Evaluation of long‐acting cabotegravir safety and pharmacokinetics in pregnant women in eastern and southern Africa: a secondary analysis of HPTN 084
Abstract Introduction Long‐acting injectable cabotegravir (CAB‐LA) for pre‐exposure prophylaxis significantly reduced HIV acquisition in HPTN 084. We report on the safety and CAB‐LA pharmacokinetics in pregnant women during the blinded period of HPTN 084. Methods Participants were randomized 1:1 to...
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2025-01-01
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| Series: | Journal of the International AIDS Society |
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| Online Access: | https://doi.org/10.1002/jia2.26401 |
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| author | Sinead Delany‐Moretlwe Brett Hanscom Xu Guo Clemensia Nkabiito Patricia Mandima Patricia Ntege Nahirya Juliet Mpendo Muchaneta Bhondai‐Mhuri Nyaradzo Mgodi Rebecca Berhanu Jennifer Farrior Estelle Piwowar‐Manning Susan L. Ford Craig W. Hendrix Alex R. Rinehart James F. Rooney Adeola Adeyeye Raphael J. Landovitz Myron S. Cohen Mina C. Hosseinipour Mark A. Marzinke the HPTN 084 Study Team |
| author_facet | Sinead Delany‐Moretlwe Brett Hanscom Xu Guo Clemensia Nkabiito Patricia Mandima Patricia Ntege Nahirya Juliet Mpendo Muchaneta Bhondai‐Mhuri Nyaradzo Mgodi Rebecca Berhanu Jennifer Farrior Estelle Piwowar‐Manning Susan L. Ford Craig W. Hendrix Alex R. Rinehart James F. Rooney Adeola Adeyeye Raphael J. Landovitz Myron S. Cohen Mina C. Hosseinipour Mark A. Marzinke the HPTN 084 Study Team |
| author_sort | Sinead Delany‐Moretlwe |
| collection | DOAJ |
| description | Abstract Introduction Long‐acting injectable cabotegravir (CAB‐LA) for pre‐exposure prophylaxis significantly reduced HIV acquisition in HPTN 084. We report on the safety and CAB‐LA pharmacokinetics in pregnant women during the blinded period of HPTN 084. Methods Participants were randomized 1:1 to either active cabotegravir (CAB) plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) placebo or active TDF/FTC plus CAB placebo. Pregnancy testing was performed at each visit; participants with a positive test had study product withheld and were offered open‐label TDF/FTC. Pregnancies were confirmed on two tests at least 4 weeks apart. All participants with a positive pregnancy test prior to November 5, 2020 are included in this analysis. Pregnancy incidence, maternal adverse event (AE) incidence, pregnancy outcomes (including composite outcome of spontaneous abortion <20 weeks, intrauterine foetal death or stillbirth ≥20 weeks, premature birth <37 weeks, or small for gestational age) were assessed. The apparent terminal phase half‐life (t1/2app) of CAB‐LA in pregnant women in HPTN 084 was compared to non‐pregnant women from the phase 2a HPTN 077 trial. Multivariable models assessed associations with t1/2app. Results Fifty‐seven pregnancies (30 CAB‐LA, 27 TDF/FTC) were confirmed over 3845 person‐years [py] (incidence 1.5/100 py, 95% CI 1.1−1.9). CAB‐LA group participants had a median 342 days (IQR 192, 497) of CAB‐LA exposure prior to pregnancy detection. Grade 2 or higher maternal AE incidence did not differ by study arm (CAB 157, 95% CI 91−271 per 100 py vs. TDF/FTC 217, 95% CI 124–380 per 100 py; p = 0.256). Most pregnancies (81%) resulted in live births (25 CAB‐LA, 22 TDF/FTC). Composite poor pregnancy outcomes did not differ significantly by group (CAB 6/30 vs. TDF/FTC 4/27; p = 0.476). No congenital anomalies were observed. The CAB t1/2app geometric mean was 52.8 days (95% CI 40.7−68.4) in pregnant women compared to 60.3 days (95% CI 47.7−76.3; p = 0.66) in non‐pregnant women; neither pregnancy nor body mass index were significantly associated with t1/2app. Conclusions CAB‐LA concentrations post‐cessation of injections were generally well tolerated in pregnant women. The t1/2app was comparable between pregnant and non‐pregnant women. Ongoing studies will examine the safety and pharmacology of CAB‐LA in women who choose to continue CAB‐LA through pregnancy and lactation. |
