The Effects on the Growth of HIV-exposed Uninfected Infants of Initiating Dolutegravir-based Versus Efavirenz-based cART in Late Pregnancy (DolPHIN-2)

Lisa Hagens; Lisanne A.H. Bevers; Thokozile R. Malaba; Sylvia Cornelia Nassiwa; Megan Mrubata; Helene Theunissen; Helen Reynolds; Nengjie He; Jim Read; David M. Burger; Mohammed Lamorde; Landon Myer; Duolao Wang; Saye Khoo; Catriona Waitt; Angela Colbers

doi:10.1097/INF.0000000000004902

The Effects on the Growth of HIV-exposed Uninfected Infants of Initiating Dolutegravir-based Versus Efavirenz-based cART in Late Pregnancy (DolPHIN-2)

Lisa Hagens
, Lisanne A.H. Bevers
, Thokozile R. Malaba
, Sylvia Cornelia Nassiwa
, Megan Mrubata
, Helene Theunissen
, Helen Reynolds
, Nengjie He
, Jim Read
, David M. Burger
, Mohammed Lamorde
, Landon Myer
, Duolao Wang
, Saye Khoo
, Catriona Waitt
, Angela Colbers

Clinical Sciences

Radboud University Nijmegen
University of Cape Town
Makerere University
University of Liverpool
Liverpool School of Tropical Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Background: In 2019, the World Health Organization (WHO) changed its recommendations for pregnant women living with HIV from efavirenz-based to dolutegravir-based therapy due to its superior efficacy, tolerability and resistance profile. Perinatal exposure to antiretrovirals may influence infant growth, but limited data exist on the effects of specific regimens over time. Aim: This study aimed to compare growth trajectories over the first 72 weeks of life among infants exposed to dolutegravir-based versus efavirenz-based therapy during late pregnancy.

Methods: The DolPHIN-2 trial was a randomized, open-label trial conducted in South Africa and Uganda, researching the efficacy of dolutegravir-based versus efavirenz-based therapy in pregnant women living with HIV, initiating treatment in the third trimester. In this secondary analysis, we compared growth trajectories until 72 weeks postpartum between HIV-exposed uninfected infants perinatally exposed to dolutegravir-based versus efavirenz-based therapy. Measures of infant weight, length and head circumference were converted to WHO-defined weight-for-age, weight-for-length, length-for-age and head circumference-for-age Z-scores. Subsequently, Z-scores were compared across treatment arms, using linear mixed-effect models.

Results: After exclusions, 232 infants remained (dolutegravir: n = 116; efavirenz: n = 116). In both crude models and models adjusted for study site and maternal height, length-for-age Z-scores were 0.277 units higher in the dolutegravir arm. No statistically significant impact of treatment was observed for other outcomes. In both study arms, a decline in mean length-for-age Z-scores occurred over the first 72 weeks, while mean weight-for-age Z-scores declined between weeks 48 and 72.

Conclusion: Our data support the WHO in recommending dolutegravir-based therapy over efavirenz-based therapy in pregnant women living with HIV.

Original language	English
Pages (from-to)	1066-1071
Number of pages	6
Journal	Pediatric Infectious Disease Journal
Volume	44
Issue number	11
Early online date	18 Jul 2025
DOIs	https://doi.org/10.1097/INF.0000000000004902
Publication status	E-pub ahead of print - 18 Jul 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

antiretroviral therapy
HIV
infant growth and pregnancy

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the_effects_on_the_growth_of_hiv_exposed.1376Final published version, 532 KBLicence: CC BY

Cite this

Hagens, L., Bevers, L. A. H., Malaba, T. R., Nassiwa, S. C., Mrubata, M., Theunissen, H., Reynolds, H., He, N., Read, J., Burger, D. M., Lamorde, M., Myer, L., Wang, D., Khoo, S., Waitt, C., & Colbers, A. (2025). The Effects on the Growth of HIV-exposed Uninfected Infants of Initiating Dolutegravir-based Versus Efavirenz-based cART in Late Pregnancy (DolPHIN-2). Pediatric Infectious Disease Journal, 44(11), 1066-1071. Advance online publication. https://doi.org/10.1097/INF.0000000000004902

