• Differential Phosphorylation of Zidovudine and Lamivudine (ZDT/3TC) Between Semen and Blood Mononuclear Cells (MCs) in HIV-1-Infected Men (Poster 530)
  Authored by S. Reddy, L. Troiani, J. Kim, J. Rodriguez, S. Fiscus, A.V. Kempen, M. Cohen, A. Kashuba
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Since the major main route of transmission for HIV is sexual intercourse, any attempt to reduce HIV shedding in semen may help reduce HIV transmission. Antiretroviral (ARV) drugs get secreted into semen at different concentrations and rates, with relation to their levels in plasma.

Of all the antiretroviral classes, nucleosides achieve the highest concentration rate with relation to the plasma levels, in the magnitude of two to six times more. These calculations are difficult to make due to the inability to understand and control the rate of secretion, elimination, and the steady state of all these drugs in the genital tract.

Although serum triphosphate (TP) concentrations have been determined for all nucleosides, there is little information on the triphosphate concentration level in semen.

Investigators at the University of Carolina, Chapel Hill were interested in elucidating the relationship of these levels. They conducted several pharmacokinetic studies to determine not only the concentrations in genital secretions of some of these antiretrovirals, but their clinical significance as well. See The Body's ICAAC 2000 review of "New Approaches With Antiretroviral Therapy."

In this poster, Dr. Reddy tried to characterize the pharmacokinetic relationships of the AZT (ZDV, zidovudine, Retrovir)/3TC (lamviduine, Epivir) triphosphate concentrations in semen and blood in 14 HIV-1-infected men currently receiving Combivir (AZT+3TC) as part of their ARV regimen.

The investigator found that in both semen and blood there were poor correlations between AZT plasma and TP exposure, and between 3TC plasma and TP exposure. The semen-to-blood ratio AUC at a 12 hours interval for 3TC was 1.0 and for AZT was 0.36. Interestingly, the seminal 3TC-TP was similar to the PBMCs, but the AZT-TP was only a fraction of that of blood levels. The author suggests that there may be a different kinase activity or cellular activation between the two compartments.

This data, although interesting, was difficult to place in clinical perspective. The clinical relevance of differential phosphorylation pathways among NRTIs has not yet been determined.

The male genital tract has been regarded as one of the most important sanctuary sites for HIV replication. Certainly it plays a very important role in transmission of infection among discordant partners. Trying to elucidate the pharmacokinetics and pharmacodynamics of antiretrovirals at that site may well play a crucial role in the future on the way we use these treatments in certain patient populations.

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