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Randomized Controlled Trial
. 2024 Jun 14;78(6):1617-1628.
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

Risa M Hoffman  1 , Sean Brummel  2 , Lauren Ziemba  2 , Lameck Chinula  3 , Katie McCarthy  4 , Lee Fairlie  5 , Patrick Jean-Philippe  6 , Nahida Chakhtoura  7 , Ben Johnston  8 , Chelsea Krotje  8 , Teacler G Nematadzira  9 , Frances Nakayiwa  10 , Victoria Ndyanabangi  11 , Sherika Hanley  12 , Gerhard Theron  13 , Avy Violari  14 , Esau João  15 , Mario Dias Correa Jr  16 , Cristina Barroso Hofer  17 , Oranich Navanukroh  18 , Linda Aurpibul  19 , Neetal Nevrekar  20 , Rebecca Zash  21 , Roger Shapiro  2 , Jeffrey S A Stringer  22 , Judith S Currier  1 , Paul Sax  23 , Shahin Lockman  24 ; IMPAACT 2010/VESTED Study Team
Collaborators, Affiliations
Randomized Controlled Trial

Weight Changes and Adverse Pregnancy Outcomes With Dolutegravir- and Tenofovir Alafenamide Fumarate-Containing Antiretroviral Treatment Regimens During Pregnancy and Postpartum

Risa M Hoffman et al. Clin Infect Dis. .

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 human immunodeficiency virus (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 Institute of Medicine 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 size for GA (<10th percentile), and a composite of these endpoints.

Results: A total of 643 participants were randomized: 217 to the DTG + FTC/TAF, 215 to the DTG + FTC/TDF, and 211 to the EFV/FTC/TDF arm. Baseline medians were as follows: GA, 21.9 weeks; HIV RNA, 903 copies/mL; and CD4 cell count, 466/μL. 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 (hazard ratio, 1.44 [95% confidence interval, 1.04-2.00]) and small size for GA (1.48 [.99-2.22]). More women in the DTG + FTC/TAF arm had a body mass index ≥25 (calculated as weight in kilograms divided by height in meters squared) 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 typically 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.

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Conflict of interest statement

Potential conflicts of interest. R. M. H. is an Elsevier ClinicalKey editorial board member. R. M. H. also reports honoraria for lectures on this topic from the Los Angeles County Division of HIV and STI Programs and the UCLA CARE Center’s continuing medical education seminars. S. B. and L. Z. reports support for the present work from the NIH Division of AIDS/Eunice Kennedy Shriver National Institute of Child Health and Human Development and ViiV/GSK, paid to their institution. L. F. reports grants or contracts for the current study through NIH/IMPAACT. S. H. reports grants or contracts from UKZN Developing Research Innovation, Localisation and Leadership in South Africa (DRILL), the Fogarty International Center, the NIH Common Fund, Office of Strategic Coordination, Office of the Director, Office of AIDS Research, the NIH Office of the Director, the National Institute of Mental Health, NIH (award D43TW010131, paid to their institution, from January 2018 to July 2023), and the SA National Research Foundation (Thuthuka funding grant, paid to their institution, from January 2019 to December 2021). R. Z. reports receipt of study medication from ViiV healthcare for a federally funded research study (as principal investigator); ViiV is donating long-acting cabotegravir for an implementation study of preexposure prophylaxis in Botswana, funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. J. S. C. is a scientific advisor for Merck, participating on its advisory board, and reports royalties or licenses from UpToDate. P. S. reports grants or contracts from Gilead and ViiV; consulting fees from Gilead, Janssen, Merck, and ViiV; and participation on a data safety monitoring board or advisory board for Merck. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Weight changes antepartum. A, Average weekly rate of change antepartum relative to Institute of Medicine (IOM) standard. B, Low, normal, and high weight gain based on IOM definitions by treatment arm. Abbreviations: DTG, dolutegravir; EFV, efavirenz; FTC, emtricitabine; TAF, tenofovir alafenamide fumarate; TDF, tenofovir disoproxil fumarate.
Figure 2.
Figure 2.
Body mass index (BMI) from before pregnancy to 50 weeks postpartum by study arm (BMI calculated as weight in kilograms divided by height in meters). Note that prepregnancy BMI was imputed for 73% of participants when prepregnancy weight data were not available. Abbreviations: DTG, dolutegravir; EFV, efavirenz; FTC, emtricitabine; TAF, tenofovir alafenamide fumarate; TDF, tenofovir disoproxil fumarate.
Figure 3.
Figure 3.
Associations between adverse pregnancy outcomes and Institute of Medicine weight gain categories. A, Low versus normal weight gain. B. High versus normal weight gain. C, Low versus normal weight gain by arm for the composite adverse pregnancy outcome. D, High versus normal weight gain by arm for the composite adverse pregnancy outcome. Models were adjusted for gestational age (GA) stratum at baseline. Abbreviations: AE, adverse event; CI, confidence interval; DTG, dolutegravir; EFV, efavirenz; FTC, emtricitabine; HR, hazard ratio; LGA, large size for GA; SGA, small size for GA; TAF, tenofovir alafenamide fumarate; TDF, tenofovir disoproxil fumarate.
Figure 4.
Figure 4.
Associations between Institute of Medicine weight category and a maternal grade ≥3 adverse event (AE) overall and by arm, adjusted for baseline gestational age category. A, Low versus normal weight gain. B, High versus normal weight gain. Abbreviations: CI, confidence interval; DTG, dolutegravir; EFV, efavirenz; FTC, emtricitabine; HR, hazard ratio; TAF, tenofovir alafenamide fumarate; TDF, tenofovir disoproxil fumarate.
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