RESUMEN
PURPOSE: The risk of developing active tuberculosis (TB) is considerably increased in people living with HIV/AIDS (PLWH). However, incidence of HIV/TB coinfection is difficult to assess as surveillance data are lacking in many countries. Here, we aimed to perform a quantitative analysis of HIV/TB coinfections within the Cologne/Bonn HIV cohort and to determine risk factors for active TB. METHODS: We systematically evaluated data of patients with HIV/TB coinfection between 2006 and 2017. In this retrospective analysis, we compared HIV/TB-coinfected patients with a cohort of HIV-positive patients. The incidence density rate (IDR) was calculated for active TB cases at different time points. RESULTS: During 2006-2017, 60 out of 4673 PLWH were diagnosed with active TB. Overall IDR was 0.181 cases/100 patient-years and ranged from 0.266 in 2006-2009 to 0.133 in 2014-2017. Patients originating from Sub-Saharan Africa had a significantly (p < 0.001) higher IDR (0.694/100 patient-years of observation, 95% CI [0.435-1.050]) in comparison to patients of German origin (0.053/100 patient-years of observation, 95% CI [0.028-0.091]). In terms of TB-free survival, individuals originating from countries with a TB incidence higher than 10/100,000 exhibited a markedly reduced TB-free survival compared to those originating from regions with lower incidence (p < 0.001). In 22 patients, TB and HIV infection were diagnosed simultaneously. CONCLUSION: Overall, we observed a decline in the incidence density rate (IDR) of HIV/TB coinfections between 2006 and 2017. Patients originating from regions with high incidence bear a higher risk of falling ill with active TB. For PLWH born in Germany, the observed risk of active TB appears to be lower compared to other groups within the cohort. These findings should be considered when developing TB containment and screening strategies for PLWH in low-incidence countries.
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Coinfección , Infecciones por VIH , Tuberculosis , Humanos , Estudios Retrospectivos , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Incidencia , Factores de Riesgo , Masculino , Tuberculosis/epidemiología , Tuberculosis/complicaciones , Femenino , Coinfección/epidemiología , Coinfección/virología , Adulto , Alemania/epidemiología , Persona de Mediana Edad , Adulto Joven , Estudios de CohortesRESUMEN
BACKGROUND AND AIMS: Liver-associated complications still frequently lead to mortality in people with HIV (PWH), even though combined antiretroviral treatment (cART) has significantly improved overall survival. The quantification of circulating collagen fragments released during collagen formation and degradation correlate with the turnover of extracellular matrix (ECM) in liver disease. Here, we analysed the levels of ECM turnover markers PC3X, PRO-C5, and PRO-C6 in PWH and correlated these with hepatic fibrosis and steatosis. METHODS: This monocentre, retrospective study included 141 PWH. Liver stiffness and liver fat content were determined using transient elastography (Fibroscan) with integrated CAP function. Serum levels of formation of cross-linked type III collagen (PC3X), formation of type V collagen (PRO-C5) and formation type VI collagen (PRO-C6), also known as the hormone endotrophin, were measured with ELISA. RESULTS: Twenty-five (17.7%) of 141 PWH had clinical significant fibrosis with liver stiffness ≥ 7.1 kPa, and 62 PWH (44.0%) had steatosis with a CAP value > 238 dB/m. Study participants with fibrosis were older (p = 0.004) and had higher levels of AST (p = 0.037) and lower number of thrombocytes compared to individuals without fibrosis (p = 0.0001). PC3X and PRO-C6 were markedly elevated in PWH with fibrosis. Multivariable cox regression analysis confirmed PC3X as independently associated with hepatic fibrosis. PRO-C5 was significantly elevated in participants with presence of hepatic steatosis. CONCLUSION: Serological levels of cross-linked type III collagen formation and endotrophin were significantly associated with liver fibrosis in PWH receiving cART and thus may be suitable as a non-invasive evaluation of liver fibrosis in HIV disease.
