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HIV Viral Load in Semen Can Vary Over a Short Time in Men on Antiretroviral Therapy

Some men on antiretroviral therapy (ART) who have undetectable blood viral load can still sometimes have detectable HIV in their semen, and levels can fluctuate even within a very short time period, according to a study published in the March 3 edition of PLoS ONE. The study also showed that detectable HIV in semen appears more likely among men taking protease inhibitors.

Effective combination ART typically lowers HCV RNA in blood plasma to an undetectable level, and research has shown that HIV treatment that fully suppresses blood viral load reduces the risk of sexual transmission to near zero. But men may shed HIV in their semen, and women in their vaginal fluid, despite undetectable blood viral load, which raises the risk of transmission.

Xavier Ferraretto from Groupe Hospitalier Bichat-Claude Bernard in Paris and colleagues conducted a retrospective study to evaluate the likelihood of detectable HIV in semen, and whether seminal shedding can be intermittent over a very short period of time.

The researchers analyzed 177 frozen sperm samples, a subset of 306 semen samples provided by 88 men enrolled in an assisted reproduction program between January 2006 and December 2011. All the men were on combination ART with undetectable blood plasma viral load for more than 6 months. 129 samples were part of a pair of samples produced within a 1-hour interval, while 48 were single samples.

Results

• HIV RNA was detected in 23 semen samples (7.5%) from 17 of the men (19.3%).
• This detection rate was stable over the 5-year study period.
• The overall median HIV RNA level in semen samples was 705 copies/mL (range 200-3000 copies/mL), with 11 samples being >1000 copies/mL.
• Among the frozen samples produced within a 1-hour interval, 12 (9.3%) showed discordance, or a mismatch of detectability, between the first and second samples.
• In 8 cases semen viral load was undetectable in the first sample and detectable in the second, while in 4 cases the reverse was observed.
• The median HIV RNA level in discordant samples was 918 copies/mL, with 6 being >1000 copies/mL
• 28.6% of men taking protease inhibitors had at detectable HIV in their semen at least once, compared with 7.7% of men taking NNRTIs and 7.7% taking other antiretroviral classes, but the differences did not quite reach statistically significance (p=0.054).

"Our results confirm the intermittent shedding of HIV-1 in semen," the study authors concluded. "While this finding has been shown by studies examining longer time intervals, to our knowledge, this has never been demonstrated over such a short time interval." They suggested that the presence of detectable semen HIV in nearly 20% of men in this study "should balance messages on the individual risk of HIV transmission through unprotected sex" as an exclusive prevention strategy.

It is not known whether there is a semen viral load threshold for HIV sexual transmission, though intermittent low-level detectable semen viral load in a minority of men does not appear to have led to increased transmission risk among discordant heterosexual couples in the large PARTNERS and HPTN 052 studies. PARTNERS also included gay male couples, but transmission risk in this population -- and for anal sex among heterosexuals -- requires further study.

4/29/14

Reference

X Ferraretto,C Estellat, F Damond, 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. March 3, 2014.