Influence of maternal use of tenofovir disoproxil fumarate or zidovudine in Vietnamese pregnant women with HIV on infant growth, renal function, and bone health

PLoS One. 2021 Apr 29;16(4):e0250828. doi: 10.1371/journal.pone.0250828. eCollection 2021.

Abstract

Tenofovir disoproxil fumarate (TDF) is still widely prescribed for human immunodeficiency virus (HIV)-infected pregnant women, despite its renal and bone toxicity. Although TDF-exposed infants often show transient growth impairment, it is not clear whether maternal TDF causes infantile rickets via maternal/fetal renal dysfunction in Asian populations. This prospective observational study was conducted in Vietnam and involved pregnant HIV-infected women treated with TDF-based regimen (TDF group) or zidovudine-based regimen (AZT-group). At birth, 3, 12, and 18 months of age, and included body length, weight, head circumference, serum alkaline phosphatase (ALP), creatinine, calcium, phosphorus, urine-β2-microglobulin (U-BMG), percentage of tubular reabsorption of phosphate (%TRP), and radiographic wrist score for rickets. Age-adjusted multivariate linear regression analysis evaluated the association of TDF/AZT use during pregnancy with fetal renal function and bone health. The study included 63 mother-infant pairs (TDF group = 53, AZT group = 10). In the mothers, detectable U-BMG (>252 μg/L) was observed more frequently in the TDF- than AZT group (89 vs 50%, p<0.001), but other renal/bone parameters were similar. In infants, maternal TDF use was not associated with growth impairment, renal dysfunction, or abnormal bone findings, but with a slightly higher ALP levels (p = 0.019). However, shorter length was associated with maternal AZT (p = 0.021), and worse radiographic scores were associated with LPV/r (p = 0.024). In Vietnamese population, TDF usage during pregnancy was not associated with infant transient rickets, growth impairment, or renal dysfunction, despite mild maternal tubular impairment. Maternal AZT and LPV/r influenced infant growth and bone health, though further studies are needed to confirm this finding.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Height / drug effects
  • Endopeptidases / blood
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Infant
  • Male
  • Maternal Exposure / adverse effects*
  • Multivariate Analysis
  • Pregnancy
  • Pregnant Women
  • Prospective Studies
  • Tenofovir / adverse effects*
  • Tenofovir / therapeutic use
  • Vietnam
  • Zidovudine / adverse effects*
  • Zidovudine / therapeutic use
  • beta 2-Microglobulin / urine*

Substances

  • beta 2-Microglobulin
  • Zidovudine
  • Tenofovir
  • Endopeptidases
  • Alp protease

Grants and funding

This research was supported by the Japan Initiative for Global Research Network on Infectious Diseases from the Japan Agency for Medical Research and development, AMED. During the study period, antiretrovirals for Vietnamese patients were provided under the financial support of the U.S. president’s emergency plan for AIDS relief (PEPFAR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.