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1.
J Antimicrob Chemother ; 78(10): 2591-2596, 2023 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-37671831

RESUMEN

OBJECTIVES: HIV infection has been associated with lower rates of sustained viral response (SVR) with direct-acting antivirals (DAAs). There are few data on glecaprevir/pibrentasvir (G/P) in HIV/HCV coinfection outside clinical trials. METHODS: The HEPAVIR-DAA cohort, which recruits HIV/HCV-coinfected patients (NCT02057003) and the GEHEP-MONO cohort (NCT02333292), including HCV-monoinfected individuals, are two concurrent ongoing multicentre cohorts of patients receiving anti-HCV treatment. Patients starting G/P included in those cohorts were analysed. Overall SVR (ITT), discontinuations due to adverse effects, and dropouts were evaluated and compared between both cohorts. RESULTS: Of the 644 patients who started G/P with evaluable SVR, 132 were HIV/HCV coinfected. Overall SVR rates were 487/512 (95.1%) in HCV-monoinfected patients versus 126/132 (95.5%) in HIV/HCV-coinfected patients (P = 1.000). One patient (0.8%) relapsed, and another (0.8%) discontinued treatment due to side effects. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected versus HCV-monoinfected patients. The main reason for not reaching SVR among HIV/HCV-coinfected patients was premature dropout linked to active drug use. CONCLUSIONS: G/P in HIV/HCV coinfection was highly effective and tolerable in clinical practice. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected compared with HCV-monoinfected patients but active drug use is still a barrier to reach HCV microelimination.


Asunto(s)
Coinfección , Infecciones por VIH , Hepatitis C Crónica , Humanos , Antivirales/farmacología , Coinfección/tratamiento farmacológico , Coinfección/complicaciones , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Ensayos Clínicos como Asunto , Estudios Multicéntricos como Asunto
2.
J Antimicrob Chemother ; 72(10): 2850-2856, 2017 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-29091196

RESUMEN

Background: New direct-acting antiviral agents (DAAs) have shown great efficacy and tolerability in clinical trials and real-life cohorts. However, data are scarce regarding efficacy and safety in cirrhotic HCV/HIV-coinfected patients. Methods: A multicentre prospective analysis was performed in 13 Spanish hospitals, including all cirrhotic HCV/HIV-coinfected patients starting DAA combinations from January to December 2015. Sustained virological response 12 weeks after treatment (SVR12) was analysed. Withdrawal due to toxicity and/or hepatic decompensation and change in liver stiffness measurement (LSM) after HCV treatment were evaluated. Results: Patients (n = 170) were mostly male (n = 125; 74.3%) with the following HCV genotype (Gt) distribution: Gt-1a, 68 (40%); Gt-1b, 21 (12.4%); Gt-4, 47 (27.6%); and Gt-3, 26 (15.3%). Baseline median LSM was 20.6 kPa (IQR 16.1-33.7) and log10 HCV-RNA 6.1 IU/mL (IQR 5.7-6.5). Most patients had a Child-Pugh class A score (n = 127; 74.7%) and 28 (16.5%) had prior hepatic decompensation. There were 89 (52.4%) pretreated patients with 40.4% (n = 36) of null responders. Preferred regimens were as follows: sofosbuvir/ledipasvir + ribavirin, 43 (25.3%) patients; sofosbuvir + simeprevir + ribavirin, 34 (20%); sofosbuvir/ledipasvir, 26 (15.3%) and sofosbuvir + daclatasvir + ribavirin, 25 (14.7%). Overall SVR12 was 92.9% (158/170), without differences between genotypes. Pretreated patients had lower SVR12 rates compared with naive (88.8% versus 97.5%; P = 0.026). Treatment failures were as follows: 7 (4.1%) relapses; 2 (1.2%) lost to follow-up; 1 (0.6%) toxicity-related discontinuation; 1 (0.6%) hepatic decompensation; and 1 (0.6%) viral breakthrough. On-treatment hepatic decompensation was recorded in four (2.4%) patients (encephalopathy and ascites, two each). Paired LSM in 33 patients showed a decrease of 5.6 kPa (95% CI 1.8-9.2; P = 0.004). Conclusions: In our cohort of cirrhotic HCV/HIV-coinfected patients, DAAs were highly safe and efficacious. Viral eradication was associated with a significant decrease in liver stiffness.


