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1.
Eur J Nucl Med Mol Imaging ; 46(10): 2065-2076, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273436

RESUMO

PURPOSE: Previous studies in patients with Parkinson's disease (PD) and impulse control disorders (ICDs) have produced heterogeneous results regarding striatal dopamine transporter (DaT) binding and activity in the mesocorticolimbic network. Our aim here was to study the relationship between striatal DaT availability and cortical metabolism, as well as motor, behavioural and cognitive features of PD patients with ICD. METHODS: In a group of PD patients with ICD (PD-ICD, n = 16) and 16 matched PD patients without ICD (PD-noICD, n = 16), DaT single-photon emission computed tomography (SPECT) imaging (DaTSCAN) was used to study DaT availability in predefined striatal volumes of interest (VOIs): putamen, caudate nucleus and ventral striatum (VS). In addition, the specific association of striatal DaT binding with cortical limbic and associative metabolic activity was evaluated by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in PD-ICD patients and investigated using statistical parametric mapping (SPM8). Finally, associations between DaT availability and motor, behavioural and cognitive features were assessed. RESULTS: PD-ICD patients had a significantly lower DaT density in the VS than PD-noICD patients, which was inversely associated with ICD severity. Lower DaT availability in the VS was associated with lower FDG uptake in several cortical areas belonging to the limbic and associative circuits, and in other regions involved in reward and inhibition processes (p < 0.0001 uncorrected; k > 50 voxels). No significant results were observed using a higher conservative threshold (p < 0.05; FDR corrected). PD-ICD patients also displayed impairment in interference and attentional Stroop Task execution, and more anxiety, all associated with reduced DaT availability in the VS and caudate nucleus. CONCLUSIONS: ICDs in PD patients are related to reduced DaT binding in the VS, which accounts for dysfunction in a complex cortico-subcortical network that involves areas of the mesolimbic and mesocortical systems, being associated with reward evaluation, salience attribution and inhibitory control processes.


Assuntos
Corpo Estriado/diagnóstico por imagem , Transtornos Disruptivos, de Controle do Impulso e da Conduta/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Doença de Parkinson/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Idoso , Corpo Estriado/metabolismo , Transtornos Disruptivos, de Controle do Impulso e da Conduta/complicações , Transtornos Disruptivos, de Controle do Impulso e da Conduta/metabolismo , Transtornos Disruptivos, de Controle do Impulso e da Conduta/patologia , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Substância Negra/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único
2.
Eur J Public Health ; 28(3): 451-457, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29325097

RESUMO

Background: In Spain, migrants are disproportionately affected by HIV and experience high rates of late diagnosis. We investigated barriers to health care access among migrants living with HIV (MLWH) in Spain. Methods: Cross sectional electronic survey of 765 adult HIV-positive migrants recruited within 18 health care settings between July 2013 and July 2015. We collected epidemiological, demographic, behavioral and clinical data. We estimated the prevalence and risk factors of self-reported barriers to health care using multivariable logistic regression. Results: Of those surveyed, 672 (88%) had information on health care access barriers: 23% were women, 63% from Latin America and Caribbean, 14% from Sub-Saharan Africa and 15% had an irregular immigration status. Men were more likely to report barriers than women (24% vs. 14%, P = 0.009). The main barriers were: lengthy waiting times for an appointment (9%) or in the clinic (7%) and lack of a health card (7%). Having an irregular immigration status was a risk factor for experiencing barriers for both men (OR: (4.0 [95%CI: 2.2-7.2]) and women (OR: 10.5 [95%CI: 3.1-34.8]). Men who experienced racial stigma (OR: 3.1 [95%CI: 1.9-5.1]) or food insecurity (OR: 2.1 [95%CI: 1.2-3.4]) were more likely to report barriers. Women who delayed treatment due to medication costs (6.3 [95%CI: 1.3-30.8]) or had a university degree (OR: 5.8 [95%CI: 1.3-25.1]) were more likely to report barriers. Conclusion: Health care barriers were present in one in five5 MLWH, were more common in men and were associated to legal entitlement to access care, perceived stigma and financial constraints.


Assuntos
Infecções por HIV/terapia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Migrantes , Adolescente , Adulto , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Fatores de Risco , Espanha/epidemiologia , Migrantes/estatística & dados numéricos , Adulto Jovem
3.
J Viral Hepat ; 22(5): 496-503, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25363502

