In-utero exposure to tenofovir-containing pre-exposure prophylaxis and bone mineral content in HIV-unexposed infants in South Africa

Introduction

Tenofovir disoproxil fumarate (TDF) is a common drug of choice for pre-exposure prophylaxis (PrEP) or as a combination HIV treatment for pregnant women. In-utero exposure to TDF was found to be associated with lower bone mineral content (BMC) in HIV-exposed uninfected neonates. Data for infants born to women taking TDF-PrEP are lacking. The CAP016 randomized control trial was conducted in South Africa between September 2017 and August 2021 and pregnant women either initiated TDF/FTC PrEP in pregnancy (Immediate PrEP arm-IP) or at cessation of breastfeeding (Deferred PrEP arm-DP). In a secondary data analysis, we evaluated BMC in HIV-unexposed infants in the CAP016 trial in the first 18 months of life in association with maternal TDF-PrEP use during pregnancy.

Methods

Infants born to women randomized to the IP arm or DP arm in the CAP016 clinical trial had BMC measurements of the whole body with head (WBH) and lumbar spine (LS) by dual energy X-ray absorptiometry (DXA) at 6, 26, 50 and 74 weeks.

Results

Of 481 infants born to women enrolled in the CAP016 clinical trial, 335 (69.6%) infants had a minimum of one DXA scan of the WBH and LS between 6 and 74 weeks of age (168 IP and 167 DP). Women in the IP arm received TDF-FTC PreP for a median of 19 weeks between initiation in pregnancy and delivery. Using a mixed linear regression model and adjusted for gestational age, sex and ever-breastfed, the mean difference (95% CI) for BMC of the WBH between IP and DP arms were −0.74 (−8.69 to 7.20), −1.26 (−10.75 to 8.23), −9.17 (−20.02 to 1.69) and 5.02 (−6.74 to 16.78) g at 6, 26, 50 and 74 weeks (p = 0.283). Mean differences in BMC of the LS were 0.07 (−0.10 to 0.23), 0.02 (−0.18 to 0.22), −0.14 (−0.36 to 0.09) and 0.14 (−0.11 to 0.38) g at 6, 26, 50 and 74 weeks, respectively (p = 0.329).

Conclusions

In a randomized controlled trial, there were no differences in BMC of the WBH and LS between infants exposed to in-utero TDF-FTC PrEP and unexposed infants in the first 18 months of life.