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

NCT ID: NCT01066858

Last Updated: 2022-09-23

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 1765 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-03-22
• Study Completion Date: 2015-11-30

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.

Conditions

HIV Infections

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Maternal/infant antepartum exposure

• HIV-infected women exposed to TDF during pregnancy
• Infants of HIV-infected women exposed to TDF during pregnancy

Tenofovir disoproxil fumarate (TDF)

Intervention Type: DRUG

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

Tenofovir disoproxil fumarate (TDF)

Intervention Type: DRUG

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

No interventions assigned to this group

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

No interventions assigned to this group

Interventions

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).

Intervention Type: DRUG

Eligibility Criteria

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

• 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

• 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)

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

George K. Siberry, MD, MPH

Role: STUDY_CHAIR

NICHD/NIH

Lynda Stranix-Chibanda, MBChB, MMED

Role: STUDY_CHAIR

University of Zimbabwe

Locations

Blantyre CRS

Blantyre, , Malawi

Malawi CRS

Lilongwe, , Malawi

Soweto IMPAACT CRS

Johannesburg, Gauteng, South Africa

Shandukani Research CRS

Johannesburg, Gauteng, South Africa

Durban Paediatric HIV CRS

Durban, KwaZulu-Natal, South Africa

Umlazi CRS

Durban, KwaZulu-Natal, South Africa

Family Clinical Research Unit (FAM-CRU) CRS

Tygerberg, Western Cape, South Africa

MU-JHU Research Collaboration (MUJHU CARE LTD) CRS

Kampala, Mpigi, Uganda

Seke North CRS

Chitungwiza, , Zimbabwe

St Mary's CRS

Chitungwiza, , Zimbabwe

Harare Family Care CRS

Harare, , Zimbabwe

Countries

Malawi; South Africa; Uganda; Zimbabwe

References

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.

Reference Type: BACKGROUND

PMID: 19459986 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18957630 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35858874 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33544759 (View on PubMed)

Other Identifiers

10790

Identifier Type: REGISTRY

Identifier Source: secondary_id

IMPAACT P1084s

Identifier Type: -

Identifier Source: secondary_id

P1084s (PROMISE)

Identifier Type: -

Identifier Source: org_study_id