RESUMO

While hepatitis C virus (HCV) infection seems to be expanding among HIV-infected men who have sex with men (MSM), the rate of coinfection in intravenous drug users (IDU) is assumed to remain constant. We evaluated the serial prevalence of HIV/HCV coinfection across all risk groups for HIV infection in Spain. We used data from 7045 subjects included in the multicentre, prospective Spanish Cohort of Adult HIV-infected Patients (CoRIS) between 2004 and 2011. We analysed risk factors for HIV/HCV coinfection by logistic regression analyses. The prevalence of HIV/HCV coinfection decreased from 25.3% (95% CI, 23.1-27.5) in 2004-2005 to 8.2% (95% CI, 6.9-9.5) in 2010-2011. This trend was consistently observed from 2004 to 2011 among all risk groups: IDU, 92.4% to 81.4%; MSM, 4.7% to 2.6%; heterosexual men, 13.0-8.9%; and heterosexual women, 14.5-4.0% (all P < 0.05). Strongest risk factors for HIV/HCV coinfection were IDU (OR, 54.9; 95% CI, 39.4-76.4), birth decade 1961-1970 (OR, 2.1; 95% CI, 1.1-3.7) and low educational level (OR, 2.4; 95% CI, 1.6-3.5). Hence, the prevalence of HIV/HCV coinfection decreased in Spain between 2004 and 2011. This decline was observed across all risk groups and is likely to be explained by a declining burden of HCV in the general population.


Assuntos
Coinfecção/epidemiologia , Infecções por HIV/complicações , Hepatite C/epidemiologia , Adulto , Animais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Espanha/epidemiologia
4.
Eur J Clin Microbiol Infect Dis ; 34(2): 267-75, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25142804

RESUMO

Visceral leishmaniasis (VL) in HIV-1-infected patients has been associated with poor immunological recovery and frequent disease relapses. The aim of this study was to analyse the role of T cell populations, Treg cells and CCR5 density in patients with VL compared to HIV-1-infected patients without leishmaniasis. A cross-sectional study of nine Leishmania-HIV-1-coinfected (LH) patients with VL receiving suppressive cART for at least 1 year were compared to 16 HIV-1-infected patients with non-immunological response (NIR, CD4 count below 250 cells/mm(3)) and 26 HIV-1-infected patients with immunological response (IR, CD4 count above 500 cells/mm(3)) without leishmaniasis. LH patients had a deep depletion of naïve T cells (p = 0.002), despite similar levels of effector T cells compared to NIR patients. CD4 Treg cells were similar compared to NIR patients, but higher compared to IR patients (p < 0.001). Interestingly, CD4 Treg CTLA-4(+) cells were higher in LH patients compared to either NIR or IR patients (p = 0.022 and p < 0.001, respectively), and the CD4 Treg/TEM ratio was similar to NIR patients, but higher compared to IR patients (p = 0.017). CCR5(+) T cell levels were higher compared to IR patients (p < 0.001), while CCR5 density on T cells were higher compared to both NIR and IR patients (p < 0.005 in both cases). Higher levels of CD4(+) CTLA-4(+) Treg cells and CCR5 density on CD8(+) T cells are strongly associated with VL in HIV-1-infected patients. Also, these patients have a poor immunological profile that might explain the persistence and relapse of the pathogen.


Assuntos
Antígeno CTLA-4/metabolismo , Infecções por HIV/imunologia , HIV-1/imunologia , Leishmania/imunologia , Leishmaniose Visceral/imunologia , Receptores CCR5/metabolismo , Linfócitos T Reguladores/imunologia , Adulto , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/imunologia , Estudos Transversais , Feminino , Infecções por HIV/complicações , Humanos , Leishmaniose Visceral/complicações , Masculino , Pessoa de Meia-Idade
5.
Infection ; 42(1): 185-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23765512

RESUMO

Peliosis hepatis is a rare histopathological entity of unknown etiology. We present a case of peliosis hepatis in a 44-year-old man with disseminated tuberculosis and acquired immunodeficiency syndrome. The diagnosis of peliosis hepatis was based on liver biopsy results which were suggestive of tuberculous etiology. Diagnosis of tuberculosis was confirmed by auramine stain, rRNA amplification and culture of Mycobacterium tuberculosis from synovial fluid of the elbow joint. The patient responded favourably to tuberculostatic treatment with four drugs and the early initiation of highly active antiretroviral therapy. Histopathological evidence of peliosis hepatis, without an obvious cause, makes it necessary to rule out tuberculosis, especially in the context of immunodeficiency diseases and immigrants from endemic areas.


Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Mycobacterium tuberculosis/isolamento & purificação , Peliose Hepática/diagnóstico , Peliose Hepática/etiologia , Tuberculose/complicações , Tuberculose/diagnóstico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Antirretrovirais/uso terapêutico , Antituberculosos/uso terapêutico , Biópsia , Articulação do Cotovelo/diagnóstico por imagem , Articulação do Cotovelo/microbiologia , Articulação do Cotovelo/patologia , Histocitoquímica , Humanos , Fígado/patologia , Masculino , Peliose Hepática/patologia , Radiografia Abdominal , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Tuberculose/tratamento farmacológico , Tuberculose/patologia
6.
HIV Med ; 14(5): 273-83, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23171059

