A new test allows to improve efficacy of HIV therapy in the patients most difficult to treat
- Researchers from the Institute for AIDS Research IrsiCaixa, jointly funded by "la Caixa" Foundation and the Catalan Government’s Department of Health, demonstrate for the first time the efficacy of a new test that allows to improve the response to treatment of patients in which most therapies are not working, the so called hard-to-treat patients.
- The test uses new ultra-sensitive sequencing platforms to detect, with high precision, Human Immunodeficiency Virus (HIV) that have become resistant to treatments. It detects more resistance than with previous tests in 25% of patients.
- The test will allow doctors to predict which drugs are effective with higher accuracy than with current methods. This will improve treatments substantially. During the study, researchers found that when the new test predicted that patients were being treated with less than 3 effective drugs, they were 5-times more likely to develop treatment failure. Treatment failure in these patients is associated with severe health complications.
- The findings have been published in the journal Clinical Infectious Diseases, and are already being translated into clinical practice: IrsiCaixa will implement ultrasensitive tests to detect HIV resistance into clinical diagnostic routine before the end of this year.
First AIDS cases were documented in 1981 and two years later, HIV, the virus that causes AIDS, was discovered. While the first antiretroviral drugs appeared in 1987, they were not very effective and had many side effects. Since then, treatments have evolved and improved, becoming simpler, less toxic and more effective. Through decades of research, and despite we do not have a cure for HIV infection yet, antiretroviral therapy (ART) has demonstrated a high level of success and the different drugs available today have contributed to increase both life expectancy and quality of life in HIV-infected people.
However, there is a group of people living with HIV in which therapies are not working, the so called hard-to-treat patients. Their viruses have become resistant to many HIV drugs, along the years of therapy. Some of them had to start treatment in the early days of the pandemic, when the combinations of drugs were not as effective as current ones, whereas others had poor adherence to medication (difficulties to follow the treatment properly). In these situations, HIV replication becomes very hard to block. Unless patients receive a highly potent treatment, their virus will continue to replicate significantly. This will lead to further accumulation of resistance, exhaustion of treatment options, severe health complications, and, sometimes, death.
To choose the right treatment for these patients, the most difficult ones to treat, physicians analyze the degree of resistance of HIV to the different drugs available. With this information, they select the combination of drugs which is more likely to block HIV. As this study confirms, current tests underestimate the true burden of HIV resistance. Thereby, clinicians miss relevant information about HIV resistance when they make their treatment choices. Accounting for such additional information could, in principle, improve antiretroviral therapy design, providing further health benefits to people living with HIV/AIDS.
Improved response to HIV therapy in hard-to-treat patients
In a study published in the journal Clinical Infectious Diseases, researchers from the Institute for AIDS Research IrsiCaixa, jointly funded by "la Caixa" Foundation and the Catalan Government’s Department of Health, demonstrate for the first time the efficacy of a new test that allows to improve the response to treatment of the so called hard-to-treat patients. The test uses new ultra-sensitive sequencing platforms to detect Human Immunodeficiency Virus (HIV) with high precision that have become resistant to treatments. It detects more resistance than with previous tests in 25% of patients.
The test will allow doctors to predict which drugs are effective with higher accuracy than with current methods. This will improve treatments substantially. During the study, researchers found that when the new test predicted that there were less than 3 effective drugs, patients were 5-times more likely to develop treatment failure. These findings are extremely important because treatment failure in this population is associated with further development of HIV resistance, exhaustion of treatment options, severe health complications and death. Ultrasensitive resistance testing allows choosing the most effective treatment and, therefore, keeping patients healthier for longer periods of time.
Roger Paredes, HIV physician and researcher at IrsiCaixa and Fight Against AIDS Foundation, at the Germans Trias Hospital, and senior author of this work, remarks that “improving drug resistance assessments will ensure that patients receive the most effective treatments and will avoid abolishing future treatment options for them”. “Moreover”, he adds, “the increased efficiency of next-generation sequencing technologies and their potential for dramatic cost reductions will impact global HIV health. In the coming years, it will facilitate access to resistance testing in resource-limited settings. In these areas, we are witnessing today an explosion of HIV drug resistance, due to the provision of treatment without laboratory monitoring because it is too expensive”.
The findings of this study are already being translated into clinical practice: IrsiCaixa will implement ultrasensitive tests to detect HIV resistance into clinical diagnostic routine before the end of 2014. “Given the fact that we have proved how important ultrasensitive testing is, we are ready to apply this system to all our patients in regular follow-up”, explains Roger Paredes. It will not only be more effective and efficient in the long-term, but it will also be cheaper, as it can process more samples in less time”, says Dr. Bonaventura Clotet, director of IrsiCaixa and head of the HIV Unit at the Germans Trias Hospital. Dr. Clotet states: “We are very proud to see that a finding lead by our team will have an immediate application in the daily management of people living with HIV”.
This project was carried out in collaboration with researchers and physicians from: the Instituto de Investigación Biomédica Hospital 12 de Octubre from Madrid, Hospital San Cecilio from Granada, Hospital MútuaTerrassa, Fight Against AIDS Foundation, Germans Trias i Pujol Hospital, in Badalona, the software company from Luxembourg Advanced Biological Laboratories (ABL, SA) and Roche Diagnostics, Spain. The study was supported through a grant from the Centro de Desarrollo Tecnológico e Industrial (CDTI) from the Spanish Ministerio de Economía y Competitividad.
Reference:
Christian Pou, Marc Noguera-Julián, Susana Pérez-Álvarez, Federico García, Rafael Delgado, David Dalmau, Miguel Álvarez-Tejado, Dimitri Gonzalez, Chalom Sayada, Natalia Chueca, Federico Pulido, Laura Ibañez, Cristina Rodríguez, Maria Casadellà, José R. Santos, Lidia Ruiz, Bonaventura Clotet, Roger Paredes. Improved Prediction of Salvage Antiretroviral Therapy Outcomes Using Ultrasensitive HIV-1 Drug Resistance Testing. Clinical Infectious Diseases. 2014. Read