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title = "The Effects on the Growth of HIV-exposed Uninfected Infants of Initiating Dolutegravir-based Versus Efavirenz-based cART in Late Pregnancy (DolPHIN-2)",

abstract = "Background: In 2019, the World Health Organization (WHO) changed its recommendations for pregnant women living with HIV from efavirenz-based to dolutegravir-based therapy due to its superior efficacy, tolerability and resistance profile. Perinatal exposure to antiretrovirals may influence infant growth, but limited data exist on the effects of specific regimens over time. Aim: This study aimed to compare growth trajectories over the first 72 weeks of life among infants exposed to dolutegravir-based versus efavirenz-based therapy during late pregnancy. Methods: The DolPHIN-2 trial was a randomized, open-label trial conducted in South Africa and Uganda, researching the efficacy of dolutegravir-based versus efavirenz-based therapy in pregnant women living with HIV, initiating treatment in the third trimester. In this secondary analysis, we compared growth trajectories until 72 weeks postpartum between HIV-exposed uninfected infants perinatally exposed to dolutegravir-based versus efavirenz-based therapy. Measures of infant weight, length and head circumference were converted to WHO-defined weight-for-age, weight-for-length, length-for-age and head circumference-for-age Z-scores. Subsequently, Z-scores were compared across treatment arms, using linear mixed-effect models. Results: After exclusions, 232 infants remained (dolutegravir: n = 116; efavirenz: n = 116). In both crude models and models adjusted for study site and maternal height, length-for-age Z-scores were 0.277 units higher in the dolutegravir arm. No statistically significant impact of treatment was observed for other outcomes. In both study arms, a decline in mean length-for-age Z-scores occurred over the first 72 weeks, while mean weight-for-age Z-scores declined between weeks 48 and 72. Conclusion: Our data support the WHO in recommending dolutegravir-based therapy over efavirenz-based therapy in pregnant women living with HIV.",

keywords = "antiretroviral therapy, HIV, infant growth and pregnancy",

author = "Lisa Hagens and Bevers, \{Lisanne A.H.\} and Malaba, \{Thokozile R.\} and Nassiwa, \{Sylvia Cornelia\} and Megan Mrubata and Helene Theunissen and Helen Reynolds and Nengjie He and Jim Read and Burger, \{David M.\} and Mohammed Lamorde and Landon Myer and Duolao Wang and Saye Khoo and Catriona Waitt and Angela Colbers",

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year = "2025",

month = jul,

day = "18",

doi = "10.1097/INF.0000000000004902",

language = "English",

volume = "44",

pages = "1066--1071",

journal = "Pediatric Infectious Disease Journal",

issn = "0891-3668",

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Hagens, L, Bevers, LAH, Malaba, TR, Nassiwa, SC, Mrubata, M, Theunissen, H, Reynolds, H, He, N, Read, J, Burger, DM, Lamorde, M, Myer, L, Wang, D, Khoo, S, Waitt, C & Colbers, A 2025, 'The Effects on the Growth of HIV-exposed Uninfected Infants of Initiating Dolutegravir-based Versus Efavirenz-based cART in Late Pregnancy (DolPHIN-2)', Pediatric Infectious Disease Journal, vol. 44, no. 11, pp. 1066-1071. https://doi.org/10.1097/INF.0000000000004902

The Effects on the Growth of HIV-exposed Uninfected Infants of Initiating Dolutegravir-based Versus Efavirenz-based cART in Late Pregnancy (DolPHIN-2). / Hagens, Lisa; Bevers, Lisanne A.H.; Malaba, Thokozile R. et al.
In: Pediatric Infectious Disease Journal, Vol. 44, No. 11, 18.07.2025, p. 1066-1071.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - The Effects on the Growth of HIV-exposed Uninfected Infants of Initiating Dolutegravir-based Versus Efavirenz-based cART in Late Pregnancy (DolPHIN-2)

AU - Hagens, Lisa

AU - Bevers, Lisanne A.H.

AU - Malaba, Thokozile R.

AU - Nassiwa, Sylvia Cornelia

AU - Mrubata, Megan

AU - Theunissen, Helene

AU - Reynolds, Helen

AU - He, Nengjie

AU - Read, Jim

AU - Burger, David M.

