HBV DNA Not Detected in Semen of Men with Chronic Hepatitis B Successfully Treated with Nucleotide Analogs

		SUMMARY: HIV positive and negative men with chronic hepatitis B who achieved undetectable serum HBV DNA during treatment with nucleotide analogs such as tenofovir (Viread) also cleared HBV genetic material in their semen, suggesting a reduced risk of sexual transmission, according to a poster presented at the 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010) this week in San Francisco.

By Liz Highleyman

Like HIV, hepatitis B virus is a sexually transmitted infection, and men who have sex with men are at elevated risk. Prior studies indicate that sexual transmission is uncommon among HBV monoinfected people who suppress serum HBV DNA to an undetectable level with antiviral therapy. However, research has shown that HIV RNA can remain in the semen even after it falls to an undetectable level in the blood with antiretroviral therapy.

Ann Marie Liapakis from New York Presbyterian Weill Cornell Medical Center and colleagues aimed to determine whether HBV DNA -- like HIV RNA -- would remain detectable in the semen of HIV positive and negative men with chronic hepatitis B who achieved serum HBV viral load suppression with nucleotide antiviral therapy that penetrates the semen compartment.

Studies of HIV positive men have shown that tenofovir penetrates the genital compartment, which is protected by a physiological barrier that keeps some drugs out.

Several antiviral medications are approved for treatment of chronic hepatitis B, including two nucleotide analogs, tenofovir -- indicated for treatment of both HBV and HIV -- and adefovir (Hepsera). Treatment guidelines recommend that HIV/HBV coinfected patients should be treated with at least 2 dually active agents, such as tenofovir plus either lamivudine (Epivir) or emtricitabine (Emtriva).

This cross-sectional study included 20 men with chronic HBV infection, as indicated by being hepatitis B surface antigen (HBsAg) positive and either positive or negative for hepatitis B "e" antigen (HBeAg).

Participants provided blood and semen samples for HBV DNA quantification. Semen was tested using the high-sensitivity HBV TaqMan real-time polymerase chain reaction (PCR) assay, with a limit of detection of 5 IU/mL.

The researchers compared semen HBV DNA levels of 10 men using tenofovir or adefovir who had undetectable serum HBV DNA (< 100 IU/mL) and 10 men with detectable blood HBV DNA.

Characteristics of the participants in the 2 groups were comparable overall, except the men in the serum detectable group were significantly younger on average (mean 35 vs 47 years). Also, 3 of the 10 men in the serum undetectable group and 1 in the serum detectable group were coinfected with HIV. In both groups, 3 patients were HBeAg positive.

In the serum undetectable group, 4 men were taking adefovir, 3 were taking tenofovir as the only anti-HBV drug, and 3 were taking tenofovir plus emtricitabine (the drugs in the Truvada pill). In addition, the sole HIV/HBV coinfected participant in the serum detectable group was also on tenofovir/emtricitabine.

Results

	Among men with undetectable serum HBV DNA, none had detectable semen HBV DNA.
	However, 3 of the 10 men with detectable blood HBV DNA also had detectable virus in their semen.
	These 3 men had semen HBV DNA viral loads of 6 IU/mL, 344 IU/mL, and 1190 IU/mL.
	All 3 of these men had very high blood HBV DNA, at 70,900 IU/mL, 338 million IU/mL, and 27 million IU/mL, respectively.
	In contrast, the remaining 7 men in the serum undetectable group who also had undetectable semen viral load had a median blood HBV DNA level of 11,000 IU/mL.
	The sole coinfected man in the serum detectable group was among the 3 with detectable semen viral load.
	2 of the 3 men with detectable serum and semen HBV DNA were HBeAg positive.
	All 7 men with detectable serum but undetectable semen HBV DNA, however, were HBeAg negative.

"In this cross-sectional analysis, HBV DNA was not detected in the semen of patients with undetectable blood level as a result of nucleotide antiviral therapy," the investigators concluded.

"These results suggest that HBV may not be transmitted sexually when serum negativity is achieved via antiviral suppression or alternatively may reflect the lack of sensitivity of the PCR assay in the semen. These findings should be confirmed in studies of larger sample size."

New York Presbyterian Weill Cornell Medical Center, New York, NY; Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI; Mt. Sinai Med Center, New York, NY.

2/19/10

Reference
AM Liapakis, M Patel, E Kula, and others. HBV DNA Is Not Detected in the Semen of Patients with Chronic Hepatitis B and Undetectable Serum HBV DNA as a Result of Nucleotide Antiviral Treatment. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. Abstract 627.