Immune checkpoint inhibitors in people living with HIV: what about anti-HIV effects?
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
01 02 2020
01 02 2020
Historique:
pubmed:
22
10
2019
medline:
20
1
2021
entrez:
22
10
2019
Statut:
ppublish
Résumé
: Immune checkpoint inhibitors (ICPi) have shown major therapeutic successes when used in various cancers. In the HIV field a double benefit of such ICPi should result from their dual ability to restore in-vitro HIV-specific CD8 T-cell functions and to enhance HIV production from reservoir cells, thus fulfilling the goals of the 'shock and kill' concept proposed as an HIV cure therapeutic strategy. We conducted a systematic review to identify studies reporting the tolerance profile of ICPi and their effects on HIV plasma loads (pVL), CD4 cell count, HIV reservoirs (cell-associated HIV-DNA) and/or HIV-specific CD8 T cells in PLWH. Thirty-one articles were included for a total 176 participants. Twelve percent of the participants experienced severe adverse events and 49% nonsevere adverse events. pVL remained stable in 91.9% participant, showed increases in 5.8% participant, and decreases in 2.3%. CD4 cell count remained stable in 60.7% participants, showed increases in 24.6%, and decreases in 14.7%. Regarding ICPi effects on HIV-DNA and HIV-specific immunity, we identified three distinct profiles: profile I, transient pVL increases followed by a boost in HIV-specific CD8 T cells concomitant to a decrease in HIV-DNA, reported in one participant. Profile II: increase in HIV-specific CD8 T cells without changes in pVL or HIV-DNA, reported in three participants. III: no effect, reported in five participants. In conclusion, the clinical, virological and immunological safety profiles of ICPi reported in about 200 PLWH appear to be favorable but there are still modest results in terms of HIV cure strategy.
Identifiants
pubmed: 31634190
doi: 10.1097/QAD.0000000000002397
pii: 00002030-202002010-00002
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Types de publication
Editorial
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
167-175Références
Deeks SG, Lewin SR, Ross AL, Ananworanich J, Benkirane M, Cannon P, et al. International AIDS Society: global scientific strategy towards an HIV Cure 2016. Nat Med 2016; 22:839–850.
Katlama C, Deeks SG, Autran B, Martinez-Picado J, van Lunzen J, Rouzioux C, et al. Barriers to a cure: new concepts in targeting and eradicating HIV-1 reservoirs. Lancet 2013; 381:2109–2117.
Banga R, Procopio FA, Noto A, Pollakis G, Cavassini M, Ohmiti K, et al. PD-1(+) and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals. Nat Med 2016; 22:754–761.
Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, Yassine-Diab B, et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med 2009; 15:893–900.
Velu V, Shetty RD, Larsson M, Shankar EM. Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options. Retrovirology 2015; 12:14.
Dahabieh MS, Battivelli E, Verdin E. Understanding HIV latency: the road to an HIV cure. Annu Rev Med 2015; 66:407–421.
Kumar A, Darcis G, Van Lint C, Herbein G. Epigenetic control of HIV-1 post integration latency: implications for therapy. Clin Epigenetics 2015; 7:103.
Lorenzo-Redondo R, Fryer HR, Bedford T, Kim E-Y, Archer J, Kosakovsky Pond SL, et al. Persistent HIV-1 replication maintains the tissue reservoir during therapy. Nature 2016; 530:51–56.
Kearney MF, Wiegand A, Shao W, McManus WR, Bale MJ, Luke B, et al. Ongoing HIV replication during ART reconsidered. Open Forum Infect Dis 2017; 4:ofx173.
Fromentin R, Bakeman W, Lawani MB, Khoury G, Hartogensis W, DaFonseca S, et al. CD4+ T cells expressing PD-1, TIGIT and LAG-3 contribute to HIV persistence during ART. PLoS Pathog 2016; 12:e1005761.
McGary CS, Deleage C, Harper J, Micci L, Ribeiro SP, Paganini S, et al. CTLA-4+PD-1- memory CD4+ T cells critically contribute to viral persistence in antiretroviral therapy-suppressed, SIV-infected rhesus macaques. Immunity 2017; 47:776.e5–788.e5.
Parry RV, Chemnitz JM, Frauwirth KA, Lanfranco AR, Braunstein I, Kobayashi SV, et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol 2005; 25:9543–9553.
Fromentin R, DaFonseca S, Costiniuk CT, El-Far M, Procopio FA, Hecht FM, et al. PD-1 blockade potentiates HIV latency reversal ex vivo in CD4+ T cells from ART-suppressed individuals. Nat Commun 2019; 10:814.
