The proposed study will assess kidney tubular dysfunction in hepatitis B virus (HBV) mono-infected women who receive a short tenofovir diprosoxil fumarate (TDF) course for the prevention of HBV mother-to-child transmission. Although this treatment has been shown generally well tolerated, previous studies have showed a possible deficit in maternal and infant bone mineral density. This deficit is likely a consequence of the toxicity on the kidney proximal tubule but the extent of this adverse effect during this specific period is not known. TDF is frequently used in combination with other antiretroviral drugs in HIV infected women to prevent mother- to-child transmission of HIV. It has been also increasingly used for the prevention of mother-to-child transmission of hepatitis B virus. TDF elimination is mainly renal, partly through proximal tubular secretion. The accumulation of TDF in epithelial cells is associated with mitochondrial toxicity leading to the development of tubular dysfunction responsible for a loss of phosphorus and ions in urine, adversely affecting bone mineralization. During the pregnancy and lactating periods, the maternal bone turnover is increased to supply large amounts of calcium needed for infant bone growth. This process can lead to a loss of 5 to 10% of the maternal bone mass. Tubular dysfunction may interfere with this process and modify the composition of breast milk, which may in turn impact infant bone development. We recently completed in Thailand a multicenter, placebo-controlled, double blind, randomized clinical trial (iTAP), which assessed the efficacy of a 5-month TDF maternal treatment, in a setting where infants received HB vaccine and immune globulin (HBIg). We hypothesize that a short maternal exposure to tenofovir is associated with at least transitory maternal proximal tubular dysfunction, which is strongly predictive of BMD abnormalities. Our primary objective is to assess the risk of proximal tubular dysfunction using urinary biomarkers in pregnant women/mothers who received TDF 300 mg once a day from 28 weeks pregnancy to 2 months post partum. For this purpose, we will assess and compare between arms biomarkers of tubular dysfunction in maternal urine samples collected at several time points during the iTAP study (prior to exposure to study treatment, during, at the end of exposure and 10 months after discontinuation). In addition, we will assess the relationship between maternal tenofovir exposure and the risk of tubular proximal dysfunction. TDF will be increasingly used in HBV infected pregnant women to prevent mother-to-child transmission of HBV, all over the world but especially in resource-limited countries. Also, the number of HIV infected pregnant women on TDF has dramatically increased in high endemic countries during the last decade (from 36% in 2009 to 80% in 2015). It is therefore essential to better characterize TDF renal toxicity in this setting to prevent consequences of such disorders, awaiting new drugs better tolerated and shown safe during pregnancy.
Tenofovir disoproxil fumarate (TDF) is used during pregnancy and lactation to prevent mother-to-child transmission of HIV or hepatitis B virus (HBV) but it may impair maternal or infant bone mineralization. It is likely that bone mineralization issues are a consequence of renal dysfunction due to TDF use. The study will assess whether maternal TDF for 3 months at the end of pregnancy and 2 months postpartum can be responsible for kidney injury.
