{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:20:57Z","timestamp":1790778057273,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T00:00:00Z","timestamp":1647475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The role of immune checkpoints (ICPs) in both anti-HIV T cell exhaustion and HIV reservoir persistence, has suggested that an HIV cure therapeutic strategy could involve ICP blockade. We studied the impact of anti-PD-1 therapy on HIV reservoirs and anti-viral immune responses in people living with HIV and treated for cancer. At several timepoints, we monitored CD4 cell counts, plasma HIV-RNA, cell associated (CA) HIV-DNA, EBV, CMV, HBV, HCV, and HHV-8 viral loads, activation markers, ICP expression and virus-specific T cells. Thirty-two patients were included, with median follow-up of 5 months. The CA HIV-DNA tended to decrease before cycle 2 (p = 0.049). Six patients exhibited a \u22650.5 log10 HIV-DNA decrease at least once. Among those, HIV-DNA became undetectable for 10 months in one patient. Overall, no significant increase in HIV-specific immunity was observed. In contrast, we detected an early increase in CTLA-4 + CD4+ T cells in all patients (p = 0.004) and a greater increase in CTLA-4+ and TIM-3 + CD8+ T cells in patients without HIV-DNA reduction compared to the others (p \u2264 0.03). Our results suggest that ICP replacement compensatory mechanisms might limit the impact of anti-PD-1 monotherapy on HIV reservoirs, and pave the way for combination ICP blockade in HIV cure strategies.<\/jats:p>","DOI":"10.3390\/cells11061015","type":"journal-article","created":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T21:25:00Z","timestamp":1647811500000},"page":"1015","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Impact of Anti PD-1 Immunotherapy on HIV Reservoir and Anti-Viral Immune Responses in People Living with HIV and Cancer"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0212-8684","authenticated-orcid":false,"given":"Marine","family":"Baron","sequence":"first","affiliation":[{"name":"INSERM U1135, CIMI, D\u00e9partement d\u2019Immunologie, AP-HP, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Sorbonne Universit\u00e9, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathia","family":"Souli\u00e9","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 1136, Institut Pierre Louis d\u2019Epid\u00e9miologie et de Sant\u00e9 Publique, D\u00e9partement de Virologie, AP-HP, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Sorbonne Universit\u00e9, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armelle","family":"Lavol\u00e9","sequence":"additional","affiliation":[{"name":"GRC #04 Theranoscan, D\u00e9partement de Pneumologie et Oncologie Thoracique, AP-HP, H\u00f4pital Tenon, Sorbonne Universit\u00e9, F-75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lambert","family":"Assoumou","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 1136, Institut Pierre Louis d\u2019Epid\u00e9miologie et de Sant\u00e9 Publique, Sorbonne Universit\u00e9, F-75013 Paris, 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Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1200\/JCO.2014.59.4358","article-title":"Immune Checkpoint Blockade in Cancer Therapy","volume":"33","author":"Postow","year":"2015","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/s41467-019-08798-7","article-title":"PD-1 Blockade Potentiates HIV Latency Reversal Ex Vivo in CD4+ T Cells from ART-Suppressed Individuals","volume":"10","author":"Fromentin","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Fromentin, R., Bakeman, W., Lawani, M.B., Khoury, G., Hartogensis, W., DaFonseca, S., Killian, M., Epling, L., Hoh, R., and Sinclair, E. (2016). CD4+ T Cells Expressing PD-1, TIGIT and LAG-3 Contribute to HIV Persistence during ART. PLOS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005761"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1097\/QAD.0000000000001849","article-title":"Programmed Cell Death-1 Contributes to the Establishment and Maintenance of HIV-1 Latency","volume":"32","author":"Evans","year":"2018","journal-title":"AIDS"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/nature05115","article-title":"PD-1 Expression on HIV-Specific T Cells Is Associated with T-Cell Exhaustion and Disease Progression","volume":"443","author":"Day","year":"2006","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.4049\/jimmunol.179.3.1979","article-title":"Programmed Death 1 Expression on HIV-Specific CD4+ T Cells Is Driven by Viral Replication and Associated with T Cell Dysfunction","volume":"179","author":"Fontenot","year":"2007","journal-title":"J. