Herpes viruses associated with shedding of HIV in the semen of gay men taking suppressive antiretroviral therapy

Michael Carter
Published: 09 May 2013

Low level HIV replication in semen persists in almost 10% of gay men taking antiretroviral therapy, investigators from the United States report in the online edition of Clinical Infectious Diseases. A low-level viral load in the blood and shedding of cytomegalovirus (CMV) and Epstein Barr virus (EBV) in semen were associated with the detection of HIV in the genital tract.

“Low levels of HIV in blood plasma between 50 and 500 copies/ml were associated with seminal shedding, suggesting that a complete suppression of HIV blood levels may minimize the risk of sexual transmission,” the researchers comment.

Antiretroviral therapy suppresses HIV replication in the blood and semen of most HIV-positive men, substantially reducing the risk of sexual transmission.

However, genital shedding of HIV can still occur in the presence of antiretroviral therapy. There have also been rare case reports of HIV transmissions in the presence of therapy that is suppressing viral load in blood plasma.

Untreated sexually transmitted infections (STIs) can cause local inflammation, possibly increasing the risk of transmission. Research involving people who have not taken HIV treatment (who are antiretroviral naive) has also shown that some human herpes viruses including CMV and EBV can cause immune activation or increase viral load in semen.

Investigators from California therefore designed a study exploring the relationship between STIs, seven herpes viruses and shedding of HIV in semen.

Their study sample comprised 114 gay and other men who have sex with men (MSM), all of whom were taking antiretroviral therapy with a blood plasma viral load below 500 copies/ml.

Semen samples were collected and tested for HIV replication and herpes viruses. The participants had a mean age of 44 years. The median duration of antiretroviral therapy was 882 days and 88% of participants had a blood plasma viral load below 50 copies/ml. The majority of participants (87%) were highly adherent to their therapy, reporting taking 90% or more of their doses in the previous month.

An asymptomatic bacterial STI was detected in 15% of individuals, including 4% with a urethral infection.

HIV was detected in the semen of 10% of participants. The median genital tract viral load in these people was 126 copies/ml. A herpes virus was detected in the semen of 63% of participants. CMV was detected in the genital tract of 49% of participants and EBV in the semen of 31% of individuals.

People with a detectable blood plasma viral load (between 50 and 500 copies/ml) were significantly more likely to shed HIV in semen than individuals with undetectable virus in blood plasma (36 vs 6%; RR = 6.0, 95% CI, 2.1-17.0, p < 0.001).

There was no relationship between genital shedding of HIV and type of antiretroviral therapy, duration of treatment or self-reported adherence.

High-level shedding of CMV (4 log10 or above) was also a predictor of genital shedding of HIV in semen. CMV at this level was present in 64% of participants with detectable HIV in semen, compared to 24% of participants with an undetectable HIV viral load in their genital tract (RR = 4.5; 95% CI, 1.4-14.3, p = 0.01).

“High-level CMV replication plays a role in HIV seminal shedding…in successfully treated HIV infected individuals,” write the authors.

Detectable EBV in semen also had a significant association with genital shedding of HIV (73 vs 26%; RR = 6.0, 95% CI, 1.7-21.3, p < 0.01).

Surprisingly, the presence of a urethral STI did not increase the risk of shedding HIV in semen. “This may be a consequence of the relatively low prevalence of urethral STIs in this asymptomatic cohort,” suggest the authors. “However, this also suggests that CMV may be a more common precipitant of HIV shedding in semen than bacterial STI during ART.”

They conclude, “the association between isolated HIV shedding and high-level CMV replication and EBV replication in the genital tract suggests that the presence of these viruses could play a role in HIV transmission…these findings have important implications for the development of strategies to reduce HIV transmission.”

Reference

Gianella S et al. Shedding of HIV and human herpesviruses in the semen of effectively treated HIV-1 infected men who have sex with men. Clin Infect Dis, online edition, 2013.