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Study of HIV-Infected and Uninfected Pregnant Woman/Child Dyads in Gaborone, Botswana

Primary Purpose

HIV, Insulin Sensitivity, Diabetes Mellitus

Status

Completed

Phase

Phase 4

Locations

Botswana

Study Type

Interventional

Intervention

Zidovudine

Nevirapine

About this trial

This is an interventional prevention trial for HIV

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

HIV-infected and uninfected pregnant women between 16-36 weeks GA are eligible for study enrollment.
Women must be 18 years of older and able to provide informed consent for themselves and their infant to participate in the study.
Participants must be Botswana citizens.
Women must have evidence of HIV infection status. Women NOT documented as HIV seropositive must have documentation of HIV seronegativity during the present pregnancy at or after 32 weeks GA. Women who have an initial negative HIV test during the present pregnancy which was done at <32 weeks GA will need to undergo repeat testing on or after 32 weeks GA in accordance with national guidelines.
HIV-uninfected women must be willing to undergo HIV pre-test counseling, rapid HIV testing and post-test counseling, referred to as HIV Testing and Counseling (HTC) during pregnancy.
Women must be willing to remain in study area with their infant and attend scheduled study visits as described above until the child's 3rd birthday.
For HIV-infected women, they must be on TDF/3TC or FTC/EFV or TDF/3TC or FTC/Dolutegravir at time of study enrollment or willing to initiate this treatment and continue throughout the period of breastfeeding, if not for their lifetime.
At enrollment, all women must be willing to breastfeed exclusively for the first six months of life.

Exclusion Criteria:

•Pre-existing maternal diabetes mellitus.

Sites / Locations

Botswana-Harvard AIDS Institute Partnership

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

No Intervention

Arm Label

Nevirapine

Zidovudine

HIV- unexposed Uninfected (HUU) Infants

Arm Description

150 HIV-Exposed Uninfected (HEU) infants on Nevirapine (NVP) Prophylaxis

150 HIV-Exposed Uninfected (HEU) infants on Zidovudine (AZT) Prophylaxis

150 HIV- unexposed Uninfected (HUU) Infants

Outcomes

Primary Outcome Measures

Homeo-static Model Assessment-Insulin Resistance (HOMA-IR)

[glucose (mg/dL) X insulin ( μU/mL)405]

Secondary Outcome Measures

Full Information

NCT ID

NCT03088410

First Posted

March 3, 2017

Last Updated

July 18, 2022

Sponsor

Ann & Robert H Lurie Children's Hospital of Chicago

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1. Study Identification

Unique Protocol Identification Number

NCT03088410

Brief Title

Study of HIV-Infected and Uninfected Pregnant Woman/Child Dyads in Gaborone, Botswana

Official Title

The Tshilo Dikotla Study: Metabolic Outcomes of Children HIV/ARV-Exposed Uninfected in Botswana (MOCHA)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Completed

Study Start Date

August 22, 2016 (Actual)

Primary Completion Date

March 31, 2022 (Actual)

Study Completion Date

March 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Ann & Robert H Lurie Children's Hospital of Chicago

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to assess the early longitudinal metabolic effects including insulin sensitivity in HIV-exposed uninfected (HEU) children compared to HIV-unexposed uninfected (HUU) children; as well as to determine differences in the effects of neonatal zidovudine (AZT) vs. nevirapine (NVP) prophylaxis on early longitudinal changes in insulin sensitivity in the first 3 years of life.

