Viral and Antiretroviral Dynamics in HIV-1 Mother-to-Child Transmission Fluids

NCT03284645 | Completed DMC FDA Drug

• 1 other identifier: NHREC/01/01/2007-05/06/2017
• Study Type: observational
• Target: 194
• Locations: 1 country
• Sites: 4

Brief Summary

More than 150,000 babies became infected with HIV in 2015 alone. When HIV drugs are started before or early in pregnancy, HIV positive women can give birth to HIV negative baby. This is possible because HIV drugs can reduce the amount of the virus in the body to the extent that they become undetectable by the time of delivery and during the breastfeeding period. However, some women do not start taking these drugs on time because they become infected during pregnancy or lactation. This leads to detectable virus at the time of delivery and puts the baby at risk of becoming infected. Also, the amounts of HIV drugs in the body have to be at certain levels for them to work effectively. But findings from some research have recently showed that pregnancy increases the rate at which the body removes some HIV drugs used to prevent the transfer of HIV from mother to child. While this may not cause any problem in women with no detectable virus before pregnancy, it may affect the rate at which the HIV virus is removed from the body in those starting treatment late and may put the baby at risk. This project will investigate whether the changes in drug exposure caused by pregnancy or other factors have any effect on the rate at which the HIV virus is removed from the body. HIV positive pregnant women and those who recently delivered will be recruited from different hospitals and follow up will be until breastfeeding ends. The investigators will not be involved in treatment decisions and the primary care provider will be responsible for prescribing antiretroviral regimen based on current guidelines. Samples will be collected to measure levels of the virus and the drugs in three fluids that transfer the virus to the baby: blood, genital fluid, and breastmilk. The HIV status of the babies will be monitored until they stop breastfeeding.

Conditions

Human Immunodeficiency Virus Infection

Outcome Measures

Primary Outcomes (8)

• Polymorphisms in antiretrovirals disposition genes

  At study enrolment

• Minimum plasma drug concentration (Cmin)

  At 2-3 months before delivery and at 10-12 weeks postpartum

• Maximum plasma drug concentration (Cmax)

  At 2-3 months before delivery and at 10-12 weeks postpartum

• Area under the concentration-time curve (AUC)

  At 2-3 months before delivery and at 10-12 weeks postpartum

• Clearance over systemic availability (Cl/F)

  At 2-3 months before delivery and at 10-12 weeks postpartum

• HIV-1 viral load (RNA & DNA) in plasma

  Through study completion (1-2 monthly)

• HIV-1 viral load (RNA & DNA) in breastmilk

  From 6 weeks postpartum through study completion (1-2 monthly)

• HIV-1 viral load (RNA & DNA) in CVF

  From week 28 to delivery (monthly)

Study Arms (3)

ART Before or Early in Pregnancy

HIV positive pregnant women who started antiretroviral therapy (ART) before or early in pregnancy for prevention of mother-to-child transmission of HIV and for their own health.

Drug: Tenofovir Disoproxil Fumarate (TDF) 300 mg + Lamivudine (3TC) 300 mg + Efavirenz (EFV) 600 mg; Drug: Abacavir (ABC) 600 mg + Lamivudine (3TC) 300 mg + Efavirenz (EFV) 600 mg; Drug: Zidovudine (AZT) 300 mg + Lamivudine (3TC) 150 mg twice daily + Efavirenz (EFV) 600 mg once daily

ART Started Third Trimester

HIV positive pregnant women starting antiretroviral therapy (ART) during the third trimester of pregnancy for prevention of mother-to-child transmission of HIV and for their own health.

Drug: Tenofovir Disoproxil Fumarate (TDF) 300 mg + Lamivudine (3TC) 300 mg + Efavirenz (EFV) 600 mg; Drug: Abacavir (ABC) 600 mg + Lamivudine (3TC) 300 mg + Efavirenz (EFV) 600 mg; Drug: Zidovudine (AZT) 300 mg + Lamivudine (3TC) 150 mg twice daily + Efavirenz (EFV) 600 mg once daily

ART Started Postpartum

HIV positive women starting antiretroviral therapy (ART) after delivery for prevention of mother-to-child transmission of HIV and for their own health.

