{"doi":"10.1002/jia2.26120","title":"Including pregnant and breastfeeding people in trials of novel LAED PrEP agents: perspectives from sub‐Saharan Africa community stakeholders","abstract":"In 2022, the World Health Organization (WHO) recommended long-acting injectable cabotegravir (CAB) for use as pre-exposure prophylaxis (PrEP) [1]. This recommendation was supported by data from two large randomized controlled trials that demonstrated the safety and efficacy of CAB compared to tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) for HIV prevention [2, 3]. CAB is one of the first in a pipeline of long-acting or extended delivery (LAED) agents that have the potential to have a significant impact on high HIV incidence rates in women in sub-Saharan Africa [4]. However, as countries plan for CAB introduction, data on the safety and pharmacology of CAB in pregnant and lactating people (PLP) are limited, presenting a challenge for programmes. Participants of child-bearing potential in HPTN 084, the trial that enrolled individuals assigned female at birth, were required to use long-acting reversible contraceptives (LARCs) with a failure rate of <1%. This stringent requirement was in response to a safety signal associated with peri-conception dolutegravir (DTG) use in women living with HIV [5]. CAB injections were discontinued in participants who declined a LARC, wished to conceive or had a positive pregnancy test, and participants were offered open-label TDF/FTC. These actions were taken out of an abundance of caution but reinforced traditional concerns about the potential harms of including PLP in pre-licensure trials. By contrast, there is growing support for a paradigm shift that recognizes PLP as a complex population better served through inclusion in research with adequate protection and monitoring, to generate data on safety, efficacy and pharmacology in pregnancy, thus avoiding delays in access to effective medications for PLP who also experience risk for HIV [6]. Community stakeholders, however, need to understand and support this paradigm shift before this aspiration can be fully realized. Good participatory practice (GPP) recommends that community stakeholders contribute to protocol development to ensure locally appropriate and acceptable trial procedures [7]. Following the HPTN 084 efficacy results, all participants were unblinded, while the protocol was amended to offer access to CAB. Prior to the implementation of protocol changes, HPTN 084 community working group members hosted a stakeholder consultation to gather community perspectives on proposed pregnancy-related amendments, including relaxation of contraceptive requirements and active CAB dosing during pregnancy and lactation. Due to COVID-19 restrictions, a 2-hour consultation (14:00−16:00 Central Africa Time) was held virtually. Zoom polls were used to gauge the strength of feelings around preference-sensitive issues, to stimulate conversation and to create space to hear opposing views, and for investigators to respond to information gaps. Overall, (N = 101) stakeholders from HPTN 084 countries (n = 82) and the United States (n = 19) attended the consultation, with most representing community (86%), global (7%) and other (7%) stakeholder groups as defined by GPP guidelines [7]. Despite the virtual meeting limitations, the consultation provided an opportunity to (1) provide updates on periconception DTG use and the diminishing evidence for a neural tube defect association; (2) socialize the ethical framework that reframes PLP as a complex population in need of protection through research and fair inclusion in trials; and (3) understand the acceptability of protocol amendments to community stakeholders in participant communities. An average of (n = 50) (range 43–52) stakeholders from sub-Saharan Africa responded to polling questions (Figure 1). While qualitative in nature, the Zoom polls confirmed that the greatest concerns related to CAB safety during pregnancy (as opposed to lactation despite virtually no available data on CAB in breast milk), and that partners were likely to be extremely influential in participants’ decisions to use CAB in pre","journal":"Journal of the International AIDS Society","year":2023,"id":387573,"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":0.9506,"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":1157037,"name":"Molly C. Dyer","orcid":null,"position":1,"is_corresponding":false},{"id":312050,"name":"Mina C. Hosseinipour","orcid":"0000-0003-2174-313X","position":2,"is_corresponding":false},{"id":443730,"name":"Sinéad Delany‐Moretlwe","orcid":"0000-0003-0376-1019","position":3,"is_corresponding":false},{"id":943126,"name":"Rhonda White","orcid":"0000-0002-0036-5144","position":0,"is_corresponding":true}],"reference_count":6,"raw_metadata":null,"created_at":"2026-07-19T01:18:08.845494Z","pmid":"37439067","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":[]}