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

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01066858
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH), Gilead Sciences (Industry)
• Enrollment: 1,765
• Locations: 11
• Actual Duration (Months): 55.4
• Patients Per Site: 160.5
• Patients Per Site Per Month: 2.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Tenofovir disoproxil fumarate (TDF)

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 1765 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• 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)
• Actual Study Start Date: Mar 22, 2011
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Maternal/infant antepartum exposure HIV-infected women exposed to TDF during pregnancy Infants of HIV-infected women exposed to TDF during pregnancy	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).
Maternal/infant postpartum exposure HIV-infected women exposed to TDF while breastfeeding Infants of HIV-infected women exposed to TDF while breastfeeding	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).
Maternal/infant antepartum no exposure HIV-infected women not exposed to TDF during pregnancy Infants of HIV-infected women not exposed to TDF during pregnancy
Maternal/infant postpartum no exposure HIV-infected women not exposed to TDF during breastfeeding Infants of HIV-infected women not exposed to TDF during breastfeeding

Outcome Measures

Primary Outcome Measures

1. Antepartum Component: Creatinine clearance (CrCl) [For women and infants: at delivery/birth, up to Week 1]

   Antepartum Component: Creatinine clearance (CrCl)

2. Antepartum Component: Bone resorption (Dpyr) [For women and infants: at delivery/birth, up to Week 1]

   Antepartum Component: Bone resorption (Dpyr)

3. Antepartum Component: Lumbar spine bone mineral density (BMD) via dual energy e-ray absorptiometry (DXA) [For women: at delivery/birth, up to Week 1]

   Antepartum Component: Lumbar spine bone mineral density (BMD) via dual energy e-ray absorptiometry (DXA)

4. Antepartum Component: Lumbar spine bone mineral content (BMC) and whole body BMC via DXA [For infants: at delivery/birth, up to Week 1]

   Antepartum Component: Lumbar spine bone mineral content (BMC) and whole body BMC via DXA

5. Antepartum Component: Length-for-age Z-score [For infants: at delivery/birth, up to Week 1 and Week 26]

   Antepartum Component: Length-for-age Z-score

6. Postpartum Component: CrCl [For women: at postpartum entry (delivery/birth, up to Week 1) and Week 74; for infants: at Week 26]

   Postpartum Component: CrCl

7. Postpartum Component: Dpyr [For women: at Week 74; for infants: at Week 26]

   Postpartum Component: Dpyr

8. Postpartum Component: Lumbar spine BMD via DXA [For women: at postpartum entry (delivery/birth, up to Week 1) and Week 74]

   Postpartum Component: Lumbar spine BMD via DXA

9. Postpartum Component: Lumbar spine BMC via DXA [For infants: at Week 26]

   Postpartum Component: Lumbar spine BMC via DXA

10. Postpartum Component: Length-for-age Z-score [For infants: at postpartum entry (delivery/birth, up to Week 1) and Week 26]

    Postpartum Component: Length-for-age Z-score

Secondary Outcome Measures

1. CrCl [For women: Weeks 6, 26, and 74; for infants: at Weeks 10, 26, and 74]

   CrCl

2. BMD [For women: at delivery and change in hip BMD from delivery to Week 74]

   BMD

3. Dpyr [For women: at Weeks 6, 26, and 74; for infants: at Weeks 10, 26, and 74]

   Dpyr

4. Mineral composition of breast milk [For women: at Weeks 1, 6, 26, and 74]

   Mineral composition of breast milk

5. Lumbar spine BMC [For infants: Week 26]

   Lumbar spine BMC

6. Infant growth [For infants: at Weeks 10 and 74]

   Infant growth

7. Concentration of hormonal growth factors (for infants) [For infants: at birth and Weeks 10, 26, and 74]

   Concentration of hormonal growth factors (for infants)

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Blantyre CRS	Blantyre		Malawi
2	Malawi CRS	Lilongwe		Malawi
3	Soweto IMPAACT CRS	Johannesburg	Gauteng	South Africa	1862
4	Shandukani Research CRS	Johannesburg	Gauteng	South Africa	2001
5	Durban Paediatric HIV CRS	Durban	KwaZulu-Natal	South Africa	4001
6	Umlazi CRS	Durban	KwaZulu-Natal	South Africa	4001
7	Family Clinical Research Unit (FAM-CRU) CRS	Tygerberg	Western Cape Province	South Africa	7505
8	MU-JHU Research Collaboration (MUJHU CARE LTD) CRS	Kampala	Mpigi	Uganda
9	Seke North CRS	Chitungwiza		Zimbabwe
10	St Mary's CRS	Chitungwiza		Zimbabwe
11	Harare Family Care CRS	Harare		Zimbabwe

Sponsors and Collaborators

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

Investigators

• Study Chair: George K. Siberry, MD, MPH, NICHD/NIH
• Study Chair: Lynda Stranix-Chibanda, MBChB, MMED, University of Zimbabwe

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01066858
• Other Study ID Numbers: P1084s (PROMISE); 10790; IMPAACT P1084s
• First Posted: Feb 10, 2010
• Last Update Posted: Nov 1, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): tenofovir; renal and bone toxicity; pregnancy; breastfeeding; mother to child transmission
• Additional relevant MeSH terms: HIV Infections; Tenofovir

Study Results

No Results Posted as of Nov 1, 2021