Study of Effects of Tenofovir on Bone Health and Kidneys During Pregnancy and Breastfeeding

HIV Infections Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01066858
• Other study ID #: P1084s (PROMISE)
• Secondary ID: 10790IMPAACT P10
• Status: Completed
• Start date: March 22, 2011
• Est. completion date: November 30, 2015

Study information

• Verified date: September 2022
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1765
• Est. completion date: November 30, 2015
• Est. primary completion date: November 30, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Tenofovir disoproxil fumarate (TDF)
Some participants will receive varying doses of TDF during pregnancy or breastfeeding as part of the larger study (IMPAACT 1077 PROMISE).

Locations

Country	Name	City	State
Malawi	Blantyre CRS	Blantyre
Malawi	Malawi CRS	Lilongwe
South Africa	Durban Paediatric HIV CRS	Durban	KwaZulu-Natal
South Africa	Umlazi CRS	Durban	KwaZulu-Natal
South Africa	Shandukani Research CRS	Johannesburg	Gauteng
South Africa	Soweto IMPAACT CRS	Johannesburg	Gauteng
South Africa	Family Clinical Research Unit (FAM-CRU) CRS	Tygerberg	Western Cape Province
Uganda	MU-JHU Research Collaboration (MUJHU CARE LTD) CRS	Kampala	Mpigi
Zimbabwe	Seke North CRS	Chitungwiza
Zimbabwe	St Mary's CRS	Chitungwiza
Zimbabwe	Harare Family Care CRS	Harare

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Gilead Sciences

Countries where clinical trial is conducted

Malawi,  South Africa,  Uganda,  Zimbabwe, 

References & Publications (2)

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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antepartum Component: Creatinine clearance (CrCl)	Antepartum Component: Creatinine clearance (CrCl)	For women and infants: at delivery/birth, up to Week 1
Primary	Antepartum Component: Bone resorption (Dpyr)	Antepartum Component: Bone resorption (Dpyr)	For women and infants: at delivery/birth, up to Week 1
Primary	Antepartum Component: Lumbar spine bone mineral density (BMD) via dual energy e-ray absorptiometry (DXA)	Antepartum Component: Lumbar spine bone mineral density (BMD) via dual energy e-ray absorptiometry (DXA)	For women: at delivery/birth, up to Week 1
Primary	Antepartum Component: Lumbar spine bone mineral content (BMC) and whole body BMC via DXA	Antepartum Component: Lumbar spine bone mineral content (BMC) and whole body BMC via DXA	For infants: at delivery/birth, up to Week 1
Primary	Antepartum Component: Length-for-age Z-score	Antepartum Component: Length-for-age Z-score	For infants: at delivery/birth, up to Week 1 and Week 26
Primary	Postpartum Component: CrCl	Postpartum Component: CrCl	For women: at postpartum entry (delivery/birth, up to Week 1) and Week 74; for infants: at Week 26
Primary	Postpartum Component: Dpyr	Postpartum Component: Dpyr	For women: at Week 74; for infants: at Week 26
Primary	Postpartum Component: Lumbar spine BMD via DXA	Postpartum Component: Lumbar spine BMD via DXA	For women: at postpartum entry (delivery/birth, up to Week 1) and Week 74
Primary	Postpartum Component: Lumbar spine BMC via DXA	Postpartum Component: Lumbar spine BMC via DXA	For infants: at Week 26
Primary	Postpartum Component: Length-for-age Z-score	Postpartum Component: Length-for-age Z-score	For infants: at postpartum entry (delivery/birth, up to Week 1) and Week 26
Secondary	CrCl	CrCl	For women: Weeks 6, 26, and 74; for infants: at Weeks 10, 26, and 74
Secondary	BMD	BMD	For women: at delivery and change in hip BMD from delivery to Week 74
Secondary	Dpyr	Dpyr	For women: at Weeks 6, 26, and 74; for infants: at Weeks 10, 26, and 74
Secondary	Mineral composition of breast milk	Mineral composition of breast milk	For women: at Weeks 1, 6, 26, and 74
Secondary	Lumbar spine BMC	Lumbar spine BMC	For infants: Week 26
Secondary	Infant growth	Infant growth	For infants: at Weeks 10 and 74
Secondary	Concentration of hormonal growth factors (for infants)	Concentration of hormonal growth factors (for infants)	For infants: at birth and Weeks 10, 26, and 74