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1038\/nm1482","article-title":"Upregulation of PD-1 Expression on HIV-Specific CD8+ T Cells Leads to Reversible Immune Dysfunction","volume":"12","author":"Trautmann","year":"2006","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/nature07662","article-title":"Enhancing SIV-Specific Immunity in Vivo by PD-1 Blockade","volume":"458","author":"Velu","year":"2009","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1093\/infdis\/jix191","article-title":"Clinical Trial of the Anti-PD-L1 Antibody BMS-936559 in HIV-1 Infected Participants on Suppressive Antiretroviral Therapy","volume":"215","author":"Gay","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1097\/QAD.0000000000002397","article-title":"Immune Checkpoint Inhibitors in People Living with HIV: What about Anti-HIV Effects?","volume":"34","author":"Abbar","year":"2019","journal-title":"AIDS Lond. Engl."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1093\/annonc\/mdx696","article-title":"Drastic Decrease of the HIV Reservoir in a Patient Treated with Nivolumab for Lung Cancer","volume":"29","author":"Guihot","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1097\/QAD.0000000000000562","article-title":"Effect of Ipilimumab on the HIV Reservoir in an HIV-Infected Individual with Metastatic Melanoma","volume":"29","author":"Wightman","year":"2015","journal-title":"AIDS Lond. Engl."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e1973","DOI":"10.1093\/cid\/ciaa1530","article-title":"Impact of Anti-PD-1 and Anti-CTLA-4 on the HIV Reservoir in People Living with HIV with Cancer on Antiretroviral Therapy: The AIDS Malignancy Consortium-095 Study","volume":"73","author":"Rasmussen","year":"2021","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_15","first-page":"5854","article-title":"EBV-Specific CD8+ T Cells from Asymptomatic Pediatric Thoracic Transplant Patients Carrying Chronic High EBV Loads Display Contrasting Features: Activated Phenotype and Exhausted Function","volume":"186","author":"Macedo","year":"2011","journal-title":"J. Immunol. Baltim. Md 1950"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1097\/QAI.0b013e31825a313c","article-title":"Increased Program Cell Death-1 (PD-1) Expression on T Lymphocytes of Patients with Progressive Multifocal Leukoencephalopathy (PML)","volume":"60","author":"Tan","year":"2012","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nri.2017.112","article-title":"Immune Checkpoint Blockade in Infectious Diseases","volume":"18","author":"Wykes","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.jhep.2019.06.028","article-title":"Anti-PD-1 Blockade with Nivolumab with and without Therapeutic Vaccination for Virally Suppressed Chronic Hepatitis B: A Pilot Study","volume":"71","author":"Gane","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Gardiner, D., Lalezari, J., Lawitz, E., DiMicco, M., Ghalib, R., Reddy, K.R., Chang, K.-M., Sulkowski, M., Marro, S.O., and Anderson, J. (2013). A Randomized, Double-Blind, Placebo-Controlled Assessment of BMS-936558, a Fully Human Monoclonal Antibody to Programmed Death-1 (PD-1), in Patients with Chronic Hepatitis C Virus Infection. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063818"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1007\/s00415-021-10414-y","article-title":"Immune Checkpoint Inhibitors for Progressive Multifocal Leukoencephalopathy: A New Gold Standard?","volume":"268","author":"Weiss","year":"2021","journal-title":"J. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.virol.2019.07.024","article-title":"Expression of PD-1 and PD-Ls in Kaposi\u2019s Sarcoma and Regulation by Oncogenic Herpesvirus Lytic Reactivation","volume":"536","author":"Chen","year":"2019","journal-title":"Virology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1093\/annonc\/mdy006","article-title":"PD-1 Blockade with Nivolumab in Endemic Kaposi Sarcoma","volume":"29","author":"Delyon","year":"2018","journal-title":"Ann. Oncol. Off. J. Eur. Soc. Med. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/S0140-6736(96)07560-5","article-title":"Prevalence of Kaposi\u2019s Sarcoma Associated Herpesvirus Infection Measured by Antibodies to Recombinant Capsid Protein and Latent Immunofluorescence Antigen","volume":"348","author":"Simpson","year":"1996","journal-title":"Lancet Lond. Engl."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1128\/JCM.38.4.1404-1408.2000","article-title":"Quantitative Analysis of Human Herpesvirus 8 Viral Load Using a Real-Time PCR Assay","volume":"38","author":"Lallemand","year":"2000","journal-title":"J. Clin. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/jmv.21390","article-title":"LTR Real-Time PCR for HIV-1 DNA Quantitation in Blood Cells for Early Diagnosis in Infants Born to Seropositive Mothers Treated in HAART Area (ANRS CO 01)","volume":"81","author":"Chaix","year":"2009","journal-title":"J. Med. