Gupta, R. K. et al. HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation. Nature 568, 244–248 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hütter, G. et al. Long-term control of HIV by CCR5Δ32/Δ32 stem-cell transplantation. N. Engl. J. Med. 360, 692–698 (2009).

Article  PubMed  Google Scholar 

Castro-Gonzalez, S., Colomer-Lluch, M. & Serra-Moreno, R. Barriers for HIV cure: the latent reservoir. AIDS Res. Hum. Retroviruses 34, 739–759 (2018).

Article  PubMed  PubMed Central  Google Scholar 

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

Article  CAS  PubMed  Google Scholar 

Ganor, Y. et al. HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy. Nat. Microbiol. 4, 633–644 (2019).

Article  CAS  PubMed  Google Scholar 

Eisele, E. & Siliciano, R. F. Redefining the viral reservoirs that prevent HIV-1 eradication. Immunity 37, 377–388 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim, Y., Anderson, J. L. & Lewin, S. R. Getting the ‘kill’ into ‘shock and kill’: strategies to eliminate latent HIV. Cell Host Microbe 23, 14–26 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, Q. et al. CARD8 is an inflammasome sensor for HIV-1 protease activity. Science 371, eabe1707 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Broz, P. & Dixit, V. M. Inflammasomes: mechanism of assembly, regulation and signaling. Nat. Rev. Immunol. 16, 407–420 (2016).

Article  CAS  PubMed  Google Scholar 

Gross, O., Thomas, C. J., Guarda, G. & Tschopp, J. The inflammasome: an integrated view. Immunol. Rev. 243, 136–151 (2011).

Article  CAS  PubMed  Google Scholar 

Johnson, D. C. et al. DPP8/9 inhibitors activate the CARD8 inflammasome in resting lymphocytes. Cell Death Dis. 11, 628 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Linder, A. et al. CARD8 inflammasome activation triggers pyroptosis in human T cells. EMBO J. 39, e105071 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hollingsworth, L. R. et al. DPP9 sequesters the C terminus of NLRP1 to repress inflammasome activation. Nature 592, 778–783 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

D’Osualdo, A. et al. CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like domain. PLoS ONE 6, e27396 (2011).

Article  PubMed  PubMed Central  Google Scholar 

Hsiao, J. C. et al. A ubiquitin-independent proteasome pathway controls activation of the CARD8 inflammasome. J. Biol. Chem. 298, 102032 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sharif, H. et al. Dipeptidyl peptidase 9 sets a threshold for CARD8 inflammasome formation by sequestering its active C-terminal fragment. Immunity 54, 1392–1404 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Figueiredo, A. et al. Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 Gag-Pol. PLoS Pathog. 2, e119 (2006).

Article  PubMed  PubMed Central  Google Scholar 

Phillips, R. E. et al. Human immunodeficiency virus genetic variation that can escape cytotoxic T-cell recognition. Nature 354, 453–459 (1991).

Article  CAS  PubMed  Google Scholar 

Kwong, P. D. et al. HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites. Nature 420, 678–682 (2002).

Article  CAS  PubMed  Google Scholar 

Caskey, M. et al. Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. Nature 522, 487–491 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rhee, S. Y. et al. HIV-1 protease, reverse transcriptase and integrase variation. J. Virol. 90, 6058–6070 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jochmans, D. et al. Selective killing of human immunodeficiency virus infected cells by non-nucleoside reverse transcriptase inhibitor-induced activation of HIV protease. Retrovirology 7, 89 (2010).

Article  PubMed  PubMed Central  Google Scholar 

Zerbato, J. M., Tachedjian, G. & Sluis-Cremer, N. Nonnucleoside reverse transcriptase inhibitors reduce HIV-1 production from latently infected resting CD4. Antimicrob. Agents Chemother. 61, e01736–16 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Boffito, M. et al. Protein binding in antiretroviral therapies. AIDS Res. Hum. Retroviruses 19, 825–835 (2003).

Article  CAS  PubMed  Google Scholar 

Almond, L. M., Hoggard, P. G., Edirisinghe, D., Khoo, S. H. & Back, D. J. Intracellular and plasma pharmacokinetics of efavirenz in HIV-infected individuals. J. Antimicrob. Chemother. 56, 738–744 (2005).

Article  CAS  PubMed  Google Scholar 

Rotger, M. et al. Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients. Pharmacogenet. Genomics 15, 1–5 (2005).

Article  CAS  PubMed  Google Scholar 

Tanaka, R. et al. Intracellular efavirenz levels in peripheral blood mononuclear cells from human immunodeficiency virus-infected individuals. Antimicrob. Agents Chemother. 52, 782–785 (2008).

Article  CAS  PubMed  Google Scholar 

Griswold, A. et al. DPP9’s enzymatic activity and not its binding to CARD8 inhibits inflammasome activation. ACS Chem. Biol. 14, 2424–2429 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wu, J. J. et al. Biochemistry, pharmacokinetics and toxicology of a potent and selective DPP8/9 inhibitor. Biochem. Pharmacol. 78, 203–210 (2009).

Article  CAS  PubMed  Google Scholar 

Lankas, G. R. et al. Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9. Diabetes 54, 2988–2994 (2005).

Article  CAS  PubMed  Google Scholar 

Ianevski, A., Giri, A. & Aittokallio, T. SynergyFinder 2.0: visual analytics of multi-drug combination strategies. Nucleic Acids Res. 48, W488–W493 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Loewe, S. The problem of synergism and antagonism of combined drugs. Arzneimiettelforschung 3, 286–290 (1953).

Google Scholar 

Nie, Z. et al. HIV-1 protease processes procaspase 8 to cause mitochondrial release of cytochrome c, caspase cleavage and nuclear fragmentation. Cell Death Differ. 9, 1172–1184 (2002).

Article  CAS  PubMed  Google Scholar 

Preston, B. D. & Dougherty, J. P. Mechanisms of retroviral mutation. Trends Microbiol. 4, 16–21 (1996).

Article  CAS  PubMed  Google Scholar 

Azijn, H. et al. TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. Antimicrob. Agents Chemother. 54, 718–727 (2010).

Article  CAS  PubMed  Google Scholar 

Waters, J. M. et al. Mutations in the thumb-connection and RNase H domain of HIV type-1 reverse transcriptase of antiretroviral treatment-experienced patients. Antivir. Ther. 14, 231–239 (2009).

Article  CAS  PubMed  Google Scholar 

King, R. W., Klabe, R. M., Reid, C. D. & Erickson-Viitanen, S. K. Potency of nonnucleoside reverse transcriptase inhibitors (NNRTIs) used in combination with other human immunodeficiency virus NNRTIs, NRTIs or protease inhibitors. Antimicrob. Agents Chemother. 46, 1640–1646 (2002).

Article  CAS