HIV is not always present at similar levels in the blood and semen. Whilst most research shows that a majority of men treated with combination antiretroviral therapy experience parallel declines in blood and semen viral load, studies find considerable individual variation.

Several studies have shown that detectable levels of HIV may persist in anorectal tissue even after the virus becomes undetectable in the blood ^[1]. One small study found that stimulation of the prostate gland released HIV into the semen, suggesting that the prostate serves as an HIV reservoir^[2].

Prolonged HIV persistence in semen may be explained by the fact that long-lived HIV-infected cells in the male genital tract can continue to produce new virus if anti-HIV drugs do not adequately penetrate this compartment. Antiretroviral drugs may be present at different levels in the blood and semen, due in part to the presence of a ‘blood-testis barrier’. Among men taking antiretroviral therapy, different HIV variants - with different degrees of drug resistance - can emerge in blood and semen, suggesting that drugs do not work equally well against virus throughout the body^[3].

Antiretroviral drugs vary widely in their ability to penetrate the male genital tract. Among the NRTIs, AZT, 3TC, and d4T have been shown to reach active levels in the semen - in some cases higher than concentrations in the blood^[4]. The nucleotide reverse transcriptase inhibitor tenofovir (Viread) accumulates in the semen, making it potentially suitable for pre-exposure prophylaxis (PrEP)^[5] . The NNRTIs nevirapine and efavirenz also appear to reach the semen. Protease inhibitors may have difficulty entering the male genital tract because they are bound to proteins. Though study data vary, amprenavir, fosamprenavir, atazanavir and indinavir appear to reach active levels in the semen. T-20, however, does not enter the male genital tract.