Some Nucleoside Reverse Transcriptase Inhibitors Are Relatively Concentrated in Seminal Fluid, but Does It Matter?

  • Zidovudine and Lamivudine (ZDV/3TC) Seminal Plasma:Blood Plasma (SP:BP) Concentration Ratios Do Not Predict Total SP Exposure (TuPeB4553)
    Authored by Y.S. Reddy, L. Troiani, A. Pereira, J. Kim, A. van Kempen, M. Cohen, A.D.M. Kashuba
    View the original abstract

The concentration of antiretroviral medications in tissues where HIV replicates determines the potency of therapy. In this regard, the concentration of medications in seminal fluid may be very important for viral control, since the testes are sanctuary sites of HIV replication. Differences in drug concentration in seminal plasma: blood plasma (SP:BP) have been implicated by the finding of different antiviral responses in semen and blood. Furthermore, since it is known that resistant HIV can be present in semen and transmitted, understanding the pharmacology of seminal fluid has important implications for the transmission of HIV.

Using an intensive pharmacokinetic analysis, this study evaluated the levels of zidovudine (ZDV or AZT) and lamivudine (3TC) in 14 HIV-infected men who received zidovudine/lamivudine as part of three-drug therapy. These types of analyses measure the drug levels in both seminal plasma (the fluid component) and blood plasma over time. Analysis of the data confirmed that both zidovudine and lamivudine are relatively concentrated in the seminal plasma at two- and six-fold, respectively above the IC50 (the concentration of drug required to inhibit viral growth 50 percent) for wild-type HIV virus.

A simple way to predict the total drug exposure in seminal fluid would be a useful research tool, since detailed pharmacokinetic studies are cumbersome to conduct. One such method might be to predict drug exposure by looking at the seminal plasma: blood plasma ratio. Unfortunately, because of a lot of variation in blood drug levels, this ratio turns out not to be a reliable predictor of drug exposure (area under-the-cure, AUC).

These data confirm previous, less rigorous studies that suggest certain nucleoside reverse transcriptase inhibitors are relatively concentrated in seminal fluid -- an important location for antiviral activity, but leaves researchers short of a simple way to predict the activity or exposure to drug. To what extent does the knowledge of seminal fluid drug availability affect treatment choices? I'd think that other issues, such as potency, tolerability or durability of the entire three- (or more) drug regimen supercede this issue. Nevertheless, having potent drug activity in all body compartments will likely be very important in issues related to transmission and the emergence of drug resistance.