Antiretroviral Drug Levels During and After Pregnancy
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.
|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|
- 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 ]
- 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
|Study Start Date:||February 2008|
|Study Completion Date:||September 2009|
|Primary Completion Date:||November 2008 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00616252
|Infectious Diseases Institute, Faculty of Medicine, Makerere University|
|Kampala, Uganda, 22418|
|Principal Investigator:||Concepta A Merry, PhD||Trinity College Dublin|