New strategies to optimize treatment for HIV-1 infection

[eng] Antiretroviral therapy has dramatically reduced morbidity and mortality associated with HIV-1 infection and converted AIDS into a manageable chronic disease. During the past 15 years, antiretroviral drugs have become less toxic, more potent and more convenient, allowing the possibility of earl...

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Detalles Bibliográficos
Autor: Monteiro D'Albuquerque, Polyana
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/67185
Acceso en línea:https://hdl.handle.net/2445/67185
http://hdl.handle.net/10803/311434
Access Level:acceso abierto
Palabra clave:VIH (Virus)
Antiretrovirals
Inhibidors enzimàtics
Sida
HIV (Viruses)
Antiretroviral agents
Enzyme inhibitors
AIDS (Disease)
Descripción
Sumario:[eng] Antiretroviral therapy has dramatically reduced morbidity and mortality associated with HIV-1 infection and converted AIDS into a manageable chronic disease. During the past 15 years, antiretroviral drugs have become less toxic, more potent and more convenient, allowing the possibility of early treatment. Changing regimens in patients with viral suppression is an approach that can be contemplated to simplify treatment and improve adherence reducing the number of pills and frequency of dosing, to prevent toxicity in the short or long term, to minimize drug interactions, and also to preserve future treatment options and even to reduce costs. We conclude that the efficacy of protease inhibitors boosted with ritonavir (PI / r) monotherapy in clinical practice is consistent with data from clinical trials. Moreover, the combination of etravirine plus raltegravir is well tolerated and maintains durable viral suppression in selected patients with virological suppression. Regarding modification of PI / r regimens in virologically suppressed patients, we found that the change of PI / r for raltegravir leads to significant changes in biomarkers associated with cardiovascular inflammation, insulin resistance, and hypercoagulability. In this context abacavir / lamivudine exhibits similar efficacy and tolerability of tenofovir / emtricitabine. Replacing the drug involved is one of the strategies to handle complications of antiretroviral therapy. However, for patients with underlying resistance mutations this approach may not be feasible. In adults receiving PI / r with hypercholesterolemia and increased cardiovascular risk, we found that rosuvastatin produced greater decreases in total cholesterol and low density than switching PI / r. Finally, we observed that 11% of patients treated with raltegravir developed significant elevation of creatine kinase during treatment with raltegravir. Symptoms were rare and unrelated to the degree of creatine kinase elevation. While knowledge about non-infectious complications of HIV-1 infection continues to prosper together with the continuous improvement of antiretroviral therapy, it is possible to develop new strategies to limit their impact on people living with HIV and to assure they can age with health and quality of life.