Clinical trial NCT03284645: Viral and Antiretroviral Dynamics in HIV-1 Mother-to-Child Transmission Fluids
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Human Immunodeficiency Virus Infection
Lead sponsor: Obafemi Awolowo University
Sponsor class: OTHER
Collaborators: name: Federal Medical Centre, Makurdi
name: University of Liverpool
name: University of California, San Diego
name: London School of Hygiene and Tropical Medicine
First posted: 2017-09-15
Enrollment: 194
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Polymorphisms in antiretrovirals disposition genes
timeFrame: At study enrolment
measure: Minimum plasma drug concentration (Cmin)
timeFrame: At 2-3 months before delivery and at 10-12 weeks postpartum
measure: Maximum plasma drug concentration (Cmax)
timeFrame: At 2-3 months before delivery and at 10-12 weeks postpartum
measure: Area under the concentration-time curve (AUC)
timeFrame: At 2-3 months before delivery and at 10-12 weeks postpartum
measure: Clearance over systemic availability (Cl/F)
timeFrame: At 2-3 months before delivery and at 10-12 weeks postpartum
measure: HIV-1 viral load (RNA & DNA) in plasma
timeFrame: Through study completion (1-2 monthly)
measure: HIV-1 viral load (RNA & DNA) in breastmilk
timeFrame: From 6 weeks postpartum through study completion (1-2 monthly)
measure: HIV-1 viral load (RNA & DNA) in CVF
timeFrame: From week 28 to delivery (monthly)
Secondary outcomes:
Other outcomes:
Locations:
city: Adikpo
country: Nigeria
facility: St. Monica's Hospital
state: Benue State
city: Ihugh
country: Nigeria
facility: St. Thomas' Hospital
state: Benue State
city: Makurdi
country: Nigeria
facility: Bishop Murray Medical Centre
state: Benue State
city: Makurdi
country: Nigeria
facility: Federal Medical Centre
state: Benue State
Study officials:
affiliation: Obafemi Awolowo University, Nigeria
name: Adeniyi Olagunju, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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