Spanish study gives reassurance: small HIV blips do not predict treatment failure

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A very low viral load (20-49 copies/ml) during HIV therapy does not increase the risk of the subsequent virological failure of treatment (viral load above 200 copies/ml), according to Spanish research published in HIV Medicine.

The findings of the study will provide reassurance that people with very low level viraemia (VLLV) do not need to change their antiretroviral therapy.

An undetectable viral load is the aim of HIV treatment. Assays in use soon after effective treatment was introduced had a lower limit of detection of 400 copies/ml. Assays sensitive to 50 copies/ml rapidly became available and persistent suppression below 50 copies/ml became widely accepted as the threshold for the virological success of antiretroviral therapy. However, in 2008/09 assays with a lower limit of detection of just 20 copies/ml were introduced into routine clinical use. The appropriate management of patients with a viral load below 20-49 copies/ml is uncertain, though current practice is generally to leave treatment unchanged.



The presence of virus in the blood.


person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.


The general term for the body’s response to injury, including injury by an infection. The acute phase (with fever, swollen glands, sore throat, headaches, etc.) is a sign that the immune system has been triggered by a signal announcing the infection. But chronic (or persisting) inflammation, even at low grade, is problematic, as it is associated in the long term to many conditions such as heart disease or cancer. The best treatment of HIV-inflammation is antiretroviral therapy.

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.


A temporary, detectable increase in the amount of HIV in the blood (viral load) that occurs after antiretroviral therapy (ART) has effectively suppressed the virus to an undetectable level. Isolated blips are not considered a sign of virologic failure.

A team of Spanish researchers therefore designed a study focusing on 4289 antiretroviral-treated people who achieved a viral load below 20 copies/ml after the introduction in May 2009 of assays sensitive to 20 copies/ml. They examined whether subsequent rebound in viral load to 50 copies/ml, 50-200 copies/ml or above 200 copies/ml was associated with virological failure – a persistent viral load above 200 copies/ml, usually the trigger to change treatment.

Adults who started HIV therapy after 1997 (when use of triple-drug treatment first became widespread) were eligible for inclusion in the study. Of these individuals, 13,671 (64%) achieved suppression below 50 copies/ml and 4289 had a viral load below 20 copies/ml after the introduction of the most sensitive assays in May 2009.

These people were followed for a median of 639 days and contributed a total of 8069 person-years of follow-up. A viral load below 20 copies/ml was maintained by 2623 individuals during 4194 person-years of follow-up and 1666 people had one or more viral loads above 20 copies/ml during 3930 person-years of follow-up. In approximately half (n = 824) of these viraemic patients viral load always remained below 50 copies/ml, whereas 563 had at least one viral load result between 50-200 copies/ml and 278 people had one or more viral load measurement above 200 copies/ml.

After controlling for potential confounders and taking into account type of antiretroviral regimen – including short-term use of boosted protease inhibitor monotherapy with a switch back to traditional therapy in the event of a viral load blip – the investigators found that very low level viraemia (20-49 copies/ml) was not associated with subsequent virological failure when compared to persistent suppression below 20 copies/ml (HR = 0.67; 95% CI, 0.44-1.00).

“In those patients of our cohort who were able to ever achieve suppression of HIV viral replication sufficient to being VL to below the level of detection of [20 copies/ml] episodic detection of VLLV (any value < 50 copies/ml) thereafter was not associated with an increased risk of virological failure,” write the authors. “The occurrence of any episode of VLLV seems to lack any major clinical significance, as long as VL remains < 50 copies/ml.”

They believe their findings support the common practice of leaving therapy unchanged when viral load increases to between 20 and 49 copies/ml. However, they call for further research to see if the chronic immune activation and inflammation which could potentially be caused by very low level viraemia have an impact on people's health.


Teira R et al. Very low level viraemia and risk of virological failure in treated HIV-1-infected patients. HIV Medicine, online edition. DOI: 10.1111/hiv.12413, 2016.