The use of highly active antiretroviral therapy (HAART) has largely modified the prognosis of HIV infection. As a consequence of improved life expectancy and quality, many young HIV-infected men and women have a strong desire for a child. However, protected intercourse is strongly recommended for HIV-serodiscordant couples in all circumstances. Thus, when men are infected, in order to avoid the risk of HIV sexual transmission to women, HIV-serodiscordant couples now have access to assisted reproductive technology (ART) program in several countries. These programs vary in the assisted reproductive technology methods chosen (intrauterine insemination, in-vitro fertilization, intracytoplasmic sperm injection) and in the type of sperm preparation used (density gradient migration alone or followed by swim-up). Good rates of pregnancy are reported when the male partner is infected (up to 30.6% per cycle) and no seroconversion has been reported to date .
Recently, the Swiss Commission Fédérale pour les problèmes liés au Sida has reported that a seropositive individual, with no other sexually transmitted disease (STD), under antiretroviral treatment and with an undetectable HIV-1 plasma viral load for at least 6 months, does not sexually transmit HIV . We agree that the risk of HIV transmission in this particular case is very low. However, several factors can interfere and may have the potential to increase this risk, such as fluctuation of adherence, drug characteristics influencing the penetration in compartments, and asymptomatic and undiagnosed STD. Moreover, compartmentalization of HIV replication in semen has been demonstrated for some men and, therefore, HIV blood viral load might not always reflect HIV replication levels in semen [3–6]. Although HAART reduces HIV loads in both blood and seminal compartments [7–11], low levels of HIV RNA can still be detected in seminal plasma and HIV-infected cells can be recovered in nonsperm cells even in those who have undergone prolonged successful treatment [8,11,12].
Since 2002, our center has managed HIV-1-serodiscordant couples with a male infected partner to allow pregnancies with assisted reproduction using sperm washing. Sperm washing consisted of a separation following density gradient centrifugation. The 90% fraction was then centrifuged and washed . HIV-1 genome detection was performed according to published methods  on the final fraction of spermatozoa obtained after sperm washing. If HIV-1 RNA and/or DNA were not detected in the isolated spermatozoa fraction, frozen–thawed spermatozoa fractions were used for ART. In parallel, HIV-1 RNA was quantified in blood and seminal plasma.
We report here, in a large dataset, the prevalence of treated patients with discordant HIV-1 RNA in blood and in seminal plasma.
One hundred and forty-five HIV-1 infected men attending the Pitié-Salpêtrière Hospital in the multidisciplinary ART program provided 264 paired blood and semen samples between January 2002 and January 2008. The number of samples provided by the patients was variable from one to six. The Cobas Taqman HIV-1 assay was used to quantify HIV-1 RNA in blood and in seminal plasma as previously described with a limit of quantification of 40 copies/ml in blood and 200 copies/ml in seminal plasma. Thirty-two blood plasma samples were detectable and the median level of HIV-1 RNA in blood was 6325 copies/ml (range = 222–28 300). Sixteen seminal plasma samples were detectable and the median level of HIV-1 RNA in semen was 1770 copies/ml (range = 255–25 100). Overall, 234 paired samples were concordant, with 225 samples with undetectable HIV-1 RNA both in blood and semen (85.3%) and nine with detectable HIV-1 RNA in blood and semen (3.4%). However, 23 blood samples had detectable HIV-1 RNA although the seminal viral load was undetectable and seven seminal samples had detectable HIV-1 RNA although the blood viral load was undetectable. These seven discordant paired samples corresponded to seven distinct patients whose characteristics are shown in Table 1. All these patients were under stable HAART with an undetectable HIV-1 RNA in blood plasma for at least 6 months and had no other STDs that are systematically screened in the program. Pharmacological measurements were performed in blood and seminal plasma and, as expected, showed that, when antiretroviral drugs such as lamivudine, tenofovir, and indinavir were present in blood, they were also detected in semen, suggesting an accumulation or a deferred filling of this compartment for these drugs.
These results show, in our cohort, that 5% of patients had detectable HIV-1 RNA in semen although they had concomitantly undetectable HIV-1 RNA in blood whereas they were under HAART. This does not seem to be related to a specific treatment, because these patients were treated by various therapies comprising a non-nucleoside reverse transcriptase inhibitor or protease inhibitor-based regimen, with, in some cases, antiretroviral drugs known to have a good diffusion in genital compartments. Moreover, these results confirm previous studies showing that HIV-1 excretion was intermittent [5,14]. Indeed, among the seven patients with discordant HIV-1 RNA, six of them had an undetectable concordant result in blood and semen on at least one occasion during follow-up.
Thus, for serodifferent couples with a desire to have a child, ART remains a preferred method, when accessible, to avoid HIV-1 transmission for several reasons: the detection of HIV-1 in 5% of seminal plasma from patients with prolonged undetectable HIV-1 RNA in blood; the possible existence of quiescent STD that can be a risk factor for HIV-1 transmission that is difficult to control for a long period; the absence of HIV-1 seroconversion to date in ART programs and a certainly low, but not null, risk of transmission in the conditions described by the Swiss study; and finally the good results with ART for couples with good fertility. These results suggest that, in HIV patients even without STD, viruses could be present in 5% of cases, and this fact has to be explained to patients who wish to have unprotected sexual intercourse.
Anne-Geneviève Marcelin, Roland Tubiana, and Catherine Poirot contributed to the writing of the manuscript and coordination of the study; Roland Tubiana, Gilles Lefebvre, Stéphanie Dominguez, Manuela Bonmarchand, Daniele Vauthier-Brouzes, Françoise Marguet, and Nathalie Mousset-Simeon contributed to patient management; Catherine Poirot and Nathalie Mousset-Simeon contributed to the assisted reproductive technology methods, Anne-Geneviève Marcelin and Sidonie Lambert-Niclot contributed to virological analyses; Gilles Peytavin contributed to pharmacological analyses; Sidonie Lambert-Niclot contributed to data monitoring; Roland Tubiana and Catherine Poirot contributed to the coordination of the assisted reproductive technology program.
This study was supported by Agence Nationale de Recherches sur le SIDA et les hépatites virales (ANRS).
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