Weight changes and adverse pregnancy outcomes with dolutegravir- and tenofovir alafenamide fumarate-containing antiretroviral treatment regimens during pregnancy and postpartum

Risa M Hoffman; Sean Brummel; Lauren Ziemba; Lameck Chinula; Katie McCarthy; Lee Fairlie; Patrick Jean-Philippe; Nahida Chakhtoura; Ben Johnston; Chelsea Krotje; Teacler G Nematadzira; Frances Nakayiwa; Victoria Ndyanabangi; Sherika Hanley; Gerhard Theron; Avy Violari; Esau João; Mario Dias Correa Junior; Cristina Barroso Hofer; Oranich Navanukroh; Linda Aurpibul; Neetal Nevrekar; Rebecca Zash; Roger Shapiro; Jeffrey S A Stringer; Judith S Currier; Paul Sax; Shahin Lockman; IMPAACT 2010/VESTED Study Team

doi:10.1093/cid/ciae001

Weight changes and adverse pregnancy outcomes with dolutegravir- and tenofovir alafenamide fumarate-containing antiretroviral treatment regimens during pregnancy and postpartum

Clin Infect Dis. 2024 Jan 5:ciae001. doi: 10.1093/cid/ciae001. Online ahead of print.

Authors

Risa M Hoffman¹, Sean Brummel², Lauren Ziemba², Lameck Chinula³, Katie McCarthy⁴, Lee Fairlie⁵, Patrick Jean-Philippe⁶, Nahida Chakhtoura⁷, Ben Johnston⁸, Chelsea Krotje⁸, Teacler G Nematadzira⁹, Frances Nakayiwa¹⁰, Victoria Ndyanabangi¹¹, Sherika Hanley¹², Gerhard Theron¹³, Avy Violari¹⁴, Esau João¹⁵, Mario Dias Correa Junior¹⁶, Cristina Barroso Hofer¹⁷, Oranich Navanukroh¹⁸, Linda Aurpibul¹⁹, Neetal Nevrekar²⁰, Rebecca Zash²¹, Roger Shapiro², Jeffrey S A Stringer²², Judith S Currier¹, Paul Sax²³, Shahin Lockman²⁴; IMPAACT 2010/VESTED Study Team

Collaborators

IMPAACT 2010/VESTED Study Team:
Sharon Nachman, James McIntyre, David P Harrington, Catherine Hill, Steven Joffe, Alwyn Mwinga, Andrew J Nunn, Merlin L Robb, Haroon Saloojee, Merlin L Robb, Jonathan Kimmelman, Graeme A Meintjes, Barbara E Murray, Stuart Campbell Ray, Haroon Saloojee, Anastasios A Tsiatis, Paul A Volberding, David Glidden, Valeria Cavalcanti Rolla, Nahida Chakhtoura, Jeanna Piper, Karin Klingman, Debika Bhattacharya, Patrick Jean-Philippe, Lynne Mofenson, Sean Brummel, Lauren Ziemba, Benjamin Johnston, Chelsea Krotje, Scott McCallister, Jean van Wyk, Mark Mirochnick, Brookie Best, Kevin Robertson, Cheryl Blanchette, Nagawa Jaliaah, Andi Fox, Frances Whalen, Kevin Knowles, William Murtaugh, Mauricio Pinilla, Yao Cheng, Emmanuel Patras

Affiliations

¹ Dept of Medicine, University of California, Los Angeles, USA.
² Harvard T.H. Chan School of Public Health, USA.
³ UNC Chapel Hill Dept OB/GYN, UNC Project Malawi, Malawi.
⁴ FHI 360, USA.
⁵ Wits Reproductive Health and HIV Institute, University of the Witwatersrand, South Africa.
⁶ Division of AIDS, National Institutes of Health, USA.
⁷ National Institute of Child Health and Human Development, National Institutes of Health, USA.
⁸ Frontier Science Foundation, USA.
⁹ University of Zimbabwe-UCSF Collaborative Research Programme, Zimbabwe.
¹⁰ MUJHU Care Limited, Kampala, Uganda.
¹¹ Baylor College of Medicine Children's Foundation Uganda.
¹² Centre for the AIDS Programme of Research and University of KwaZulu-Natal, Department of Family Medicine, South Africa.
¹³ Stellenbosch University, South Africa.
¹⁴ Perinatal HIV Research Unit, University of the Witwatersrand, South Africa.
¹⁵ Hospital Federal dos Servidores do Estado, Brazil.
¹⁶ Universidade Federal de Minas Gerais, Brazil.
¹⁷ Universidade Federal do Rio de Janeiro, Brazil.
¹⁸ Siriraj Hospital, Mahidol University, Thailand.
¹⁹ Research Institute for Health Sciences, Chiang Mai University, Thailand.
²⁰ Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University, Pune, India.
²¹ Beth Israel Deaconess Medical Center, USA.
²² University of North Carolina School of Medicine, USA.
²³ Dept of Medicine, Brigham and Women's Hospital, USA.
²⁴ Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health, USA.

PMID: 38180851
DOI: 10.1093/cid/ciae001

Abstract

Background: We evaluated associations between antepartum weight change and adverse pregnancy outcomes and between antiretroviral therapy (ART) regimens and week-50 postpartum body mass index in IMPAACT 2010.

Methods: Women with HIV-1 in 9 countries were randomized 1:1:1 at 14-28 weeks gestational age (GA) to start dolutegravir(DTG)+emtricitabine(FTC)/tenofovir alafenamide fumarate(TAF) versus DTG+FTC/tenofovir disoproxil fumarate(TDF) versus efavirenz (EFV)/FTC/TDF. Insufficient antepartum weight gain was defined using IOM guidelines. Cox-proportional hazards regression models were used to evaluate the association between antepartum weight change and adverse pregnancy outcomes: stillbirth (≥20 weeks GA), preterm delivery (<37 weeks GA), small for gestational age (SGA<10th percentile), and a composite of these endpoints.

Results: 643 participants were randomized: 217 in DTG+FTC/TAF, 215 in DTG+FTC/TDF, and 211 in EFV/FTC/TDF arms. Baseline medians were: GA 21.9 weeks, HIV RNA 903 copies/mL, CD4 count 466 cells/uL. Insufficient weight gain was least frequent with DTG+FTC/TAF (15.0%) versus DTG+FTC/TDF (23.6%) and EFV/FTC/TDF (30.4%). Women in the DTG+FTC/TAF arm had the lowest rate of composite adverse pregnancy outcome. Low antepartum weight gain was associated with higher hazard of composite adverse pregnancy outcome (HR 1.44, 95%CI 1.04, 2.00) and SGA (HR 1.48, 95%CI 0.99, 2.22). More women in the DTG+FTC/TAF arm had body mass index ≥25 kg/m2 at 50 weeks postpartum (54.7%) versus the DTG+FTC/TDF (45.2%) and EFV/FTC/TDF (34.2%) arms.

Conclusions: Antepartum weight gain on DTG regimens was protective against adverse pregnancy outcomes traditionally associated with insufficient weight gain, supportive of guidelines recommending DTG-based ART for women starting ART during pregnancy. Interventions to mitigate postpartum weight gain are needed.

Keywords: HIV; adverse pregnancy outcomes; antepartum weight change; postpartum weight; women's health.

Grants and funding

UM1 AI068616/AI/NIAID NIH HHS/United States