{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T06:58:29Z","timestamp":1764140309579,"version":"3.46.0"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1154174"],"award-info":[{"award-number":["OPP1154174"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI068613","UM1AI068617","UM1AI068619"],"award-info":[{"award-number":["UM1AI068613","UM1AI068617","UM1AI068619"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Int AIDS Soc."],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>HPTN 084 found that long\u2010acting cabotegravir (CAB\u2010LA) was well\u2010tolerated and significantly reduced the risk of HIV acquisition in women compared to tenofovir disoproxil fumarate\/emtricitabine (F\/TDF). During the blinded phase of the trial, participants were required to use an effective method of contraception, including an injectable or implantable hormonal contraceptive (HC) agent. A contraceptive sub\u2010study assessed the pharmacokinetic interactions between pre\u2010exposure prophylaxis agents (CAB\u2010LA or F\/TDF) and etonogestrel (ENG), medroxyprogesterone acetate (MPA) or norethindrone enanthate (NET\u2010EN).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Participants were enrolled in a nested sub\u2010study between 24 February 2020 and 26 October 2020. Via a convenience sampling strategy, plasma concentrations of ENG, MPA and NET\u2010EN were evaluated at enrolment and weeks 25, 49 and 73; plasma tenofovir (TFV) and CAB concentrations were determined at contemporaneous visits. Participants were allowed to switch contraceptives, and HC assessments were adjusted accordingly. Geometric mean concentrations were calculated and compared using\n                      <jats:italic>t<\/jats:italic>\n                      \u2010tests or Fisher's exact tests.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>One hundred and seventy participants were included in this analysis. Hormone concentrations at all study visits were comparable between the CAB\u2010LA and F\/TDF study arms. Among participants randomized to the CAB\u2010LA arm, geometric mean concentrations declined from enrolment to the follow\u2010up period for ENG (335 to 202 pg\/ml), MPA (1520 to 1138 pg\/ml) and NET\u2010EN (3715 to 1888 pg\/ml); similar findings were observed among participants randomized to the F\/TDF arm. Observed HC declines are likely attributed to the timing of contraceptive administration relative to sampling; the percentage of participants with hormone concentrations above thresholds associated with ovulation suppression was high (73\u2212100%) and did not differ between arms. CAB concentrations were comparable across contraceptive types, with 97.8\u221298.1% of participants yielding trough CAB concentrations above the protocol\u2010specified target threshold. TFV concentrations were unquantifiable for most participants, irrespective of contraceptive agent, rendering comparisons largely uninformative.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Given the comparable hormone concentrations between arms and the likely influence of the timing of sample collection on observed measurements, clinically significant interactions between CAB\u2010LA and HC are not expected. Associations between F\/TDF and hormone concentrations could not be effectively evaluated due to low adherence to F\/TDF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>NCT0316456<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jia2.70056","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:15:32Z","timestamp":1761894932000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of pharmacokinetic interactions between long\u2010acting cabotegravir or emtricitabine\/tenofovir disoproxil fumarate and hormonal contraceptive agents: a tertiary analysis of South African participants in HPTN 084"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1670-8786","authenticated-orcid":false,"given":"Mark A.","family":"Marzinke","sequence":"first","affiliation":[{"name":"School of Medicine Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brett","family":"Hanscom","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division Fred Hutchinson Cancer Center  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Haines","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division Fred Hutchinson Cancer Center  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly K.","family":"Scarsi","sequence":"additional","affiliation":[{"name":"College of Pharmacy University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaw","family":"Agyei","sequence":"additional","affiliation":[{"name":"School of Medicine Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estelle","family":"Piwowar\u2010Manning","sequence":"additional","affiliation":[{"name":"School of Medicine Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5696-8665","authenticated-orcid":false,"given":"Craig W.","family":"Hendrix","sequence":"additional","affiliation":[{"name":"School of Medicine Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryann","family":"Gollings","sequence":"additional","affiliation":[{"name":"School of Medicine Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Rose","sequence":"additional","affiliation":[{"name":"FHI 360  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carrie","family":"Mathew","sequence":"additional","affiliation":[{"name":"Wits RHI University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravindre","family":"Panchia","sequence":"additional","affiliation":[{"name":"Perinatal HIV Research Unit University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1498-8131","authenticated-orcid":false,"given":"Elizabeth","family":"Spooner","sequence":"additional","affiliation":[{"name":"HIV and Other Infectious Diseases Research Unit