How does TDF exposure in late pregnancy affect HIV-exposed uninfected neonates?

When administered during the third trimester of pregnancy, tenofovir disoproxil fumarate (TDF) is associated with increased urinary loss of phosphate and lower serum concentrations of 25-hydroxy vitamin D in HIV-exposed uninfected neonates, according to study results published in the Journal of Pediatric Infectious Diseases Society.

Researchers conducted a study between April 2011 and June 2013 to assess the mechanisms underlying the observed reduction in bone mineral content among HIV-exposed uninfected neonates born mothers with HIV who received TDF during the third trimester of pregnancy. Data for the analysis were sourced from an ongoing, prospective cohort study comprising HIV-exposed uninfected neonates. Singleton neonates with a gestational age of at least 36 weeks who were born to HIV-positive women who received at least 8 weeks of TDF treatment in the third trimester were eligible for study enrollment. The study also included a comparator group of neonates with no maternal history of TDF exposure during late pregnancy. Kidney function and bone mineral content were assessed via blood and urine samples collected cross-sectionally within 30 days of birth. Locally weighted scatter smoother plots were used to evaluate all samples collected between 4 and 30 days after birth.

A total of 141 neonates were included in the study, of whom 77 were exposed to TDF and 64 had no history of exposure. Overall, blood and urine samples were collected between 4 and 30 days after birth for 43 TDF-exposed and 19 TDF-unexposed neonates. Of neonates in the TDF-exposed group, the median time of maternal TDF initiation in pregnancy was at 99 (IQR, 0-163) days.

Among neonates from whom samples were collected between 4 and 30 days after birth, no differences were observed between the tenofovir-exposed and tenofovir-unexposed groups for the following kidney and bone biomarkers:

• Serum creatinine (difference in slope, 0.002 mg/dL/day; 95% CI, -0.008 to 0.012);
• Serum phosphate (difference in slope, -0.01 mg/dL/day; 95% CI, -0.07 to 0.05);
• Estimated glomerular filtration rate (eGFR; difference in slope, 0.31; 95% CI, -1.83 to 2.46);
• Urine cross-linked N-telopeptide of type 1 collagen normalized for urine creatinine (difference in slope, -4.49; 95% CI, -12.75 to 3.74); and
• Serum 25-hydroxy vitamin D (difference in slope, 0.03 ng/mL/day; 95% CI, -0.68 to 0.73).

The researchers noted that the tubular reabsorption rate of phosphate decreased more rapidly among TDF-exposed neonates (slope, -.058; 95% CI, 0.74 to -0.04) compared with TDF-unexposed neonates (slope, -0.08; 95% CI, -0.44 to 0.27).

For blood and urine samples collected between 4 and 30 days after birth, there was no between-group difference in slopes of 25-hydroxy vitamin D; however, serum concentrations were lower among TDF-exposed neonates (-5.22; 95% CI, -10.83 to 0.39).

No between-group differences were observed for any other biomarkers.

Study limitations include the small sample size and inability to longitudinally collect blood and urine assay results for the same patients.

According to the researchers, “[F]urther studies to determine whether enhanced supplementation of vitamin D is needed for TDF-exposed infants, and if potential renal and bone metabolic effects of TDF exposure produce clinically relevant or lasting consequences.”

By Janelle McSwiggin, MSN RN

References:

Purswani MU, Jacobson DL, DiMeglio LA, et al. Phosphaturia in HIV-exposed uninfected neonates associated with maternal use of tenofovir disoproxil fumarate in late pregnancy. J Pediatric Infect Dis Soc. Published online May 31, 2024. doi:10.1093/jpids/piae054