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Colágeno Tipo III , Colágeno Tipo VI , Colágeno Tipo V , Hígado Graso , Infecciones por VIH , Cirrosis Hepática , Humanos , Biomarcadores/sangre , Biomarcadores/metabolismo , Colágeno Tipo III/sangre , Colágeno Tipo III/metabolismo , Colágeno Tipo VI/sangre , Colágeno Tipo VI/metabolismo , Hígado Graso/sangre , Hígado Graso/complicaciones , Hígado Graso/diagnóstico por imagen , Hígado Graso/metabolismo , Infecciones por VIH/sangre , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , Hígado/diagnóstico por imagen , Hígado/metabolismo , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/etiología , Cirrosis Hepática/metabolismo , Estudios Retrospectivos , Matriz Extracelular/metabolismo , Terapia Antirretroviral Altamente Activa , Colágeno Tipo V/sangre , Colágeno Tipo V/metabolismo , Procolágeno/sangre , Procolágeno/metabolismoRESUMEN
BACKGROUND: Previous studies have shown that men with HIV and germ cell cancer (HIV-GCC) have inferior overall survival (OS) in comparison with their HIV-negative counterparts. However, little information is available on treatments and outcomes of HIV-GCC in the era of combination antiretroviral therapy (cART). METHODS: This study examined men living with HIV who were 18 years old or older and had a diagnosis of histologically proven germ cell cancer (GCC). The primary outcomes were OS and progression-free survival (PFS). RESULTS: Data for 89 men with a total of 92 HIV-GCCs (2 synchronous GCCs and 1 metachronous bilateral GCC) were analyzed; among them were 64 seminomas (70%) and 28 nonseminomas (30%). The median age was 36 years, the median CD4 T-cell count at GCC diagnosis was 420 cells/µL, and 77% of the patients on cART had an HIV RNA load < 500 copies/mL. Stage I disease was found in 44 of 79 gonadal GCCs (56%). Among 45 cases with primary disseminated GCC, 78%, 18%, and 4% were assigned to the good-, intermediate-, and poor-prognosis groups, respectively, of the International Germ Cell Cancer Collaborative Group. Relapses occurred in 14 patients. Overall, 12 of 89 patients (13%) died. The causes of death were refractory GCC (n = 5), an AIDS-defining illness (n = 3), and other causes (n = 4). After a median follow-up of 6.5 years, the 5- and 10-year PFS rates were 81% and 73%, respectively, and the 5- and 10-year OS rates were 91% and 85%, respectively. CONCLUSIONS: The 5- and 10-year PFS and OS rates of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients. LAY SUMMARY: Men living with HIV are at increased risk for germ cell cancer (GCC). Previous studies have shown that the survival of men with HIV-associated germ cell cancer (HIV-GCC) is poorer than the survival of their HIV-negative counterparts. This study examined the characteristics, treatments, and outcomes of 89 men with HIV-GCC in the era of effective combination antiretroviral therapies. The long-term outcomes of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients.
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Infecciones por VIH , Neoplasias de Células Germinales y Embrionarias , Seminoma , Neoplasias Testiculares , Adolescente , Adulto , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Recurrencia Local de Neoplasia , Seminoma/patología , Neoplasias Testiculares/patologíaRESUMEN
OBJECTIVES: Although direct-acting antivirals (DAAs) can clear HCV in nearly all HIV/HCV-coinfected individuals, high rates of reinfection may hamper efforts to eliminate HCV in this population. We investigated reinfection after sustained virological response (SVR) in HIV/HCV-coinfected individuals in Europe. METHODS: Factors associated with odds of reinfection by 2 years after SVR in EuroSIDA participants with one or more HCV-RNA test and 2 years follow-up were assessed using logistic regression. RESULTS: Overall, 1022 individuals were included. The median age was 50 (interquartile range: 43-54 years), and most were male (78%), injection drug users (52%), and received interferon (IFN)-free DAAs (62%). By 24 months, 75 [7.3%, 95% confidence interval (CI): 5.7-8.9%] individuals were reinfected. Among individuals treated prior to 2014, 16.1% were reinfected compared with 4.2% and 8.3%, respectively, among those treated during or after 2014 with IFN-free and IFN-based therapy. After adjustment, individuals who had started treatment during or after 2014 with IFN-free or IFN-based therapy had significantly lower odds of reinfection (adjusted odds ratio = 0.21, 95% CI: 0.11-0.38; 0.43, 95% CI: 0.22-0.83) compared with those who had received therapy before 2014. There were no significant differences in odds of reinfection according to age, gender, European region, HIV transmission risk group or liver fibrosis. CONCLUSIONS: Among HIV/HCV-coinfected individuals in Europe, 7.3% were reinfected with HCV within 24 months of achieving SVR, with evidence suggesting that this is decreasing over time and with use of newer HCV regimens. Harm reduction to reduce reinfection and surveillance to detect early reinfection with an offer of treatment are essential to eliminate HCV.
