FP770THE EFFECT OF IN-UTERO EXPOSURE TO TENOFOVIR DISOPROXIL FUMARATE ON THE RENAL FUNCTION OF NEWBORNS OF HIV-POSITIVE MOTHERS

Abstract

Introduction and Aims: Combined antiretroviral therapy(c-ART) decreased mother-to-child transmission of HIV by to 1%. However, since the introduction of option B, and subsequently the B + option in2012,tenofovir disoproxil fumarate(TDF) has become a major drug in the c-ART regimen used for prevention of mother-to-child transmission. TDF passively diffuses across the placenta and may therefore be potentially toxic to the foetal kidney. Previous studies suggesting renal safety in children exposed in utero are based on serum creatinine and phosphate. We sought to evaluate the effect of in-utero exposure to tenofovir TDF on the renal function of newborns of HIV positive mothers using novel biomarkers of renal function. Methods: This was a retrospective cohort study including newborns of HIV-positive mothers exposed to TDF in utero and newborns of HIV-negative mothers not exposed to TDF who were born in Yaounde between January 2017 and April 2017. Newborns with asphyxia, renal malformations, early neonatal infections, or preterm, were excluded. All neonates were examined within the first two days of life, then venous blood collected for serum creatinine assay. At the same time, urine samples were collected, centrifuged and stored at-80 ° C. for subsequent assay of Retinol Binding Protein 4 (RBP-4) and beta-2 microglobulin ((3-2M) by Luminex at the Biotechnology Center of the University of Yaounde I. The study was approved by the regional ethics committee. Results: We included 43 neonates exposed to TDF and 39 non-exposed. The average gestational age was 39.47 6 1.12 weeks and comparable in both groups. The mean duration of exposure to TDF was 31 6 10.82 weeks. The median urinary level of P-2M was significantly higher in the exposed compared to the non-exposed group (5.76 vs. 1.97mg/l, p = 0.028). The median urinary level of RBP-4 was higher in TDF-exposed neonates compared to non-exposed subjects without a statistically significant difference (0.75 vs 0.45 mg/l,p = 0.568). Mean serum creatinine levels were also higher in the exposed group but the difference did not attain statistical significance (7.52 vs 7.15 mg/l, p = 0.57). Conclusions: Exposure to TDF during pregnancy may cause renal dysfunction in the newborn. Follow up studies are needed to evaluate the clinical significance of this findings.