Clinical trial NCT04070482: Impact of in Utero and Breastfeeding Exposure to Tenofovir on Renal Function in HIV-exposed Uninfected Children
Official title: The Impact of in Utero and Breastfeeding Exposure to Tenofovir on Renal Function in HIV-exposed Uninfected Children in Cameroon: The PREVENT-IT Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Renal Injury
Keywords: Tenofovir
HIV-exposed infants
renal injury
Lead sponsor: University of Yaounde 1
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2019-08-28
Enrollment: 400
Sex: ALL
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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

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

Eligibility criteria: 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

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  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

Primary outcomes:
measure: 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
timeFrame: Birth
measure: 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
timeFrame: 0 to 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Yaoundé
country: Cameroon
facility: CASS
city: Yaoundé
country: Cameroon
facility: Cité Verte DH
city: Yaoundé
country: Cameroon
facility: Efoulan DH
Study officials:
affiliation: University of Yaounde 1
name: Gabriel L Ekali, MD,MH
role: PRINCIPAL_INVESTIGATOR
References: