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

Investigating Influence of Pregnancy-induced Changes in Antiretroviral Pharmacokinetics, Together With Polymorphisms in Drug Disposition Genes, on Viral Decay Dynamics in HIV Positive Women Starting Therapy Late in Pregnancy and Postpartum

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.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus Infection
• Intervention / Treatment: 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

• Study Type: Observational
• Enrollment (Actual): 194

Contacts and Locations

Study Locations

• Nigeria
  • Benue State
    • Adikpo, Benue State, Nigeria
      • St. Monica's Hospital
    • Ihugh, Benue State, Nigeria
      • St. Thomas' Hospital
    • Makurdi, Benue State, Nigeria
      • Bishop Murray Medical Centre
    • Makurdi, Benue State, Nigeria
      • Federal Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• 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.

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; Fixed-dose combination of 300 mg TDF, 300 mg 3TC and 600 mg EFV taken once daily.; Drug: Abacavir (ABC) 600 mg + Lamivudine (3TC) 300 mg + Efavirenz (EFV) 600 mg; Fixed-dose combination of 600 mg ABC, 300 mg 3TC and 600 mg EFV taken once daily.; Drug: Zidovudine (AZT) 300 mg + Lamivudine (3TC) 150 mg twice daily + Efavirenz (EFV) 600 mg once daily; Fixed-dose combination of 300 mg AZT and 150 mg 3TC taken twice daily, plus 600 mg EFV taken 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; Fixed-dose combination of 300 mg TDF, 300 mg 3TC and 600 mg EFV taken once daily.; Drug: Abacavir (ABC) 600 mg + Lamivudine (3TC) 300 mg + Efavirenz (EFV) 600 mg; Fixed-dose combination of 600 mg ABC, 300 mg 3TC and 600 mg EFV taken once daily.; Drug: Zidovudine (AZT) 300 mg + Lamivudine (3TC) 150 mg twice daily + Efavirenz (EFV) 600 mg once daily; Fixed-dose combination of 300 mg AZT and 150 mg 3TC taken twice daily, plus 600 mg EFV taken 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; Fixed-dose combination of 300 mg TDF, 300 mg 3TC and 600 mg EFV taken once daily.; Drug: Abacavir (ABC) 600 mg + Lamivudine (3TC) 300 mg + Efavirenz (EFV) 600 mg; Fixed-dose combination of 600 mg ABC, 300 mg 3TC and 600 mg EFV taken once daily.; Drug: Zidovudine (AZT) 300 mg + Lamivudine (3TC) 150 mg twice daily + Efavirenz (EFV) 600 mg once daily; Fixed-dose combination of 300 mg AZT and 150 mg 3TC taken twice daily, plus 600 mg EFV taken once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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)

Collaborators and Investigators

• Sponsor: Obafemi Awolowo University
• Collaborators: London School of Hygiene and Tropical Medicine; University of California, San Diego; University of Liverpool; Federal Medical Centre, Makurdi
• Investigators: Principal Investigator: Adeniyi Olagunju, PhD, Obafemi Awolowo University, Nigeria

Publications and helpful links

General Publications

• 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

Helpful Links

• Wellcome Open Research

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2017
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): September 17, 2020

Study Registration Dates

• First Submitted: September 2, 2017
• First Submitted That Met QC Criteria: September 12, 2017
• First Posted (Actual): September 15, 2017

Study Record Updates

• Last Update Posted (Actual): October 14, 2020
• Last Update Submitted That Met QC Criteria: October 12, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Lamivudine; Zidovudine; Efavirenz; Abacavir
• Other Study ID Numbers: NHREC/01/01/2007-05/06/2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No