The presence of drug-resistant HIV minority variants doubles the risk of virologic failure in patients

• Researchers at IrsiCaixa AIDS Research Institute participated in a study showing that some HIV-positive people have drug-resistant HIV minority variants which are not detectable with regular resistance tests.
• The study, led by Harvard University, shows that the presence of these drug-resistant minority variants doubles the risk of treatment failure, which is a similar risk to not taking the medication properly.
• IrsiCaixa is working to incorporate new resistance tests far more sensitive than current, which would avoid the failure of antiretroviral therapy in 1 of every 11 patients in which the current tests do not detect resistance.

The Journal of the American Medical Association, one of the world's leading medical journals, published in the April 6 issue a study showing that the presence of drug-resistant HIV minority variants doubles the risk of virologic failure.

Dr. Roger Paredes, researcher at IrsiCaixa AIDS Research Institute -founded by "la Caixa" Foundation and the Department of Health of Generalitat de Catalunya- and physician at the HIV Unit of Germans Trias i Pujol Hospital in Badalona, participated in the study, led by Harvard University. Several international institutions, like the University of Zurich, Yale University and University College of London also participated in it.

HIV minority variants
Every HIV patient is infected with thousands of slightly different HIV virus, called viral variants. Some variants are more common than others, and some of them incorporate mutations that cause drug resistance, ie, make the treatment less effective. Before a patient starts antiretroviral treatment, it is always verified that the virus is not resistant to that medication, by the so called "resistance tests".

Current resistance tests only detect the most common viral variants, those that are present in more than 15% or 20% of the viruses infecting each patient. But the treatment also fails in some patients who apparently do not have resistant viruses. The study published in JAMA shows that, in some cases, this is because, in reality, these patients have resistant minority variants not detected by standard methods.

Minority variants and treatment failure
Researchers analyzed samples from 985 patients that, according to standard resistance tests, had no resistant virus. Massive sequencing techniques where used to detect variants present in up to 0.1% of the HIV virus in the body. With these ultra-sensitive tests it was revealed that 14% of patients who apparently had no resistant virus, in fact, had resistant minority variants which had not been detected.

The treatment failed in 15% of the patients who did not have resistances of any kind, while in patients with minority variants failure was of 35%. Therefore, the study shows that the presence of minority resistant variants doubles the risk of virologic failure, which is a similar risk to not taking the medication properly.
 
Detection of drug-resistant minority variants, which could not be detected with commonly used resistance tests, has been made possible by the application of virus genome sequencing tools in clinical diagnosis. These tools can make more precise resistance tests, and thereby improve diagnosis and the treatment of HIV patients. If these more sensitive resistance tests were widespread, treatment failure could be prevented in 1 of every 11 patients.

This form of diagnosis, which is currently in being tested, is expected to be applied to all HIV-positive patients within two years. These are the calculations of IrsiCaixa’s Molecular Epidemiology group, a research group who pioneers the development of ultra-sensitive tools for diagnosis of antiretroviral drug resistance. The group is led by Dr. Roger Paredes and is integrated by the researchers Christian Pou, Marc Noguera, Susana Perez, Rocio Bellido, Mattia Schiaulini and Cristina Rodriguez.