Viral load in semen

A review article published in 2008analysing the results of 19 studies published or presented between 1996 and 2006 examining the correlation between HIV in blood and semen concluded that the level of HIV in blood and semen is usually, but not always, correlated.¹

A consistent finding of the review was that viral load tended to be lower in semen than in blood, and that men who had undetectable virus in their semen almost always had an undetectable viral load in their blood. But two studies identified individuals who had levels of HIV in their semen that were equal to or greater than in their blood.

Several factors were identified that could potentially influence the relationship between viral load in blood and semen:

• adherence to antiretroviral therapy;
• penetration of antiretrovirals into the genital tract;
• drug resistance;
• number of sexual partners;
• sexually transmitted infections; and
• stage of HIV infection.

Only one study in the review found an almost perfect concordance between viral load in blood and semen. This was the only study in which all participants were on potent antiretroviral therapy (all had viral load in the blood below 400 copies/ml) and none had sexually transmitted infections. The investigators estimated with 95% certainty, that fewer than 4% of men with a blood plasma viral load below 400 copies/ml would have detectable viral load in semen.²

Studies published since this review continue to suggest that, in most cases, men with an undetectable viral load in the blood also have an undetectable viral load in semen, but that there are always exceptions. Notably, there are conflicting data regarding the influence of sexually transmitted infections on seminal viral load.

A study by Politch and colleagues³ of 101 gay men in Boston found that of the 83 men with undetectable HIV in their blood, 21 (25%) had detectable HIV in their semen. The median seminal viral load in these men was 200 copies/ml and ranged from 80 to 2560 copies/ml. 

The study found a very strong association with detectable HIV in semen and having either an inflamed urethra (urethritis) or a current sexually transmitted infection (STI). After adjusting for other factors the researchers concluded that men who had an STI and/or urethritis were 29 times more likely to have HIV undetectable in blood but detectable in semen (known as ‘virally discordant’).

However, a more recent study by Ghosn and colleagues⁴ of 151 gay men in Paris found no association between STIs and viral discordance, adding to the lack of clarity on the role of STIs in viral discordance. This is the first ‘real world’ study to track seminal viral load over time in gay men and other men who have sex with men on stable therapy with undetectable viral loads in blood.

On average, the men had been on a stable antiretroviral regimen for a median of 2.1 years and had an undetectable viral load for a median of 3.3 years. Almost two thirds were in a steady relationship, though 63% also had sex outside of the relationship. The median number of sexual partners in the past three months was ten (range 1 to 160).

The study found detectable HIV in 23 of 304 (7.6%) semen samples. They found no association with asymptomatic sexually transmitted infections (STIs) nor with the number of sexual partners, specific antiretrovirals, or length of time on treatment. Only HIV levels above 318 copies per million cells in peripheral blood mononuclear cells (PBMCs) predicted HIV detection in semen despite undetectable viral load in blood. 

In another study from Paris, this time in 304 HIV-positive heterosexual men in stable relationships who sought sperm washing (and who were, therefore, considered low risk for STIs), Lambert-Niclot and colleagues⁵ found that 20 men (6.6%) had undetectable HIV in blood but detectable virus in their semen. The seminal viral load ranged from 135 to 2365 copies/ml. They also noted that the proportion of men with viral discordance did not vary over time, despite the development of more sophisticated and potent HIV regimens.

However, a more recent study from California suggests that asymptomatic infection with herpes viruses, notably cytomegalovirus (CMV) and Epstein Barr virus (EBV) does appear to impact viral discordance. Gianella and colleagues⁶ studied the shedding of HIV in semen in 114 gay and other men who have sex with men, 88% of whom had blood plasma viral loads below 50 copies/ml. HIV was detected in the semen of 10% of participants, with a median seminal viral load of 126 copies/ml. Although an asymptomatic bacterial STI was detected in 15% of individuals this was not associated with an increase in viral discordance. CMV was detected in the genital tract of 49% of participants, and EBV in the semen of 31% of individuals and both of these herpes viruses were strongly associated with genital shedding of HIV in semen. CMV increased the risk 4.5-fold and EBV increased the risk 6-fold. The researchers 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.”