South African Medical Research Council  Durban South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nishanta","family":"Singh","sequence":"additional","affiliation":[{"name":"HIV and Other Infectious Diseases Research Unit South African Medical Research Council  Durban South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3211-6078","authenticated-orcid":false,"given":"Peter","family":"Bock","sequence":"additional","affiliation":[{"name":"Desmond Tutu TB Centre Department of Paediatrics Stellenbosch University  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex R.","family":"Rinehart","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan L.","family":"Ford","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Research Triangle Park North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James F.","family":"Rooney","sequence":"additional","affiliation":[{"name":"Gilead Sciences  Foster City California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia","family":"Soto\u2010Torres","sequence":"additional","affiliation":[{"name":"Division of AIDS National Institute of Allergy and Infectious Diseases  Rockville Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myron S.","family":"Cohen","sequence":"additional","affiliation":[{"name":"University of North Carolina (UNC) at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2174-313X","authenticated-orcid":false,"given":"Mina C.","family":"Hosseinipour","sequence":"additional","affiliation":[{"name":"University of North Carolina (UNC) at Chapel Hill  Chapel Hill North Carolina USA"},{"name":"UNC Project\u2010Malawi  Lilongwe Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0376-1019","authenticated-orcid":false,"given":"Sinead","family":"Delany\u2010Moretlwe","sequence":"additional","affiliation":[{"name":"Wits RHI University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"HPTN 084 Study Team","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"e_1_2_13_2_1","unstructured":"UNAIDS.IN DANGER: UNAIDS Global AIDS Update 2022.Geneva:Joint United Nations Programme on HIV\/AIDS;2022."},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(23)00079-6"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000168"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00538-4"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiab576"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(23)00108-X"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(20)30268-X"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.4155\/tde.11.19"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-021-01005-1"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2018.1460357"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498254.2015.1060372"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498254.2015.1081993"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13236"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000002409"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/14730782.2000.12288981"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1079"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-7824(98)00120-6"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2013.07.002"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2015.0182"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2023.115321"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(20)30106-5"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1248707"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1310\/hct1405-192"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000172"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0010-7824(84)90018-0"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.11.002"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conx.2022.100073"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0010-7824(91)90030-J"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003026"},{"key":"e_1_2_13_31_1","unstructured":"United Nations.Department of Economic and Social Affairs. Population Division. Contraceptive Use by Method 2019: Data Booklet. vol. ST\/ESA\/SER.A\/435.2019."},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00936-9"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12978\u2010016\u20100268\u2010z"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e31827e818a"},{"key":"e_1_2_13_35_1","first-page":"249","article-title":"Factors affecting the duration of action of the injectable contraceptive norethisterone enanthate","volume":"2","author":"Fotherby K","year":"1981","journal-title":"Contracept Deliv Syst"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0010-7824(81)90065-2"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-016-0452-7"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2024.110490"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000003113"},{"key":"e_1_2_13_40_1","unstructured":"Center for Drug Evaluation and Research.Clinical Drug Interaction Studies with Combined Oral Contraceptives Guidance for Industry.2023."}],"container-title":["Journal of the International AIDS Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jia2.70056","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T06:53:31Z","timestamp":1764140011000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jia2.70056"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,31]]},"references-count":39,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/jia2.70056"],"URL":"https:\/\/doi.org\/10.1002\/jia2.70056","archive":["Portico"],"relation":{},"ISSN":["1758-2652","1758-2652"],"issn-type":[{"type":"print","value":"1758-2652"},{"type":"electronic","value":"1758-2652"}],"subject":[],"published":{"date-parts":[[2025,10,31]]},"assertion":[{"value":"2025-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70056"}}