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Randomized Controlled Trial
. 2023 Aug 15;93(5):431-437.
doi: 10.1097/QAI.0000000000003218.

Bone and Renal Health in Infants With or Without Breastmilk Exposure to Tenofovir-Based Maternal Antiretroviral Treatment in the PROMISE Randomized Trial

Tichaona Vhembo  1 , Kristin Baltrusaitis  2 , Camlin Tierney  2 , Maxensia Owor  3 , Sufia Dadabhai  4 , Avy Violari  5 , Gerhard Theron  6 , Dhayendre Moodley  7 , Cynthia Mukwasi-Kahari  8 , Kathleen George  9 , John Shepherd  10 , George K Siberry  11 , Renee Browning  12 , Mary Glenn Fowler  13 , Lynda Stranix-Chibanda  1   14 ; IMPAACT P1084s study team
Affiliations
Randomized Controlled Trial

Bone and Renal Health in Infants With or Without Breastmilk Exposure to Tenofovir-Based Maternal Antiretroviral Treatment in the PROMISE Randomized Trial

Tichaona Vhembo et al. J Acquir Immune Defic Syndr. .

Abstract

Background: We assessed bone and kidney outcomes in infants randomized postdelivery as mother-infant pairs within the IMPAACT PROMISE trial to maternal tenofovir disoproxil fumarate-based antiretroviral treatment (mART) or infant nevirapine prophylaxis (iNVP) to prevent breastfeeding HIV transmission.

Methods: Infants were coenrolled in the P1084s substudy on randomization day and followed through Week 74. Lumbar spine bone mineral content (LS-BMC) was assessed at entry (6-21 age days) and Week 26 by dual-energy x-ray absorptiometry. Creatinine clearance (CrCl) was calculated at entry; Weeks 10, 26, and 74. Student t tests compared mean LS-BMC and CrCl at Week 26 and mean change from entry between arms.

Results: Of 400 enrolled infants, the mean (SD; n) for entry LS-BMC was 1.68 g (0.35; n = 363) and CrCl was 64.2 mL/min/1.73 m 2 (24.6; n = 357). At Week 26, 98% of infants were breastfeeding and 96% on their assigned HIV prevention strategy. The mean (SD) Week 26 LS-BMC was 2.64 g (0.48) for mART and 2.77 g (0.44) for iNVP; mean difference (95% confidence interval [CI]) -0.13 g (-0.22 to -0.04), P = 0.007, n = 375/398 (94%). Mean absolute (-0.14 g [-0.23 to -0.06]) and percent (-10.88% [-18.53 to -3.23]) increase in LS-BMC from entry was smaller for mART than iNVP. At Week 26, the mean (SD) CrCl was 130.0 mL/min/1.73 m 2 (34.9) for mART vs. 126.1 mL/min/1.73 m 2 (30.0) for iNVP; mean difference (95% CI) 3.8 (-3.0 to 10.7), P = 0.27, n = 349/398 (88%).

Conclusion: Week 26 mean LS-BMC was lower in infants in the mART group compared with the iNVP group. However, this difference (∼0.23 g) was less than one-half SD, considered potentially clinically relevant. No infant renal safety concerns were observed.

Trial registration: ClinicalTrials.gov NCT01061151.

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Conflict of interest statement

The authors have no funding or conflicts of interest to disclose.

Figures

FIGURE 1.
FIGURE 1.
CONSORT flow diagram.
FIGURE 2.
FIGURE 2.
Infant entry and week 26 LS-BMC by study arm. Purple boxes represent the mART arm. Green boxes represent the iNVP arm. Box plots represent medians (bar), 25th percentile (lower limit of box), and 75th percentile (upper limit of box). The mean of the arms are shown by a small black diamond. Whiskers are drawn to the maximum (minimum) observation below (above) the upper (lower) fence, which is 1.5× interquartile range (IQR) above (below) the 75th (25th) percentiles. Values outside of the whiskers are represented by circles.
FIGURE 3.
FIGURE 3.
Infant entry, week 10, week 26, and week 74 calculated CrCl by study arm. Purple boxes represent the mART arm. Green boxes represent the iNVP arm. Box plots represent medians (bar), 25th percentile (lower limit of box), and 75th percentile (upper limit of box). The mean of the arms are shown by a small black diamond. Whiskers are drawn to the maximum (minimum) observation below (above) the upper (lower) fence, which is 1.5× interquartile range (IQR) above (below) the 75th (25th) percentiles. Values outside of the whiskers are represented by circles.
See this image and copyright information in PMC

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