If suppressed for 12 months, low risk of viral load rebound above 1000 copies

Michael Carter
Published: 31 March 2010

Once suppressed, the risk of viral load rising to levels associated with onward transmission is extremely low in patients taking antiretroviral therapy who have maintained a long-term undetectable viral load, Danish investigators report in the online edition of HIV Medicine.

However, they found that during the first year of HIV treatment, viral load was above the threshold of 1000 copies/ml associated with onward transmission for approximately 5% of the time.

“In this nationwide population-based cohort study of Danish HIV-infected patients on HAART [highly active antiretroviral therapy] with more than six months of suppressed viral load, we found that the risk of experiencing a viral load above 1000 copies/ml and thereby transmitting HIV sexually was very low”, comment the investigators.

There is intense debate about the risk of people with HIV taking antiretroviral therapy and who have an undetectable viral load transmitting HIV to their sex partners if they do not use condoms.

This debate was kick-started by a statement from the Swiss Federal Commission for HIV/AIDS that said “a seropositive person without additional sexually transmitted disease on antiretroviral treatment with suppressed viral load cannot transmit HIV sexually.”

In order to be considered uninfectious, the Swiss said that an individual must fulfil three conditions:

  • Be taking a stable antiretroviral regimen with a viral load below 50 copies/ml for at least six months.
  • Have good adherence to treatment.
  • Be free of any untreated sexually transmitted infections.

The Swiss also noted that their recommendations were based on data obtained from heterosexual couples in reportedly monogamous relationships.

Although no country has changed its official guidance advising condom use to prevent HIV transmission, there is some evidence that HIV-positive individuals and their partners have accepted the Swiss recommendations.

Danish HIV physicians wished to assess the likelihood of viral load increasing to levels associated with onward transmission in patients taking suppressive HIV treatment.

They therefore analysed the viral load results of 2680 patients obtained between 2000 and 2007.

The investigators defined a plasma viral load above 1000 copies/ml as being potentially infectious, and a viral load below this level as being uninfectious. This threshold was based in part on research in heterosexual couples not receiving treatment in the Rakai district of Uganda. That study showed that no infections occurred when the HIV-positive partner had a viral load below 1500 copies/ml.

Just over a third (38%) of patients reported being in a relationship, and 78% said that they always had safer sex.

Viral load tests were performed on average every three months. The patients contributed 9348 person-years of follow-up, and the investigators calculated that for 0.6% of this time, patients had a potentially infectious viral load.

The risk of transmission was especially high during the first six months of HIV therapy, when 8% of the time was spent with a viral load above 1000 copies/ml. During the next six months, viral load was at potentially infectious levels for a little over 1% of the time.

Thereafter, viral load was above the potentially infectious threshold for an average of 0.6% of the follow-up period.

However, amongst patients who had been taking suppressive HIV treatment for over five years, only 0.03% of the follow-up period was spent with a viral load above 1000 copies.

Analysis by subgroup did not greatly affect these results. But the researchers did notice that injecting drug users taking suppressive HIV treatment had a potentially infectious level of viral load 1.5% of the time. This was attributed to poorer treatment adherence in this population.

“Assuming that there is a viral threshold of infectiousness, our results indicate that the risk of viraemia is very low in patients on successful antiretroviral treatment”, write the investigators.

Noting that “HIV-infected patients have, however, an increased risk of abrupt viraemia in not just the first six months but the first twelve months of episodes with undetectable viral load”, the investigators recommend “there would be a substantial gain in reducing the risk of infecting the sexual partner, if the time limit recommended by the Swiss…was extended from six months to at least twelve months.”

An important limitation of this study is the inability of the investigators to assess the extent to which plasma viral load differed from viral load in genital fluids, and the extent to which any divergence might be influenced either by time on therapy, drug regimen or sexually transmitted infections.

Some sexually transmitted infections have been associated with an increased likelihood of detectable virus in genital fluids even when plasma viral load is undetectable, leading some experts to argue that in populations with high rates of sexually transmitted infections, undetectable viral load may be an unreliable markers for assessing an individual's risk of transmitting HIV.

Reference

Engsig FN et al. Risk of high-level viraemia in HIV-infected patients on successful antiretroviral treatment for more than 6 months. HIV Med, online edition, DOI: 10. 1111/j.1468-1293.2009.00813.x, 2010.

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