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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Tenofovir disoproxil fumarate (TDF)


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Maternal/infant antepartum exposure<br>HIV-infected women exposed to TDF during pregnancy Infants of HIV-infected women exposed to TDF during pregnancy | Drug: Tenofovir disoproxil fumarate (TDF)<br>* Some participants will receive varying doses of TDF during pregnancy or breastfeeding as part of the larger study (IMPAACT 1077 PROMISE).<br>|
| Maternal/infant postpartum exposure<br>HIV-infected women exposed to TDF while breastfeeding Infants of HIV-infected women exposed to TDF while breastfeeding | Drug: Tenofovir disoproxil fumarate (TDF)<br>* Some participants will receive varying doses of TDF during pregnancy or breastfeeding as part of the larger study (IMPAACT 1077 PROMISE).<br>|
| Maternal/infant antepartum no exposure<br>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<br>HIV-infected women not exposed to TDF during breastfeeding Infants of HIV-infected women not exposed to TDF during breastfeeding | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CrCl | CrCl | For women: Weeks 6, 26, and 74; for infants: at Weeks 10, 26, and 74 | 
| BMD | BMD | For women: at delivery and change in hip BMD from delivery to Week 74 | 
| Dpyr | Dpyr | For women: at Weeks 6, 26, and 74; for infants: at Weeks 10, 26, and 74 | 
| Mineral composition of breast milk | Mineral composition of breast milk | For women: at Weeks 1, 6, 26, and 74 | 
| Lumbar spine BMC | Lumbar spine BMC | For infants: Week 26 | 
| Infant growth | Infant growth | For infants: at Weeks 10 and 74 | 
| Concentration of hormonal growth factors (for infants) | Concentration of hormonal growth factors (for infants) | For infants: at birth and Weeks 10, 26, and 74 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tenofovir, renal and bone toxicity, pregnancy, breastfeeding, mother to child transmission