Impact of in Utero and Breastfeeding Exposure to Tenofovir on Renal Function in HIV-exposed Uninfected Children

The Impact of in Utero and Breastfeeding Exposure to Tenofovir on Renal Function in HIV-exposed Uninfected Children in Cameroon: The PREVENT-IT Study

The goal of this project is to determine whether and how in utero exposure to Tenofovir affects renal function in HIV-exposed uninfected infants

Study Overview

• Status: Unknown
• Conditions: Renal Injury
• Intervention / Treatment: Other: Tenofovir exposure in utero and during breastfeeding

Detailed Description

There is a growing use of Tenofovir (TDF) in sub-Saharan Africa with the use of Option B+ for prevention of mother-to-child HIV transmission. TDF has been associated to renal function abnormalities both in macaques and HIV-infected adults and infants. Therefore concerns have been raised about its renal safety in exposed infants of women on Option B+. Data for HEU is sparse and routine measures of renal function (creatinine, proteinuria), may not be appropriate to detect TDF-associated renal injury early. The goal of our study is to assess whether TDF use in pregnancy and breastfeeding affects the function of the kidney function of the child. Pregnant women who consent during their first antenatal consultation to take antiretroviral drugs for PMTCT after testing positive, will be enrolled and followed till birth, for adherence using HPLC. Their terms infants who are HIV negative by DNA PCR at 6 weeks (HEU), will have urine collected at 1.5, 3, 6, 9 months. Using appropriate and more sensitive markers (RBP4, KIM1, NAG, β2M), proximal tubular function will be assessed in 159 HEU infants and same number of controls. Nutritional status and drug history data will be collected for both mother and child. RBP, KIM1, β2M will be measured using XMAP assay while ELISA will be used for NAG according to manufacturer recommendations. Creatinine, phosphates and urinary tract infection will be measured using standard methods. Values of these markers will be compared between the 2 groups. Results will confirm/infirm renal safety of TDF in pregnancy, improve prevention of long term renal injury through early detection, contribute to promote development of routine rapid diagnostic tests for acute renal tubular injury

• Study Type: Observational
• Enrollment (Anticipated): 400

Contacts and Locations

Study Locations

• Cameroon
  • Yaoundé, Cameroon
    • CASS
  • Yaoundé, Cameroon
    • Cité Verte DH
  • Yaoundé, Cameroon
    • Efoulan DH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Our study population will be primarily made up of mother-infant pairs with and without infant exposure in utero to TDF and HIV

Description

Inclusion Criteria:

• Mothers

  1. HIV seropositive pregnant women on Option B+ protocol containing TDF.
  2. HIV seronegative pregnant women
  3. Pregnant women who provide informed consent.
  4. Woman is living in Yaounde and is not planning to relocate in the next 2 years. Children
  1. Children born to HIV-infected mothers (and HIV-uninfected mothers for controls).
  2. TDF- and HIV-exposed in utero (and age-matched unexposed controls).
  3. HIV negative after birth by DNA PCR 4.0 to 12 months of age (included in study at birth and followed up till 12 months)

Exclusion Criteria:

• Refusal of parent(s) to give consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HIV-exposed uninfected infants; These are children to women who are living with HIV but who are not infected with the virus (HIV PCR results at 6 weeks is negative)	Other: Tenofovir exposure in utero and during breastfeeding; Exposed in utero and during breastfeeding to Tenofovir-containing antiretroviral drugs
HIV-unexposed uninfected infants; These are children born to women who are not infected with HIV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in urinary RBP, NAG, KIM-1and B2M levels at birth between neonates born to mothers living with HIV, exposed in utero to TDF and those born to mothers without HIV and not exposed to TDF	In urine samples collected at birth from HIV-EU TDF-exposed neonates and an equal number of TDF-unexposed controls, RBP, KIM-1, B2M will be measured using multianalyte platform (xMAP) assay, while NAG will be measured using ELISA. Levels of these correlates of proximal tubular function will be compared between the two groups, adjusting for confounders	Birth
Difference in urinary RBP, NAG, KIM-1and B2M levels after birth and within the first year of life between HEU infants, exposed in utero to TDF and HUU infants, not exposed to TDF	Trends in urinary RBP:Cr, NAG:Cr, KIM-1 and B2M will be tracked during and beyond breastfeeding between HIV-EU TDF+ and unexposed controls by conducting serial measurements of these markers at 6 weeks then 3, 6, 12 months using same methods described in outcome 1	0 to 12 months

Collaborators and Investigators

• Sponsor: University of Yaounde 1
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Gabriel L Ekali, MD,MH, University of Yaounde 1

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Actual): April 30, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: August 26, 2019
• First Submitted That Met QC Criteria: August 26, 2019
• First Posted (Actual): August 28, 2019

Study Record Updates

• Last Update Posted (Actual): August 29, 2019
• Last Update Submitted That Met QC Criteria: August 26, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Tenofovir; renal injury; HIV-exposed infants
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: 2016/449-LON

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No