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

• ClinicalTrials.gov Identifier: NCT01066858
• Recruitment Status: Completed
• First Posted: February 10, 2010
• Last Update Posted: January 14, 2016
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Gilead Sciences
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

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
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)
• Study Start Date: March 2011
• Actual Primary Completion Date: November 2015
• Actual Study Completion Date: November 2015

Groups and Cohorts

Group/Cohort	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) [ Time Frame: For women and infants: at delivery/birth, up to Week 1 ]
2. Antepartum Component: Bone resorption (Dpyr) [ Time Frame: For women and infants: at delivery/birth, up to Week 1 ]
3. Antepartum Component: Lumbar spine bone mineral density (BMD) via dual energy e-ray absorptiometry (DXA) [ Time Frame: For women: at delivery/birth, up to Week 1 ]
4. Antepartum Component: Lumbar spine bone mineral content (BMC) and whole body BMC via DXA [ Time Frame: For infants: at delivery/birth, up to Week 1 ]
5. Antepartum Component: Length-for-age Z-score [ Time Frame: For infants: at delivery/birth, up to Week 1 and Week 26 ]
6. Postpartum Component: CrCl [ Time Frame: For women: at postpartum entry (delivery/birth, up to Week 1) and Week 74; for infants: at Week 26 ]
7. Postpartum Component: Dpyr [ Time Frame: For women: at Week 74; for infants: at Week 26 ]
8. Postpartum Component: Lumbar spine BMD via DXA [ Time Frame: For women: at postpartum entry (delivery/birth, up to Week 1) and Week 74 ]
9. Postpartum Component: Lumbar spine BMC via DXA [ Time Frame: For infants: at Week 26 ]
10. Postpartum Component: Length-for-age Z-score [ Time Frame: For infants: at postpartum entry (delivery/birth, up to Week 1) and Week 26 ]

Secondary Outcome Measures :

1. CrCl [ Time Frame: For women: Weeks 6, 26, and 74; for infants: at Weeks 10, 26, and 74 ]
2. BMD [ Time Frame: For women: at delivery and change in hip BMD from delivery to Week 74 ]
3. Dpyr [ Time Frame: For women: at Weeks 6, 26, and 74; for infants: at Weeks 10, 26, and 74 ]
4. Mineral composition of breast milk [ Time Frame: For women: at Weeks 1, 6, 26, and 74 ]
5. Lumbar spine BMC [ Time Frame: For infants: Week 26 ]
6. Infant growth [ Time Frame: For infants: at Weeks 10 and 74 ]
7. Concentration of hormonal growth factors (for infants) [ Time Frame: For infants: at birth and Weeks 10, 26, and 74 ]

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

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

Contacts and Locations

Locations

Malawi

Blantyre CRS

Blantyre, Malawi

Malawi CRS

Lilongwe, Malawi

South Africa

Soweto IMPAACT CRS

Johannesburg, Gauteng, South Africa, 1862

Shandukani Research CRS

Johannesburg, Gauteng, South Africa, 2001

Durban Paediatric HIV CRS

Durban, KwaZulu-Natal, South Africa, 4001

Umlazi CRS

Durban, KwaZulu-Natal, South Africa, 4001

Family Clinical Research Unit (FAM-CRU) CRS

Tygerberg, Western Cape Province, South Africa, 7505

Uganda

MU-JHU Research Collaboration (MUJHU CARE LTD) CRS

Kampala, Mpigi, Uganda

Zimbabwe

Seke North CRS

Chitungwiza, Zimbabwe

St Mary's CRS

Chitungwiza, Zimbabwe

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

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01066858
• Other Study ID Numbers: P1084s (PROMISE); 10790 ( Registry Identifier: DAIDS ES ); IMPAACT P1084s
• First Posted: February 10, 2010
• Last Update Posted: January 14, 2016
• Last Verified: January 2016

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; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Tenofovir; Antiviral Agents; Anti-Infective Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Retroviral Agents; Anti-HIV Agents