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Coinfección , Infecciones por VIH , Hepatitis C Crónica , Antivirales/uso terapéutico , Coinfección/complicaciones , Coinfección/tratamiento farmacológico , Europa (Continente)/epidemiología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , ReinfecciónRESUMEN
Since 2002, a global epidemic of acute hepatitis C virus (HCV) infection has been noted in men who have sex with men (MSM). Transmission of HCV, particularly in the context of traumatic sex practices that increase the risk of blood-blood contacts (eg, anal sex and fisting), was initially found in human immunodeficiency virus (HIV)-coinfected and more recently in HIV-uninfected MSM, especially those receiving pre-exposure prophylaxis (PrEP). Early HCV treatment with all-oral direct-acting antiviral combination therapy has been associated with very high HCV cure rates of up to 100%. Indeed, immediate treatment of recently acquired HCV directly after new HCV diagnosis, or after 4 weeks if no 2-log10 drop in HCV RNA level occurs, promises rapid HCV elimination. Reports from the Netherlands, Switzerland, and the United Kingdom all show that with increased treatment uptake in this particular patient group, dramatic reductions in new HCV infections can be achieved. A general consensus on how to best screen for and manage acute HCV infections, along with broad access to rapid HCV therapy initiation, is crucial to attaining HCV elimination, a goal that is challenged by high HCV reinfection rates among MSM.
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Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Homosexualidad Masculina/estadística & datos numéricos , Coinfección , Erradicación de la Enfermedad , Hepatitis C/transmisión , Humanos , Masculino , Países Bajos , ARN Viral/genética , Suiza , Reino Unido , Carga ViralRESUMEN
Abnormal liver enzymes (LE) are common in patients infected with the human immunodeficiency virus (HIV) even in the absence of viral hepatitis or alcohol abuse. With availability of antiretroviral combination therapy, life expectancy has improved dramatically and as a consequence the spectrum of liver disease is changing. Increased reports on the development of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) in HIV coinfected patients raise questions around prevalence, clinical manifestations, and clinical outcome of these liver diseases in HIV coinfection. Moreover, the potential impact of combination antiretroviral therapy as well as direct HIV effects on the emergence of non-alcoholic fatty liver disease needs to be explored. This review summarizes the recent literature on NAFLD and NASH in HIV.
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Terapia Antirretroviral Altamente Activa , Hígado Graso/etiología , Infecciones por VIH/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Fármacos Anti-VIH/uso terapéutico , Hígado Graso/diagnóstico , Infecciones por VIH/complicaciones , Humanos , PrevalenciaRESUMEN
The introduction of highly potent direct-acting antivirals (DAAs) has revolutionized hepatitis C virus treatment. Nevertheless, viral eradication worldwide remains a challenge also in the era of DAA treatment, because of the high associated costs, high numbers of undiagnosed patients, high re-infection rates in some risk groups and suboptimal drug efficacies associated with host and viral factors as well as advanced stages of liver disease. A correct determination of the HCV genotype allows administration of the most appropriate antiviral regimen. Additionally, HCV genetic sequencing improves our understanding of resistance-associated variants, either naturally occurring before treatment, acquired by transmission at HCV infection, or emerging after virological failure. Because treatment response rates, and the prevalence and development of drug resistance variants differ for each DAA regimen and HCV genotype, this review summarizes treatment opportunities per HCV genotype, and focuses on viral genetic sequencing to guide clinical decision making. Although approval of the first pan-genotypic DAA-only regimen is expected soon, HCV genetic sequencing will remain important because when DAA therapies fail, genotyping and resistance testing to select a new active DAA combination will be essential. Copyright © 2016 John Wiley & Sons, Ltd.
