Antiretroviral Drug Levels During and After Pregnancy

This study has been completed.
Sponsor:
Collaborator:
Northwestern University
Information provided by:
Makerere University
ClinicalTrials.gov Identifier:
NCT00616252
First received: February 4, 2008
Last updated: December 3, 2010
Last verified: December 2010
  Purpose

In HIV-infected women, the use of combination therapy with antiretrovirals (ARV) in pregnancy prevents HIV related morbidity and mortality and prevents mother-to-child transmission of the HIV virus.

Specifically, suppression of the virus to an undetectable level is important during the delivery of the baby to minimize potential HIV exposure. In Sub-Saharan Africa, the use of ARV combinations containing nevirapine is the cornerstone of current HIV therapy, due to an affordable cost, availability in a fixed dose combination pill, and generic availability. Maintaining the efficacy and preventing development of resistance against this agent by the HIV virus is imperative, as second line therapies are often more difficult to obtain, are more expensive, and present more challenges in drug storage in clinics and in the community.

Pregnancy adds another dimension to the challenge of treating women with HIV, as the physiologic and metabolic changes can affect levels of antiretroviral agents in the body. Though these changes are known to exist, few trials have evaluated the effect of these factors on the pharmacokinetics of antiretroviral agents and their impact has yet to be demonstrated.

We wish to evaluate if the physiologic changes that occur during pregnancy impact the levels of stavudine, lamivudine, and nevirapine compared to those of a non-pregnant, HIV-infected Ugandan female. These data are imperative to ensure adequate suppression of the HIV virus throughout pregnancy.


Condition
Pharmacokinetics

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Comparison of the Pharmacokinetics of Antiretroviral Agents in HIV Infected Ugandan Women During and After Pregnancy

Resource links provided by NLM:


Further study details as provided by Makerere University:

Primary Outcome Measures:
  • To evaluate differences in the trough concentration (C12hr) of nevirapine during the second and third trimester of pregnancy and after delivery in the same patient [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate differences in the clearance (Cl/F), area under the curve (AUC), Volume of distribution (V/F), maximum concentration (Cmax), time to maximum concentration (Tmax), and half-life (T1/2) of nevirapine as a result of pregnancy. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • To evaluate potential changes in intracellular triphosphate concentration of NRTIs that may occur as a result of pregnancy [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • To evaluate pharmacogenomic differences in this East African population. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • To establish pharmacokinetic levels seen in non-pregnant East African women as compared to the levels seen in the western population, based on the post-partum levels. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Human plasma Red cell pellets


Enrollment: 16
Study Start Date: February 2008
Study Completion Date: September 2009
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 39 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

HIV positive women attending ante-natal care clinic at Mulago Hospital, Kampala Uganda

Criteria

Inclusion Criteria:

  • HIV-infected pregnant female in her second or third trimester who requires ARV therapy during her pregnancy
  • Antiretroviral therapy includes nevirapine in addition to two NRTI agents
  • Informed consent obtained

Exclusion Criteria:

  • If primary physician feels the required blood draws would be potentially dangerous to the patient or fetus
  • Haemoglobin <8 g/dL
  • Liver Function tests > 2x normal
  • CD4 cell count >250 cells/mL if ART naive
  • Calculated Creatinine Clearance < 30 ml/min at any visit during the study period
  • Patients receiving any medications that may interact with the cytochrome p450 enzyme system metabolism of nevirapine
  • Concurrent herbal medication use.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00616252

Locations
Uganda
Infectious Diseases Institute, Faculty of Medicine, Makerere University
Kampala, Uganda, 22418
Sponsors and Collaborators
Makerere University
Northwestern University
Investigators
Principal Investigator: Concepta A Merry, PhD Trinity College Dublin
  More Information

No publications provided

Responsible Party: Dr Concepta Merry, Infectious Diseases Institute
ClinicalTrials.gov Identifier: NCT00616252     History of Changes
Other Study ID Numbers: CPR 002
Study First Received: February 4, 2008
Last Updated: December 3, 2010
Health Authority: Uganda: National Council for Science and Technology
Uganda: Research Ethics Committee

Keywords provided by Makerere University:
Antiretroviral
Pharmacokinetics
Pregnancy

ClinicalTrials.gov processed this record on September 22, 2014