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.
Highlights
Tenofovir disoproxil fumarate (TDF) is still widely used for treatment of human immunodeficiency virus (HIV) infection
The main finding of the present study was that TDF use by pregnant Vietnamese women was not associated with infant growth impediment, renal dysfunction, or nutritional rickets, it correlated with mild maternal renal tubular dysfunction
TDF-associated maternal renal tubular dysfunction during late pregnancy can cause blunted fetal growth based on inadequate supply of phosphate [21]
Summary
Tenofovir disoproxil fumarate (TDF) is still widely used for treatment of human immunodeficiency virus (HIV) infection. TDF is known to be nephrotoxic [2], mainly causing proximal tubular dysfunction [3, 4], which results in renal loss of phosphorus with a subsequent decrease in bone mineral density (BMD) in both the lumbar spine and pelvic bones [5, 6]. While whole-body bone mineral content was lower in TDF-exposed infants at the first 4 weeks after birth [13], lumbar spine BMD showed comparable level at 12 months after birth [14]. These findings suggest that maternal TDF can cause transient nutritional rickets due to maternal renal loss of phosphates, which can be overcome by nutritional replacement after birth. There is limited information on the effects of maternal TDF on infant growth in Asian population [14, 15], despite being considered vulnerable to TDF-associated nephrotoxicity due to the small body size [16]
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