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Antivirales/farmacología , Antivirales/uso terapéutico , Farmacorresistencia Viral , Genotipo , Hepacivirus/clasificación , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Técnicas de Genotipaje , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana , Mutación , Selección Genética , Resultado del TratamientoRESUMEN
BACKGROUND: In 2016, the World Health Organization (WHO) adopted a new Global Health Sector Strategy on HIV for 2016-2021. It establishes 15 ambitious targets, including the '90-90-90' target calling on health systems to reduce under-diagnosis of HIV, treat a greater number of those diagnosed, and ensure that those being treated achieve viral suppression. DISCUSSION: The WHO strategy calls for person-centered chronic care for people living with HIV (PLHIV), implicitly acknowledging that viral suppression is not the ultimate goal of treatment. However, it stops short of providing an explicit target for health-related quality of life. It thus fails to take into account the needs of PLHIV who have achieved viral suppression but still must contend with other intense challenges such as serious non-communicable diseases, depression, anxiety, financial stress, and experiences of or apprehension about HIV-related discrimination. We propose adding a 'fourth 90' to the testing and treatment target: ensure that 90 % of people with viral load suppression have good health-related quality of life. The new target would expand the continuum-of-services paradigm beyond the existing endpoint of viral suppression. Good health-related quality of life for PLHIV entails attention to two domains: comorbidities and self-perceived quality of life. CONCLUSIONS: Health systems everywhere need to become more integrated and more people-centered to successfully meet the needs of virally suppressed PLHIV. By doing so, these systems can better meet the needs of all of their constituents - regardless of HIV status - in an era when many populations worldwide are living much longer with multiple comorbidities.
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Infecciones por VIH/patología , Política de Salud/legislación & jurisprudencia , Calidad de Vida , Humanos , Carga ViralRESUMEN
UNLABELLED: Human immunodeficiency virus (HIV) and hepatitis virus coinfection amplify and accelerate hepatic injury. MicroRNAs (miRNAs) are small regulatory RNAs suggested as biomarkers for liver injury. We analyzed the circulating levels of miRNAs in HIV patients with regard to the extent and etiology of liver injury. Total RNA was extracted from 335 serum samples of HIV patients and 22 healthy control participants using Qiazol. Comprehensive polymerase chain reaction (PCR) array analyses (768 miRNA) were performed in serum samples of eight HIV, eight HIV/HCV (hepatitis C virus), six HCV patients, and three healthy controls. Reverse transcription (RT)-PCR measured levels of miRNA-122, miRNA-22, and miRNA-34a in serum samples of 335 patients and 19 healthy control participants. Liver injury and fibrosis in these patients were defined using aspartate aminotransferase (AST) levels, fibrosis-4 (FIB-4) index and AST-to-platelet ratio index (APRI) score. The miRNA pattern of HIV/HCV samples showed altered expression of 57 and 33 miRNA compared to HCV and HIV infection, respectively. miRNA-122, miRNA-22, and miRNA-34a were highly up-regulated in HIV/HCV patients. Analyzing the entire cohort, these miRNAs were correlated with liver function tests and were independent predictors of liver injury (AST >2 × ULN). miRNA-122 and miRNA-22 were associated with relevant fibrosis (FIB-4 >1.45; APRI >1). Circulating levels of miRNA-122 were independent predictors for relevant fibrosis in HIV patients. Interestingly, miRNA-122 and miRNA-34a levels were higher in HIV/HCV patients, miRNA-22 levels were highest in HIV/HBV patients, and circulating levels of miRNA-34a correlated positively with illicit drug use and ethanol consumption. CONCLUSION: Circulating miRNA-122, miRNA-22, and miRNA-34a correlates with the etiology of liver injury in HIV patients. These biomarkers not only mirror different mechanisms of hepatic injury, but also are independent predictors of liver injury in HIV patients.
