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

NCT01066858 | Completed DMC

• 3 other identifiers: P1084s (PROMISE)10790IMPAACT P1084s
• Study Type: observational
• Target: 1,765
• Locations: 4 countries
• Sites: 11

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.

Conditions

HIV Infections

Keywords

tenofovir; renal and bone toxicity; pregnancy; breastfeeding; mother to child transmission

Outcome Measures

Primary Outcomes (10)

• Antepartum Component: Creatinine clearance (CrCl)

  Antepartum Component: Creatinine clearance (CrCl)

  For women and infants: at delivery/birth, up to Week 1

• Antepartum Component: Bone resorption (Dpyr)

  Antepartum Component: Bone resorption (Dpyr)

  For women and infants: at delivery/birth, up to Week 1

• 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

• 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

• 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

• 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

• Postpartum Component: Dpyr

  Postpartum Component: Dpyr

  For women: at Week 74; for infants: at Week 26

• 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

• Postpartum Component: Lumbar spine BMC via DXA

  Postpartum Component: Lumbar spine BMC via DXA

  For infants: at Week 26

• 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 Outcomes (7)

• CrCl

  For women: Weeks 6, 26, and 74; for infants: at Weeks 10, 26, and 74

• BMD

  For women: at delivery and change in hip BMD from delivery to Week 74

• Dpyr

  For women: at Weeks 6, 26, and 74; for infants: at Weeks 10, 26, and 74

• Mineral composition of breast milk

  For women: at Weeks 1, 6, 26, and 74

• Lumbar spine BMC

  For infants: Week 26

Study Arms (4)

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)

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)

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

Interventions

Tenofovir disoproxil fumarate (TDF) 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 exposure; Maternal/infant postpartum exposure

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (11)

Blantyre CRS

Blantyre, Malawi

Location

Malawi CRS

Lilongwe, Malawi

Location

Soweto IMPAACT CRS

Johannesburg, Gauteng, 1862, South Africa

Location

Shandukani Research CRS

Johannesburg, Gauteng, 2001, South Africa

Location

Durban Paediatric HIV CRS

Durban, KwaZulu-Natal, 4001, South Africa

Location

Umlazi CRS

Durban, KwaZulu-Natal, 4001, South Africa

Location

Family Clinical Research Unit (FAM-CRU) CRS

Tygerberg, Western Cape, 7505, South Africa

Location

MU-JHU Research Collaboration (MUJHU CARE LTD) CRS

Kampala, Mpigi, Uganda

Location

Seke North CRS

Chitungwiza, Zimbabwe

Location

St Mary's CRS

Chitungwiza, Zimbabwe

Location

Harare Family Care CRS

Harare, Zimbabwe

Location

Related Publications (4)

• 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.

  PMID: 19459986 BACKGROUND

• 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.

  PMID: 18957630 BACKGROUND

• 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.

  PMID: 35858874 DERIVED

• 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.

  PMID: 33544759 DERIVED

MeSH Terms

Conditions

HIV Infections; Breast Feeding

Interventions

Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Feeding Behavior; Behavior

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• George K. Siberry, MD, MPH

  NICHD/NIH

  STUDY CHAIR

• Lynda Stranix-Chibanda, MBChB, MMED

  University of Zimbabwe

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2010
• First Posted: February 10, 2010
• Study Start: March 22, 2011
• Primary Completion: November 30, 2015
• Study Completion: November 30, 2015
• Last Updated: September 23, 2022

Record last verified: 2022-09

Locations

MA (2); ZI (3); UG (1); ZA (5)