Evans VA, van der Sluis RM, Solomon A, Dantanarayana A, McNeil C, Garsia R, et al. Programmed cell death-1 contributes to the establishment and maintenance of HIV-1 latency. AIDS 2018; 32:1491–1497.
Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES, Reddy S, et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 2006; 443:350–354.
Kaufmann DE, Kavanagh DG, Pereyra F, Zaunders JJ, Mackey EW, Miura T, et al. Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction. Nat Immunol 2007; 8:1246–1254.
Trautmann L, Janbazian L, Chomont N, Said EA, Gimmig S, Bessette B, et al. Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat Med 2006; 12:1198–1202.
Cockerham LR, Jain V, Sinclair E, Glidden DV, Hartogenesis W, Hatano H, et al. Programmed death-1 expression on CD4+ and CD8+ T cells in treated and untreated HIV disease. AIDS 2014; 28:1749–1758.
Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015; 373:23–34.
Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015; 373:1803–1813.
Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. KEYNOTE-189 Investigators. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 2018; 378:2078–2092.
Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA, Brice P, et al. KEYNOTE-087. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol 2017; 35:2125–2132.
Shan L, Deng K, Shroff NS, Durand CM, Rabi SA, Yang H-C, et al. Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity 2012; 36:491–501.
Søgaard OS, Graversen ME, Leth S, Olesen R, Brinkmann CR, Nissen SK, et al. The depsipeptide romidepsin reverses HIV-1 latency in vivo. PLoS Pathog 2015; 11:e1005142.
Rasmussen TA, Tolstrup M, Brinkmann CR, Olesen R, Erikstrup C, Solomon 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 2014; 1:e13–e21.
Elliott JH, Wightman F, Solomon A, Ghneim K, Ahlers J, Cameron MJ, et al. Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy. PLoS Pathog 2014; 10:e1004473.
Spivak AM, Andrade A, Eisele E, Hoh R, Bacchetti P, Bumpus NN, 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 2014; 58:883–890.
Achenbach CJ, Assoumou L, Deeks SG, Wilkin TJ, Berzins B, Casazza JP, et al. EraMune 02 study team. Effect of therapeutic intensification followed by HIV DNA prime and rAd5 boost vaccination on HIV-specific immunity and HIV reservoir (EraMune 02): a multicentre randomised clinical trial. Lancet HIV 2015; 2:e82–e91.
Andrés C, Plana M, Guardo AC, Alvarez-Fernández C, Climent N, Gallart T, et al. HIV-1 reservoir dynamics after vaccination and antiretroviral therapy interruption are associated with dendritic cell vaccine-induced T cell responses. J Virol 2015; 89:9189–9199.
Guihot A, Cadranel J, Lambotte O, Lavolé A, Autran B, Spano J-P. Biological follow-up of patients with HIV treated with anti-PD-1 or anti-PD-L1 for nonsmall cell bronchial carcinoma: a task group proposal. Rev Mal Respir 2016; 33:419–421.
Guihot A, Marcelin A-G, Massiani M-A, Samri A, Soulié C, Autran B, et al. Drastic decrease of the HIV reservoir in a patient treated with nivolumab for lung cancer. Ann Oncol 2018; 29:517–518.
Scully EP, Rutishauser RL, Simoneau CR, Delagrèverie H, Euler Z, Thanh C, et al. Inconsistent HIV reservoir dynamics and immune responses following anti-PD-1 therapy in cancer patients with HIV infection. Ann Oncol 2018; 29:2141–2142.
Gay CL, Bosch RJ, Ritz J, Hataye JM, Aga E, Tressler RL, et al. AIDS Clinical Trials 5326 Study Team. Clinical trial of the anti-PD-L1 antibody BMS-936559 in HIV-1 infected participants on suppressive antiretroviral therapy. J Infect Dis 2017; 215:1725–1733.
Le Garff G, Samri A, Lambert-Niclot S, Even S, Lavolé A, Cadranel J, et al. Transient HIV-specific T cells increase and inflammation in an HIV-infected patient treated with nivolumab. AIDS 2017; 31:1048–1051.
Wightman F, Solomon A, Kumar SS, Urriola N, Gallagher K, Hiener B, et al. Effect of ipilimumab on the HIV reservoir in an HIV-infected individual with metastatic melanoma. AIDS 2015; 29:504–506.
Burke MM, Kluger HM, Golden M, Heller KN, Hoos A, Sznol M. Case report: response to ipilimumab in a patient with HIV with metastatic melanoma. J Clin Oncol 2011; 29:e792–e794.