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Infecciones por VIH/complicaciones , Insuficiencia Hepática/sangre , Hepatitis Viral Humana/complicaciones , Cirrosis Hepática/sangre , MicroARNs/sangre , Adulto , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Coinfección/sangre , Femenino , Infecciones por VIH/sangre , Voluntarios Sanos , Insuficiencia Hepática/diagnóstico , Insuficiencia Hepática/virología , Hepatitis Viral Humana/sangre , Hepatitis Viral Humana/virología , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Adulto JovenRESUMEN
PURPOSE: Despite established HIV prevention strategies and broadly available diagnostic strategies in developed western countries, rates of HIV new infections remain high. Alternative strategies for HIV prevention, particularly among men who have sex with men (MSM), are crucial. HIV pre-exposure prophylaxis (PrEP) has been discussed as one additional option that this review seeks to explore. METHODS: An online search identifying PrEP-relevant literature from 1st January 2010 to 1st August, 2015 was performed. RESULTS: The iPrEx study, first published in 2010, demonstrated a reduction in relative risk (RRR) of HIV seroconversion of 44 % for continuous PrEP with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) in MSM. The efficacy of PrEP has been confirmed for continuous PrEP in the PROUD study and for intermittent PrEP in the IPERGAY study (RRR = 86 % in both studies). The PrEP was well tolerated in all studies, and the evolution of HIV resistance has been low. Compensatory increased sexual risk behavior was not observed in recent studies. In contrast to the high efficacy of risk reduction for HIV transmission in MSM, the results of TDF PrEP and TDF/FTC PrEP studies using microbicidal agents or pills among heterosexual women were different (RRR 6-75 %). CONCLUSIONS: Continuous and intermittent PrEP demonstrated high efficacy in preventing HIV seroconversion, notably among MSM. PrEP was well tolerated. Adherence was critical for high efficacy in all studies. Further studies to evaluate implementation strategies and cost-effectiveness in different risk populations are needed as well as drug approval in Europe.
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Antirretrovirales/administración & dosificación , Infecciones por VIH/prevención & control , Profilaxis Pre-Exposición/métodos , Administración Oral , Humanos , Cumplimiento de la Medicación , Resultado del TratamientoRESUMEN
BACKGROUND: About one third of patients infected with human immunodeficiency virus (HIV) also have chronic hepatitis due to hepatitis C virus (HCV). HCV therapy with simeprevir, pegylated interferon alfa (PegIFNα) and ribavirin (RBV) have been shown to be superior to PegIFNα + RBV alone in non-HIV patients, but no randomized trials in patients with HCV genotype 1 (HCV-1)/HIV coinfection are available. METHODS: This was a historical comparison of study C212 (simeprevir + PegIFNα-2a + RBV in patients with HCV-1/HIV coinfection) with studies in which HCV-1/HIV coinfected patients were treated with PegIFNα-2a + RBV alone. A systematic literature search was performed to identify eligible studies. Efficacy and safety results of PegIFNα-2a + RBV studies were combined in random- and fixed-effects inverse-variance weighted meta-analyses of proportions using the Freeman-Tukey double arcsin transformation method, and compared with the results of study C212. RESULTS: The literature search revealed a total of 2392 records, with 206 articles selected for full-text review. Finally, 11 relevant articles reporting on 12 relevant study groups were included. Results on sustained virologic response 24 weeks after end of treatment (SVR24) were available from all 12 study groups. Pooled SVR24 for PegIFNα-2a + RBV from the random-effects meta-analysis was 28.2% (95% CI 23.8% to 32.9%). The comparison between study C212 (SVR24 = 72.6%; 95% CI 63.1% to 80.9%) revealed substantial superiority of simeprevir + PegIFNα-2a + RBV compared to PegIFNα-2a + RBV alone, with an absolute risk difference of 45% (95% CI 34 to 55). This finding was robust in a sensitivity analysis that only included historical studies with a planned treatment duration of at least 48 weeks and the same RBV dose as in study C212. No increases in the frequency of important adverse event categories including anemia were identified, but these analyses were limited by the low number of studies. CONCLUSION: This historical comparison provides first systematic evidence for the superiority of simeprevir + PegIFNα-2a + RBV compared to PegIFNα-2a + RBV in patients with HCV-1/HIV coinfection. Given the limitations of the historical comparison for safety endpoints, additional data on the comparative safety of simeprevir in patients with HCV-1/HIV coinfection would be desirable. TRIAL REGISTRATION: Identifier for study TMC435-TiDP16-C212 (ClinicalTrials.gov): NCT01479868.
