[en] Human immunodeficiency virus (HIV) uses different types of cells as a target of infection, with CD4+ T lymphocytes being the main target. HIV infects cells of the immune system, destroying or impairing their function. Infection with the virus results in progressive deterioration of the immune system, leading to the appearance of diseases defining the acquired immune deficiency syndrome (AIDS). The introduction of high-efficacy antiretroviral therapy (ART) has drastically changed the prognosis of HIV infection, with a significant reduction in AIDS-related morbidity and mortality, making HIV infection a chronic disease. The evolution of HIV infection in countries with access to treatment is conditioned by several factors: related to the patient (i.e. epidemiological factors, immunological status, adherence to treatment), to the virus (i.e. plasma viral load, presence of drug resistance mutations) or to antiretroviral drugs (i.e. efficacy, tolerability, interactions). Nowadays, national and international clinical guidelines recommend treating all HIV-infected patients regardless of their immunological status. National and international guidelines for initial treatment of HIV-infected patients recommend the use of two nucleoside analogue reverse transcriptase inhibitors (NRTIs) plus a third active drug: an integrase strand transfer inhibitor (INSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a boosted protease inhibitor (PI). Based on the good efficacy and safety profile demonstrated in clinical trials, the INSTI (raltegravir, elvitegravir, dolutegravir and bictegravir) have been positioned as preferred options compared to the rest of families, acquiring great relevance its use in clinical practice. Therefore, it is important to know the epidemiological, clinical and virological characteristics, as well as the efficacy and tolerability of antiretroviral therapy based on INI in our health area to establish and optimize the clinical management strategies of HIV patients. In this thesis, three studies have been developed: - Study 1. Epidemiological, clinical and immunovirological characteristics, and efficacy and tolerability of antiretroviral treatment in HIV patients with Dolutegravir and Elvitegravir/cobicistat prescription in the health area of A Coruña during the period January 2015 to January 2017 were described. More than 90% of naïve and experienced patients had virological suppression after 48 weeks of treatment. During follow-up, a high percentage of adverse events discontinuations not previously described in clinical trials has been observed, especially with DTG (10.2%). Female gender and DTG treatment were identified as risk factors for AE discontinuation. In the case of DTG, treatment interruptions were mainly related to neuropsychiatric disturbances (70.4%) and EVG/c with gastrointestinal discomfort (50.0%). DTG-based therapies, especially in combination with the NRTI abacavir/lamivudine, were associated with an increased risk of treatment discontinuation due to neuropsychiatric adverse events. - Study 2. Virological response in HIV naïve patients who initiated antiretroviral treatment based on INSTI from January 2015 to February 2017 and who were infected with the two most frequent genetic subtypes in our population, subtype B (54.4%) and subtype F (27.2%), were evaluated. Virological response rates to antiretroviral therapy based on integrase inhibitor were significantly lower among F subtypes compared with B subtypes at weeks 12 (25.0% vs. 75.0%) and 24 (59.1% vs. 95.0%). Subtype F was independently associated with poor virological response to INI-based regimens at 24 weeks. - Study 3. Changes in the lipid profile of naïve and experienced HIV patients who started treatment with EVG/c/FTC/TAF and EVG/c/FTC/TDF from January 2015 to January 2018 were evaluated. A significantly negative influence in the lipid profile parameters were observed after 48 weeks of treatment with EVG/c/FTC/TAF, while these parameters remained stable in the EVG/c/FTC/TDF group. During follow-up, a greater proportion of patients had lipid levels above the normal range (63.1% TC, 56.2% LDL-C) and new lipid-modifying drugs were prescribed (11.9%) in the EVG/c/FTC/TAF group. In this group, the mean total cholesterol to HDL-C ratio in the first 48 weeks of the study treatment was associated with a higher likelihood of lipid-lowering prescription in multivariate analysis [OR 1.6 (95% CI 1.12–2.52); p=0.011]. In summary, the results obtained during the development of this thesis have allowed a detailed knowledge of the efficacy and safety of INSTI-based regimens in patients of our health area. Among the main findings, we must highlight the high percentage of discontinuations due to adverse events not previously described in clinical trials, especially with DTG (10.2%), the worst response to the INSTI in subtype F HIV infected patients compared with subtype B and the worsening of lipid profile when patients receive EVG/c/FTC/TAF.

