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

Human Immunodeficiency Virus Infection Clinical Trial

— VADICT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03284645
• Other study ID #: NHREC/01/01/2007-05/06/2017
• Status: Completed
• Start date: December 22, 2017
• Est. completion date: September 17, 2020

Study information

• Verified date: October 2020
• Source: Obafemi Awolowo University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 194
• Est. completion date: September 17, 2020
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus Infection

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
Nigeria	St. Monica's Hospital	Adikpo	Benue State
Nigeria	St. Thomas' Hospital	Ihugh	Benue State
Nigeria	Bishop Murray Medical Centre	Makurdi	Benue State
Nigeria	Federal Medical Centre	Makurdi	Benue State

Sponsors (5)

Lead Sponsor	Collaborator
Obafemi Awolowo University	Federal Medical Centre, Makurdi, London School of Hygiene and Tropical Medicine, University of California, San Diego, University of Liverpool

Country where clinical trial is conducted

Nigeria, 

References & Publications (1)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Polymorphisms in antiretrovirals disposition genes		At study enrolment
Primary	Minimum plasma drug concentration (Cmin)		At 2-3 months before delivery and at 10-12 weeks postpartum
Primary	Maximum plasma drug concentration (Cmax)		At 2-3 months before delivery and at 10-12 weeks postpartum
Primary	Area under the concentration-time curve (AUC)		At 2-3 months before delivery and at 10-12 weeks postpartum
Primary	Clearance over systemic availability (Cl/F)		At 2-3 months before delivery and at 10-12 weeks postpartum
Primary	HIV-1 viral load (RNA & DNA) in plasma		Through study completion (1-2 monthly)
Primary	HIV-1 viral load (RNA & DNA) in breastmilk		From 6 weeks postpartum through study completion (1-2 monthly)
Primary	HIV-1 viral load (RNA & DNA) in CVF		From week 28 to delivery (monthly)

External Links

•   Wellcome Open Research