Tenofovir (Viread) rapidly suppresses HIV in semen and could help prevent the sexual transmission of HIV, according to a small study published in the March 1st edition of the Journal of Acquired Immune Deficiency Sydromes. Levels of tenofovir in semen were several times those seen in blood.
The risk of the sexual transmission of HIV is associated with the level of HIV in the male and female genital tract. There is also some evidence that the male genital tract acts as a “reservoir” for HIV, with the virus reproducing there independently to the blood . Therefore, anti-HIV treatment that gets into the genital tract could reduce HIV viral load and the risk of transmission, and also the help reduce the risk of drug drug-resistant HIV developing.
Tenofovir is a powerful anti-HIV drug that belongs to the nucleotide reverse transcriptase inhibitor family of antiretrovirals. It is contained in the combination pills Truvada and Atripla and is a popular choice for first-line antiretroviral therapy.
Laboratory studies involving monkeys have shown that tenofovir works against HIV in the female genital tract and studies are currently underway to assess its safety and effectiveness as a microbicide. The drug is used in post-exposure prophylaxis (PEP) regimes and is being invested as pre-exposure prophylaxis (PREP).
But little is known about the ability of tenofovir to get into the male genital tract and to reduce viral load in semen.
Investigators at the University of North Carolina therefore designed a small study involving nine HIV-positive men to measure concentrations of tenofovir in the genital tract after the first and then multiple doses, and to see the effect of the drug on viral load in both the blood and semen.
The study was conducted between 2003 and 2005. All the men had an HIV viral load above 200 copies/ml on entry to the study. Eight of the men were not taking any antiretroviral therapy. These patients were provided with 14 days of tenofovir monotherapy at a standard daily dose of 300mg and then started multi-drug anti-HIV treatment. The remaining patient added tenofovir to an antiretroviral regimen that was failing to suppress his viral load. The study lasted 28 days. Paired blood and semen samples were obtained from the men throughout the study.
After the first dose, concentrations of tenofovir in semen were 4.4-fold higher than those in blood. After subsequent doses tenofovir maintained a higher concentration in semen than in plasma, this concentration being 5.1-fold higher at the end of the study.
But tenofovir could only be detected in the cells of three of these men. In these three patients intracellular concentrations of tenofovir in the genital tract were 9-fold higher than those in peripheral blood mononuclear cells after the first dose of tenofovir and 17.5-fold higher after the seventh dose.
After 14 days of treatment, median viral load was 866 copies/ml in blood and below 400 copies/ml (the lower limit of detection) in semen in the eight men who received monotherapy. The magnitude of the fall in viral load in blood and semen from baseline was comparable at approximately 1 log10 copies/ml.
The single patient who added tenofovir to his existing antiretroviral regimen had an undetectable viral load in his semen for the duration of the study. The viral load in his blood was 366 copies/ml on entry to the study and 709 copies/ml at the end of the study.
Resistance tests were conducted in the four patients who had a tenofovir viral load above 1000 copies/ml in blood (four patients) or semen (one patient). No patient developed the K65R mutation that confers resistance to tenofovir.
On the basis of these findings the investigators conclude that tenofovir may have the potential “to reduce the sexual transmission of HIV.”
Vourvahis M et al. The pharmacokinetics and viral activity of tenofovir in the male genital tract. J Acquir Immune Defic Syndr 47: 329 – 333, 2008.