Drug: Tenofovir Disoproxil Fumarate (TDF) 300 mg + Lamivudine (3TC) 300 mg + Efavirenz (EFV) 600 mg; Drug: Abacavir (ABC) 600 mg + Lamivudine (3TC) 300 mg + Efavirenz (EFV) 600 mg; Drug: Zidovudine (AZT) 300 mg + Lamivudine (3TC) 150 mg twice daily + Efavirenz (EFV) 600 mg once daily

Interventions

Tenofovir Disoproxil Fumarate (TDF) 300 mg + Lamivudine (3TC) 300 mg + Efavirenz (EFV) 600 mg DRUG

Fixed-dose combination of 300 mg TDF, 300 mg 3TC and 600 mg EFV taken once daily.

ART Before or Early in Pregnancy; ART Started Postpartum; ART Started Third Trimester

Abacavir (ABC) 600 mg + Lamivudine (3TC) 300 mg + Efavirenz (EFV) 600 mg DRUG

Fixed-dose combination of 600 mg ABC, 300 mg 3TC and 600 mg EFV taken once daily.

ART Before or Early in Pregnancy; ART Started Postpartum; ART Started Third Trimester

Zidovudine (AZT) 300 mg + Lamivudine (3TC) 150 mg twice daily + Efavirenz (EFV) 600 mg once daily DRUG

Fixed-dose combination of 300 mg AZT and 150 mg 3TC taken twice daily, plus 600 mg EFV taken once daily.

ART Before or Early in Pregnancy; ART Started Postpartum; ART Started Third Trimester

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This is cohort study of HIV positive pregnant or recently postpartum women receiving WHO recommended first-line ART regimen. Pregnant women and nursing mothers initiating ART \< 4 months before delivery (n = 60) and \< 6 weeks postpartum (n = 60), respectively, and a comparison group of pregnant women who initiated ART ≥ 4 months before delivery (n = 120) will be recruited from four hospitals providing PMTCT services in Nigeria.

You may qualify if:

• ≥ 18 years old
• Planned exclusive breastfeeding until 6 months of age
• Able to understand study information and comply with follow-up schedule

You may not qualify if:

• Severe maternal or infant illness
• Planned exclusive formula feeding
• Taking medication with known or uncertain interaction with study drugs

Sponsors & Collaborators

• Obafemi Awolowo University: lead
• Federal Medical Centre, Makurdi: collaborator
• University of Liverpool: collaborator
• University of California, San Diego: collaborator
• London School of Hygiene and Tropical Medicine: collaborator

Study Sites (4)

St. Monica's Hospital

Adikpo, Benue State, Nigeria

Location

St. Thomas' Hospital

Ihugh, Benue State, Nigeria

Location

Bishop Murray Medical Centre

Makurdi, Benue State, Nigeria

Location

Federal Medical Centre

Makurdi, Benue State, Nigeria

Location

Related Publications (2)

• Olagunju A, Anweh D, Okafor O et al. Viral and antiretroviral dynamics in HIV mother-to-child transmission fluids (VADICT) - Protocol and data analysis plan for a cohort study [version 1; referees: awaiting peer review]. Wellcome Open Res 2019, 4:34

  BACKGROUND

• Eniayewu O, Akinloye A, Shenkoya B, Azuka U, Bolaji O, Adejuyigbe E, Owen A, Olagunju A. Prenatal efavirenz exposure is independently associated with maternal, but not fetal CYP2B6 genotype. Pharmacogenet Genomics. 2024 Oct 1;34(8):253-260. doi: 10.1097/FPC.0000000000000542. Epub 2024 Jun 24.

  PMID: 38934229 DERIVED

Related Links

• Wellcome Open Research

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Tenofovir; Lamivudine; efavirenz; abacavir; Zidovudine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Thymidine

Study Officials

• Adeniyi Olagunju, PhD

  Obafemi Awolowo University, Nigeria

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 2, 2017
• First Posted: September 15, 2017
• Study Start: December 22, 2017
• Primary Completion: December 31, 2019
• Study Completion: September 17, 2020
• Last Updated: October 14, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

NG (4)