Infectiousness and antiretroviral therapy: reports look set to further fuel the debate

A man transmitted HIV to his regular male partner despite taking antiretroviral treatment and having an undetectable viral load in his blood, German doctors report in the journal Antiviral Therapy. The authors believe that this is the first recorded instance of an individual with an undetectable viral load infecting a sexual partner with HIV.

In an editorial accompanying the case report, two of the authors of what has come to be known as the “Swiss Statement”, whilst acknowledging a “very low” risk of transmission from individuals taking antiretroviral therapy with an undetectable viral load, highlight what they believe to be some weaknesses in the documentation of this case. Furthermore, they point out that in their own experience “all suspected cases of transmission during antiretroviral therapy turned out to have another source.”

And a separately published study looks likely to further fuel the already fierce debate about the infectiousness (or otherwise) of patients being treated with antiretroviral drugs. French investigators report in the August 20^th edition of AIDS that 5% of antiretroviral-treated men with an undetectable viral load in their blood had detectable HIV in their semen. None of these men had a sexually transmitted infection.

In January this year, senior HIV doctors in Switzerland issued a statement saying that HIV-positive patients treated with antiretroviral drugs with good adherence to their treatment, a viral load below 40 copies/ml for at least six months, and no sexually transmitted infections should not be considered capable of transmitting HIV sexually. The statement has proved controversial and there was a lively debate about the infectiousness of patients taking successful antiretroviral therapy at the recent International AIDS Conference in Mexico City.

The conference was also told that the lowest blood viral load in a documented case of HIV transmission was approximately 300 copies/ml. But now doctors in Germany have reported a case of transmission when a patient taking antiretroviral therapy had a sustained undetectable viral load in his blood.

The case involved a 39 year-old gay man who first started HIV treatment in 1999. Since 2000 he had been taking a combination of anti-HIV drugs including AZT, 3TC and nevirapine and had maintained an undetectable viral load. Since 2000 this patient had been in a reportedly monogamous relationship with a man of the same age.

The patient’s partner reported having had had an anonymous HIV test in 2002, and a search of the records of anonymous tests conducted at the facility the patient attended showed that only one anonymous test was performed on a man at this time, the result being negative . The couple reported unprotected anal intercourse on a number of occasions since May 2003. There is no information in the case report about whether the patient and his partner were insertive, receptive, or both, and the authors failed to clarify this issue when contacted by aidsmap.com e-mail.

In July 2004, the patient’s partner was diagnosed with HIV, and tests conducted shortly after showed that his CD4 cell count was 338 cells/mm³ and his viral load 21,800 copies/ml. Such a viral load would have been modest for an individual experiencing HIV seroconversion.

The investigators performed phylogenetic analysis which suggested a close relationship between the virus in the patient and his partner. Neither partner reported a sexually transmitted infection.

“We feel confident”, write the report’s authors, “that the present case report suggests that transmission can occur despite undetectable plasma viral load. Therefore, we cannot support any recommendations that abandon the use of safer-sex practices in this context without mentioning the possibility of HIV transmission.”

But the authors of the editorial accompanying the case report highlight what they believe are some weaknesses with the reporting of the case. Although they acknowledge that the phylogenetic analysis indicated a linkage between the virus in the two individuals, they write “an infection by an epidemiologically linked third individual is only ruled out by sexual history, which is notoriously unreliable”. They also suggest that “the recollection of a non-documented HIV antibody test more than 5 years earlier is a considerable weakness of this report.”

However, the editorial’s authors also believe that even a well-documented case report of sexual transmission of HIV involving a patient taking anti-HIV drugs with an undetectable viral load would “not indicate that this practice is associated with a risk of sufficient magnitude to have public health implications.” They draw an analogy with oral sex, where individual cases of HIV transmission have been reported.

Detectable viral load in semen when viral load is undetectable in blood

A separate French study has found that 5% of 145 HIV-positive men enrolled in an assisted conception study had detectable viral load in their semen, despite having an undetectable viral load in their blood.

The men provided paired blood and semen samples between 2002 and January 2008. The lower limit of detection for HIV in blood was 40 copies/ml and 200 copies/ml for semen. In the vast majority of samples (85%), HIV was undetectable in both blood and semen.

But in 3% of samples HIV was detectable in both body fluids, and in 6% viral load was undetectable in semen, but detectable in blood. The remaining 5% of paired samples showed that HIV was undetectable in blood, but detectable in semen.

The investigators note that the patients in this 5% had all been taking antiretroviral therapy for at least six months and had maintained a blood viral load below 40 copies/ml. Furthermore none of these patients had a documented sexually transmitted infection.

On the basis of these findings the investigators conclude, “for serodiscordant couples with a desire to have a child, assisted reproduction technology remains a preferred method, when accessible to avoid HIV transmission”.