For people living with HIV, effective antiretroviral therapy (ART) not only suppresses the virus and protects immune system health but has the added benefit of reducing the risk of transmitting HIV to sex partners. This side benefit, known as “treatment as prevention,” has been established by recent studies with mixed-HIV-status couples.
For example, in the PARTNER study, zero new HIV transmissions occurred through more than 44,000 condomless sex acts within 767 mixed-HIV-status couples in which the HIV-positive partner’s viral load was suppressed below 200 copies/mL, and where the HIV-negative partner did not use PrEP or PEP to prevent infection.
Standard viral load tests look for HIV RNA (genetic material from the virus) in blood, not semen—and the amount of RNA in these two fluids doesn’t always match. And as researchers report in the March 3 online edition of PLoS ONE, not only can individuals with undetectable blood viral load have detectable levels in semen, those levels can change from hour to hour.
Xavier Ferraretto and colleagues from the Bichat-Claude Bernard Hospital in Paris looked for HIV RNA in 306 seminal plasma samples (SPSs) from 88 men enrolled in the hospital’s assisted reproduction program. All participants were on ART and had undetectable blood viral load (defined here as below 50 copies/mL) for more than six months. Semen samples were obtained by masturbation after two to seven days of sexual abstinence, and each man provided, if possible, two samples within a one-hour interval.
The results? “HIV RNA was detected in at least one SPS for 17 patients (19.3%) during the study period, corresponding to 23 SPSs (7.5%).” HIV RNA levels ranged from 200 to 3,000 copies/mL, with a median (middle of the range) of 705 copies/mL.
In addition, researchers analyzed viral load in 129 samples given by the same individuals one hour after their original sample. Of these, 12 (9.3%) showed a different seminal plasma viral load, or spVL: “In 8 cases, a spVL was undetectable in the first [sample] and detectable in the second. In 4 cases, a spVL was first detectable and later undetectable.” In these 12 cases, spVL ranged from 200 to more than 1,000 copies/mL, with a median of 918 copies/mL.
The researchers found no association between detectable spVL and participants’ age, geographic origin, sperm characteristics, CD4 cell count nadir, route of HIV transmission, or co-infection with hepatitis B or C.
Interestingly, more men on protease inhibitor (PI)–based ART had at least one sample with detectable HIV RNA, compared with men taking non-nucleoside reverse transcriptase inhibitors (NNRTIs) and other antiretroviral drugs; however, the association did not reach statistical significance. “The tendency towards a higher risk of a detectable spVL in patients given the PI-containing [ART] regimen compared to a regimen containing an NNRTI might be explained by the poor diffusion of most PIs in the male genital tract,” the researcher team writes.
What do these findings mean for HIV transmission risk? While the results show that viral “shedding” can occur within a one-hour interval among men with undetectable blood viral load, “this timing should not be considered to place individuals at greater risk for HIV transmission than previously reported,” the authors state. They do conclude, however, that the nearly 20% proportion of men with detectable HIV RNA in semen despite stable undetectable blood viral load “should balance messages on the individual risk of HIV transmission through unprotected sex as an exclusive preventive strategy in serodifferent couples with procreation desires.”
That said, no study to date has identified a seminal viral load “threshold” at which HIV transmission becomes likely. Questions clearly remain about the links between HIV viral load, viral load in semen, and risk for HIV transmission in the setting of antiretroviral treatment.