RESUMO

OBJECTIVES: The objective of the study was to analyse key HIV-related outcomes in migrants originating from Latin America and the Spanish-speaking Caribbean (LAC) or sub-Saharan Africa (SSA) living in Spain compared with native Spaniards (NSP). METHODS: The Cohort of the Spanish AIDS Research Network (CoRIS) is an open, prospective, multicentre cohort of antiretroviral-naïve patients representing 13 of the 17 Spanish regions. The study period was 2004-2010. Multivariate logistic or Fine and Gray regression models were fitted as appropriate to estimate the adjusted effect of region of origin on the different outcomes. RESULTS: Of the 6811 subjects in CoRIS, 6278 were NSP (74.2%), LAC (19.4%) or SSA (6.4%). For these patients, the follow-up time was 15870 person-years. Compared with NSP, SSA and LAC under 35 years of age had a higher risk of delayed diagnosis [odds ratio (OR) 2.0 (95% confidence interval (CI) 1.5-2.8) and OR 1.7 (95% CI 1.4-2.1), respectively], as did LAC aged 35-50 years [OR 1.3 (95% CI 1.0-1.6)]. There were no major differences in time to antiretroviral therapy (ART) requirement or initiation. SSA exhibited a poorer immunological and virological response [hazard ratio (HR) [corrected] 0.8 (95% CI 0.7-1.0) and HR [corrected] 0.7 (95% CI 0.6-0.9), respectively], while no difference was found for LAC. SSA and LAC showed an increased risk of AIDS for ages between 35 and 50 years [HR 2.0 (95% CI 1.1-3.7) and HR [corrected] 1.6 (95% CI 1.1-2.4), respectively], which was attributable to a higher incidence of tuberculosis. However, no statistically significant differences were observed in mortality. CONCLUSIONS: Migrants experience a disproportionate diagnostic delay, but no meaningful inequalities were identified regarding initiation of treatment after diagnosis. A poorer virological and immunological response was observed in SSA. Migrants had an increased risk of AIDS, which was mainly attributable to tuberculosis.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Soropositividade para HIV/epidemiologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Adesão à Medicação/estatística & dados numéricos , Migrantes , Tuberculose/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/etnologia , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Adulto , África Subsaariana/epidemiologia , Contagem de Linfócito CD4 , Diagnóstico Tardio/estatística & dados numéricos , Atenção à Saúde , Progressão da Doença , Feminino , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/etnologia , Soropositividade para HIV/imunologia , Disparidades em Assistência à Saúde/etnologia , Humanos , América Latina/epidemiologia , Masculino , Adesão à Medicação/etnologia , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Socioeconômicos , Espanha/epidemiologia , Análise de Sobrevida , Tuberculose/tratamento farmacológico , Tuberculose/etnologia , Tuberculose/imunologia , Carga Viral
7.
HIV Clin Trials ; 7(4): 210-4, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17065033

RESUMO

PURPOSE: To determine the long-term efficacy of a simplification strategy in the clinical setting when used to improve adherence. METHOD: Prospective study of 70 patients included in a regimen with ddI plus 3TC plus an NNRTI, after viral suppression with a PI-containing regimen, due to decreasing adherence. Adherence to PI was calculated as the percentage of doses taken last week before inclusion, and patients were stratified as high and low adherence (95% and <95% of doses). RESULTS: Overall, 19 patients (27%) related adherence to PI <95% at inclusion (6 patients [9%], with adherence <80%). Mean adherence improved, with only 8% of patients presenting values <95%. At 104 weeks, 88% of patients on therapy had viral load suppression, but only 43% by ITT analysis. The main cause of therapy change or withdrawal was toxicity or drug interactions (26%). Notably, 16% of patients were lost to follow-up or left therapy, especially in the group of initially low adherent (26% vs. 12%, p = .02). CONCLUSION: The use of a simplification strategy could be associated with long-term high risk of treatment failure, when used to improve adherence in the clinical setting.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Cooperação do Paciente , Adulto , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/toxicidade , Didanosina/uso terapêutico , Interações Medicamentosas , Feminino , Inibidores da Protease de HIV/toxicidade , Humanos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Falha de Tratamento
8.
Mucosal Immunol ; 8(4): 760-72, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25407519

RESUMO

Altered interplay between gut mucosa and microbiota during treated HIV infection may possibly contribute to increased bacterial translocation and chronic immune activation, both of which are predictors of morbidity and mortality. Although a dysbiotic gut microbiota has recently been reported in HIV+ individuals, the metagenome gene pool associated with HIV infection remains unknown. The aim of this study is to characterize the functional gene content of gut microbiota in HIV+ patients and to define the metabolic pathways of this bacterial community, which is potentially associated with immune dysfunction. We determined systemic markers of innate and adaptive immunity in a cohort of HIV-infected individuals on successful antiretroviral therapy without comorbidities and in healthy non-HIV-infected subjects. Metagenome sequencing revealed an altered functional profile, with enrichment of the genes involved in various pathogenic processes, lipopolysaccharide biosynthesis, bacterial translocation, and other inflammatory pathways. In contrast, we observed depletion of genes involved in amino acid metabolism and energy processes. Bayesian networks showed significant interactions between the bacterial community, their altered metabolic pathways, and systemic markers of immune dysfunction. This study reveals altered metabolic activity of microbiota and provides novel insight into the potential host-microbiota interactions driving the sustained inflammatory state in successfully treated HIV-infected patients.