Detailed Description

This study will consist of a nested randomized component of HIV-infected (HIV+) and -uninfected (HIV-) pregnant woman/child dyads in Botswana which will take place in Gaborone, Botswana at Botswana-Harvard AIDS Institute Partnership's (BHPs) clinical research facilities. A total of 300 HIV+ pregnant woman/fetus dyads on cART and 150 HIV- pregnant woman/fetus dyads will be evaluated for insulin sensitivity and followed through the child's 3rd birthday. Amongst HEU infants, participants will be randomized at birth 1:1 with 150 to receive neonatal AZT prophylaxis and 150 to receive neonatal NVP prophylaxis. Targeted metabolomics will be used to assess the role intermediary metabolites in insulin resistance and directly assess mitochondrial function using Seahorse XF96e technology. At the time of study enrollment, all women must be willing to exclusively breastfeed for the infant's first 6 months of life. If in utero and neonatal HIV/ARV exposures are found to be associated with derangements in intermediary metabolism such that HEU infants are at increased risk for insulin resistance by 3 years of age, this would impact screening and prevention strategies for diabetes in this vulnerable population and argue for further research to identify prenatal and neonatal ARV regimens with superior PMTCT efficacy but minimal adverse metabolic consequences.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV, Insulin Sensitivity, Diabetes Mellitus

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Masking Description

Single blind - one party, either the investigator or participant, is unaware of the intervention assignment.

Allocation

Randomized

Enrollment

495 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Nevirapine

Arm Type

Experimental

Arm Description

150 HIV-Exposed Uninfected (HEU) infants on Nevirapine (NVP) Prophylaxis

Arm Title

Zidovudine

Arm Type

Active Comparator

Arm Description

150 HIV-Exposed Uninfected (HEU) infants on Zidovudine (AZT) Prophylaxis

Arm Title

HIV- unexposed Uninfected (HUU) Infants

Arm Type

No Intervention

Arm Description

150 HIV- unexposed Uninfected (HUU) Infants

Intervention Type

Drug

Intervention Name(s)

Zidovudine

Other Intervention Name(s)

AZT

Intervention Description

neonatal 4 weeks prophylactic

Intervention Type

Drug

Intervention Name(s)

Nevirapine

Other Intervention Name(s)

NVP

Intervention Description

neonatal 4 weeks prophylactic

Primary Outcome Measure Information:

Title

Homeo-static Model Assessment-Insulin Resistance (HOMA-IR)

Description

[glucose (mg/dL) X insulin ( μU/mL)405]

Time Frame

up to 3 years

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: HIV-infected and uninfected pregnant women between 16-36 weeks GA are eligible for study enrollment. Women must be 18 years of older and able to provide informed consent for themselves and their infant to participate in the study. Participants must be Botswana citizens. Women must have evidence of HIV infection status. Women NOT documented as HIV seropositive must have documentation of HIV seronegativity during the present pregnancy at or after 32 weeks GA. Women who have an initial negative HIV test during the present pregnancy which was done at <32 weeks GA will need to undergo repeat testing on or after 32 weeks GA in accordance with national guidelines. HIV-uninfected women must be willing to undergo HIV pre-test counseling, rapid HIV testing and post-test counseling, referred to as HIV Testing and Counseling (HTC) during pregnancy. Women must be willing to remain in study area with their infant and attend scheduled study visits as described above until the child's 3rd birthday. For HIV-infected women, they must be on TDF/3TC or FTC/EFV or TDF/3TC or FTC/Dolutegravir at time of study enrollment or willing to initiate this treatment and continue throughout the period of breastfeeding, if not for their lifetime. At enrollment, all women must be willing to breastfeed exclusively for the first six months of life. Exclusion Criteria: •Pre-existing maternal diabetes mellitus.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jennifer Jao, MD, MPH

Organizational Affiliation

Ann & Robert H Lurie Children's Hospital of Chicago

Official's Role

Principal Investigator

Facility Information:

Facility Name

Botswana-Harvard AIDS Institute Partnership

City

Gaborone

Country

Botswana

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32910067

Citation

Banda FM, Powis KM, Sun S, Makhema J, Masasa G, Yee LM, Jao J. Fetal biometry following in-utero exposure to dolutegravir-based or efavirenz-based antiretroviral therapy. AIDS. 2020 Dec 1;34(15):2336-2337. doi: 10.1097/QAD.0000000000002674. No abstract available.

Results Reference

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Study of HIV-Infected and Uninfected Pregnant Woman/Child Dyads in Gaborone, Botswana

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