Viral load in semen

A review article¹ analysing the results of 19 studies examining the correlation between HIV in blood and semen published or presented between 1996 and 2006 concluded that the level of HIV in blood and semen is usually related, but not always.

A consistent finding of the review was that viral load tended to be lower in semen than 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.

Four factors were identified that could potentially influence the relationship between viral load in blood and semen: sexually transmitted infections; antiretroviral therapy and adherence; drug resistance; and the stage of HIV infection. Some studies also suggested that a greater numbers of sexual partners and higher rates of sexual intercourse also increased genital shedding of HIV.

Most of the studies showed that potent antiretroviral treatment suppressed viral load in semen. But there was also evidence that certain drugs did not penetrate the blood and semen with equal efficiency. Poor adherence to treatment was associated with detectable HIV in semen in some studies; another study found that the men who missed the fewest treatment doses had the greatest degree of HIV suppression in semen over time.

The one study² that found an almost perfect concordance between viral load in blood and semen was the most rigorously designed study, with all the men taking effective antiretroviral therapy (all had viral load in the blood below 400 copies/ml) and none having a sexually transmitted infection. It estimated, with 95% certainty, that fewer than 4% of men with a blood plasma viral load below 400 copies/ml will have detectable viral load in semen.

Studies published since this review confirm 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. However, the threshold level of seminal viral load that corresponds to a significant transmission risk remains unknown.

Of 145 HIV-positive men enrolled in an assisted conception study in France,^{3 4} 85% had an undetectable viral load in their semen (defined here as below 200 copies/ml) and an undetectable viral load in their blood (defined here as below 40 copies/ml).

However, seven men (5%) were found to have detectable virus in their semen despite having an undetectable viral load in their blood, with seminal HIV RNA levels ranging from 255 to 1230 copies/ml. A further 6% had an undetectable viral load in semen, but detectable virus in blood. The remaining men had a detectable viral load in both blood and semen.

Most of the detectable seminal viral load occurred as 'blips' – six of the seven men had previously had undetectable viral loads in both blood and semen on at least one other occasion. The men were on a variety of antiretroviral regimens, and the antiretroviral drugs present in the blood were consistently detectable in semen as well. The investigators note that all of these men had been taking antiretroviral therapy for at least six months and none had a documented sexually transmitted infection. However, there were no cases of transmission from any of the men with a blood plasma undetectable viral load – even in those with detectable seminal viral loads.

A 2009 Canadian study⁵ which included a prospective cohort of 25 men initiating antiretroviral treatment, found that seminal viral load became undetectable (<300 copies/ml) in nearly 70% by week 4, but was still detectable in a minority of participants by week 24; in contrast all achieved an undetectable (<50 copies/ml) blood plasma viral load after 16 weeks.

A second part of the study examined single samples from 13 men in whom HIV had been suppressed on treatment for a median of 82 months and found detectable virus in the seminal fluid of four (31%). Although this was a small study, which may limit the significance of their findings, the investigators found no difference between men on PI-based versus NNRTI-based regimens, nor due to varying drug concentrations in seminal fluid.

HIV is present in semen both as cell-free virus, measurable as RNA in the seminal fluid itself, and as proviral DNA contained within lymphocytes (white blood cells) in the semen. Until recently, it was not known which of these was responsible for sexual transmission.  

A recent study⁶ from the University of California, San Diego which presented data on four cases of male-to-male sexual transmission, concluded that cell-free virus in semen – not proviral DNA in infected cells – was the means of transmission in all four cases. The source of the cell-free virus itself – seminal lymphocytes or the blood – is still unclear, however. A third source may be the prostate. Three of nine men with an undetectable HIV viral load in both their blood and semen, had at least one semen sample each with detectable HIV after prostate massage.⁷

The role of drug penetration into the male genital tract is still not completely understood, either. Although studies have shown that men on PI- or NNRTI-regimens have suppressed semen viral loads despite poor penetration of these drugs into semen,⁸ penetration of these drugs into the tissues that make up the male genital tract, where it is likely to matter most, is not poor. It is also possible that the N(t)RTI component, which can reach high levels in the semen,^{9 10} may be enough to suppress HIV in seminal fluid.