| format | Article |
| id | doaj-art-f6c09e01dbeb4ff89789d6fcb38bb14d |
| institution | Kabale University |
| issn | 1758-2652 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
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| series | Journal of the International AIDS Society |
| spelling | doaj-art-f6c09e01dbeb4ff89789d6fcb38bb14d2025-01-24T08:18:07ZengWileyJournal of the International AIDS Society1758-26522025-01-01281n/an/a10.1002/jia2.26401Evaluation of long‐acting cabotegravir safety and pharmacokinetics in pregnant women in eastern and southern Africa: a secondary analysis of HPTN 084Sinead Delany‐Moretlwe0Brett Hanscom1Xu Guo2Clemensia Nkabiito3Patricia Mandima4Patricia Ntege Nahirya5Juliet Mpendo6Muchaneta Bhondai‐Mhuri7Nyaradzo Mgodi8Rebecca Berhanu9Jennifer Farrior10Estelle Piwowar‐Manning11Susan L. Ford12Craig W. Hendrix13Alex R. Rinehart14James F. Rooney15Adeola Adeyeye16Raphael J. Landovitz17Myron S. Cohen18Mina C. Hosseinipour19Mark A. Marzinke20the HPTN 084 Study TeamWits RHI University of the Witwatersrand Johannesburg South AfricaStatistical Centre for HIV/AIDS Research Prevention Fred Hutchinson Cancer Research Institute Seattle Washington USAStatistical Centre for HIV/AIDS Research Prevention Fred Hutchinson Cancer Research Institute Seattle Washington USAMakerere University ‐ Johns Hopkins University Research Collaboration Kampala UgandaUniversity of Zimbabwe Clinical Trials Research Centre Harare ZimbabweBaylor College of Medicine Children's Foundation Uganda Kampala UgandaUVRI‐IAVI Entebbe UgandaUniversity of Zimbabwe Clinical Trials Research Centre Harare ZimbabweUniversity of Zimbabwe Clinical Trials Research Centre Harare ZimbabweWits RHI University of the Witwatersrand Johannesburg South AfricaFHI 360 Durham North Carolina USADepartment of Pathology Johns Hopkins University School of Medicine Baltimore Maryland USAViiV Healthcare Durham North Carolina USADepartment of Medicine Johns Hopkins University School of Medicine Baltimore Maryland USAViiV Healthcare Durham North Carolina USAGilead Sciences Foster City California USADivision of AIDS National Institute for Allergy and Infectious Diseases Rockville Maryland USACenter for Clinical AIDS Research and Education University of California Los Angeles California USAUniversity of North Carolina (UNC) at Chapel Hill Chapel Hill North Carolina USAUniversity of North Carolina (UNC) at Chapel Hill Chapel Hill North Carolina USADepartment of Pathology Johns Hopkins University School of Medicine Baltimore Maryland USAAbstract Introduction Long‐acting injectable cabotegravir (CAB‐LA) for pre‐exposure prophylaxis significantly reduced HIV acquisition in HPTN 084. We report on the safety and CAB‐LA pharmacokinetics in pregnant women during the blinded period of HPTN 084. Methods Participants were randomized 1:1 to either active cabotegravir (CAB) plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) placebo or active TDF/FTC plus CAB placebo. Pregnancy testing was performed at each visit; participants with a positive test had study product withheld and were offered open‐label TDF/FTC. Pregnancies were confirmed on two tests at least 4 weeks apart. All participants with a positive pregnancy test