{"doi":"10.17615/5gpt-sx52","title":"In Vivo Suppression of HIV Rebound by Didehydro-Cortistatin A, a “Block-and-Lock” Strategy for HIV-1 Treatment","abstract":"HIV-1 Tat activates viral transcription and limited Tat transactivation correlates with latency establishment. We postulated a “block-and-lock” functional cure approach based on properties of the Tat inhibitor didehydro-Cortistatin A (dCA). HIV-1 transcriptional inhibitors could block ongoing viremia during antiretroviral therapy (ART), locking the HIV promoter in persistent latency. We investigated this hypothesis in human CD4+ T cells isolated from aviremic individuals. Combining dCA with ART accelerates HIV-1 suppression and prevents viral rebound after treatment interruption, even during strong cellular activation. We show that dCA mediates epigenetic silencing by increasing nucleosomal occupancy at Nucleosome-1, restricting RNAPII recruitment to the HIV-1 promoter. The efficacy of dCA was studied in the bone marrow-liver-thymus (BLT) mouse model of HIV latency and persistence. Adding dCA to ART-suppressed mice systemically reduces viral mRNA in tissues. Moreover, dCA significantly delays and reduces viral rebound levels upon treatment interruption. Altogether, this work demonstrates the potential of block-and-lock cure strategies. Tat inhibitors are amenable to functional cure approaches, which aim to reduce residual viremia during ART and limit viral rebound during treatment interruption. Using didehydro-Cortistatin A (dCA), Kessing et al. demonstrate the concept in human CD4+ T cells from aviremic individuals and in the bone marrow-liver-thymus mouse model of HIV latency.","journal":"UNC Libraries","year":2020,"id":132697,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":369630,"name":"Lydie Trautmann","orcid":"0000-0002-3012-0009","position":1,"is_corresponding":false},{"id":588724,"name":"Jenna B. Honeycutt","orcid":"0000-0002-4715-6796","position":2,"is_corresponding":false},{"id":589037,"name":"Chaun Li","orcid":null,"position":3,"is_corresponding":false},{"id":234657,"name":"Phong T. Ho","orcid":null,"position":4,"is_corresponding":false},{"id":456275,"name":"Hiroshi Takata","orcid":"0000-0003-1457-6919","position":5,"is_corresponding":false},{"id":451298,"name":"Cari F. Kessing","orcid":"0000-0003-1315-9734","position":6,"is_corresponding":false},{"id":588725,"name":"Guillaume Mousseau","orcid":"0009-0007-4252-6894","position":7,"is_corresponding":false},{"id":233498,"name":"J. Víctor García","orcid":"0000-0003-3726-0482","position":8,"is_corresponding":false},{"id":588726,"name":"Perry Tsai","orcid":"0000-0002-1796-0169","position":9,"is_corresponding":false},{"id":291490,"name":"Susana T. Valente","orcid":"0000-0002-7854-7554","position":10,"is_corresponding":false},{"id":234653,"name":"Christopher C. Nixon","orcid":null,"position":11,"is_corresponding":false},{"id":57486,"name":"Mohammad Fallahi","orcid":"0000-0003-4146-7320","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:14.071209Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}