Clinical trial NCT01066858: Study of Effects of Tenofovir on Bone Health and Kidneys During Pregnancy and Breastfeeding
Official title: Maternal and Infant Monitoring for Evidence of Toxicity Related to Tenofovir Exposure: The Bone and Kidney Health Substudy of the IMPAACT 1077 PROMISE Protocol (Promoting Maternal and Infant Survival Everywhere)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: tenofovir
renal and bone toxicity
pregnancy
breastfeeding
mother to child transmission
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Gilead Sciences
First posted: 2010-02-10
Enrollment: 1765
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: For antepartum (AP) exposure part of P1084s: Mother/infant pairs enrolled in the antepartum components of 1077BF or 1077FF (1077BA and 1077FA respectively) at African clinical sites approved as P1084s DXA sites.

For postpartum (PP) exposure part of P1084s: Mothers and their infants enrolled in the postpartum component of 1077BF (107BP) at African clinical sites approved as P1084s DXA sites.

Brief summary: The purpose of this study is to look at the effects of tenofovir disoproxil fumarate (an anti-HIV medication) on the bone health and kidneys of women with HIV during pregnancy and while breastfeeding. The study will also look at the changes in overall health, bone health and how the kidneys work in the infants of these women.

Detailed description: A small number of adults (who are not pregnant) and children who take anti-HIV medications develop problems with their kidneys and with the strength of their bones. These problems may be more common when tenofovir disoproxil fumarate (TDF) is used. Studies about these bone and kidney effects have not been done in pregnant and breastfeeding women and their infants.

This is a substudy of a larger study (IMPAACT 1077 PROMISE \[Promoting Maternal and Infant Survival Everywhere\]) to evaluate the safety of anti-HIV medications used in pregnancy and during breastfeeding. Only participants in the larger study randomly assigned to receive maternal tenofovir disoproxil fumarate (TDF) or no maternal TDF during pregnancy or during breastfeeding will be enrolled in this substudy.

This substudy will look at two groups of participants:

* An antepartum exposure group to look at the effects of TDF during pregnancy
* A postpartum exposure group to look at the effects of TDF during breastfeeding

All mother-infant pairs in the substudy will be followed for 74 weeks after delivery. During this time, the women and their infants will have medical checkups and tests. The tests will include tests of blood, urine, cord blood, and breast milk. Some of the women and infants will have a special x-ray called a dual energy e-ray absorptiometry (DXA) scan to measure bone strength. The timing of the tests-at enrollment, at delivery, at 6, 10, 26, or 74 weeks-will vary dependent on which part of this substudy women and infants are enrolled in. Those in charge of the substudy will try to schedule medical visits and tests at the same time as tests scheduled for the larger IMPAACT 1077 study.

Eligibility criteria: Antepartum (AP) Part of Study (TDF Exposure During Pregnancy)

Inclusion Criteria:

* Mother-infant pair enrolled in 1077BA or 1077FA
* At a clinical site that has been approved as a P1084s DXA site
* Enrolled in the substudy up to the Week 2 visit of 1077BA/1077FA (within 21 days after 1077BA/1077FA study entry) and prior to the start of labor
* Willing and able to provide written informed consent to participate in this substudy

Exclusion Criteria:

* None

Postpartum (PP) Part of Substudy (TDF Exposure During Breastfeeding) (Note: this applies only to the new enrollment to P1084s, i.e., those who were not enrolled to P1084s while on the AP component)

Inclusion Criteria:

* Mother and their infant enrolled in 1077BP
* At a clinical site that has been approved as a P1084s DXA site
* Enrolled in the substudy within 6 to 14 days of delivery, on the same day as enrollment in 1077BP
* Willing and able to provide written informed consent to participate in this substudy

Exclusion Criteria:

* TDF exposure during pregnancy \[NOTE: TDF use for up to 12 days beginning at labor allowed\]
* Enrolled in the AP part of P1084s