Assuntos
Microbioma Gastrointestinal , Infecções por HIV/imunologia , Infecções por HIV/microbiologia , HIV-1/imunologia , Imunidade Adaptativa , Terapia Antirretroviral de Alta Atividade , Teorema de Bayes , Biodiversidade , Estudos de Casos e Controles , Análise por Conglomerados , Progressão da Doença , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Humanos , Imunidade Inata , Cadeias de Markov , Metaboloma , Metabolômica , Metagenoma , RNA Ribossômico 16S
9.
AIDS ; 13(5): 615-20, 1999 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-10203387

RESUMO

BACKGROUND: As prisons have a high prevalence of tuberculosis and HIV infection, we studied the possibility of multiple tuberculosis infections in a selected population of HIV-infected inmates. METHODS: Two groups of patients with special characteristics were selected from 226 HIV-infected inmates diagnosed with tuberculosis in the prisons of Madrid (Spain) between 1993 and 1994. The first group contained nine patients who remained culture positive 4 months after the initiation of therapy and the second group contained 28 patients with Mycobacterium tuberculosis isolated from different anatomical sites. DNA typing with IS6110 was performed on all isolates from these patients. In some patients a secondary DNA typing with the plasmid pTBN12 was performed. RESULTS: Two patients from group A had a second M. tuberculosis strain obtained 4 and 18 months after the initial isolate, with different IS6110 and pTBN12 patterns. In one patient the second strain was multidrug resistant and in the other patient both strains had the same drug-susceptible pattern. The clinical and microbiologic evidence in both patients was consistent with the presence of active tuberculosis caused by a new strain of M. tuberculosis. In group B, the isolates from 27 patients shared similar fingerprint pattern; however, in one patient isolates from sputum and urine showed different IS6110 and pTBN12 patterns, although both strains showed the same drug-susceptible phenotype. CONCLUSION: This study provides evidence that HIV-infected inmates living under conditions of high environmental infectivity can be infected with two different strains of M. tuberculosis. This finding has implications for the tuberculosis-control programs in prison.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Mycobacterium tuberculosis , Prisioneiros , Tuberculose/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/transmissão , Adulto , Feminino , Humanos , Masculino , Mycobacterium tuberculosis/isolamento & purificação , Espanha/epidemiologia , Tuberculose/epidemiologia , Tuberculose/transmissão
10.
AIDS ; 12(11): F131-5, 1998 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-9708403

RESUMO

OBJECTIVE: To assess the rate of long-term effectiveness and factors associated with response to protease inhibitor therapy in a cohort of HIV-infected patients. DESIGN AND SETTING: Prospective, non-randomized study in a tertiary care centre. PATIENTS: A total of 400 HIV-infected patients who started on protease inhibitor therapy (saquinavir, 28%; ritonavir, 26%; indinavir, 46%) from March 1996 to March 1997. MAIN OUTCOMES MEASURES: Long-term virological and immunological effectiveness were defined as HIV RNA levels below 200 copies/ml and CD4+ cell count increase greater than 100 x 10(6)/l, respectively, after 12 months of therapy. RESULTS: Fifty-seven per cent of patients had a prior AIDS-defining illness, and 91% had received nucleoside analogues for a median time of 28 months. Median CD4+ count was 86 x 10(6) cells/l and HIV RNA level was 4.46 log10 copies/ml. The global rate of virological and immunological effectiveness at 1 year was 45 and 59%, respectively. In a logistic regression analysis, treatment failure was associated with higher baseline HIV load [relative risk (RR), 2.10; P<0.01], prior antiretroviral therapy (RR, 2.07; P<0.01), and use of saquinavir (RR, 1.55; P = 0.03), whereas a reduction of more than 1 log10 in HIV load within the first 3 months on therapy was strongly associated with response (RR, 0.65; P<0.01). There was no strict correlation between virological and immunological effectiveness (r = -0.35; P = 0.01). CONCLUSIONS: Nearly half of the patients maintain undetectable HIV load after 1 year of therapy, although important immunological benefit can be obtained in a greater proportion of patients. These data suggest the use of the most potent antiretroviral therapy in pretreated patients with high HIV load, and the capacity of initial virological decline to predict the long-term outcome.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1 , Indinavir/uso terapêutico , Ritonavir/uso terapêutico , Saquinavir/uso terapêutico , Adulto , Idoso , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , RNA Viral/sangue , Fatores de Tempo
11.
AIDS ; 14(9): F95-101, 2000 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-10894269

