Longer viral load is undetectable, lower the risk of rebound

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The longer a patient taking HIV treatment maintains an undetectable viral load, the lower their risk of virologic rebound, Canadian investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

“We found that once viral suppression was initially achieved, high levels of adherence were still needed for at least the first year. Over time, however, the risk of viral rebound decreased with maintained viral suppression irrespective of the level of adherence”, comment the investigators.

Nevertheless, the investigators emphasise that patients should aim to take all their doses correctly.

Glossary

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

Treatment with combination antiretroviral therapy can extend the life expectancy of HIV-positive patients to near normal levels.

To get the maximum benefit from their treatment, it is necessary for patients to take their treatment correctly. The best outcomes are seen in individuals who take at least 95% of their doses. Adherence below that level has been associated with an increase in viral load and the development of drug-resistant virus.

However, Canadian researchers hypothesised that once initial suppression of HIV was achieved after starting therapy, lower levels of adherence would be needed to needed to maintain an undetectable viral load. This is because the amount of virus capable of reproduction diminishes with longer duration of suppression.

To test their theory, the investigators performed a retrospective study involving 1305 patients starting HIV therapy for the first time between 2000 and 2006. All the patients achieved a viral load below 50 copies/ml. The investigators analysed the factors associated with a subsequent sustained increase in viral load to above 400 copies/ml.

Overall, 274 (21%) of patients experienced virologic rebound. The median time from suppression to below 50 copies/ml and a sustained rebound in viral load was two years.

Factors associated with an increase in viral load were female sex, a history of injecting drug use, starting treatment in 2000-2001, being younger, baseline resistance to antiretroviral drugs, and taking an unboosted protease inhibitor (all p < 0.01).

The duration of prior viral suppression was also important.

Each month of continuous suppression of HIV lowered the risk of rebound by 8%.

At all levels of adherence, the longer HIV was suppressed, the lower the risk of rebound.

For patients with a high level of adherence (95% or better), the probability of rebound was 0.10 when viral load was suppressed for less than twelve months. However, the probability was just 0.04 after viral load had been suppressed for 72 months.

Among individuals with moderate adherence (80% to 94%), the probability of rebound was 0.85 with suppression for up to twelve months and 0.08 at 72 months.

For those with low adherence, the probability of rebound was 0.68 after suppression for twelve months and 0.05 after 72 months.

However, even after taking into account the duration of suppression, patients who took at least 95% of their doses were 11% less likely than with the poorest adherence.

“Our results reinforce the message of to individuals that sustained and near perfect adherence increase the probability of long-term viral suppression, particularly critical at the earliest stages of treatment”, write the authors.

Nevertheless, they conclude that “because the resilience of HAART [highly active antiretroviral therapy] increases over time, it is possible that individuals remain fully suppressed even after missing some doses of medication."

References

Lima VD et al. Risk of viral failure decline with duration of suppression on highly active antiretroviral therapy irrespective of adherence level. J Acquir Immune Defic Syndr, advance online publication, September 16, 2010. (For abstract and link to article full text click here).