AU - Lamorde, Mohammed

AU - Myer, Landon

AU - Wang, Duolao

AU - Khoo, Saye

AU - Waitt, Catriona

AU - Colbers, Angela

PY - 2025/7/18

Y1 - 2025/7/18

N2 - Background: In 2019, the World Health Organization (WHO) changed its recommendations for pregnant women living with HIV from efavirenz-based to dolutegravir-based therapy due to its superior efficacy, tolerability and resistance profile. Perinatal exposure to antiretrovirals may influence infant growth, but limited data exist on the effects of specific regimens over time. Aim: This study aimed to compare growth trajectories over the first 72 weeks of life among infants exposed to dolutegravir-based versus efavirenz-based therapy during late pregnancy. Methods: The DolPHIN-2 trial was a randomized, open-label trial conducted in South Africa and Uganda, researching the efficacy of dolutegravir-based versus efavirenz-based therapy in pregnant women living with HIV, initiating treatment in the third trimester. In this secondary analysis, we compared growth trajectories until 72 weeks postpartum between HIV-exposed uninfected infants perinatally exposed to dolutegravir-based versus efavirenz-based therapy. Measures of infant weight, length and head circumference were converted to WHO-defined weight-for-age, weight-for-length, length-for-age and head circumference-for-age Z-scores. Subsequently, Z-scores were compared across treatment arms, using linear mixed-effect models. Results: After exclusions, 232 infants remained (dolutegravir: n = 116; efavirenz: n = 116). In both crude models and models adjusted for study site and maternal height, length-for-age Z-scores were 0.277 units higher in the dolutegravir arm. No statistically significant impact of treatment was observed for other outcomes. In both study arms, a decline in mean length-for-age Z-scores occurred over the first 72 weeks, while mean weight-for-age Z-scores declined between weeks 48 and 72. Conclusion: Our data support the WHO in recommending dolutegravir-based therapy over efavirenz-based therapy in pregnant women living with HIV.

AB - Background: In 2019, the World Health Organization (WHO) changed its recommendations for pregnant women living with HIV from efavirenz-based to dolutegravir-based therapy due to its superior efficacy, tolerability and resistance profile. Perinatal exposure to antiretrovirals may influence infant growth, but limited data exist on the effects of specific regimens over time. Aim: This study aimed to compare growth trajectories over the first 72 weeks of life among infants exposed to dolutegravir-based versus efavirenz-based therapy during late pregnancy. Methods: The DolPHIN-2 trial was a randomized, open-label trial conducted in South Africa and Uganda, researching the efficacy of dolutegravir-based versus efavirenz-based therapy in pregnant women living with HIV, initiating treatment in the third trimester. In this secondary analysis, we compared growth trajectories until 72 weeks postpartum between HIV-exposed uninfected infants perinatally exposed to dolutegravir-based versus efavirenz-based therapy. Measures of infant weight, length and head circumference were converted to WHO-defined weight-for-age, weight-for-length, length-for-age and head circumference-for-age Z-scores. Subsequently, Z-scores were compared across treatment arms, using linear mixed-effect models. Results: After exclusions, 232 infants remained (dolutegravir: n = 116; efavirenz: n = 116). In both crude models and models adjusted for study site and maternal height, length-for-age Z-scores were 0.277 units higher in the dolutegravir arm. No statistically significant impact of treatment was observed for other outcomes. In both study arms, a decline in mean length-for-age Z-scores occurred over the first 72 weeks, while mean weight-for-age Z-scores declined between weeks 48 and 72. Conclusion: Our data support the WHO in recommending dolutegravir-based therapy over efavirenz-based therapy in pregnant women living with HIV.

KW - antiretroviral therapy

KW - HIV

KW - infant growth and pregnancy

U2 - 10.1097/INF.0000000000004902

DO - 10.1097/INF.0000000000004902

M3 - Article

AN - SCOPUS:105011322740

SN - 0891-3668

VL - 44

SP - 1066

EP - 1071

JO - Pediatric Infectious Disease Journal

JF - Pediatric Infectious Disease Journal

IS - 11

ER -

The Effects on the Growth of HIV-exposed Uninfected Infants of Initiating Dolutegravir-based Versus Efavirenz-based cART in Late Pregnancy (DolPHIN-2)

Abstract

UN SDGs

Keywords

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