More Evidence that HIV Persists in Semen despite Undetectable Blood Viral Load

By Liz Highleyman

The issue of HIV transmission from individuals on HAART has recently been a topic of considerable debate, following a statement by the Swiss Federal Commission for HIV/AIDS earlier this year suggesting that HIV positive individuals on antiretroviral therapy who are fully adherent, maintain an undetectable viral load for at least 6 months, and have no concurrent sexually transmitted infections essentially cannot transmit HIV through heterosexual vaginal intercourse.

In the August 20 issue of AIDS, French researchers reported that 5% of men from serodiscordant heterosexual couples enrolled in an assisted reproduction program had detectable HIV in their semen despite a blood plasma viral load of less than 40 copies/mL.

Research suggests that HIV virus replication is compartmentalized between blood and semen. Thus an undetectable viral load in blood may not indicate an undetectable viral load in semen. Similarly, treating HIV in blood may not treat HIV in semen.

In the correspondence section of the September 12 issue of the same journal, another French team described the case of a man with persistent HIV RNA shedding into his semen despite HAART-controlled blood viral load.

As background, the authors noted that HAART usually reduces HIV blood plasma viral load (BPVL) to undetectable levels in most treatment-naive patients within 3 months, and that semen viral load (SVL) is typically correlated with blood levels if HAART is effective. But some cross-sectional studies have found differences between blood and semen viral loads, as well as differences in the rates at which virus levels in the blood and semen decrease.

Thus, they wrote, "patients on effective HAART with an undetectable BPVL may have unsuspected HIV-1 genital tract replication that could influence the long-term efficiency of HAART or result in the sexual transmission of HIV during unprotected intercourse."

The researchers described a 34-year-old initially untreated man with HIV-1 who presented for medically assisted procreation in February 2006. He had no serological evidence of infection with hepatitis B or C, syphilis, or chlamydia, and no reported history of other sexually transmitted infections.

The man started HAART in June 2006 because his SVL was greater than 4 log copies/mL in 2 successive samples. His BPVL was undetectable 4 months later, but his SVL remained unchanged after 6 months.

The man's treatment regimen was modified in May 2007. After 1 month, his BPVL was still undetectable, but his SVL remained unchanged after 6 months on the new combination. Subsequently, however, his SVL decreased slowly to < 400 copies/mL after 11 months on the new regimen -- or 22 months after first starting HAART.

The authors performed genotypic testing of HIV in the man's blood and semen in an attempt to understand why shedding into the semen persisted. They found that HIV in both the blood and semen was wild-type -- that is, without resistance mutations -- before treatment initiation and again in November 2007.

They also reported that the man's adherence to treatment seemed good, since he had 10 undetectable BPVL tests during the 2-year course of follow-up.

This case report, the researchers wrote, "confirms that HAART may act at different rates in the blood and semen and that HIV-1 may continue to be shed into the semen despite effective control of HIV-1 in the blood."

"No biological factors known to be associated with HIV-1 shedding were present, and the patient was asymptomatic, although his SVL was higher than his BPVL before treatment," they added. "The absence of any response to HAART during the first regimen and the retarded response to the second were probably linked to the poor penetration of the antiretroviral drugs, particularly protease inhibitors, into the male genital tract."

"This rate of SVL reduction does not indicate that HAART has a direct effect on virus replication in the genital tract but that HIV-1 replication may be slowly stopped by interrupting the supply of HIV-1-infected cells from the blood," they suggested. "This absence of virus selection in the genital tract, despite high virus replication, indicates that the intracellular drug concentrations are too low to inhibit virus replication and to induce virus selection."

In conclusion, the authors wrote, "Counseling on the prevention of sexual transmission should include the possibility of occult persistent HIV-1 replication within the genital tract, particularly in the context of giving a 'license to love' to patients with undetectable BPVL."

Service de Virologie, CHU de Toulouse, Institut Fédératif de Biologie, France; INSERM, U563, Centre de Physiopathologie de Toulouse Purpan, France; Facultés de Médecine et de Pharmacie, Université Toulouse III Paul Sabatier, France; Human Fertility Research Group, Université Toulouse III Paul Sabatier (EA 3694) and CECOS Midi-Pyrénées, CHU de Toulouse, Hôpital Paule de Viguier, France; Laboratoire de Toxicologie, CHU de Toulouse, Institut Fédératif de Biologie, Toulouse, France.

9/05/08

Reference
C Pasquier, N Moinard, K Sauné, and others. Persistent differences in the antiviral effects of highly active antiretroviral therapy in the blood and male genital tract [Correspondence]. AIDS 22(14): 1894-1896. September 12, 2008.