{"doi":"10.1101/2022.05.06.22274780","title":"Estimating Counterfactual Placebo HIV Incidence in HIV Prevention Trials Without Placebo Arms Based on Markers of HIV Exposure","abstract":"S ummary Given recent advances in HIV prevention, future trials of many experimental interventions are likely to be “active-controlled” designs, whereby HIV negative individuals are randomized to the experimental intervention or an active control known to be effective based on a historical trial. The efficacy of the experimental intervention to prevent HIV infection relative to placebo cannot be evaluated directly based on the trial data alone. One approach that has been proposed is to leverage an HIV exposure marker, such as incident rectal gonorrhea which is highly correlated with HIV infection in populations of men who have sex with men (MSM). Assuming we can fit a model associating HIV incidence and incidence of the exposure marker, based on data from multiple historical studies, incidence of the marker in the active-controlled trial population can be used to infer the HIV incidence that would have been observed had a placebo arm been included, i.e. a “counterfactual placebo”, and to evaluate efficacy of the experimental intervention relative to this counterfactual placebo. We formalize this approach and articulate the underlying assumptions, develop an estimation approach and evaluate its performance in finite samples, and discuss the implications of our findings for future development and application of the approach in HIV prevention. Improved HIV exposure markers and careful assessment of assumptions and study of their violation are needed before the approach is applied in practice.","journal":"medRxiv","year":2022,"id":300113,"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":0.944,"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":415504,"name":"Fei Gao","orcid":"0000-0001-6797-5468","position":1,"is_corresponding":false},{"id":316641,"name":"David V. Glidden","orcid":"0000-0001-5888-1419","position":2,"is_corresponding":false},{"id":334960,"name":"Deborah Donnell","orcid":"0000-0002-0587-7480","position":3,"is_corresponding":false},{"id":30696,"name":"Holly Janes","orcid":"0000-0002-3237-984X","position":4,"is_corresponding":false},{"id":519126,"name":"Yifan Zhu","orcid":"0000-0001-7872-4533","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T00:31:49.412501Z","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":[]}