{"doi":"10.1161/circresaha.124.323891","title":"Inflammation in HIV and Its Impact on Atherosclerotic Cardiovascular Disease","abstract":"<jats:p>\n            People living with HIV have a 1.5- to 2-fold increased risk of developing cardiovascular disease. Despite treatment with highly effective antiretroviral therapy, people living with HIV have chronic inflammation that makes them susceptible to multiple comorbidities. Several factors, including the HIV reservoir, coinfections, clonal hematopoiesis of indeterminate potential (CHIP), microbial translocation, and antiretroviral therapy, may contribute to the chronic state of inflammation. Within the innate immune system, macrophages harbor latent HIV and are among the prominent immune cells present in atheroma during the progression of atherosclerosis. They secrete inflammatory cytokines such as IL (interleukin)-6 and tumor necrosis-α that stimulate the expression of adhesion molecules on the endothelium. This leads to the recruitment of other immune cells, including cluster of differentiation (CD)8\n            <jats:sup>+</jats:sup>\n            and CD4\n            <jats:sup>+</jats:sup>\n            T cells, also present in early and late atheroma. As such, cells of the innate and adaptive immune systems contribute to both systemic inflammation and vascular inflammation. On a molecular level, HIV-1 primes the NLRP3 (NLR family pyrin domain containing 3) inflammasome, leading to an increased expression of IL-1β, which is important for cardiovascular outcomes. Moreover, activation of TLRs (toll-like receptors) by HIV, gut microbes, and substance abuse further activates the NLRP3 inflammasome pathway. Finally, HIV proteins such as Nef (negative regulatory factor) can inhibit cholesterol efflux in monocytes and macrophages through direct action on the cholesterol transporter ABCA1 (ATP-binding cassette transporter A1), which promotes the formation of foam cells and the progression of atherosclerotic plaque. Here, we summarize the stages of atherosclerosis in the context of HIV, highlighting the effects of HIV, coinfections, and antiretroviral therapy on cells of the innate and adaptive immune system and describe current and future interventions to reduce residual inflammation and improve cardiovascular outcomes among people living with HIV.\n          </jats:p>","journal":"Circulation Research","year":2024,"id":634658,"datarank":0.7037021823343717,"base_score":4.6913478822291435,"endowment":4.6913478822291435,"self_citation_contribution":0.7037021823343717,"citation_network_contribution":0.0,"self_endowment_contribution":0.7037021823343717,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":108,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":368570,"name":"Tecla M. Temu","orcid":"0000-0002-0056-4143","position":1,"is_corresponding":false},{"id":40986,"name":"Simon A. Mallal","orcid":null,"position":2,"is_corresponding":false},{"id":401488,"name":"Celestine N. Wanjalla","orcid":"0000-0001-9159-5414","position":3,"is_corresponding":false},{"id":1277944,"name":"Laventa M. Obare","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Inflammation in HIV and Its Impact on Atherosclerotic Cardiovascular Disease","abstract":"<jats:p>\n            People living with HIV have a 1.5- to 2-fold increased risk of developing cardiovascular disease. Despite treatment with highly effective antiretroviral therapy, people living with HIV have chronic inflammation that makes them susceptible to multiple comorbidities. Several factors, including the HIV reservoir, coinfections, clonal hematopoiesis of indeterminate potential (CHIP), microbial translocation, and antiretroviral therapy, may contribute to the chronic state of inflammation. Within the innate immune system, macrophages harbor latent HIV and are among the prominent immune cells present in atheroma during the progression of atherosclerosis. They secrete inflammatory cytokines such as IL (interleukin)-6 and tumor necrosis-α that stimulate the expression of adhesion molecules on the endothelium. This leads to the recruitment of other immune cells, including cluster of differentiation (CD)8\n            <jats:sup>+</jats:sup>\n            and CD4\n            <jats:sup>+</jats:sup>\n            T cells, also present in early and late atheroma. As such, cells of the innate and adaptive immune systems contribute to both systemic inflammation and vascular inflammation. On a molecular level, HIV-1 primes the NLRP3 (NLR family pyrin domain containing 3) inflammasome, leading to an increased expression of IL-1β, which is important for cardiovascular outcomes. Moreover, activation of TLRs (toll-like receptors) by HIV, gut microbes, and substance abuse further activates the NLRP3 inflammasome pathway. Finally, HIV proteins such as Nef (negative regulatory factor) can inhibit cholesterol efflux in monocytes and macrophages through direct action on the cholesterol transporter ABCA1 (ATP-binding cassette transporter A1), which promotes the formation of foam cells and the progression of atherosclerotic plaque. Here, we summarize the stages of atherosclerosis in the context of HIV, highlighting the effects of HIV, coinfections, and antiretroviral therapy on cells of the innate and adaptive immune system and describe current and future interventions to reduce residual inflammation and improve cardiovascular outcomes among people living with HIV.\n          </jats:p>","is_dataset_classified":null,"base_score":4.653960350157523,"endowment":4.653960350157523,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38781301","pmcid":"PMC11122788","openalex_id":"https://openalex.org/W4398250276","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"K23 HL156759","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"P30 AI110527","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"K01 HL147723","title":null},{"funder_name":"National Institutes of Health","grant_id":"5K23HL156759-02","title":"Anti-cytomegalovirus Immune Responses in Atherosclerotic Cardiovascular Disease in Persons Living with HIV"},{"funder_name":"National Institutes of Health","grant_id":"5K01HL147723-03","title":"The Gut Microbiota, Inflammation and Cardiovascular Disease in HIV-InfectedIndividuals."},{"funder_name":"National Institutes of Health","grant_id":"5P30AI110527-04","title":"Tennessee Center for AIDS Research (TN-CFAR)"}],"total_grants":6,"fwci":58.4066,"citation_percentile":0.9995986,"influential_citations":0,"citation_trend":[{"year":2024,"count":11},{"year":2025,"count":48},{"year":2026,"count":45}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://www.ahajournals.org/doi/pdf/10.1161/CIRCRESAHA.124.323891?download=true","host_type":"journal"},{"url":"https://www.ahajournals.org/doi/pdf/10.1161/CIRCRESAHA.124.323891?download=true","host_type":"publisher"},{"url":"https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.124.323891","host_type":"publisher"},{"url":"https://doi.org/10.1161/circresaha.124.323891","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38781301","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11122788","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11122788/pdf/res-134-1515.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11122788","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11122788?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1161/CIRCRESAHA.124.323891","host_type":""}],"fields_of_study":["HIV-related health complications and treatments","HIV Research and Treatment","Inflammasome and immune disorders","0301 basic medicine","0303 health sciences","03 medical and health sciences","Humans","HIV Infections","Atherosclerosis","Inflammation","Animals","Immunity, Innate"],"mesh_terms":["Animals","Humans","Immunity, Innate","Inflammation","HIV Infections","Atherosclerosis"],"keywords":["Inflammation","Inflammasome","Immunology","Immune system","Pyrin domain","Systemic inflammation","Atheroma","Innate immune system","Biology","Tumor necrosis factor alpha","ABCA1","Macrophage","Medicine","Internal medicine","Transporter","Atherosclerosis","Cardiovascular diseases","HIV","Endothelial Cells","risk factors","Clinical Relevance","Humans","Animals","HIV Infections","HIV and Cardiovascular Disease Review Series","Immunity, Innate"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T13:58:25.461906Z","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":[]}