{"doi":"10.3390/v17111453","title":"Within-Subtype HIV-1 Polymorphisms and Their Impacts on Intact Proviral DNA Assay (IPDA) for Viral Reservoir Quantification","abstract":"The Intact Proviral DNA Assay (IPDA) is widely used to quantify genome-intact HIV proviruses in people living with HIV, but viral sequence diversity has been observed to cause assay failures due to primer/probe mismatches. Adapted for subtype C, IPDA-BC is a modified version of the IPDA validated on South African HIV-1 subtype C. India is also impacted by subtype C, but IPDA performance within-subtype across geographical regions is not well studied. We analyzed Indian (IN) and South African (ZA) subtype C sequences in silico, hypothesizing that IPDA-BC may underperform with IN viruses. Primer/probe binding was predicted using three increasingly stringent nucleotide mismatch criteria, whose sensitivity and specificity were evaluated against experimental IPDA outcomes. Phylogenetic analyses confirmed that IN and ZA subtype C sequences form distinct clusters with significant compartmentalization (p < 0.003). Across criteria, up to 6–10% decreases in primer/probe binding were observed in IN versus ZA, with the env forward primer being the most affected. These criteria showed low sensitivity (18–53%) and variable specificity (67–100%) in predicting experimental outcomes. In conclusion, even within subtype, HIV-1 variation across geographical regions may impact IPDA performance, underscoring the need for improved predictive models to guide assay design for global HIV cure research.","journal":"Viruses","year":2025,"id":535267,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9596,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":366696,"name":"Jyoti S. Mathad","orcid":"0000-0001-9487-7775","position":1,"is_corresponding":false},{"id":709766,"name":"Kavidha Reddy","orcid":"0000-0002-7024-0574","position":2,"is_corresponding":false},{"id":448318,"name":"Nicole Reddy","orcid":null,"position":3,"is_corresponding":false},{"id":252002,"name":"Thumbi Ndung’u","orcid":"0000-0003-2962-3992","position":4,"is_corresponding":false},{"id":446862,"name":"Kathryn Dupnik","orcid":"0000-0001-7100-2917","position":5,"is_corresponding":false},{"id":355439,"name":"Guinevere Q. Lee","orcid":"0000-0002-9412-886X","position":6,"is_corresponding":false},{"id":1418848,"name":"Mohith Reddy Arikatla","orcid":"0000-0002-7199-4570","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-19T02:51:56.297114Z","pmid":"41305478","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":[]}