High probability that HIV viral load remains suppressed between tests: implications for infectiousness debate

Individuals who are taking antiretroviral therapy and have had their viral load suppressed to undetectable levels can be confident that it will remain undetectable between tests, the results of a Swiss study published in the September edition of HIV Medicine suggests. Most increases in viral load were low-level and transient, but a small number of patients experienced a rebound in their viral load to the potentially infectious level of 1000 copies/ml or above without there being any ready explanation. The findings of this research will inform debates about the potential infectiousness (or otherwise) of individuals taking suppressive HIV therapy.

In January 2008, senior HIV doctors in Switzerland issued a statement that concluded that patients taking antiretroviral therapy who had had their viral load suppressed to undetectable levels of at least six months were extremely unlikely to be infectious for their heterosexual partners.

Considerable controversy surrounded the statement, and one of the objections raised against it was the reliability of an undetectable viral load: could an HIV-positive individual who had an undetectable viral load the last time it was measured be confident that it was still undetectable when they had sexual intercourse?

To test this, investigators from the Swiss HIV Cohort looked at the likelihood of successive viral load tests being undetectable. “By analogy”, they write, “this likelihood also applies to sexual contact some time after a measured undetectable viral load, a situation where real-time measurements are not practicable.”

The study population involved 6168 patients taking antiretroviral therapy who had at least two successive viral load measurements below 50 copies/ml between May 2003 and the end of 2007.

Just under two-thirds of these patients started antiretroviral therapy with a potent triple-drug combination.

At the time viral load was measured, 80% of patients stated that they had been 100% adherent to their antiretroviral therapy in the previous four weeks. However, the investigators think this is likely to be an over-estimate given the social-desirability of reporting good adherence to the study interviewers.

Viral load rebounded to above 50 copies/ml on at least one occasion in 43% of patients, and above 1000 copies/ml – the level at which transmissions have been recorded – in 7% of patients. The median interval between viral load measurements was 93 days.

If more than one dose of HIV treatment was missed between viral load measurements, the probability of it remaining undetectable between tests was 70%. If one dose was missed the probability increased to 85% and if no doses were missed to 86%.

Viral load was more likely to remain suppressed in successive tests in individuals who started HIV therapy with a triple-drug combination, with the probability of sequential undetectable viral load measurements being 95%.

Factors significantly associated with successive undetectable viral loads included a higher number of previous visits with suppressed HIV, type of antiretroviral therapy, being on initial HIV treatment combination, and interval between tests (all p < 0.001).

Most increases in viral load were low and transient. In 66% of patients it rebounded to below 200 copies/ml, and in two-thirds of patients whose viral load increased to below 1000 copies/ml it was once again undetectable in the following test. The same was true for 30% of individuals whose viral load increased to over 1000 copies/ml.

Overall, there was a 98% probability that viral load would not rebound from undetectable to the potentially infectious level of 1000 copies/ml or above in successive tests. If an individual had started HIV treatment with a triple combination of drugs this increased to 99%.

The investigators examined rebounds in viral load to 1000 copies/ml or more in greater detail. In 78% of cases there was an explanation for this, for example poor adherence. However, “for the remaining 22%, no plausible explanation could be found.”

Adherence and the potency of HIV treatment were the two key factors associated with suppression of viral load in successive viral load tests, stress the investigators. They note that both of these issues were noted as factors affecting viral load suppression in the Swiss Statement on infectiousness.

Although the results of the study showed a high degree of probability that viral load remained suppressed in individuals between tests, the “data leave open the possibility that unexplained rises in viral load above 1,000 copies/ml, although rare, may occur.”