RESUMO

OBJECTIVE: To evaluate the importance of the number of active drugs, as determined by phenotypic resistance testing, in achieving virological response in successive salvage regimens. DESIGN: Phenotypic study of 57 plasma samples corresponding to 24 patients who had sequentially received three protease inhibitor-containing regimens. Phenotypic susceptibility to a drug (active drug) was defined as less than a four-fold-increase in the IC50 in comparison with the wild type. MAIN OUTCOME MEASURE: Virological response according to the number of active drugs (three versus two or fewer), HIV load, length of antiretroviral exposure, and line of protease inhibitor-based therapy (first, second and third regimen). RESULTS: Before the first protease inhibitor-based therapy, the median time on antiretroviral treatment was 42 months, and before the second and third protease inhibitor-salvage regimens it was 10 and 8 months, respectively. The number of patients receiving three active drugs simultaneously was 24, 35 and 31% in each line of therapy. At week 12, a close correlation was found between the presence of three active drugs in the antiretroviral regimen and the rate of virological response, in comparison with those patients receiving two or fewer active drugs [76 versus 45%, relative risk (RR), 1.7; 95% confidence interval (CI) 1.1-2.6; P = 0.028]. In a multivariate analysis, the use of two or fewer active drugs was an independent predictor of lack of response, regardless of HIV load, length of previous antiretroviral exposure and line of salvage therapy (RR, 4.5; 95%CI, 1.1-18.3; P = 0.03). Of note, a higher rate of response was observed in patients receiving the first protease inhibitor-containing regimen in comparison with those in subsequent protease inhibitor-based salvage regimens (83 versus 50 versus 28%, P < 0.01), even when only those patients receiving three active drugs were included (100 versus 71 versus 60%). CONCLUSIONS: This data confirm the usefulness of phenotypic testing in guiding antiretroviral therapy in heavily pretreated patients. The number of active drugs and the line of salvage therapy are independent predictors of virological response, regardless of HIV load and the length of antiretroviral exposure.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1/genética , Estudos de Coortes , Intervalos de Confiança , Resistência Microbiana a Medicamentos , Quimioterapia Combinada , Infecções por HIV/sangue , Infecções por HIV/virologia , Inibidores da Protease de HIV/farmacologia , HIV-1/efeitos dos fármacos , Humanos , Fenótipo , Valor Preditivo dos Testes , Prognóstico , RNA Viral/sangue , Terapia de Salvação , Fatores de Tempo , Carga Viral
12.
AIDS ; 14(2): F1-7, 2000 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-10708276

RESUMO

OBJECTIVE: To determine the rate of nevirapine resistance in patients failing a nevirapine plus protease inhibitor (PI)-based regimen, and whether these isolates remain susceptible to other non-nucleoside reverse transcriptase inhibitors (NNRTI). DESIGN AND SETTING: A retrospective cohort study in two tertiary university hospitals. PATIENTS: Eighty-eight HIV-infected, NNRTI-naive patients receiving nevirapine plus PI as a rescue regimen after PI treatment failure. MAIN OUTCOME MEASURES: Genotypic and phenotypic resistance data at inclusion (73 and 60 plasma samples, respectively) and after 24 weeks (53 and 42 samples). RESULTS: Baseline phenotypic susceptibility to nevirapine was found in 70% of patients, and similar data were observed for efavirenz (91%) and delavirdine (71%). NNRTI resistance-associated mutations were found in 11 patients (12.5%). At 24 weeks, resistant isolates to nevirapine were found in 92% of patients, and correlated with similar resistance to efavirenz (68%) and delavirdine (73%). In the genotypic analysis, the Y181 C mutation was observed in 76% of mutants, and the most common changes were a combination of mutations at positions Y181C/K103N (23%) and the single mutation Y181C (15%). The development of nevirapine resistance was associated with baseline resistance to PI included in the regimen (P= 0.01). For isolates containing the single amino acid substitution Y181C, 29% remained fully susceptible to efavirenz, whereas 14% showed intermediate resistance to efavirenz and delavirdine. CONCLUSION: The failure of a nevirapine plus PI-containing regimen is associated with nevirapine resistance in most patients, with the most common mutation occurring at amino acid residue 181. Although there is a high degree of cross-resistance among NNRTI, nearly one third of resistant isolates carrying the single Y181C mutation remain susceptible to efavirenz.