Li D, He C, Xia Y, Du Y, Zhang J. Pembrolizumab combined with stereotactic body radiotherapy in a patient with human immunodeficiency virus and advanced nonsmall cell lung cancer: a case report. J Med Case Rep 2018; 12:104.
Serrao A, Canichella M, De Luca ML, Tartaglia G, Annechini G, D’Elia GM, Pulsoni A. Nivolumab as a safe and effective treatment in an HIV patient with refractory Hodgkin lymphoma. Ann Hematol 2018; 98:1505–1506.
Husnain M, Park W, Ramos JC, Johnson TE, Chan J, Dasari A, et al. Complete response to ipilimumab and nivolumab therapy in a patient with extensive extrapulmonary high-grade small cell carcinoma of the pancreas and HIV infection. J Immunother Cancer 2018; 6:66.
Chang E, Rivero G, Patel NR, Chiao EY, Lai S, Bajaj K, et al. HIV-related refractory Hodgkin lymphoma: a case report of complete response to nivolumab. Clin Lymphoma Myeloma Leuk 2018; 18:e143–e146.
Hentrich M, Schipek-Voigt K, Jäger H, Schulz S, Schmid P, Stötzer O, Bojko P. Nivolumab in HIV-related nonsmall-cell lung cancer. Ann Oncol 2017; 28:2890.
McCullar B, Alloway T, Martin M. Durable complete response to nivolumab in a patient with HIV and metastatic nonsmall cell lung cancer. J Thorac Dis 2017; 9:E540–E542.
Tomsitz D, Hein R, Biedermann T, Kohlmeyer J. Treatment of a patient with HIV and metastatic melanoma with consequitive ipilimumab and nivolumab. J Eur Acad Dermatol Venereol 2018; 32:e26–e28.
Sandoval-Sus JD, Mogollon-Duffo F, Patel A, Visweshwar N, Laber DA, Kim R, et al. Nivolumab as salvage treatment in a patient with HIV-related relapsed/refractory Hodgkin lymphoma and liver failure with encephalopathy. J Immunother Cancer 2017; 5:49.
Linge A, Rauschenberg R, Blum S, Spornraft-Ragaller P, Meier F, Troost EGC. Successful immunotherapy and irradiation in a HIV-positive patient with metastatic Merkel cell carcinoma. Clin Transl Radiat Oncol 2018; 15:42–45.
Davar D, Wilson M, Pruckner C, Kirkwood JM. PD-1 blockade in advanced melanoma in patients with hepatitis C and/or HIV. Case Rep Oncol Med 2015; 2015: Article ID 737389, 5 pages.
Boozalis E, Kwatra SG, Marrone KA. Bilateral lower extremity skin eruptions in an HIV-positive man receiving pembrolizumab monotherapy for non-small cell lung cancer. JAMA Oncol 2019; 5:261–262.
Al Homsi MU, Mostafa M, Fahim K. Favorable response to treatment with avelumab in an HIV-positive patient with advanced merkel cell carcinoma previously refractory to chemotherapy. Case Rep Oncol 2018; 11:467–475.
Ruzevick J, Nicholas S, Redmond K, Kleinberg L, Lipson EJ, Lim M. A patient with HIV treated with ipilimumab and stereotactic radiosurgery for melanoma metastases to the brain. Case Rep Oncol Med 2013; 2013:
Lavolé A, Guihot A, Veyri M, Lambotte O, Autran B, Cloarec N, et al. PD-1 blockade in HIV-infected patients with lung cancer: a new challenge or already a strategy?. Ann Oncol 2018; 29:1065–1066.
Ostios-Garcia L, Faig J, Leonardi GC, Adeni AE, Subegdjo SJ, Lydon CA, et al. Safety and efficacy of PD-1 inhibitors among HIV-positive patients with non-small cell lung cancer. J Thorac Oncol 2018; 13:1037–1042.
Chang E, Sabichi AL, Kramer JR, Hartman C, Royse KE, White DL, et al. Nivolumab treatment for cancers in the HIV-infected population. J Immunother 2018; 41:379–383.
Galanina N, Goodman AM, Cohen PR, Frampton GM, Kurzrock R. Successful treatment of HIV-associated kaposi sarcoma with immune checkpoint blockade. Cancer Immunol Res 2018; 6:1129–1135.
Heppt MV, Schlaak M, Eigentler TK, Kähler KC, Kiecker F, Loquai C, et al. Checkpoint blockade for metastatic melanoma and Merkel cell carcinoma in HIV-positive patients. Ann Oncol 2017; 28:3104–3106.
