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Sex Transm Infect ; 96(5): 337-341, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32245779


OBJECTIVE: To provide insight on viral kinetics and genetic diversity of HIV in seminal plasma at baseline and 1 month after initiating antiretroviral therapy (ART). PATIENTS AND METHODS: Blood and seminal samples from patients with newly diagnosed HIV were obtained before ART initiation (T0) and 1 month after ART initiation (T1). HIV env genetic diversity was studied using deep sequencing Nextera and V3 chemistry in a MiSeq Illumina platform. The number of viral quasispecies (5% cut-off) and Shannon Index were used to analyse diversity. RESULTS: Forty-seven ART-naive patients were recruited between September 2016 and November 2018. At enrolment, the number of quasispecies in blood (median 4 (IQR 2-5)) was lower than in the seminal compartment (median 6, (IQR 4-8)) (p<0.01); the Shannon Index was also higher (p<0.001) in the seminal compartment than in blood (1.77 vs 0.64). At T1, for the 13 patients with detectable HIV in both blood/seminal plasma, viral diversity remained higher (p=0.139) in seminal plasma (median 2 (IQR 1-4.5)) than in blood (median 1 (IQR 1-1.5)) Integrase inhibitors (INI)-based regimens achieved higher levels of undetectability and led more frequently to lower variability (p<0.001) than protease inhibitors (PI) or non-nucleoside reverse transcriptase inhibitors (NNRTI). CONCLUSION: We provide here further evidence of a larger genetic diversity in seminal plasma, both at diagnosis and short term after ART initiation. Our results strengthen previous findings on HIV diversity in seminal plasma. In addition, INIs decrease variability more rapidly than PI and NNRTI in both blood and seminal plasma.

Antirretrovirais/uso terapêutico , Sangue/virologia , Variação Genética , Infecções por HIV/tratamento farmacológico , HIV/genética , Sêmen/virologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética , Adulto , Infecções por HIV/sangue , Infecções por HIV/metabolismo , Inibidores de Integrase de HIV/uso terapêutico , Inibidores da Protease de HIV/uso terapêutico , Humanos , Masculino , Inibidores da Transcriptase Reversa/uso terapêutico
Eur J Intern Med ; 52: 40-48, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29409744


BACKGROUND: Echocardiography plays an important role in infective endocarditis (IE) diagnosis according with the modified Duke criteria. We evaluated the implications of a positive echocardiography in the prognosis of a cohort of patients with IE. METHODS: Prospective multicentre study in 31 Spanish centres. From January 2008 to September 2016, 3467 patients were included (2765 definite IE, 702 possible IE). The main outcome was in-hospital mortality. Echocardiography diagnosis was based on modified Duke criteria for the diagnosis of IE. RESULTS: Median age was 69 years (interquartile range: 57-77 years). Comorbidity was high (mean Charlson index 4.7 ±â€¯2.8). Transoesophageal echocardiography was performed in 2680 (77.3%). The overall inhospital mortality rate was 26.7%. Univariate analysis showed that, in patients with definite IE, inhospital mortality was similar in patients with positive and negative echocardiography (27.7% vs. 24.6%, respectively, p = 0.121). In possible IE these figures were 27.5% vs. 16.7%, respectively, p < 0.001. Complications (cardiac and extracardiac [embolic, immunological, and septic shock]) were more frequent with positive than with negative echocardiography, regardless of clinical suspicion (definite IE 35.5% vs. 16.8%, respectively, p < 0.001; possible IE 20.8% vs. 7.6%, respectively, p < 0.001). Positive echocardiography was a predictor of inhospital death by logistic regression modelling, after adjusting for confounders, definite IE (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.02-1.76, p = 0.036), possible IE (OR 1.59, 95% CI 1.02-2.45, p = 0.036). CONCLUSIONS: A positive echocardiography in patients with IE is associated with increased inhospital mortality, in addition to other clinical factors and comorbidities.

Ecocardiografia Transesofagiana , Endocardite/diagnóstico por imagem , Endocardite/mortalidade , Mortalidade Hospitalar , Idoso , Comorbidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia
Addiction ; 111(7): 1235-45, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26890155