prior to November 5, 2020 are included in this analysis. Pregnancy incidence, maternal adverse event (AE) incidence, pregnancy outcomes (including composite outcome of spontaneous abortion <20 weeks, intrauterine foetal death or stillbirth ≥20 weeks, premature birth <37 weeks, or small for gestational age) were assessed. The apparent terminal phase half‐life (t1/2app) of CAB‐LA in pregnant women in HPTN 084 was compared to non‐pregnant women from the phase 2a HPTN 077 trial. Multivariable models assessed associations with t1/2app. Results Fifty‐seven pregnancies (30 CAB‐LA, 27 TDF/FTC) were confirmed over 3845 person‐years [py] (incidence 1.5/100 py, 95% CI 1.1−1.9). CAB‐LA group participants had a median 342 days (IQR 192, 497) of CAB‐LA exposure prior to pregnancy detection. Grade 2 or higher maternal AE incidence did not differ by study arm (CAB 157, 95% CI 91−271 per 100 py vs. TDF/FTC 217, 95% CI 124–380 per 100 py; p = 0.256). Most pregnancies (81%) resulted in live births (25 CAB‐LA, 22 TDF/FTC). Composite poor pregnancy outcomes did not differ significantly by group (CAB 6/30 vs. TDF/FTC 4/27; p = 0.476). No congenital anomalies were observed. The CAB t1/2app geometric mean was 52.8 days (95% CI 40.7−68.4) in pregnant women compared to 60.3 days (95% CI 47.7−76.3; p = 0.66) in non‐pregnant women; neither pregnancy nor body mass index were significantly associated with t1/2app. Conclusions CAB‐LA concentrations post‐cessation of injections were generally well tolerated in pregnant women. The t1/2app was comparable between pregnant and non‐pregnant women. Ongoing studies will examine the safety and pharmacology of CAB‐LA in women who choose to continue CAB‐LA through pregnancy and lactation.https://doi.org/10.1002/jia2.26401cabotegravirHIV preventionlong‐actingPrEPpregnancywomen |
| spellingShingle | Sinead Delany‐Moretlwe Brett Hanscom Xu Guo Clemensia Nkabiito Patricia Mandima Patricia Ntege Nahirya Juliet Mpendo Muchaneta Bhondai‐Mhuri Nyaradzo Mgodi Rebecca Berhanu Jennifer Farrior Estelle Piwowar‐Manning Susan L. Ford Craig W. Hendrix Alex R. Rinehart James F. Rooney Adeola Adeyeye Raphael J. Landovitz Myron S. Cohen Mina C. Hosseinipour Mark A. Marzinke the HPTN 084 Study Team Evaluation of long‐acting cabotegravir safety and pharmacokinetics in pregnant women in eastern and southern Africa: a secondary analysis of HPTN 084 Journal of the International AIDS Society cabotegravir HIV prevention long‐acting PrEP pregnancy women |
| title | Evaluation of long‐acting cabotegravir safety and pharmacokinetics in pregnant women in eastern and southern Africa: a secondary analysis of HPTN 084 |
| title_full | Evaluation of long‐acting cabotegravir safety and pharmacokinetics in pregnant women in eastern and southern Africa: a secondary analysis of HPTN 084 |
| title_fullStr | Evaluation of long‐acting cabotegravir safety and pharmacokinetics in pregnant women in eastern and southern Africa: a secondary analysis of HPTN 084 |
| title_full_unstemmed | Evaluation of long‐acting cabotegravir safety and pharmacokinetics in pregnant women in eastern and southern Africa: a secondary analysis of HPTN 084 |
| title_short | Evaluation of long‐acting cabotegravir safety and pharmacokinetics in pregnant women in eastern and southern Africa: a secondary analysis of HPTN 084 |
| title_sort | evaluation of long acting cabotegravir safety and pharmacokinetics in pregnant women in eastern and southern africa a secondary analysis of hptn 084 |
| topic | cabotegravir HIV prevention long‐acting PrEP pregnancy women |
| url | https://doi.org/10.1002/jia2.26401 |
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