Many men with undetectable HIV in blood still have low levels in their semen, studies find

A study of 101 gay men at the Fenway Health HIV clinic in Boston, USA (Politch) has found that a quarter of men with undetectable viral loads in their blood nonetheless had detectable HIV in their semen. 

Although seminal viral load in these men was low (median 200 copies/ml), the researchers suggest that this is still enough to be one of the explanations for ongoing transmission in gay men despite a high proportion being on antiretroviral therapy.

There was a very strong association with detectable HIV in semen and having a current sexually transmitted infection (STI). Six of the eight men whose HIV was undetectable in blood but detectable in semen (so-called virally discordant) had a urethral 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 viral discordancy.

A quarter of ‘undetectable’ gay men have HIV in semen...

In the Boston study, participants were on average 43 years old and three-quarters were white. They had all been on antiretroviral therapy (ART) for more than three months and 80% for over a year.

Nearly three-quarters were judged as being at high risk of acquiring an STI because they had had unprotected sex in the last three months. Nine of the men were diagnosed with an STI (gonorrhoea, syphilis, chlamydia or non-gonococcal urethritis) and 24 had leukocytospermia or white cells from the immune system in the sperm, indicative of urethral inflammation.

Eighteen of the 101 men had a detectable viral load in their blood; their median blood plasma viral load was 560 copies/ml and ranged from 80 to 640,000 copies/ml. Nine of these 18 men also had detectable HIV in their semen (50%).

Of the 83 men without detectable 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 ranges from 80 to 2560 copies/ml.    

As well as having an STI, in multivariate analysis, two other factors remained strongly associated with having detectable HIV in semen in men without it in blood. High levels of the inflammatory cytokine TNF-α were associated with a 14-fold greater risk of a discordant seminal viral load, and having had unprotected insertive anal sex (being ‘top’), which was associated with a more than sevenfold greater risk.

There were therefore in this study low but detectable levels of HIV in the semen of a quarter of men who would register as being virologically suppressed on a viral load blood test. To what extent might this be contributing to ongoing HIV transmission in gay men? This is unknown, but the researchers point out that although a viral load below 1000 had rarely been associated with transmission in heterosexual studies, some infections have occurred and animal models suggest that HIV is five times more transmissible via anal than vaginal sex – so a median viral load of 200 would imply a low but definite risk of transmission.

A 2008 study from San Francisco (Butler) found that the median seminal viral load in men transmitting HIV to partners was just 4300 copies/ml and the lowest was 110 copies/ml, while a 2009 study from Brighton in the UK (Fisher) that linked HIV infections in gay men genetically found that two out of 41 transmissions of HIV (5%) were from men with an apparently undetectable viral load.

However, studies of the link between viral load and transmission suffer from it being difficult to pin down transmitters in a cohort of gay men with multiple partners and where viral load may be measured months after the transmission (in the Butler study, the average gap between transmission and viral load test was 103 days).

One interesting aspect of this study was the higher risk of seminal viral load associated with unprotective insertive sex. The researchers suggest that urethritis in these HIV-positive gay men could be caused by infections with fecal bacteria acquired during sex or even that the virus detected could be passively carried virus from other HIV-positive gay men. Either way, this would tend to increase the infectiousness of HIV-positive men if they have insertive sex with negative men.

...as do one-in-16 ‘low-risk’ heterosexual men

If STIs are implicated in seminal HIV, it might be assumed that low-risk men with undetectable blood level of HIV would not have it in their semen. However, another study from France (Lambert-Niclot), of HIV-positive heterosexual men in stable relationships who sought sperm-washing, found that 20 out of 304 men (6.6%) had HIV in their semen.

The study was a longitudinal one of 304 heterosexual men who attended a clinic in France seeking sperm-washing for conception between 2001 and 2011. These men between them provided 628 paired blood and semen samples. HIV was detectable in 107 blood samples (17%) and 49 seminal samples (8%). During this time 20 participants (6.6%) provided at least one paired sample where HIV was undetectable in blood (below 40 copies/ml) but detectable in semen. The seminal viral load ranged from 135 to 2365 copies/ml in these samples.

The proportion of men with a discordant seminal viral load did not vary over time, despite the development of more sophisticated and potent HIV regimens.

Both studies warn that men with undetectable viral load results should not assume they are non-infectious and should be warned that HIV treatment does not appear to reduce the risk of transmitting HIV to zero.