In-utero exposure to tenofovir disoproxil fumarate pre-exposure prophylaxis and growth metrics in HIV unexposed breastfed infants in South Africa: a post hoc analysis of the CAP 016 PrEP in pregnancy RCT

Megeshinee Naidoo; Kimesh L Naidoo; Carl Lombard; Alicia C Desmond; Richard Clark; James F Rooney; Glenda Gray; Dhayendre Moodley

doi:10.3389/fped.2024.1447173

In-utero exposure to tenofovir disoproxil fumarate pre-exposure prophylaxis and growth metrics in HIV unexposed breastfed infants in South Africa: a post hoc analysis of the CAP 016 PrEP in pregnancy RCT

Front Pediatr. 2024 Aug 9:12:1447173. doi: 10.3389/fped.2024.1447173. eCollection 2024.

Authors

Megeshinee Naidoo¹, Kimesh L Naidoo², Carl Lombard^{3

4}, Alicia C Desmond¹, Richard Clark⁵, James F Rooney⁵, Glenda Gray⁶, Dhayendre Moodley^{1

7}

Affiliations

¹ Centre for the Program of AIDS Research in South Africa (CAPRISA), Durban, South Africa.
² Department of Paediatrics and Child Health, School of Clinical Medicine, University of KwaZulu Natal, Durban, South Africa.
³ Biostatistics Unit, South African Medical Research Council, Tygerberg, South Africa.
⁴ Division of Epidemiology and Biostatistics, Department of Global Health, University of Stellenbosch, Tygerberg, South Africa.
⁵ Gilead Sciences Inc, Foster City, CA, United States.
⁶ South African Medical Research Council, Cape Town, South Africa.
⁷ Department of Obstetrics and Gynaecology, School of Clinical Medicine, University of KwaZulu Natal, Durban, South Africa.

Abstract

Objective: We evaluated growth metrics in HIV unexposed African breastfed infants in the first 18 months of life in association with in-utero exposure to Tenofovir Diphosphate Fumarate (TDF) containing pre-exposure prophylaxis (PrEP).

Design: We conducted a secondary data analysis of a TDF-PrEP randomized control trial (CAP016 RCT). Pregnant women without HIV were randomized to initiating TDF-PrEP in pregnancy (Immediate-PrEP-IP) or deferred initiation of TDF-PrEP at cessation of breastfeeding (Deferred-PrEP-DP).

Methods: Infant weight (W), length (L), and head circumference (HC) were measured at birth and 6, 26, 50, and 74 weeks of age. Stored dried blood spot samples from pregnant women randomized to the IP arm were used to measure tenofovir-diphosphate (TFV-DP) levels. Age-stratified mean weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ), and head circumference-for-age (HCAZ) Z-scores were compared between infants exposed to varying TFV-DP concentrations and infants in the DP arm.

Results: A total of 455 mother-infant pairs were included in the secondary analysis, 228 in the IP arm and 227 in the DP arm. WAZ, LAZ, WLZ, and HCAZ scores were comparable between infants in the Deferred-PrEP arm and Immediate-PrEP arm. In a mixed-effects linear regression model adjusting for maternal age, body mass index, socioeconomic and newborn characteristics, in-utero exposure to varying TFV-DP levels was not associated with WAZ (β = -0.52), LAZ (β = -0.46), WLZ (β = -0.43) and HCAZ (β = -0.11) scores over time.

Conclusion: There was no evidence of an association between growth metrics in the first 18 months of life and in-utero exposure to TFV-DP among breastfed HIV unexposed infants.

Keywords: breastfeeding; exposure; growth; in-utero; preexposure prophylaxis (PrEP).

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was funded by Gilead Sciences Inc (Grant Number CO-EU-276-4399) and the South African Medical Research Council (Grant Number 2753/CO324/AP/2020). Study drugs were supplied by Gilead Sciences Inc. The funder (Gilead Sciences Inc.) was not involved in the study design, collection, analysis and interpretation of data, writing of this article or the decision to submit it for publication.