Assuntos
Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Nevirapina/uso terapêutico , Inibidores de Proteases/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Alcinos , Benzoxazinas , Estudos de Coortes , Ciclopropanos , Delavirdina/farmacologia , Resistência Microbiana a Medicamentos , Resistência a Múltiplos Medicamentos , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , HIV-1/genética , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Oxazinas/farmacologia , RNA Viral/análise , RNA Viral/genética , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/farmacologia , Fatores de Tempo , Carga Viral
13.
Antivir Ther ; 4(2): 117-21, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10682157

RESUMO

Sequential use of antiretroviral therapy with protease inhibitors (PI) is frequently prescribed owing to failure or intolerance of the first selected agent. Controversial data exist about the virological and immunological outcome of patients in whom a change to a second PI regimen is needed. A prospective study of 113 HIV-positive patients (male, 84%; mean age 36 years; previous AIDS-defining event, 35%; previous antiretroviral therapy with nucleoside analogues, 94%) who started a saquinavir-containing regimen between March 1996 and March 1997 and had to change to indinavir (n = 79) owing to intolerance, failure or medical criteria was performed. At the time of the switch, median CD4 cell count was 221 cells/mm3 and the HIV RNA level was 3.98 log10 copies/ml. The rate of viral suppression (HIV RNA levels below 200 copies/ml) was 40% at 3 months and 28% at month 6 after indinavir was instituted. In a logistic regression analysis, only the baseline viral load [relative risk (RR), 2.85; 95% confidence interval (CI), 1.31-6.05; P = 0.007] was statistically associated with the lack of viral suppression on indinavir. Although there are not sufficient data about the best therapeutic option if a change in PI-containing regimens therapy is considered, this study supports the recommendation of an early change of the PI-containing regimens, before the HIV-1 viral load reaches high levels.


Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1/isolamento & purificação , Indinavir/uso terapêutico , RNA Viral/sangue , Saquinavir/uso terapêutico , Síndrome da Imunodeficiência Adquirida/virologia , Adulto , Contagem de Linfócito CD4 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
Antivir Ther ; 5(4): 243-8, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11142618

RESUMO

OBJECTIVE: To assess the long-term effectiveness of and factors associated with response to protease inhibitors (PIs) in a cohort of treatment-naive HIV-infected patients. DESIGN AND SETTING: Prospective study in a tertiary care centre. SUBJECTS: A total of 207 treatment-naive patients starting PIs from March 1996 to May 1998. MAIN OUTCOME MEASURES: Clinical, virological and immunological outcomes, and adherence to therapy after 12 months. RESULTS: Baseline median CD4 cell count and viral load were 160 cells/mm3 and 5 log10 copies/ml, respectively. After 48 weeks, 168 patients (81%) reached plasma HIV-RNA levels below 400 copies/ml, and the mean increase in CD4 cell count was 196 cells/mm3. Clinical events were observed in 29 patients (14%) after a median time of 100 days on therapy, yet mortality was extremely low (0.9%). By multivariate analysis, adherence over 90% [relative risk (RR), 16.66; 95% confidence interval (CI), 5.26-50; P=0.00001] and AIDS diagnosis at baseline (RR 0.35; 95% CI, 0.14-0.90; P=0.02) were the strongest predictors for virological suppression. An immunological recovery over 100 cells/mm3 was significantly associated with an initial virological response (RR 2.94; 95% CI, 1.31-6.66; P=0.009) and adherence over 90% (RR 3.44; 95% CI, 1.61-7.69; P=0.005). There were high rates of change with the first PI (40%), mostly due to adverse events (51%), but it did not compromise long-term effectiveness. CONCLUSIONS: Initial PI treatment in the clinical setting is able to reach equally good outcomes as those found in controlled trials. Changes in therapy due to toxicity do not compromise a successful outcome, which clearly depends on an adequate adherence to therapy.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , HIV-1 , Inibidores da Transcriptase Reversa/uso terapêutico , Adolescente , Adulto , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Estudos Prospectivos , Resultado do Tratamento , Carga Viral
15.
Antivir Ther ; 4(3): 157-61, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-12731755

RESUMO

OBJECTIVES: To determine the effect of adherence on the rate of protease inhibitor (PI) treatment failure among human immunodeficiency virus (HIV)-infected patients. METHODS: A prospective study of a cohort of 282 patients who initiated PI therapy from March 1996 to December 1997. Adherence was quantified as the percentage of prescribed doses reportedly taken and treatment failure was defined as HIV RNA levels above 200 copies/ml after 1 year on therapy. RESULTS: Overall, 190 patients (67%) missed prescribed doses. However, mean percentage of doses taken was 91% (range, 21-100%). Demographic, virological and immunological characteristics could not predict adherence outcomes. The causes of non-adherence included intolerance or side effects (35%), complexity of treatment (23%), or recurrence in active drug abuse (17%), whereas abandonment owing to HIV-related disease was uncommon (6%). A degree of adherence above 90% correlated significantly with viral suppression [relative risk (RR) 1.69; 95% confidence interval (CI) 1.1-2.56; P<0.01]. In a multivariate analysis, a lower degree of adherence (RR, 0.96; P=0.006), a higher HIV viral load (RR, 2.03; P=0.0001), prior antiretroviral therapy (RR, 2.5; P=0.01), and use of saquinavir-hard gel capsules (saquinavir-HGC) (RR, 1.77; P=0.03) were strongly associated with treatment failure. CONCLUSION: The percentage of adherence and initial HIV viral load are the most important determinants of virological response to PI therapy and non-adherence is related to treatment-related factors in the majority of cases.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Cooperação do Paciente , Adulto , Idoso , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Falha de Tratamento , Carga Viral
16.
AIDS Res Hum Retroviruses ; 17(2): 93-8, 2001 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-11177388

