Sexual transmission of HIV-1 is dependent on the semen viral load. Seminal viral load may fluctuate and is increased by several HIV-1 related factors and prevailing conditions within the male genital tract. The precise reservoirs of virus production within the male genital tract, whether cell-associated of cell-free, are undefined. The ability of antiretroviral drugs to penetrate the male genital tract and reach therapeutic concentrations is correlated with the degree of viral suppression and therefore relative infectivity. The basic physicochemical properties of the drugs themselves do not predict penetration of semen and other factors, such as active drug transport, may be involved. Measurement of seminal viral load and antiretroviral drug concentration are affected by the physiology of semen and non-standardised methodology (type of test used, specimen collection methods, data presentation issues, and pharmacokinetic assumptions) between studies.