Primary outcomes:
measure: Antepartum Component: Creatinine clearance (CrCl)
timeFrame: For women and infants: at delivery/birth, up to Week 1
measure: Antepartum Component: Bone resorption (Dpyr)
timeFrame: For women and infants: at delivery/birth, up to Week 1
measure: Antepartum Component: Lumbar spine bone mineral density (BMD) via dual energy e-ray absorptiometry (DXA)
timeFrame: For women: at delivery/birth, up to Week 1
measure: Antepartum Component: Lumbar spine bone mineral content (BMC) and whole body BMC via DXA
timeFrame: For infants: at delivery/birth, up to Week 1
measure: Antepartum Component: Length-for-age Z-score
timeFrame: For infants: at delivery/birth, up to Week 1 and Week 26
measure: Postpartum Component: CrCl
timeFrame: For women: at postpartum entry (delivery/birth, up to Week 1) and Week 74; for infants: at Week 26
measure: Postpartum Component: Dpyr
timeFrame: For women: at Week 74; for infants: at Week 26
measure: Postpartum Component: Lumbar spine BMD via DXA
timeFrame: For women: at postpartum entry (delivery/birth, up to Week 1) and Week 74
measure: Postpartum Component: Lumbar spine BMC via DXA
timeFrame: For infants: at Week 26
measure: Postpartum Component: Length-for-age Z-score
timeFrame: For infants: at postpartum entry (delivery/birth, up to Week 1) and Week 26
Secondary outcomes:
measure: CrCl
timeFrame: For women: Weeks 6, 26, and 74; for infants: at Weeks 10, 26, and 74
measure: BMD
timeFrame: For women: at delivery and change in hip BMD from delivery to Week 74
measure: Dpyr
timeFrame: For women: at Weeks 6, 26, and 74; for infants: at Weeks 10, 26, and 74
measure: Mineral composition of breast milk
timeFrame: For women: at Weeks 1, 6, 26, and 74
measure: Lumbar spine BMC
timeFrame: For infants: Week 26
measure: Infant growth
timeFrame: For infants: at Weeks 10 and 74
measure: Concentration of hormonal growth factors (for infants)
timeFrame: For infants: at birth and Weeks 10, 26, and 74
Other outcomes:
Locations:
city: Blantyre
country: Malawi
facility: Blantyre CRS
city: Lilongwe
country: Malawi
facility: Malawi CRS
city: Johannesburg
country: South Africa
facility: Soweto IMPAACT CRS
state: Gauteng
city: Johannesburg
country: South Africa
facility: Shandukani Research CRS
state: Gauteng
city: Durban
country: South Africa
facility: Durban Paediatric HIV CRS
state: KwaZulu-Natal
city: Durban
country: South Africa
facility: Umlazi CRS
state: KwaZulu-Natal
city: Tygerberg
country: South Africa
facility: Family Clinical Research Unit (FAM-CRU) CRS
state: Western Cape Province
city: Kampala
country: Uganda
facility: MU-JHU Research Collaboration (MUJHU CARE LTD) CRS
state: Mpigi
city: Chitungwiza
country: Zimbabwe
facility: Seke North CRS
city: Chitungwiza
country: Zimbabwe
facility: St Mary's CRS
city: Harare
country: Zimbabwe
facility: Harare Family Care CRS
Study officials:
affiliation: NICHD/NIH
name: George K. Siberry, MD, MPH
role: STUDY_CHAIR
affiliation: University of Zimbabwe
name: Lynda Stranix-Chibanda, MBChB, MMED
role: STUDY_CHAIR
References:
citation: Foster C, Lyall H, Olmscheid B, Pearce G, Zhang S, Gibb DM. Tenofovir disoproxil fumarate in pregnancy and prevention of mother-to-child transmission of HIV-1: is it time to move on from zidovudine? HIV Med. 2009 Aug;10(7):397-406. doi: 10.1111/j.1468-1293.2009.00709.x. Epub 2009 May 12.
citation: Nurutdinova D, Onen NF, Hayes E, Mondy K, Overton ET. Adverse effects of tenofovir use in HIV-infected pregnant women and their infants. Ann Pharmacother. 2008 Nov;42(11):1581-5. doi: 10.1345/aph.1L083. Epub 2008 Oct 28.
citation: Baltrusaitis K, Makanani B, Tierney C, Fowler MG, Moodley D, Theron G, Nyakudya LH, Tomu M, Fairlie L, George K, Heckman B, Knowles K, Browning R, Siberry GK, Taha TE, Stranix-Chibanda L; PROMISE P1084s Study Team. Maternal and infant renal safety following tenofovir disoproxil fumarate exposure during pregnancy in a randomized control trial. BMC Infect Dis. 2022 Jul 20;22(1):634. doi: 10.1186/s12879-022-07608-8.
citation: Stranix-Chibanda L, Tierney C, Sebikari D, Aizire J, Dadabhai S, Zanga A, Mukwasi-Kahari C, Vhembo T, Violari A, Theron G, Moodley D, George K, Fan B, Sommer MJ, Browning R, Mofenson LM, Shepherd J, Nelson B, Fowler MG, Siberry GK; PROMISE P1084s study team. Impact of postpartum tenofovir-based antiretroviral therapy on bone mineral density in breastfeeding women with HIV enrolled in a randomized clinical trial. PLoS One. 2021 Feb 5;16(2):e0246272. doi: 10.1371/journal.pone.0246272. eCollection 2021.