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Infant Stunting Worse With Maternal
EFV Than DTG, Similar With TAF and TDF
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2022 CROI, February 12-16 and 22-24, 2022
Mark Mascolini
High proportions of infants in a 9-country 617-infant trial had stunting 26 and 50 weeks after birth, but growth was slower in infants of mothers taking efavirenz (EFV) than in those whose mothers took dolutegravir (DTG) [1]. Growth rates did not differ between infants whose mothers took tenofovir disoproxil (TDF) versus tenofovir alafenamide (TAF).
IMPAACT 2010 compared virologic and other outcomes in HIV-positive mothers randomized to one of three regimens starting 12 to 26 weeks before delivery: DTG + emtricitabine (FTC)/TAF, DTG + FTC/TDF, or EFV/FTC/TDF. In the primary analysis, the DTG regimens controlled HIV better at delivery than the EFV combination [2]. Composite adverse pregnancy outcomes and neonatal deaths were least frequent with DTG/FTC/TAF.
IMPAACT 2010 recruited antiretroviral-naive participants in several African countries, Brazil, India, Thailand, and the US. Weight gain during pregnancy was closer to expected rates in women assigned to DTG than in those randomized to EFV. A higher proportion of women taking EFV had infants weighing under 2500 g at birth. Similar proportions of women in each study arm, about 77%, began breastfeeding, and breastfeeding lasted a median of 50 weeks in each arm. Only 4 infants overall became infected with HIV.
Researchers figured infant growth with WHO z-scores calculated at weeks 26 and 50 for infants who remained in the study: length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WHZ).
At week 26 length-for-age proved significantly lower in infants of women taking the EFV combination versus the DTG/TDF regimen (average difference 0.4, 0.1 to 0.6, P = 0.0056) or the DTG/TAF combo (average difference 0.4, 0.1 to 0.7, P = 0.0047). At week 50 this difference favoring the DTG regimens reached statistical significance only for DTG + FTC/TDF (average difference 0.3, 0.1 to 0.6, P = 0.010). Length-for-age differed hardly at all between infants of mothers taking the two DTG regimens at week 26 or 50.
Similarly, weight-for-age was significantly (or almost significantly) worse in infants of mothers taking the EFV combination versus either DTG regimen at weeks 26 and 50. Week-50 weight- for-age difference comparing DTG +FTC/TDF with EFV/FTC/TDF averaged 0.3, 0.1 to 0.6, P = 0.0094; comparing DTG + FTC/TAF with EFV/FTC/TDF the difference averaged 0.3, 0.1 to 0.6, P = 0.019. And again there was virtually no difference in weight-for-age between the two DTG combos. Weight-for-length did not differ significantly in any two-regimen comparison.
Stunting rates were high in every study arm, but higher in infants of mothers taking EFV/FTC/TDF (1 in 5) than in infants of mothers taking either DTG combination (1 in 7). This analysis turned up no increase in infant obesity between infants of mothers taking DTG versus EFV.
The IMPAACT team underlined three potential limitations of their analysis: infant follow-up stopped around 1 year of age; the analysis involved women who started ART in pregnancy, not women taking ART at delivery; most women in the study group were breastfeeding and from Africa.
The investigators urged that infant growth be considered when picking optimal antiretroviral combinations for mothers during pregnancy and breastfeeding. They stressed that “EFV use in pregnancy [is] associated with concerning low growth parameters during the first year of life.” Stunting in infancy, they reminded colleagues, could affect cognitive development and adult height.
References
1. Stranix-Chibanda L, Ziemba L, Brummel S, et al. Growth of infants with perinatal exposure to maternal DTG vs EFV and TDF vs TAF. 2022 CROI, February 12-16 and 22-24, 2022. Abstract 30.
2. Lockman S, Brummel SS, Ziemba L, et al. Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet. 2021;397:1276-1292. doi: 10.1016/S0140-6736(21)00314-7.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00314-7/fulltext
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