Tio M, Rai R, Ezeoke OM, McQuade JL, Zimmer L, Khoo C, et al. Anti-PD-1/PD-L1 immunotherapy in patients with solid organ transplant, HIV or hepatitis B/C infection. Eur J Cancer 2018; 104:137–144.
Spano J-P, Veyri M, Gobert A, Guihot A, Perré P, Kerjouan M, et al. Immunotherapy for cancer in people living with HIV: safety with an efficacy signal from the series in real life experience. AIDS 2019; 33:F13–F19.
Bari S, Muzaffar J, Chan A, Jain SR, Haider AM, Adams Curry M, et al. Outcomes of programmed cell death protein 1 (PD-1) and programmed death-ligand 1(PD-L1) inhibitor therapy in HIV patients with advanced cancer. J Oncol 2019; 2019: Article ID 2989048, 5 pages.
Colston E, Grasela D, Gardiner D, Bucy RP, Vakkalagadda B, Korman AJ, et al. An open-label, multiple ascending dose study of the anti-CTLA-4 antibody ipilimumab in viremic HIV patients. PLoS One 2018; 13:e0198158.
Uldrick TS, Gonçalves PH, Abdul-Hay M, Claeys AJ, Emu B, Ernstoff MS, et al. Cancer Immunotherapy Trials Network (CITN)-12 Study Team. Assessment of the safety of pembrolizumab in patients with HIV and advanced cancer-a phase 1 study. JAMA Oncol 2019; [Epub ahead of print].
Pembrolizumab induces HIV latency reversal in HIV+ individuals on ART with cancer. CROI Conference. Available at: https://www.croiconference.org/sessions/pembrolizumab-induces-hiv-latency-reversal-hiv-individuals-art-cancer.
Man J, Ritchie G, Links M, Lord S, Lee CK. Treatment-related toxicities of immune checkpoint inhibitors in advanced cancers: a meta-analysis. Asia Pac J Clin Oncol 2018; 14:141–152.
Cook MR, Kim C. Safety and efficacy of immune checkpoint inhibitor therapy in patients with HIV infection and advanced-stage cancer: a systematic review. JAMA Oncol 2019; 5:1049–1054.
Vandergeeten C, Fromentin R, DaFonseca S, Lawani MB, Sereti I, Lederman MM, et al. Interleukin-7 promotes HIV persistence during antiretroviral therapy. Blood 2013; 121:4321–4329.
Katlama C, Lambert-Niclot S, Assoumou L, Papagno L, Lecardonnel F, Zoorob R, et al. Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized trial. AIDS 2016; 30:221–230.
Lévy Y, Sereti I, Tambussi G, Routy JP, Lelièvre JD, Delfraissy JF, et al. Effects of recombinant human interleukin 7 on T-cell recovery and thymic output in HIV-infected patients receiving antiretroviral therapy: results of a phase I/IIa randomized, placebo-controlled, multicenter study. Clin Infect Dis 2012; 55:291–300.
Wang C, Edilova MI, Wagar LE, Mujib S, Singer M, Bernard NF, et al. Effect of IL-7 therapy on phospho-ribosomal protein S6 and TRAF1 expression in HIV-specific CD8 T cells in patients receiving antiretroviral therapy. J Immunol 2018; 200:558–564.
Ghiglione Y, Trifone C, Salido J, Rhodes A, Ruiz MJ, Polo ML, et al. PD-1 expression in HIV-specific CD8+ T cells before antiretroviral therapy is Associated with HIV persistence. J Acquir Immune Defic Syndr 2019; 80:1–6.
Avettand-Fènoël V, Hocqueloux L, Ghosn J, Cheret A, Frange P, Melard A, et al. Total HIV-1 DNA, a marker of viral reservoir dynamics with clinical implications. Clin Microbiol Rev 2016; 29:859–880.
Chesney J, Puzanov I, Collichio F, Singh P, Milhem MM, Glaspy J, et al. Randomized, open-label phase II study evaluating the efficacy and safety of talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone in patients with advanced, unresectable melanoma. J Clin Oncol 2018; 36:1658–1667.
Borducchi EN, Cabral C, Stephenson KE, Liu J, Abbink P, Ng’ang’a D, et al. Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys. Nature 2016; 540:284–287.
Escolano A, Dosenovic P, Nussenzweig MC. Progress toward active or passive HIV-1 vaccination. J Exp Med 2017; 214:3–16.