipeptide romidepsin reverses HIV-1 latency in vivo. PLoS Pathog. 11, e1005142 (2015).

11. 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).

12. Elliott, J. H. et al. Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. Lancet HIV 2, e520–e529 (2015).

13. 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 (2018).

14. Del Prete, G. Q. et al. TLR7 agonist administration to SIV-infected macaques receiving early initiated cART does not induce plasma viremia. JCI Insight 4, e127717 (2019).

15. Bekerman, E. et al. PD-1 blockade and TLR7 activation lack therapeutic benefit in chronic simian immunodeficiency virus-infected macaques on antiretroviral therapy. Antimicrob. Agents Chemother. 63, e01163-19 (2019).

16. Borducchi, E. N. et al. Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys. Nature 563, 360–364 (2018).

17. Nixon, C. C., Mavigner, M., Silvestri, G. & Garcia, J. V. In vivo models of human immunodeficiency virus persistence and cure strategies. J. Infect. Dis. 215, S142–S151 (2017).

18. Cartwright, E. K. et al. CD8+ lymphocytes are required for maintaining viral suppression in SIV-infected macaques treated with short-term antiretroviral therapy. Immunity 45, 656–668 (2016).

19. Xu, W. et al. Efficacy and mechanism-of-action of a novel superagonist interleukin-15: interleukin-15 receptor αSu/Fc fusion complex in syngeneic murine models of multiple myeloma. Cancer Res. 73, 3075–3086 (2013).

20. Han, K. P. et al. IL-15:IL-15 receptor alpha superagonist complex: high-level co-expression in recombinant mammalian cells, purification and characterization. Cytokine 56, 804–810 (2011).

21. Rhode, P. R. et al. Comparison of the superagonist complex, ALT-803, to IL15 as cancer immunotherapeutics in animal models. Cancer Immunol. Res. 4, 49–60 (2016).

22. Jones, R. B. et al. A subset of latency-reversing agents expose HIV-infected resting CD4+ T-cells to recognition by cytotoxic T-lymphocytes. PLoS Pathog. 12, e1005545 (2016).

23. Hofmann-Lehmann, R. et al. Sensitive and robust one-tube real-time reverse transcriptase-polymerase chain reaction to quantify SIV RNA load: comparison of one- versus two-enzyme systems. AIDS Res. Hum. Retroviruses 16, 1247–1257 (2010).

24. Del Prete, G. Q. et al. Effect of suberoylanilide hydroxamic acid (SAHA) administration on the residual virus pool in a model of combination antiretroviral therapy-mediated suppression in SIVmac239-infected Indian rhesus macaques. Antimicrob. Agents Chemother. 58, 6790–6806 (2014).

25. Hansen, S. G. et al. Immune clearance of highly pathogenic SIV infection. Nature 502, 100–104 (2013).

26. Li, H. et al. Envelope residue 375 substitutions in simian–human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques. Proc. Natl Acad. Sci. USA 113, E3413–E3422 (2016).

27. Dornadula, G. et al. Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. J. Am. Med. Assoc. 282, 1627–1632 (1999).

28. Maldarelli, F. et al. ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog. 3, e46 (2007).

29. Chun, T. W. et al. Relationship between residual plasma viremia and the size of HIV proviral DNA reservoirs in infected individuals receiving effective antiretroviral therapy. J. Infect. Dis. 204, 135–138 (2011).

30. Chowdhury, A. et al. Differential impact of in vivo CD8+ T lymphocyte depletion in controller versus progressor simian immunodeficiency virus-infected macaques. J. Virol. 89, 8677–8686 (2015).

31. Spivak, A. M. et al. A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapy. Clin. Infect. Dis. 58, 883–890 (2014).

32. Kulpa, D. A. et al. Differentiation to an effector memory phenotype potentiates HIV-l latency reversal in CD4+ T cells. J. Virol. 93, e00969-19 (2019).

33. Okoye, A. A. et al. Early antiretroviral therapy limits SIV reservoir establishment to delay or prevent post-treatment viral rebound. Nat. Med. 24, 1430–1440 (2018).

34. Reed, L. J. & Muench, H. A simple method of estimating fifty per cent endpoints. Am. J. Epidemiol. 27, 493–497 (1938).

35. Chahroudi, A. et al. Target cell availability, rather than breast milk factors, dictates mother-to-infant transmission of SIV in sooty mangabeys and rhesus macaques. PLoS Pathog. 10, e1003958 (2014).

36. Kumar, N. A. et al. Antibody-mediated CD4 depletion induces homeostatic CD4+ T cell proliferation without detectable virus reactivation in antiretroviral therapy-treated simian immunodeficiency virus-infected macaques. J. Virol. 92, e01235-18 (2018).

37. Deleage, C. et al. Defining HIV and SIV reservoirs in lymphoid tissues. Pathog. Immun. 1, 68–106 (2016).

38. Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).

39. Liberzon, A. et al. Molecular signatures database (MSigDB) 3.0. Bioinformatics 27, 1739–1740 (2011).

40. Smith, S. A. et al. Diversification in the HIV-1 envelope hyper-variable domains V2, V4, and V5 and higher probability of transmitted/founder envelope glycosylation favor the development of heterologous neutralization breadth. PLoS Pathog. 12, e1005989 (2016).

41. Smith, S. A. et al. Signatures in simian immunodeficiency virus SIVsmE660 envelope gp120 are associated with mucosal transmission but not vaccination breakthrough in rhesus macaques. J. Virol. 90, 1880–1887 (2016).

42. 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).

43. Denton, P. W. et al. Antiretroviral pre-exposure prophylaxis prevents vaginal transmission of HIV-1 in humanized BLT mice. PLoS Medicine 5, e16 (2008).

44. Denton, P. W. et al. Generation of HIV latency in humanized BLT mice. J. Virol. 86, 630–634 (2011).

45. Denton, P. W. et al. One percent tenofovir applied topically to humanized BLT mice and used according to the CAPRISA 004 experimental design demonstrates partial protection from vaginal HIV infection, validating the BLT model for evaluation of new microbicide candidates. J. Virol. 85, 7582–7593 (2011).

46. Melkus, M. W. et al. Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1. Nat. Med. 12, 1316–1322 (2006).

47. Honeycutt, J. B. et al. T cells establish and maintain CNS viral infection in HIV-infected humanized mice. J. Clin. Invest. 128, 2862–2876 (2018).

48. Kessing, C. F. et al. In vivo suppression of HIV rebound by didehydro-cortistatin A, a “block-and-lock” strategy for HIV-1 treatment. Cell Rep. 21, 600–611 (2017).