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Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Simeprevir/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Coinfección/tratamiento farmacológico , Quimioterapia Combinada , Genotipo , Infecciones por VIH/complicaciones , VIH-1/genética , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Humanos , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
Chronic HCV infections represent a major worldwide public health problem and are responsible for a large proportion of liver related deaths, mostly because of HCV-associated hepatocellular carcinoma and cirrhosis. The treatment of HCV has undergone a rapid and spectacular revolution. In the past 5â years, the launch of direct acting antiviral drugs has seen sustained virological response rates reach 90% and above for many patient groups. The new treatments are effective, well tolerated, allow for shorter treatment regimens and offer new opportunities for previously excluded groups. This therapeutic revolution has changed the rules for treatment of HCV, moving the field towards an interferon-free era and raising the prospect of HCV eradication. This manuscript addresses the new challenges regarding treatment optimisation in the real world, improvement of antiviral efficacy in 'hard-to-treat' groups, the management of patients whose direct acting antiviral drug treatment was unsuccessful, and access to diagnosis and treatment in different parts of the world.
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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Accesibilidad a los Servicios de Salud , Humanos , Resultado del TratamientoRESUMEN
There is an international epidemic of hepatitis C virus (HCV) infection among human immunodeficiency virus-infected men who have sex with men. Transmission of HCV variants that are resistant to recently approved direct-acting antivirals (DAAs) could be an important clinical and public health problem. We document a case of transmission of a DAA-resistant variant of HCV from a patient who was treated with telaprevir to his sexual partner. The transmission of HCV DAA-resistant variants could impair therapeutic regimens that include DAAs.
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Antivirales/uso terapéutico , Coinfección , Farmacorresistencia Viral/genética , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Hepacivirus/genética , Hepatitis C/transmisión , Homosexualidad Masculina , Inhibidores de Proteasas/uso terapéutico , Genotipo , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Hepacivirus/efectos de los fármacos , Hepacivirus/aislamiento & purificación , Hepatitis C/complicaciones , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Humanos , Masculino , Fenotipo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Sexo Inseguro , Carga Viral , Proteínas no Estructurales Virales/antagonistas & inhibidores , Proteínas no Estructurales Virales/genéticaRESUMEN
Much of our knowledge about HIV infection has been obtained from cohort studies, including description of the natural history of infection, identification of CD4 count and viral load as good surrogate markers of clinical progression, identification of co-factors [including older age and viral infections (CMV, HCV)] for progression of HIV-related disease and assessment of impact of highly active antiretroviral therapy on clinical outcomes. The Cologne-Bonn cohort was founded by Gerd Fätkenheuer and Bernd Salzberger after introduction of combination antiretroviral therapy in 1996 and has delivered important findings which have helped to improve treatment strategies as well as quality of overall care in HIV infection in these two cities. Indeed, the first pivotal paper from the cohort reported on an unexpectedly high rate of virological treatment failure of protease inhibitor therapy in an unselected cohort of HIV-infected patients. The subsequent analysis of risk factors for virological failure initiated the development of more potent HIV combination therapy. This review summarizes some of the major findings and contributions from the Cologne-Bonn cohort since 1996.
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Terapia Antirretroviral Altamente Activa , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Recuento de Linfocito CD4 , Estudios de Cohortes , Infecciones por VIH/inmunología , Infecciones por VIH/mortalidad , Seropositividad para VIH , Humanos , Factores de Riesgo , Insuficiencia del Tratamiento , Carga ViralRESUMEN
BACKGROUND: Simeprevir is an oral, once-daily, hepatitis C virus (HCV) NS3/4A protease inhibitor for the treatment of chronic HCV genotype 1 infection. Human immunodeficiency virus (HIV) coinfection accelerates progression of liver disease. This uncontrolled, open-label trial explored the safety and efficacy of simeprevir in patients with HCV genotype 1/HIV type 1 (HIV-1) coinfection. METHODS: Patients received simeprevir (150 mg once daily) with pegylated interferon alfa-2a/ribavirin (peg-IFN/RBV) for 12 weeks. Noncirrhotic HCV treatment-naive patients and prior relapsers received response-guided therapy (RGT) with peg-IFN/RBV for 24 or 48 weeks. Prior null responders, prior partial responders, and patients with cirrhosis received peg-IFN/RBV for 48 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). RESULTS: One hundred and six patients (93 on antiretroviral therapy) were enrolled and treated. SVR12 rates were 79.2% in HCV treatment-naive patients, 57.1% in prior null responders, 86.7% in prior relapsers, and 70.0% in prior partial responders. Fifty-four of 61 eligible patients (88.5%) met RGT criteria for 24 weeks of peg-IFN/RBV, of whom 87.0% (47/54) achieved SVR12. SVR12 rates were 80.0% (36/45) and 63.6% (14/22) for patients with METAVIR scores of F0-F2 and F3-F4, respectively. Common adverse event (AE) rates were consistent with peg-IFN/RBV therapy (fatigue, headache, nausea, neutropenia). Most AEs were grade 1/2; serious AEs occurred in 5.7% of patients, none of which were fatal. CONCLUSIONS: Simeprevir was generally well tolerated with safety similar to that observed in HCV-monoinfected patients and high SVR12 rates in HCV treatment-naive patients, prior relapsers, prior partial responders, and prior null responders with HIV-1 coinfection. CLINICAL TRIALS REGISTRATION: NCT01479868.
