{"doi":"10.1016/j.ebiom.2020.103113","title":"A complex system of chemokines may hold the key to optimal CD4+ T-cell recovery after antiretroviral therapy","abstract":"Widely validated research has established that various co-morbidities, including cardiovascular disease, malignancies, liver/renal disease, and neurocognitive decline, appear earlier and with greater frequency in people with HIV (PWH) on antiretroviral therapy (ART) compared to HIV-negative individuals with otherwise similar risk factors. Moreover, higher levels of inflammatory biomarkers and persistently low CD4+ T-cell counts have been associated with these co-morbidities and with early mortality, despite virologic suppression attributable to ART [[1]Helleberg M Kronborg G Larsen CS Pedersen G Pedersen C Obel N et al.CD4 decline is associated with increased risk of cardiovascular disease, cancer, and death in virally suppressed patients with HIV.Clin Infect Dis. 2013; 57: 314-321Crossref PubMed Scopus (34) Google Scholar]. Strategies to intensify or modify ART have not been successful in reducing inflammation or improving CD4+ T-cell counts [[2]Cuzin L Trabelsi S Delobel P Barbuat C Reynes J Allavena C et al.Maraviroc intensification of stable antiviral therapy in HIV-1-infected patients with poor immune restoration: MARIMUNO-ANRS 145 study.J Acquired Immune Def Syndromes. 2012; 61: 557-564Crossref PubMed Scopus (38) Google Scholar]. Chemokines play an important role in the immune system, including regulation of leukocyte maturation and traffic, and positioning of immune cells [[3]Hughes CE Nibbs RJB A guide to chemokines and their receptors.FEBS J. 2018; 285: 2944-2971Crossref PubMed Scopus (350) Google Scholar]. Certain chemokines and their receptors are involved in HIV pathogenesis as well as immune recovery after ART. Circulating levels of these chemokines and chemokine receptors have been specifically associated with CD4+ T-cell recovery among ART-treated PWH via both viral replication-dependent and independent mechanisms. In particular, Ahuja et al. demonstrated a relationship between CCR5/CCL3L1 genetic risk groups and CD4+ T-cell recovery that was independent of virologic suppression and HLA alleles [[4]Ahuja SK Kulkarni H Catano G Agan BK Camargo JF He W et al.CCL3L1-CCR5 genotype influences durability of immune recovery during antiretroviral therapy of HIV-1-infected individuals.Nat Med. 2008; 14: 413-420Crossref PubMed Scopus (110) Google Scholar]. Restrepo et al. also found an association between CXCL12/CCR2 genotypes and CD4+ T-cell recovery [[5]Restrepo C Gutierrez-Rivas M Pacheco YM Garcia M Blanco J Medrano LM et al.Genetic variation in CCR2 and CXCL12 genes impacts on CD4 restoration in patients initiating cART with advanced immunesupression.PLoS One. 2019; 14e0214421Crossref PubMed Scopus (8) Google Scholar]. Although recent studies have attempted to identify candidate genes associated with CD4 response to ART, the findings have not been consistent, often due to inadequate sample size, limited SNP coverage, and varying phenotype definitions across differing populations [[6]Peraire J Vilades C Pacheco YM Lopez-Dupla M Domingo P Gutierrez M et al.Evaluation of the pharmacogenetics of immune recovery in treated HIV-infected patients.Expert Opinion Drug Metabolism Toxicol. 2014; 10: 81-101Crossref PubMed Scopus (7) Google Scholar]. In this issue of EBioMedicine, Yeregui et al. have conducted a targeted analysis of baseline predictors for immune non-response (INR) and immune response (IR) in patients who started ART with a CD4+ T-cell count below 200 cells/µL compared to patients starting treatment with a count >200 cells/µL [[7]Yeregui E VC Domingo P Ceausu A Pacheco YM Veloso S et al.High circulating SDF-1and MCP-1 levels and genetic variations in CXCL12, CCL2 and CCR5: prognostic signature of immune recovery status in treated HIV-positive patients.EBioMedicine. 2020; https://doi.org/10.1016/j.ebiom.2020.103077Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar]. They found that baseline MCP-1 (i.e., CCL2) and SDF-1 (i.e., CXCL12) levels accounted for 9% and 4% of the variance of the baseline and ","journal":"EBioMedicine","year":2020,"id":131592,"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":0.952,"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":104965,"name":"Vincent C. Marconi","orcid":"0000-0001-8409-4689","position":1,"is_corresponding":false},{"id":22017,"name":"Yan V. Sun","orcid":"0000-0002-2838-1824","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-18T23:16:03.875886Z","pmid":"33181464","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":[]}