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Randomized Controlled Trial
. 2024 Nov 15;230(5):1224-1234.
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

Denise L Jacobson  1 , Krista S Crider  2 , Patricia DeMarrais  1 , Sean Brummel  1 , Mindy Zhang  3 , Christine M Pfeiffer  3 , Cynthia A Moore  4 , Katie McCarthy  5 , Benjamin Johnston  6 , Terence Mohammed  7 , Tichaona Vhembo  8 , Enid Kabugho  9 , Gerald Agaba Muzorah  10 , Haseena Cassim  11 , Lee Fairlie  12 , Elizabeth S Machado  13 , James S Ngocho  14 , Roger L Shapiro  15 , Lena Serghides  16 , Nahida Chakhtoura  17 , Lameck Chinula  18 , Shahin Lockman  19   20
Affiliations
Randomized Controlled Trial

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

Denise L Jacobson et al. J Infect Dis. .

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.

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Conflict of interest statement

Potential conflicts of interest. P. D. and S. B. have received funds from ViiV/GSK that were paid to Harvard. All other authors report no potential conflicts of interest. 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.
Box plot of red blood cell (RBC) folate concentrations at entry and delivery in pregnant women with human immunodeficiency virus and in infants at birth by treatment arm. The y-axis is displayed on the logarithmic scale, but the actual RBC folate levels are displayed. Diamond is the mean. The box indicates median and interquartile range. The whiskers indicate the minimum and maximum data values, not including outliers. Outliers are those points >75th percentile + 1.5 × interquartile range or analogous points below. Abbreviations: DTG, dolutegravir; EFV, efavirenz; FTC, emtricitabine; RBC, red blood cell; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.
Figure 2.
Figure 2.
Red blood cell folate concentrations in pregnant women with human immunodeficiency virus at delivery versus infant concentrations at birth. Abbreviations: DTG, dolutegravir; EFV, efavirenz; FTC, emtricitabine; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.
See this image and copyright information in PMC

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