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Nakid-Cordero, C., Arzouk, N., Gauthier, N., Tarantino, N., Larsen, M., Choquet, S., Burrel, S., Autran, B., Vieillard, V., and Guihot, A. (2019). Skewed T Cell Responses to Epstein-Barr Virus in Long-Term Asymptomatic Kidney Transplant Recipients. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0224211"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1182\/blood-2007-03-080648","article-title":"Multicentric Castleman Disease Is Associated with Polyfunctional Effector Memory HHV-8-Specific CD8+ T Cells","volume":"111","author":"Guihot","year":"2008","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e82","DOI":"10.1016\/S2352-3018(15)00026-0","article-title":"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","volume":"2","author":"Achenbach","year":"2015","journal-title":"Lancet HIV"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1097\/QAD.0000000000000987","article-title":"Treatment Interruption in Chronically HIV-Infected Patients with an Ultralow HIV Reservoir","volume":"30","author":"Calin","year":"2016","journal-title":"AIDS Lond. Engl."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Michot, J.-M., Mouraud, S., Adam, J., Lazarovici, J., Bigenwald, C., Rigaud, C., Tselikas, L., Dartigues, P., Danu, A., and Bigorgne, A. (2021). CD8+ T Lymphocytes Immune Depletion and LAG-3 Overexpression in Hodgkin Lymphoma Tumor Microenvironment Exposed to Anti-PD-1 Immunotherapy. Cancers, 13.","DOI":"10.3390\/cancers13215487"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.immuni.2017.09.018","article-title":"CTLA-4+PD-1\u2212 Memory CD4+ T Cells Critically Contribute to Viral Persistence in Antiretroviral Therapy-Suppressed, SIV-Infected Rhesus Macaques","volume":"47","author":"McGary","year":"2017","journal-title":"Immunity"},{"key":"ref_32","first-page":"ji1901191","article-title":"Combination Immune Checkpoint Blockade to Reverse HIV Latency","volume":"204","author":"Kumar","year":"2020","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Saleh, R., Toor, S.M., Khalaf, S., and Elkord, E. (2019). Breast Cancer Cells and PD-1\/PD-L1 Blockade Upregulate the Expression of PD-1, CTLA-4, TIM-3 and LAG-3 Immune Checkpoints in CD4+ T Cells. Vaccines, 7.","DOI":"10.3390\/vaccines7040149"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1172\/jci.insight.59125","article-title":"Clinical Implications of Monitoring Nivolumab Immunokinetics in Non\u2013Small Cell Lung Cancer Patients","volume":"3","author":"Osa","year":"2018","journal-title":"JCI Insight"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1128\/CVI.00387-05","article-title":"Evaluation of the interlaboratory concordance in quantification of human immunodeficiency virus-specific T cells with a gamma interferon enzyme-linked immunospot assay","volume":"13","author":"Samri","year":"2006","journal-title":"Clin. Vaccine. Immunol. CVI"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1084\/jem.20042408","article-title":"Repertoire, diversity, and differentiation of specific CD8 T cells are associated with immune protection against human cytomegalovirus disease","volume":"201","author":"Sacre","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S0161-5890(01)00082-7","article-title":"Quantity and quality of virus-specific CD8 cell response: Relevance to the design of a therapeutic vaccine for chronic HBV infection","volume":"38","author":"Webster","year":"2001","journal-title":"Mol. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5707","DOI":"10.1128\/JVI.78.11.5707-5719.2004","article-title":"Longitudinal analysis of CD8+ T cells specific for structural and nonstructural hepatitis B virus proteins in patients with chronic hepatitis B: Implications for immunotherapy","volume":"78","author":"Webster","year":"2004","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1128\/JVI.01505-07","article-title":"Rational Design of a Multiepitope Vaccine Encoding T-Lymphocyte Epitopes for Treatment of Chronic Hepatitis B Virus Infections","volume":"82","author":"Depla","year":"2008","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.micinf.2004.12.022","article-title":"In vivo hierarchy of immunodominant and subdominant HLA-A*0201-restricted T-cell epitopes of HBx antigen of hepatitis B virus","volume":"7","author":"Malmassari","year":"2005","journal-title":"Microbes Infect."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jim.2003.11.005","article-title":"A method to increase tetramer staining efficiency of CD8+ T cells with MHC\u2013peptide complexes: Therapeutic applications in monitoring cytotoxic T lymphocyte activity during hepatitis B and C treatment","volume":"285","author":"Tsai","year":"2004","journal-title":"J. Immunol. 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