Some Men Shed HIV in Semen Despite ART, Linked to Herpesvirus Coinfection

About 10% of gay men in a U.S. study had detectable HIV in their semen despite suppression of blood plasma viral load with antiretroviral therapy (ART), which has implications for HIV transmission, according to a study described in the April 17, 2013, advance online edition of Clinical Infectious Diseases. Having a low but detectable blood viral load and coinfection with cytomegalovirus or Epstein-Barr virus were associated with increased likelihood of semen HIV shedding.

Studies have shown that effective antiretroviral therapy dramatically reduces the risk of HIV transmission within stable heterosexual couples, as well as between men. But sexual transmission can still occur, and may be attributable to the fact that virus may remain present in semen even when suppressed by ART in the blood. Presence of co-existing infections -- such as the human herpesviruses cytomegalovirus (CMV, HHV-5) and Epstein-Barr virus (EBV, HHV-4) -- may also play a role by increasing immune activation and inflammation.

Sara Gianella from the University of California at San Diego and colleagues looked at the frequency and predictors of HIV shedding in semen among 114 men who have sex with men (mean age 44 years) who were on ART (median duration 2.4 years) with blood plasma HIV < 500 copies/mL, although most (88%) had < 50 copies/mL.

The researchers measured levels of HIV and 7 herpesviruses in semen and screened participants for bacterial sexually transmitted infections (STIs) and non-specific genital inflammation. They determined predictors of HIV in semen both for the group as a whole and for a subset of 100 men with blood viral load < 50 copies/mL.

Results

• 11 participants (9.6%) had detectable HIV in their semen, with a median level of 2.1 log copies/mL, or about 125 copies/mL.
• 72 men (63%) had at least 1 herpesvirus detected in their semen or genital tract, including 49% with CMV and 31% with EBV.
• 15% were found to have asymptomatic bacterial STIs.
• HIV in semen was detected 6 times more often among men with blood viral load between 50 and 500 copies/mL, compared to those with <50 copies/mL (36% vs 6%, respectively).
• In an analysis of participants with blood viral load < 50 copies/mL, a high level of CMV in semen (> 4 log copies/mL) was the only significant predictor of semen HIV shedding.
• There was no observed association between HIV in semen and type of ART, duration of therapy, self-reported adherence.
• There was also no association between semen HIV shedding and presence of urethral STIs.

Based on these findings the study authors concluded, "Low-level HIV replication in blood and high-level seminal CMV shedding, but not presence of asymptomatic STIs, is associated with seminal shedding of HIV in men receiving ART, conferring a potential risk for HIV transmission."

"CMV may be a more common precipitant of HIV shedding in semen than bacterial STI during ART," they suggested, adding that, "completely suppressing HIV in the blood may minimize the risk of sexual transmission."

5/22/13

Reference

S Gianella, DM Smith, MV Vargas, et al. Shedding of HIV and human herpesviruses in the semen of effectively treated HIV-1 infected men who have sex with men. Clinical Infectious Diseases. April 17, 2013 (Epub ahead of print).