RESUMO

The high rate of protease inhibitor treatment failure in clinical cohorts makes it necessary to define novel salvage therapies. In a prospective study of 31 HIV-infected patients included in a salvage regimen with stavudine, nevirapine, nelfinavir, and saquinavir, viral load decreased a median of 1.65 log(10) and 1.95 log(10) after 6 and 12 months of treatment, respectively, and 35 and 56% of patients had an HIV RNA level below 50 copies/ml at the same time points. At baseline, the mean number of mutations in the protease gene was 10 (2-19), and the V82A and L90M mutations were present in 54 and 21% of patients. The presence of the V82A mutation did not affect significantly the rate of response (36 vs. 38%), whereas the L90M mutation was associated with treatment failure (0 vs. 43%). Plasma trough levels of nelfinavir (NFV) and saquinavir (SQV), in a twice daily dosing regimen, were above the protein-corrected IC(95) in most patients despite the addition of an enzymatic inducer such as nevirapine, and peak levels were 2- and 5-fold increased with respect to standard doses. However, pharmacokinetics of saquinavir-hard gel capsule (SQV-hgc) did not improve significantly in the three times daily dosing regimen. In conclusion, the combination of stavudine, nevirapine, nelfinavir, and saquinavir increased plasma drug levels and produced an adequate virological response in patients who had failed indinavir or ritonavir therapy. This degree of response is not significantly decreased in the presence of genotypic mutations associated with indinavir/ritonavir (IDV/RTV) resistance.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Nevirapina/uso terapêutico , Estavudina/uso terapêutico , Adulto , Idoso , Combinação de Medicamentos , Resistência Microbiana a Medicamentos , Quimioterapia Combinada , Feminino , HIV/enzimologia , HIV/genética , Infecções por HIV/virologia , Protease de HIV/genética , Inibidores da Protease de HIV/farmacocinética , Humanos , Indinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mutação , Nelfinavir/farmacocinética , Nelfinavir/uso terapêutico , Estudos Prospectivos , RNA Viral/sangue , Ritonavir/uso terapêutico , Saquinavir/farmacocinética , Saquinavir/uso terapêutico , Falha de Tratamento , Carga Viral
17.
AIDS Res Hum Retroviruses ; 17(3): 211-5, 2001 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-11177403

RESUMO

Cross-resistance to nelfinavir (NFV) is observed in patients failing protease inhibitor (PI)-containing therapies. We performed a study with 111 patients who started an NFV-based salvage regimen after failing PI-based therapy to evaluate genotypic changes and to identify factors associated with resistance to NFV. Genotypic and phenotypic resistance data at entry (111 and 51 samples) and after NFV failure (74 and 31 samples) were available. Median CD4(+) cell count was 208 x 10(6)/liter, HIV RNA level was 4.6 log(10) copies/ml, and median number of mutations in the protease was 9. At baseline, 51 and 14% of viral isolates showed high or intermediate phenotypic resistance to NFV. Phenotypic data correlated with virological outcome, reaching undetectability at the third month in 40, 14, and 0% of those patients with susceptible, intermediate, or resistant viral isolates, respectively. Phenotypic resistance to NFV was associated with the presence of the L90M mutation: 46% for resistant vs. 6% in susceptible strains. The number of mutations in the protease correlated with the fold-increase in the IC(50)-NFV. The D30N mutation was detected in only 1 of 74 patients who failed. In a logistic regression analysis, the number of mutations in the protease was associated with NFV cross-resistance (RR, 2.09 per each additional mutation; 95% CI 1.23-3.55; p < 0.01). In conclusion, phenotypic cross-resistance to NFV for PI-experienced patients can be predicted by the number of mutations in the protease. The L90M mutation is significantly associated with the subsequent failure of NFV-containing regimens. The presence of the D30N mutation was rare and not useful in identifying NFV-resistant isolates.


Assuntos
Inibidores da Protease de HIV/farmacologia , Protease de HIV/genética , HIV-1/efeitos dos fármacos , Mutação , Nelfinavir/farmacologia , Adulto , Idoso , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Resistência Microbiana a Medicamentos/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Protease de HIV/efeitos dos fármacos , Inibidores da Protease de HIV/uso terapêutico , HIV-1/enzimologia , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Nelfinavir/uso terapêutico , Fenótipo
18.
HIV Clin Trials ; 1(1): 13-9, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11590485

