Dolutegravir- Versus Efavirenz-Based Treatment in Pregnancy: Impact on Red Blood Cell Folate Concentrations in Pregnant Women and Their Infants

Denise L Jacobson; Krista S Crider; Patricia DeMarrais; Sean Brummel; Mindy Zhang; Christine M Pfeiffer; Cynthia A Moore; Katie McCarthy; Benjamin Johnston; Terence Mohammed; Tichaona Vhembo; Enid Kabugho; Gerald Agaba Muzorah; Haseena Cassim; Lee Fairlie; Elizabeth S Machado; James S Ngocho; Roger L Shapiro; Lena Serghides; Nahida Chakhtoura; Lameck Chinula; Shahin Lockman

doi:10.1093/infdis/jiae308

Dolutegravir- Versus Efavirenz-Based Treatment in Pregnancy: Impact on Red Blood Cell Folate Concentrations in Pregnant Women and Their Infants

J Infect Dis. 2024 Nov 15;230(5):1224-1234. doi: 10.1093/infdis/jiae308.

Authors

Denise L Jacobson¹, Krista S Crider², Patricia DeMarrais¹, Sean Brummel¹, Mindy Zhang³, Christine M Pfeiffer³, Cynthia A Moore⁴, Katie McCarthy⁵, Benjamin Johnston⁶, Terence Mohammed⁷, Tichaona Vhembo⁸, Enid Kabugho⁹, Gerald Agaba Muzorah¹⁰, Haseena Cassim¹¹, Lee Fairlie¹², Elizabeth S Machado¹³, James S Ngocho¹⁴, Roger L Shapiro¹⁵, Lena Serghides¹⁶, Nahida Chakhtoura¹⁷, Lameck Chinula¹⁸, Shahin Lockman^{19

20}

Affiliations

¹ Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
² National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia.
³ National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
⁴ Goldbelt Professional Services, LLC, Chesapeake, Virginia.
⁵ FHI 360, Durham, North Carolina.
⁶ Frontier Science Foundation, Amherst, New York.
⁷ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
⁸ University of Zimbabwe Clinical Trials Research Centre, Harare, Zimbabwe.
⁹ Makarere University-Johns Hopkins University Research Collaboration, Kampala, Uganda.
¹⁰ Clinical Research site, Baylor-Uganda, Kampala, Uganda.
¹¹ Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersand, South Africa.
¹² Wits RHI, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
¹³ Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro, Brazil.
¹⁴ Kilimanjaro Christian Medical University College, Moshi, Tanzania.
¹⁵ Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
¹⁶ University Health Network and Department of Immunology and Institute of Medical Sciences, University of Toronto, Ontario, Canada.
¹⁷ Pregnancy and Perinatal Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
¹⁸ University of North Carolina Project-Malawi, Lilongwe, Malawi.
¹⁹ Botswana Harvard Health Partnership, Brigham and Women's Hospital.
²⁰ Harvard T. H. Chan School of Public Health, Boston, Massachusetts.

Abstract

Background: In the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 2010/VESTED study, pregnant women were randomized to initiate dolutegravir (DTG) + emtricitabine (FTC)/tenofovir alafenamide (TAF), DTG + FTC/tenofovir disoproxil fumarate (TDF), or efavirenz (EFV)/FTC/TDF.

Methods: We assessed red blood cell (RBC) folate concentrations at maternal study entry and delivery, and infant birth. RBC folate outcomes were (1) maternal change entry to delivery (trajectory), (2) infant, and (3) ratio of infant-to-maternal delivery. Generalized estimating equation models for each log(folate) outcome were fit to estimate adjusted geometric mean ratio (Adj-GMR)/GMR trajectories (Adj-GMRTs) of each arm comparison in 340 mothers and 310 infants.

Results: Overall, 90% of mothers received folic acid supplements and 78% lived in Africa. At entry, median maternal age was 25 years, gestational age was 22 weeks, CD4 count was 482 cells/μL, and log10 HIV RNA was 3 copies/mL. Entry RBC folate was similar across arms. Adj-GMRT of maternal folate was 3% higher in the DTG + FTC/TAF versus EFV/FTC/TDF arm (1.03 [95% confidence interval {CI}, 1.00-1.06]). The DTG + FTC/TAF arm had an 8% lower infant-maternal folate ratio (0.92 [95% CI, .78-1.09]) versus EFV/FTC/TDF.

Conclusions: Results are consistent, with no clinically meaningful differences between arms for all RBC folate outcomes, and they suggest that cellular uptake of folate and folate transport to the infant do not differ in pregnant women starting DTG- versus EFV-based antiretroviral therapy.

Clinical trials registration: NCT03048422.

Keywords: dolutegravir; efavirenz; infant; pregnancy; red blood cell folate concentrations.

© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

Publication types

Randomized Controlled Trial

MeSH terms

Adolescent
Adult
Alkynes*
Anti-HIV Agents* / administration & dosage
Anti-HIV Agents* / therapeutic use
Benzoxazines* / administration & dosage
Benzoxazines* / therapeutic use
Cyclopropanes*
Emtricitabine / administration & dosage
Emtricitabine / therapeutic use
Erythrocytes* / chemistry
Female
Folic Acid* / administration & dosage
Folic Acid* / blood
HIV Infections* / blood
HIV Infections* / drug therapy
Heterocyclic Compounds, 3-Ring* / administration & dosage
Heterocyclic Compounds, 3-Ring* / therapeutic use
Humans
Infant
Infant, Newborn
Oxazines* / therapeutic use
Piperazines* / therapeutic use
Pregnancy
Pregnancy Complications, Infectious* / blood
Pregnancy Complications, Infectious* / drug therapy
Pregnancy Complications, Infectious* / virology
Pyridones* / therapeutic use
Tenofovir / therapeutic use
Young Adult

Substances

Alkynes
efavirenz
Cyclopropanes
Heterocyclic Compounds, 3-Ring
Piperazines
Benzoxazines
Oxazines
dolutegravir
Anti-HIV Agents
Folic Acid
Pyridones
Emtricitabine
Tenofovir

Associated data

ClinicalTrials.gov/NCT03048422

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding