{"doi":"10.1101/2023.02.07.527421","title":"Aminobisphosphonates reactivate the latent reservoir in people living with HIV-1","abstract":"ABSTRACT Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure HIV-1 infection include “shock and kill” strategies to disrupt latency using small molecules or latency-reversing agents (LRAs) to induce expression of HIV-1 enabling cytotoxic immune cells to eliminate infected cells. The modest success of current LRAs urges the field to identify novel drugs with increased clinical efficacy. Aminobisphosphonates (N-BPs) that include pamidronate, zoledronate, or alendronate, are the first-line treatment of bone-related diseases including osteoporosis and bone malignancies. Here, we show the use of N-BPs as a novel class of LRA: we found in ex vivo assays using primary cells from ART-suppressed people living with HIV-1 that N-BPs induce HIV-1 from latency to levels that are comparable to the T cell activator phytohemagglutinin (PHA). RNA sequencing and mechanistic data suggested that reactivation may occur through activation of the activator protein 1 signaling pathway. Stored samples from a prior clinical trial aimed at analyzing the effect of alendronate on bone mineral density, provided further evidence of alendronate-mediated latency reversal and activation of immune effector cells. Decay of the reservoir measured by IPDA was however not detected. Our results demonstrate the novel use of N-BPs to reverse HIV-1 latency while inducing immune effector functions. This preliminary evidence merits further investigation in a controlled clinical setting possibly in combination with therapeutic vaccination.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":394132,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":926858,"name":"Ann Marie Weideman","orcid":"0000-0002-1653-9102","position":1,"is_corresponding":false},{"id":290041,"name":"Adam R. Ward","orcid":"0000-0002-7038-5597","position":2,"is_corresponding":false},{"id":452805,"name":"Matthew L. Clohosey","orcid":"0000-0002-5986-057X","position":3,"is_corresponding":false},{"id":848311,"name":"Susana García‐Recio","orcid":"0000-0003-3820-1679","position":4,"is_corresponding":false},{"id":445381,"name":"Sara R. Selitsky","orcid":"0000-0001-8765-5269","position":5,"is_corresponding":false},{"id":350331,"name":"Brendan T. Mann","orcid":"0000-0003-0694-7353","position":6,"is_corresponding":false},{"id":1132125,"name":"Marie A. Iannone","orcid":null,"position":7,"is_corresponding":false},{"id":997033,"name":"Chloe P. Whitworth","orcid":"0000-0001-5726-6158","position":8,"is_corresponding":false},{"id":443393,"name":"Alisha Chitrakar","orcid":"0000-0002-4599-6070","position":9,"is_corresponding":false},{"id":356353,"name":"Carolina Garrido","orcid":"0000-0001-7697-6876","position":10,"is_corresponding":false},{"id":299316,"name":"Jennifer Kirchherr","orcid":"0000-0003-3559-7356","position":11,"is_corresponding":false},{"id":659641,"name":"Alisha R. Coffey","orcid":"0000-0003-1792-7999","position":12,"is_corresponding":false},{"id":584347,"name":"Yi‐Hsuan Tsai","orcid":"0000-0002-8891-3124","position":13,"is_corresponding":false},{"id":767371,"name":"Shahryar Samir","orcid":null,"position":14,"is_corresponding":false},{"id":546734,"name":"Yinyan Xu","orcid":"0000-0002-8905-363X","position":15,"is_corresponding":false},{"id":347659,"name":"Dennis C. Copertino","orcid":"0000-0002-3217-4713","position":16,"is_corresponding":false},{"id":95314,"name":"Alberto Bosque","orcid":"0000-0002-8800-2160","position":17,"is_corresponding":false},{"id":984843,"name":"Brad Jones","orcid":null,"position":18,"is_corresponding":false},{"id":13902,"name":"Joel S. Parker","orcid":"0000-0003-2080-6901","position":19,"is_corresponding":false},{"id":130929,"name":"Michael G. Hudgens","orcid":"0000-0002-9106-4194","position":20,"is_corresponding":false},{"id":249716,"name":"Nilu Goonetilleke","orcid":"0000-0003-2278-1656","position":21,"is_corresponding":false},{"id":444949,"name":"Natalia Soriano-Sarabia","orcid":"0000-0002-2349-263X","position":22,"is_corresponding":false},{"id":895277,"name":"Marta Sanz","orcid":"0000-0002-3252-9748","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T01:19:10.334330Z","pmid":"36798291","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":[]}