Arlene S. Pereira, Ph.D.

Dissertation research performed under the guidence of Dr. Richard R. Tidwell

ABSTRACT
    This thesis demonstrates fast and easy methods for measuring antiretroviral concentrations in seminal plasma using HPLC-MS/MS.  The methods presented here have been validated and used to measure zidovudine, lamivudine, and amprenavir in seminal plasma collected from two different clinical studies.  Based upon these studies, it appears all three drugs penetrate the male genital tract and enter the seminal compartment.  The nucleosides, lamivudine and zidovudine, appear to distribute from the systemic circulation into the seminal compartment more than the protease inhibitor, amprenavir.  This is not surprising.  Nucleosides have a larger volume of distribution than protease inhibitors.  It also appears that lamivudine, of the three drugs tested, has the greatest ability to penetrate the male genital tract and concentrate in semen.  Those drugs, which enter the male genital tract, must do so in concentrations sufficient to reduce seminal shedding of HIV-1.  Without reduction of seminal shedding of HIV-1, it may be impossible to reduce the sexual transmission of HIV-1/AIDS.