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  16th CROI
Conference on Retroviruses and Opportunistic Infections Montreal, Canada
February 8-11, 2009
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HIV Sometimes Detectable in Semen When Undetectable in Blood
  16th Conference on Retroviruses and Opportunistic Infections, February 8-11,
2009, Montrea
Mark Mascolini
Separate studies from Canada and France found that HIV may remain detectable in semen after antiretrovirals make viral loads undetectable in blood [1,2]. Seminal detection rates in men with undetectable blood plasma loads varied from 5% to 31% depending on the group studied. Although other research correlates lower blood plasma loads with a lower risk of HIV transmission, the Canadian and French results clearly suggest that men with an undetectable load in blood may infect their sex partners.
The first part of the Canadian study involved 25 men beginning their first antiretroviral regimen with a median plasma HIV RNA of 50,000 copies (range 120 to more than 500,000) and a median seminal load of 5136 copies (range fewer than 300 to 86,856 copies) [1]. Everyone had an undetectable plasma load after 16 weeks of therapy, but HIV RNA remained detectable in some men's semen: During at least one study visit, 12 of 25 men (48%) had detectable seminal HIV RNA. Nine of these 12 (36% of 25) had detectable seminal HIV RNA after virus could no longer be spotted in blood. Three of these 12 (12% of 25) had seminal loads above 5000 copies (range 6672 to 16,026 copies).
Type of antiretroviral regimen did not appear to influence seminal HIV shedding. Prameet Sheth and coworkers saw HIV RNA in 5 of 13 people taking a protease inhibitor (PI) regimen and in 7 of 12 taking a nonnucleoside regimen (P = 0.4). Although antiretroviral concentrations in semen differed widely (with lamivudine levels highest, followed by abacavir and efavirenz, followed by boosted PIs), drug concentrations did not correlate with viral shedding in semen. No seminal viral specimens had evidence of resistance to antiretrovirals. Seminal shedding did not correlate with pretreatment CD4 count, pretreatment blood viral load, or herpesvirus serostatus. But higher pretreatment seminal load predicted a detectable seminal load during treatment.
In the second part of their study, Sheth and colleagues analyzed blood plasma and seminal loads in 13 men with an undetectable blood plasma load for more than 4 years (median 82 months). The investigators could detect no high-level seminal shedding in these men. But 8 of 13 (31%) had seminal loads ranging from 378 to 828 copies.
Anne-Genevieve Marcelin and colleagues in Paris studied 145 HIV-infected men who provided 264 paired blood and semen samples from January 2002 to January 2008 [2]. Of the 264 samples, 32 blood samples had a load above 40 copies (median 6325, range 222 to 28,300), and 16 seminal samples had a load above 200 copies (median 1770, range 255 to 25,100). All told, 234 of 264 samples (89%) were concordant, including 225 with undetectable loads in blood and semen and 9 with detectable loads in blood and semen.
Thirty samples were discordant, including 23 with detectable HIV RNA in blood but an undetectable seminal load (median 2580, range 222 to 14,200) and 7 with detectable HIV RNA in semen but an undetectable plasma load. These 7 samples came from 7 individual men (5% of 145), all of whom had an undetectable plasma load for at least 6 months and no sexually transmitted diseases. Six of these 7 men had an undetectable load in both blood and semen at one or more points during follow-up. As in the Canadian study, type of antiretroviral regimen did not correlate with a detectable seminal load despite an undetectable blood load. Both researchers noted that detectable virus in semen may not be infectious virus. But in the Canadian study, cell-free virus in the man with the highest seminal load was infectious. Another conference study yielded strong evidence that cell-free virus accounts for sexual transmission between gay men [3]. Marcelin concluded that RNA shedding in semen with an undetectable load in blood suggests that "a residual risk of transmission is still possible during unprotected sexual intercourse" involving such men.
1. Sheth P, Kovacs C, Kemal K, et al. Persistent HIV RNA shedding in semen despite effective ART. 16th Conference on Retroviruses and Opportunistic Infections. February 8-11, 2009. Montreal. Abstract 50.
2. Marcelin AG, Tubiana R, Lambert-Niclot S, et al. Detection of HIV-1 RNA in seminal plasma samples from treated patients with undetectable HIV-1 RNA in blood plasma. 16th Conference on Retroviruses and Opportunistic Infections. February 8-11, 2009. Montreal. Abstract 51.
3. Butler D, Lakdawala M, Richman D, Little S, Smith D. Cell-free virus in seminal plasma is the origin of sexually transmitted HIV among men who have sex with men. 16th Conference on Retroviruses and Opportunistic Infections. February 8-11, 2009. Montreal. Abstract 49LB.
(Slide presentations available online at http://www.retroconference.org/2009/data/files/webcast.htm. Click on Monday, then on Play Audio and Slides at HIV Transmission: Characteristics and Prevention, then on Index, then on Sheth or Marcelin or Butler.)