Advisory Committee Chair
Edward Acosta
Advisory Committee Members
Stephen Barnes
Victoria Johnson
William Parker
Craig Wilson
Document Type
Dissertation
Date of Award
2007
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
The human immunodeficiency virus (HIV) pandemic is a growing concern, affecting almost 40 million people worldwide. Treatment for HIV infection consists of highly active antiretroviral therapy (HAART) to block different steps in the viral lifecycle, ultimately reducing HIV RNA to undetectable levels in the plasma. However, HIV RNA can be detected in numerous reservoirs outside of the blood despite the use of HAART. Therefore, measurement of antiretroviral (ARV) drugs in other biological matrices is important to broaden our understanding of HIV transmission, the development of viral resistance with sub-optimal ARV exposure, and fetal and neonatal drug exposure. This work describes the development of novel liquid chromatography methodologies and the subsequent quantitation of specific ARVs in four alternative biological matrices. Three ARVs commonly used in the developing world were tested for their shortterm stability in whole blood. These drugs were shown to be stable in whole blood for at least 24 hr when stored at room temperature or incubated at 37 to 40°C. Next, we measured nevirapine (NVP) concentrations in breast milk since it is regularly administered to prevent maternal transmission. Our data suggests that NVP concentrations may be sufficient to provide protection against HIV transmission for the breast-feeding infant. We iii then investigated amniotic fluid concentrations of three ARV agents highly prescribed during pregnancy. Our results show that lamivudine (3TC) and zidovudine (ZDV) concentrations in the amniotic fluid exceed those in maternal plasma leading to significant fetal exposure. In contrast, the low nelfinavir (NFV) concentrations observed are unlikely to provide fetal protection against HIV transmission and the sub-therapeutic levels may lead to the development of resistance mutations. Last, we examined ARV quantitation in the female genital tract using a novel cervicovaginal secretion collection methodology. Our methods were able to quantitate drugs from three ARV classes and will be applied to future studies examining the differential penetration of ARVs into the female genital tract. This work can subsequently be used when selecting optimal treatment regimens for prophylaxis of HIV transmission, to decrease HIV RNA in sanctuary sites, and to prevent the development of resistance mutations due to sub-optimal ARV exposure.
Recommended Citation
Hood, Chantelle Bennetto, "Quantitation Of Antiretrovirals In Alternative Matrices" (2007). All ETDs from UAB. 3718.
https://digitalcommons.library.uab.edu/etd-collection/3718