{"doi":"10.1073/pnas.2210584119","title":"Elevation of cell-associated HIV-1 transcripts in CSF CD4+ T cells, despite effective antiretroviral therapy, is linked to brain injury","abstract":"Antiretroviral therapy (ART) can attain prolonged undetectable HIV-1 in plasma and cerebrospinal fluid (CSF), but brain injury remains prevalent in people living with HIV-1 infection (PLHIV). We investigated cell-associated (CA)-HIV-1 RNA transcripts in cells in CSF and blood, using the highly sensitive Double-R assay, together with proton Magnetic Resonance Spectroscopy ( 1 H MRS) of major brain metabolites, in sixteen PLHIV. 14/16 CSF cell samples had quantifiable CA-HIV-1 RNA, at levels significantly higher than in their PBMCs (median 9,266 vs 185 copies /106 CD4+ T-cells; p<0.0001). In individual PLHIV, higher levels of HIV-1 transcripts in CSF cells were associated with greater brain injury in the frontal white matter (Std β=-0.73; p=0.007) and posterior cingulate (Std β=-0.61; p=0.03). 18-colour flow cytometry revealed that the CSF cells were 91% memory T-cells, equally CD4+ and CD8+ T-cells, but fewer B cells (0.4 %), and monocytes (3.1%). CXCR3 + CD49d + integrin β7-, CCR5 + CD4 + T-cells were highly enriched in CSF, compared with PBMC (p <0.001). However, CA-HIV-1 RNA could not be detected in 10/16 preparations of highly purified monocytes from PBMC, and was extremely low in the other six. Our data show that elevated HIV-1 transcripts in CSF cells were associated with brain injury, despite suppressive ART. The cellular source is most likely memory CD4 + T cells from blood, rather than trafficking monocytes. Future research should focus on inhibitors of this transcription to reduce local production of potentially neurotoxic and inflammatory viral products.","journal":"Proceedings of the National Academy of Sciences","year":2022,"id":241379,"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":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9633,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":535011,"name":"John Zaunders","orcid":"0000-0002-5912-5989","position":1,"is_corresponding":false},{"id":870248,"name":"Thomas M. Gates","orcid":"0000-0003-0113-8282","position":2,"is_corresponding":false},{"id":870249,"name":"Angelique Levert‐Mignon","orcid":"0000-0003-4352-0228","position":3,"is_corresponding":false},{"id":870738,"name":"Shannen Butterly","orcid":null,"position":4,"is_corresponding":false},{"id":870250,"name":"Zhixin Liu","orcid":"0000-0003-3337-0692","position":5,"is_corresponding":false},{"id":215066,"name":"Takaomi Ishida","orcid":null,"position":6,"is_corresponding":false},{"id":286757,"name":"Sarah Palmer","orcid":"0000-0002-9195-3805","position":7,"is_corresponding":false},{"id":483112,"name":"Caroline Rae","orcid":"0000-0003-0673-8084","position":8,"is_corresponding":false},{"id":870251,"name":"Lauriane Jugé","orcid":"0000-0002-4136-8069","position":9,"is_corresponding":false},{"id":483114,"name":"Lucette A. Cysique","orcid":"0000-0002-7711-6373","position":10,"is_corresponding":false},{"id":483113,"name":"Bruce J. Brew","orcid":"0000-0003-0622-1392","position":11,"is_corresponding":false},{"id":870247,"name":"Kazuo Suzuki","orcid":"0000-0002-2531-794X","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T00:22:56.227656Z","pmid":"36413502","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":[]}