HIV genetic evolution among individuals under antiretroviral therapy

Abstract

HIV - 1 is notorious for its high rates of replication and high genetic diversity generated upon infection. These features are in fact essential to the success of this pathogen, favoring evasion of the immune system, selection antiretroviral resistant strains and also impairing the development of preventive vaccines. The antiretroviral treatment prevents the progression of the disease but does not completely abrogate HIV related chronic inflammatory process. The antiretroviral treatment does not eradicate HIV infection due to viral latency and residual viral replication. As diversity and genetic divergence of HIV-1 are a result of viral replication, antiretroviral treatment was supposed to fully suppress genetic evolution of this pathogen. We hypothesized that the conventional antiretroviral treatment which leads to undetectable viral load is not fully suppressive and thus there would still be a window of opportunity for an improvement in treatment potential, a fundamental aim for HIV - 1sterilizing cure. This study aims for the first time in literature to assess the diversity and genetic diversity of HIV-1 in patients with suppressive antiretroviral therapy using a massive parallel sequencing. 50 HIV-treated patients will be evaluated in two stages: pre-antiretroviral treatment and after four years of suppressive antiretroviral treatment initiation, demonstrated by the presence of undetectable viral load during this period of time. Blood samples will be subjected to viral RNA and proviral DNA extraction and regions of the gene encoding the env C2V3C3 and gp41 will be amplified by nested-PCR. Then the PCR products will be subjected to ultra deep sequencing and the generated sequences will be phylogenetically analyzed. Interleukins and Markers related to Inflammation and bacterial translocation will also be analyzed before and after the treatment initiation as well as HIV - 1genetic diversity and divergence. (AU)