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 Jun 15:jiae308. doi: 10.1093/infdis/jiae308. Online ahead of print.

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 Lockman¹⁹

Affiliations

¹ Center for Biostatistics in AIDS Research, Harvard TH Chan School of Public Health, Boston, MA, USA.
² National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USA.
³ National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
⁴ Goldbelt Professional Services, LLC, Chesapeake, VA, USA.
⁵ FHI 360, Durham, NC, USA.
⁶ Frontier Science Foundation, Amherst, NY, USA.
⁷ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
⁸ University of Zimbabwe Clinical Trials Research Centre, Harare, Zimbabwe.
⁹ MU-JHU Research Collaboration, Kampala, Uganda.
¹⁰ Baylor Uganda, Clinical Research site, Kampala, Uganda.
¹¹ Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
¹² Wits RHI, Faculty of Health Sciences, University of the Witwatersrand, South Africa.
¹³ Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
¹⁴ Kilimanjaro Christian Medical University College, Tanzania.
¹⁵ Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, MA, USA.
¹⁶ University Health Network and Department of Immunology and Institute of Medical Sciences, University of Toronto, Toronto, Canada.
¹⁷ Pregnancy and Perinatal Branch, NICHD, Bethesda, MD.
¹⁸ University of North Carolina Project-Malawi, Lilongwe, Malawi.
¹⁹ Botswana Harvard Health Partnership; Brigham and Women's Hospital, Boston, MA; Harvard TH Chan School of Public Health, Boston, MA, USA.

PMID: 38877762
DOI: 10.1093/infdis/jiae308

Abstract

In IMPAACT 2010/VESTED, pregnant women were randomized to initiate dolutegravir (DTG)+emtricitabine (FTC)/tenofovir alafenamide (TAF), DTG+FTC/tenofovir disoproxil fumarate (TDF), or efavirenz (EFV)/FTC/TDF. We assessed red blood cell folate concentrations (RBC-folate) at maternal study entry and delivery, and infant birth. RBC-folate outcomes were: 1) maternal change entry to delivery (trajectory), 2) infant, 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-GMRT) of each arm comparison in 340 mothers and 310 infants. 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/mm3 and log10HIV 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%CI 1.00, 1.06). The DTG+FTC/TAF arm had an 8% lower infant-maternal folate ratio (0.92, 95%CI 0.78, 1.09) versus EFV/FTC/TDF. 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- vs. EFV-based ART.

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

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