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Infecciones por VIH/tratamiento farmacológico , VIH-1/aislamiento & purificación , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Sulfonamidas/uso terapéutico , Adolescente , Adulto , Anciano , Antivirales/efectos adversos , Antivirales/uso terapéutico , Femenino , Infecciones por VIH/virología , Hepatitis C Crónica/virología , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Humanos , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Polietilenglicoles/efectos adversos , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Ribavirina/efectos adversos , Simeprevir , Sulfonamidas/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
From a global perspective, cardiovascular disease (CVD) in human immunodeficiency virus (HIV) may result from cardiac involvement upon presentation of opportunistic infections in the presence of advanced immunosuppression, be a consequence of HIV-induced immune activation or derive from antiretroviral therapy-associated dyslipidaemia and insulin resistance. Indeed, in developed countries with unlimited access to antiretroviral therapy CVD has become one of the major causes of death in HIV. Therefore, cardiovascular risk reduction and lifestyle modifications are essential and careful selection of the antiretroviral drugs according to underlying cardiovascular risk factors of great importance. In developing countries with delayed roll-out of antiretroviral therapy pericardial disease (often related to TB), HIV-associated cardiomyopathy, and HIV-associated pulmonary hypertension are the most common cardiac manifestations in HIV. In Africa, the epicentre of the HIV epidemic, dynamic socio-economic and lifestyle factors characteristic of epidemiological transition appear to have positioned the urban African community at the cross-roads between historically prevalent and 'new' forms of CVD, such as coronary artery disease. In this context, cardiovascular risk assessment of HIV-infected patients will become a critical element of care in developing countries similar to the developed world, and access to antiretroviral therapy with little or no impact on lipid and glucose metabolism of importance to reduce CVD in HIV.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Cardiopatías/virología , Cardiomiopatías/virología , Coinfección/complicaciones , Enfermedad de la Arteria Coronaria/virología , Angiopatías Diabéticas/virología , Interacciones Farmacológicas , Quimioterapia Combinada , Salud Global , Infecciones por VIH/complicaciones , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Hipertensión Pulmonar/virología , Terapia de Inmunosupresión , Pericarditis/virología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Factores de Riesgo , Conducta de Reducción del Riesgo , Tuberculosis/complicacionesRESUMEN
BACKGROUND: Displacement has been associated with an increased risk of HIV transmission. In light of the lack of data from Libya on sexual behavior and HIV/AIDS knowledge, the effort was undertaken to assess HIV/AIDS knowledge and attitudes towards HIV and condom use in Libyan internally displaced males (IDPs) in Tripoli. METHODS: Cross-sectional study design using purposive sampling to identify internally displaced Libyan males from five camps in Tripoli. HIV/AIDS knowledge, attitudes towards HIV and condom use, and prevention practices were evaluated through a self-administered, close/ended anonymous questionnaire in Arabic. RESULTS: The study population consisted of 390 participants, all Muslims, with a mean age of 32.81 years (SD = 8.93). Overall, the average HIV and prevention knowledge score was 6.34 (SD = 1.98). The majority of the respondents thereby had an insufficient or low knowledge' level of HIV and prevention knowledge (58.70%). The mean attitude score indicated overall a negative attitude towards condom use (Mean = 32.60, SD = 7.97). CONCLUSIONS: This is the first biobehavioral survey among IDPs in Libya demonstrating a low level of HIV and prevention knowledge as well as a prevailing negative attitude level of HIV/AIDS and condom use.