AIMS: To compare patients who acquired HIV infection through use of injected drugs (HIV-IDU) with patients who acquired HIV by sexual transmission (HIV-ST) in terms of late presentation (LP), delay in anti-retroviral treatment (ART) initiation, virological and immunological response to ART, mortality and progression to AIDS. DESIGN: Prospective multi-centre cohort study of HIV-infected subjects naive to ART at entry (Cohort of the Spanish HIV Research Network: CoRIS). SETTING: Thirty-one centres from the Spanish public health-care system. PARTICIPANTS: A total of 9355 patients were included (1064 HIV-IDU and 8291 HIV-ST) during 2004-13. MEASUREMENTS: We compared LP (defined as presentation for care with a CD4 cell count < 350/µl and/or AIDS-defining illness), delayed ART initiation (defined as initiating treatment more than 6 months after the date when treatment was indicated by the guidelines, or not initiating treatment at all when it was indicated), virological and immunological response to ART (defined as viral load < 50 HIV-1 RNA copies/ml and a CD4 count increase of at least 100 cells/µl, respectively, after 1 year of treatment), mortality and progression to AIDS in HIV-IDU and HIV-ST. FINDINGS: Compared with HIV-ST, HIV-IDU had higher risk of LP [odds ratio (OR) = 1.76; 95% confidence interval (CI) = 1.41-2.18], delayed ART initiation (OR 1.87; 95% CI = 1.46-2.40) and higher mortality [hazard ratio (HR) = 1.43; 95% CI = 1.03-2.01] and risk of progression to AIDS [subhazard ratio (SHR) = 1.68; 95% CI = 1.29-2.18]. Virological suppression due to ART was lower in HIV-IDU than in patients with HIV-ST only among patients without hepatitis C virus (HCV) infection [adjusted OR (aOR) = 0.59; 95% CI = 0.36-0.95]; among patients with HCV infection, virological suppression due to ART did not show significant differences between HIV-IDU and HIV-ST. There were no significant differences in immunological response after adjusting by HCV (aOR = 0.74; 95% CI = 0.52-1.06). CONCLUSIONS: In Spain, patients who acquire HIV infection through use of injected drugs appear to have a higher risk of late presentation, delayed initiation of anti-retroviral treatment and progression to AIDS and death than patients who acquire HIV by sexual transmission.

Infecções por HIV/transmissão , Doenças Virais Sexualmente Transmissíveis , Abuso de Substâncias por Via Intravenosa , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Diagnóstico Tardio , Progressão da Doença , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Humanos , Masculino , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Prospectivos , Espanha , Tempo para o Tratamento , Resultado do Tratamento , Carga Viral
PLoS One ; 11(2): e0148924, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26872331


BACKGROUND AND OBJECTIVE: Significant controversy still exists about ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv) as a simplification strategy that is used up to now to treat patients that have not experienced previous virological failure (VF) while on protease inhibitor (PI) -based regimens. We have evaluated the effectiveness of two mtPI/rtv regimens in an actual clinical practice setting, including patients that had experienced previous VF with PI-based regimens. METHODS: This retrospective study analyzed 1060 HIV-infected patients with undetectable viremia that were switched to lopinavir/ritonavir or darunavir/ritonavir monotherapy. In cases in which the patient had previously experienced VF while on a PI-based regimen, the lack of major HIV protease resistance mutations to lopinavir or darunavir, respectively, was mandatory. The primary endpoint of this study was the percentage of participants with virological suppression after 96 weeks according to intention-to-treat analysis (non-complete/missing = failure). RESULTS: A total of 1060 patients were analyzed, including 205 with previous VF while on PI-based regimens, 90 of whom were on complex therapies due to extensive resistance. The rates of treatment effectiveness (intention-to-treat analysis) and virological efficacy (on-treatment analysis) at week 96 were 79.3% (CI95, 76.8-81.8) and 91.5% (CI95, 89.6-93.4), respectively. No relationships were found between VF and earlier VF while on PI-based regimens, the presence of major or minor protease resistance mutations, the previous time on viral suppression, CD4+ T-cell nadir, and HCV-coinfection. Genotypic resistance tests were available in 49 out of the 74 patients with VFs and only four patients presented new major protease resistance mutations. CONCLUSION: Switching to mtPI/rtv achieves sustained virological control in most patients, even in those with previous VF on PI-based regimens as long as no major resistance mutations are present for the administered drug.

Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1/genética , Ritonavir/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Farmacorresistência Viral , Feminino , Infecções por HIV/mortalidade , Infecções por HIV/virologia , Protease de HIV/genética , Inibidores da Protease de HIV/farmacologia , HIV-1/enzimologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos , Ritonavir/farmacologia , Resultado do Tratamento , Adulto Jovem
J Clin Microbiol ; 51(5): 1555-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23390288


After 1 year of follow-up, patients on HAART with a baseline viral load (VL) of <20 copies/ml showed significantly lower odds of virological rebound to two consecutive VLs of >50 copies/ml than those with baseline VLs of 20 to 39 and 40 to 49 (P < 0.001). The time to virological rebound was also significantly shorter (P < 0.001) for the groups with baseline VLs of 20 to 39 and 40 to 49.

Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/fisiologia , Carga Viral , Adulto , Terapia Antirretroviral de Alta Atividade , Feminino , Infecções por HIV/diagnóstico , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Viral/análise , Recidiva , Viremia