[gl] O virus da inmunodeficiencia humana (VIH) utiliza diferentes tipos de células como branco de infección sendo os linfocitos T CD4+ a súa principal diana. A infección por VIH é capaz de producir un deterioro progresivo do sistema inmunolóxico que conduce á aparición de enfermidades definitorias do síndrome de inmunodeficiencia humana adquirida (SIDA). A introdución da terapia antirretroviral (TAR) de alta eficacia cambiou drasticamente o prognóstico da infección por VIH, con unha diminución significativa da morbilidade e a mortalidade relacionada co SIDA e converténdoa nunha patoloxía crónica. A evolución da infección polo VIH en países con acceso ó tratamento está condicionada por diferentes factores: relacionados co paciente (exemplos son factores epidemiolóxicos, situación inmunolóxica, adherencia ó tratamento), co virus (exemplos son a carga viral plasmática, presenza de mutacións de resistencia) ou cos fármacos antirretrovirales (exemplo son a eficacia, tolerabilidade, resistencias, interaccións). Na actualidade as guías clínicas nacionais e internacionais recomendan tratar a todos os pacientes infectados polo VIH independentemente de seu estado inmunolóxico. As pautas recomendadas no momento actual para o tratamento de inicio na infección polo VIH consisten na combinación de tres fármacos que inclúen dous inhibidores da transcriptasa inversa análogos de nucleósidos ou nucleótidos (ITIAN) asociados a un inhibidor da integrasa (INI) ou un inhibidor da transcriptasa inversa non análogo de nucleósido (ITINN) ou un inhibidor da proteasa potenciado (IP). Baseándose no bo perfil de eficacia y seguridade demostrado nos ensaios clínicos, os INI (raltegravir, elvitegravir, dolutegravir e bictegravir) posicionáronse como opcións preferentes fronte ó resto de familias, adquirindo gran relevancia o seu uso na práctica clínica. Resumen 12 Polo tanto, é importante coñecer as características epidemiolóxicas, clínicas e virolóxicas, así como o perfil de eficacia e tolerabilidade da terapia antirretroviral baseada en INI na nosa área sanitaria para establecer e optimizar as estratexias de manexo clínico dos pacientes con infección por VIH. Na presente tese desenrólanse tres estudos: - Estudo 1. Analizáronse as características epidemiolóxicas, clínicas e inmunovirolóxicas e a eficacia e tolerabilidade do tratamento antirretroviral nos pacientes con infección por VIH nos que foron prescritos os INI Dolutegravir e Elvitegravir/cobicistat na área sanitaria da Coruña durante o período xaneiro 2015 a xaneiro 2017. Mais do 90% dos pacientes naïve e pretratados tiveron supresión virolóxica ás 48 semanas de iniciar o tratamento. Durante o seguimento, observouse un alto porcentaxe de abandonos por efectos adversos non descritos previamente nos ensaios clínicos, especialmente con DTG (10.2%). Concretamente, o sexo feminino e o tratamento con DTG se identificaron como factores de risco para a interrupción por efectos adversos. No caso de DTG, as interrupcións de tratamento se relacionaron principalmente con alteracións neuropsiquiátricas (70.4%) e EVG/c con molestias gastrointestinais (50.0%). Identificáronse como factores de risco de suspensión do tratamento debido a efectos adversos neuropsiquiátricos as terapias baseadas en DTG, especialmente en combinación cos ITIAN abacavir/lamivudina. - Estudo 2. Avaliouse a resposta virolóxica en pacientes VIH naïve que iniciaron tratamento antirretroviral baseado en INI desde xaneiro de 2015 hasta febreiro de 2017 e que estaban infectados cos dous subtipos xenéticos mais frecuentes na nosa poboación, o subtipo B (54.4%) e o subtipo F (27.2%). A taxa de supresión virolóxica foi significativamente menor nos pacientes infectados polo subtipo F do VIH en comparación cos pacientes infectados polo subtipo B na semana 12 (25.0% vs. 75.0%) e 24 (59.1% vs. 95.0%) do tratamento. A infección polo subtipo F foi o único factor predictor independente de unha peor resposta ó tratamento con INI na semana 24. - Estudo 3. Avaliaronse as modificacións no perfil lipídico dos pacientes VIH naïve e pretratados que iniciaron tratamento con EVG/c/FTC/TAF e EVG/c/FTC/TDF dende xaneiro 2015 ata xaneiro 2018. Os pacientes que iniciaron tratamento con EVG/c/FTC/TAF tiveron un empeoramento dos valores de colesterol total, LDL-C e triglicéridos tras 48 semanas de tratamento; non houbo cambios significativos nestes parámetros no grupo a tratamento con EVG/c/FTC/TDF. No seguimento dos pacientes do grupo con EVG/c/FTC/TAF comprobouse que un alto porcentaxe tivo niveles de lípidos por encima do rango normal ás 48 semanas (63.1% niveis por encima do rango normal de colesterol total e 56.2% de LDL-C) e un 11.9% dos pacientes neste grupo tiveron que recibir fármacos hipolipemiantes. No análise multivariante realizado neste grupo, o cociente colesterol total/HDL-C durante as primeiras 48 semanas de tratamento asociouse con una maior probabilidade de prescrición de hipolipemiantes [OR 1.6 (95% CI 1.12–2.52); p=0.011]. En resumo, os resultados obtidos durante o desenrolo desta tese permitiron un coñecemento detallado da eficacia e seguridade dos tratamentos antirretrovirais baseados en INI nos pacientes tratados de nosa área sanitaria. Entre os principais achados hai que destacar o alto porcentaxe de abandonos por efectos adversos non descritos previamente en ensaios clínicos, especialmente con DTG (10.2%), a peor resposta virolóxica dos pacientes infectados polo subtipo F do VIH ós inhibidores da integrasa en comparación co subtipo B e o empeoramento do perfil lipídico cando os pacientes reciben EVG/c/FTC/TAF.