{"doi":"10.1172/jci.insight.142640","title":"HIV-specific T cell responses reflect substantive in vivo interactions with antigen despite long-term therapy","abstract":"Antiretroviral therapies (ARTs) abrogate HIV replication; however, infection persists as long-lived reservoirs of infected cells with integrated proviruses, which reseed replication if ART is interrupted. A central tenet of our current understanding of this persistence is that infected cells are shielded from immune recognition and elimination through a lack of antigen expression from proviruses. Efforts to cure HIV infection have therefore focused on reactivating latent proviruses to enable immune-mediated clearance, but these have yet to succeed in reducing viral reservoirs. Here, we revisited the question of whether HIV reservoirs are predominately immunologically silent from a new angle: by querying the dynamics of HIV-specific T cell responses over long-term ART for evidence of ongoing recognition of HIV-infected cells. In longitudinal assessments, we show that the rates of change in persisting HIV Nef-specific responses, but not responses to other HIV gene products, were associated with residual frequencies of infected cells. These Nef-specific responses were highly stable over time and disproportionately exhibited a cytotoxic, effector functional profile, indicative of recent in vivo recognition of HIV antigens. These results indicate substantial visibility of the HIV-infected cells to T cells on stable ART, presenting both opportunities and challenges for the development of therapeutic approaches to curing infection.","journal":"JCI Insight","year":2021,"id":153138,"datarank":0.6394019815561974,"base_score":4.2626798770413155,"endowment":4.2626798770413155,"self_citation_contribution":0.6394019815561974,"citation_network_contribution":0.0,"self_endowment_contribution":0.6394019815561974,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":70,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9481,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":290041,"name":"Adam R. Ward","orcid":"0000-0002-7038-5597","position":1,"is_corresponding":false},{"id":266646,"name":"Ronald Truong","orcid":"0000-0002-0336-7970","position":2,"is_corresponding":false},{"id":529933,"name":"Allison S. Thomas","orcid":"0000-0001-8607-3099","position":3,"is_corresponding":false},{"id":266638,"name":"Szu-Han Huang","orcid":"0000-0003-1420-3186","position":4,"is_corresponding":false},{"id":364988,"name":"Thomas R. Dilling","orcid":"0000-0001-9714-1122","position":5,"is_corresponding":false},{"id":402480,"name":"Sandra Terry","orcid":"0000-0003-2620-5306","position":6,"is_corresponding":false},{"id":258960,"name":"John Bui","orcid":"0000-0002-0746-4137","position":7,"is_corresponding":false},{"id":266645,"name":"Talia M. Mota","orcid":"0000-0002-8925-0158","position":8,"is_corresponding":false},{"id":369379,"name":"Ali Danesh","orcid":"0000-0002-0383-1040","position":9,"is_corresponding":false},{"id":355439,"name":"Guinevere Q. Lee","orcid":"0000-0002-9412-886X","position":10,"is_corresponding":false},{"id":355438,"name":"Andrea Gramatica","orcid":"0000-0002-7131-933X","position":11,"is_corresponding":false},{"id":556592,"name":"Pragya Khadka","orcid":null,"position":12,"is_corresponding":false},{"id":266640,"name":"Winiffer D. Conce Alberto","orcid":"0000-0002-4097-9861","position":13,"is_corresponding":false},{"id":88092,"name":"Rajesh T. Gandhi","orcid":"0000-0002-9701-6062","position":14,"is_corresponding":false},{"id":259561,"name":"Deborah K. McMahon","orcid":"0000-0002-4374-3539","position":15,"is_corresponding":false},{"id":464996,"name":"Christina M. Lalama","orcid":"0000-0001-6711-481X","position":16,"is_corresponding":false},{"id":69653,"name":"Ronald J. Bosch","orcid":"0000-0002-1774-4140","position":17,"is_corresponding":false},{"id":259559,"name":"Bernard Macatangay","orcid":"0000-0002-0405-0991","position":18,"is_corresponding":false},{"id":258961,"name":"Joshua C. 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