RESUMO

PURPOSE: The purpose of our study was to evaluate the efficacy of indinavir (IDV) in a twice daily dosing regimen with coadministration of 100 mg ritonavir (RTV) and to explore the influence of plasma drug levels in the rate of virologic response. METHOD: We performed a prospective study of 59 patients who switched to a salvage regimen with two nucleoside analogs plus the combination of 100 mg RTV plus 800 mg IDV twice daily. Pharmacokinetics of IDV and RTV were assessed in 11 patients. RESULTS: Previous antiretroviral exposure was 44 months, and 78% and 39% of patients had previously failed regimens with either IDV or RTV. Median CD4 count was 248 x 10(6)/L and HIV load was 3.9 log(10) copies/mL. The median number of mutations in the protease gene was 9 (3-14), predominantly at residues 82 (53%), 90 (42%), and 46 (32%). After 24 weeks, 61% of patients had a viral load decrease greater than 1 log(10), and 38% had a viral load below 50 copies/mL. Nephrolitiasis, hematuria, or flank pain was observed in 13 patients (22%), leading to withdrawal in six cases (10%). IDV trough levels were well above the IC(95) (median 1.75 mg/L, interquartile range 1.07-2.57), but RTV trough levels were below the IC(95) in 88% of patients. There was a close correlation between higher peak levels of IDV, virological response, and renal toxicity. CONCLUSION: RTV/IDV 100/800 mg in a twice daily dosing regimen is associated with a significant virological response in patients with antiretroviral treatment failure. The correlation between plasma drug levels, toxicity, and response suggests the usefulness of individualized drug monitoring.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1 , Indinavir/uso terapêutico , Ritonavir/uso terapêutico , Terapia de Salvação , Fármacos Anti-HIV/uso terapêutico , Quimioterapia Combinada , Infecções por HIV/virologia , Inibidores da Protease de HIV/farmacocinética , HIV-1/efeitos dos fármacos , HIV-1/genética , HIV-1/fisiologia , Humanos , Indinavir/farmacocinética , Estudos Prospectivos , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/farmacocinética , Resultado do Tratamento , Carga Viral
19.
Med Clin (Barc) ; 106(16): 622-3, 1996 Apr 27.
Artigo em Espanhol | MEDLINE | ID: mdl-8656771

RESUMO

Kaposi sarcoma (KS) is the most frequent neoplasm found in AIDS patients. The disease is often disseminated and preferentially involves the skin and the lymphatic and digestive systems. Hepatosplenic involvement which is considered as a frequent autopsy finding is rarely diagnosed at life. A 27-year-old male HIV positive patient with severe immunosuppression who developed a rapidly progressive laterocervical cutaneous KS confirmed by pathologic study is presented. Abdominal echography and thoracoabdominal CT scand demonstrated lesions highly suggestive of pulmonary, lymph node, hepatic, splenic and rectal involvement by KS. The administration of 2 chemotherapy cycles produced subjective improvement and remission of the cutaneous lesions. Severe pulmonary superinfection led to death. An autopsy study was not performed. Hepatosplenic involvement by KS, diagnosed while the patient is alive is rare. The imaging techniques are useful to diagnose with high probability visceral involvement of KS. Systemic searching for visceral involvement in KS patients would lead to a marked increase in the cases such as that herein described with evident therapeutic and prognostic implications.


Assuntos
Síndrome da Imunodeficiência Adquirida/patologia , HIV-1 , Neoplasias Hepáticas/secundário , Sarcoma de Kaposi/patologia , Neoplasias Cutâneas/patologia , Neoplasias Esplênicas/secundário , Adulto , Evolução Fatal , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Masculino , Neoplasias Esplênicas/patologia , Abuso de Substâncias por Via Intravenosa/complicações
20.
Med Clin (Barc) ; 105(7): 251-4, 1995 Sep 09.
Artigo em Espanhol | MEDLINE | ID: mdl-7475465

RESUMO

BACKGROUND: HTLV-II is a human retrovirus considered to be responsible for the genesis of some lymphoproliferative and neurologic syndromes. The virus is endemic in some Amerindian and African tribes as well amongst injecting drug addicts (IDA) in North America and Europe. METHODS: The clinical, epidemiologic and virologic characteristics of the patients with HTLV-II infection identified in Spain up to November 1994 are described. RESULTS: One hundred thirteen subjects have been identified with HTLV-II infection in Spain with 4 being African immigrants residing in Madrid and the remaining being IDA from other European countries. Most were males (94/113; 83%). All were IDA except six (5 had acquired the infection by sexual contact and one by blood transfusion). Most of the IDA infected with HTLV-II were coinfected with HIV-1 (93/113; 83%). No patient showed clinical manifestations attributable to HTLV-II infection although one drug addict male coinfected with HIV-1 and HTLV-II developed a non-inflammatory proximal myopathy. CONCLUSIONS: Infection by HTLV-II is present in Spain and affects with preference to injecting drug addicts. It has been shown to be of growing incidence with a current global prevalence of 2% in IDA.


Assuntos
Infecções por HTLV-II/epidemiologia , Adulto , Feminino , Humanos , Masculino , Espanha/epidemiologia
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