HIV can be intermittently detectable in the semen of men taking long-term antiretroviral therapy that is achieving full suppression of viral load in the blood, French investigators report in PLOS ONE. They also found evidence that viral load in semen can fluctuate over a very short period. However, it is unclear whether the levels of viral load detected in this study pose a substantial risk for the transmission of HIV.
Antiretroviral therapy can suppress viral load in both the blood and semen. This is of real significance to HIV prevention initiatives. It has been demonstrated that starting antiretroviral therapy and the achievement of an undetectable viral load in blood reduces the risk of sexual transmission of HIV in heterosexual couples by 96%. Interim results from the ongoing PARTNER study showed that there were no HIV transmissions in serodiscordant heterosexual and gay couples when the HIV-positive partner was taking antiretroviral therapy and had an undetectable viral load in blood.
Despite this, several studies have shown that viral load can be intermittently detected in the semen of men who are taking treatment and who have an undetectable blood viral load.
Investigators from a unit in Paris offering assisted conception to HIV serodiscordant couples designed a study involving 88 men living with HIV who received care at the clinic between 2006 and 2011. All were taking HIV therapy and had an undetectable viral load in blood for at least six months. Using frozen sperm samples obtained from these men, the investigators calculated the detection rate of viral load in semen and also evaluated if the shedding of HIV in semen could change over a very short period of time.
A total of 306 frozen semen samples were available for evaluation. The samples were obtained by masturbation after two to seven days of sexual abstinence. If possible, each man provided two samples within a one-hour interval.
HIV was detected in at least one semen sample for 17 men (19%) and in 23 samples in total (7.5%).
Median viral load in these samples was 705 copies/ml, but in eleven samples it was above 1000 copies/ml.
Of the 129 samples in which two semen specimens were provided within one hour, twelve (9%) had discordant results – viral load undetectable in one specimen but detectable in the other. Median viral load in the detectable samples was 918 copies/ml, and in six cases was above 1000 copies/ml.
“We show that intermittent shedding of HIV-1 RNA [viral load] in the semen of patients given efficient cART [combination antiretroviral therapy] could occur within a one-hour interval,” write the authors.
It is unclear whether these levels of viral load in semen are sufficiently high to pose a significant risk of HIV transmission. A study conducted in Rakai, Uganda, in serodiscordant couples prior to the introduction of antiretroviral therapy found no cases of HIV transmission where the HIV-positive partner had a blood viral load below 1500 copies/ml during a two-year follow-up period. A similar threshold has not been defined for viral load in semen.
The study found a trend towards a higher frequency of detectable HIV in the semen of men taking protease inhibitor-based treatment.
Over a quarter (28.6%) of men taking HIV treatment based on a protease inhibitor (PI) had at least one episode of detectable virus in their semen compared to 7.7% of men taking HIV treatment based on a non-nucleoside reverse transcriptase inhibitor (NNRTI) and 7.7% of men taking a combination based on another type of anti-HIV drug. These differences were marginally short of significance (p = 0.054).
"The tendency towards a higher risk of a detectable sp VL [seminal plasma viral load] in patients given PI-containing cART compared to a regimen containing an NNRTI might be explained by the poor diffusion of most PIs in the male genital tract,” suggest the authors.
The authors believe their findings that approximately a fifth of men had HIV detected in their semen and that virus was detected in 7.5% of all samples “should balance messages on the individual risk of HIV transmission through unprotected sex as an exclusive preventive strategy in serodifferent couples with procreation desires.”
The authors cite previous calculations suggesting that the risk of HIV transmission is in the order of three cases per 10,000 episodes of vaginal intercourse when seminal viral load is 1,000 copies/ml.
However, the accumulating evidence of the extremely low risk of sexual transmission of HIV in the context of virologically effective HIV treatment suggests that the possibility of small fluctuations in viral load in semen has not translated into cases of HIV infection in either a large clinical trial (HPTN 052) or a closely-monitored large cohort (the Partner study).
Ferraretto X et al. Timing of intermittent seminal HIV-1 RNA shedding in patients with undetectable plasma viral load under combination antiretroviral therapy. PLOS ONE 9(3): e88922, doi: 10.1037/journalpone.00889922, 2014.