Evaluation of transmitted resistance in individuals infected with Human Immunodeficiency Virus 1 and failing HAART using next generation sequencing

Abstract

Highly Active Antiretroviral Therapy (HAART) was introduced in 1996 and reduced both the mortality and morbidity of HIV-1 infected patients. However, HAART may lead to emergence of drug-resistant viral populations because of the the selective pressure of drugs. These viral populations arise from the lack of patient adherence to treatment, pharmacokinetics dependent of host genetics, presence of sanctuaries tissues and others reasons. With these reasons, has the presence of mutations transmitted of antiretrovirals (ARVs), where the individual is infected by a virus already resistant. For these reasons, to search new drugs that aim different targets of the viral cycle is essential, because these searches can be used in rescue therapy for individuals in the HAART failure. Although the monitoring of ARV resistance mutations, there is no sufficient data related to transmitted resistance and polymorphisms caused by drugs used to treat rescue. There is much disagreement about the importance of minority variants in the antiretroviral treatment. Currently, the classes of drugs used to rescue individuals in failure to HAART, are: Integrase Inhibitor - Raltegravir, Protease Inhibitor - Darunavir and Second-Generation Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) - Etravirine. These drugs have effective action against all viral variants resistant to ARV used nowadays. Thus, the main objective of this study is to evaluate through the next-generation sequencing the occurrence of transmitted resistance and/or polymorphisms that could prevent or decrease susceptibility to ARVs Raltegravir, Etravirine and Darunavir in patients who don't respond to HAART therapy in the São Paulo City. (AU)