Asunto(s)
Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/complicaciones , ARN Viral/efectos de los fármacos , Antivirales/administración & dosificación , Antivirales/efectos adversos , Bencimidazoles/administración & dosificación , Bencimidazoles/efectos adversos , Bencimidazoles/uso terapéutico , Estudios de Cohortes , Coinfección/virología , Quimioterapia Combinada/efectos adversos , Femenino , Fluorenos/administración & dosificación , Fluorenos/efectos adversos , Fluorenos/uso terapéutico , Genotipo , VIH/efectos de los fármacos , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ribavirina/administración & dosificación , Ribavirina/efectos adversos , Ribavirina/uso terapéutico , Simeprevir/administración & dosificación , Simeprevir/efectos adversos , Simeprevir/uso terapéutico , Sofosbuvir , España/epidemiología , Respuesta Virológica Sostenida , Resultado del Tratamiento , Uridina Monofosfato/administración & dosificación , Uridina Monofosfato/efectos adversos , Uridina Monofosfato/análogos & derivados , Uridina Monofosfato/uso terapéutico
3.
J Infect ; 85(3): 322-326, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35700867

RESUMEN

OBJECTIVES: Real world data on glecaprevir/pibrentasvir (G/P) among active drug users are scarce. We evaluated the sustained virological response (SVR) rates of G/P among individuals with and without active drug use in routine clinical practice. METHODS: Two ongoing prospective multicenter cohorts of individuals starting G/P were analyzed. Overall SVR intention-to-treat (ITT), discontinuations due to adverse effects and dropouts were evaluated. Results in patients with active, past and without active drug use were compared. RESULTS: Overall, 644 individuals started G/P and have reached the date of SVR evaluation. Of them, 613 (95.2%) individuals achieved SVR. There were two (0.3%) relapses, one (0.2%) discontinuation due to side effects and 35 (5.4%) dropouts. SVR rates for patients with active drug use, past drug use and those who never used drugs were 85.4%(n/N = 70/82), 96.1%(n/N = 320/333) and 97.4%(n/N = 223/229) respectively (p < 0.001). After adjustment by sex, age, HCV genotype and opioid agonist therapy, active drug use was the only factor independently associated with SVR (ITT) [adjusted OR (95%confidence interval): 0.29(0.09-0.99),p = 0.048]. CONCLUSIONS: Active drug use was independently associated with lower SVR rates to G/P, mainly due to voluntary dropout. G/P could be particularly beneficial in this scenario but specific strategies designed to increase the retention in care are needed.


Asunto(s)
Hepacivirus , Hepatitis C , Ácidos Aminoisobutíricos , Antivirales/farmacología , Bencimidazoles , Ciclopropanos , Combinación de Medicamentos , Genotipo , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Prolina/análogos & derivados , Estudios Prospectivos , Pirrolidinas , Quinoxalinas , Sulfonamidas , Resultado del Tratamiento
4.
Clin Infect Dis ; 49(6): 892-900, 2009 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-19663689

RESUMEN

BACKGROUND: Nucleoside reverse-transcriptase inhibitor (NRTI)-related mitochondrial toxicity has been suggested as a key factor in the induction of antiretroviral-related lipoatrophy. This study aimed to evaluate in vivo the effects of NRTI withdrawal on mitochondrial parameters and body fat distribution. METHODS: A multicenter, prospective, randomized trial assessed the efficacy and tolerability of switching to lopinavir-ritonavir plus nevirapine (nevirapine group; n = 34), compared with lopinavir-ritonavir plus 2 NRTIs (control group; n = 33) in a group of human immunodeficiency virus-infected adults with virological suppression. A subset of 35 individuals (20 from the nevirapine group and 15 from the control group) were evaluated for changes in the mitochondrial DNA (mtDNA) to nuclear DNA ratio and cytochrome c oxidase (COX) activity after NRTI withdrawal. Dual-energy X-ray absorptiometry (DEXA) scans were used to objectively quantify fat redistribution over time. RESULTS: The nevirapine group experienced a progressive increase in mtDNA content (a 40% increase at week 48; P = .039 for comparison between groups) and in the COX activity (26% and 32% at weeks 24 and 48, respectively; P = .01 and P = .09 for comparison between groups, respectively). There were no statistically significant between-group differences in DEXA scans at week 48, although a higher fat increase in extremities was observed in the nevirapine group. No virologic failures occurred in either treatment arm. CONCLUSIONS: Switching to a nucleoside-sparing regimen of nevirapine and lopinavir-ritonavir maintained full antiviral efficacy and led to an improvement in mitochondrial parameters, which suggests a reversion of nucleoside-associated mitochondrial toxicity. Although DEXA scans performed during the study only revealed slight changes in fat redistribution, a longer follow-up period may show a positive correlation between reduced mitochondrial toxicity and a clinical improvement of lipodystrophy.


Asunto(s)
Fármacos Anti-VIH/efectos adversos , Composición Corporal/efectos de los fármacos , ADN Mitocondrial/análisis , Síndrome de Lipodistrofia Asociada a VIH/inducido químicamente , Inhibidores de la Transcriptasa Inversa/efectos adversos , Absorciometría de Fotón , Adulto , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Quimioterapia Combinada , Complejo IV de Transporte de Electrones/metabolismo , Extremidades , Femenino , Estudios de Seguimiento , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , Síndrome de Lipodistrofia Asociada a VIH/metabolismo , Síndrome de Lipodistrofia Asociada a VIH/patología , Humanos , Lípidos/sangre , Lopinavir , Masculino , Persona de Mediana Edad , Nevirapina/uso terapéutico , Pirimidinonas/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Ritonavir/uso terapéutico , Resultado del Tratamiento , Carga Viral
5.
AIDS Res Hum Retroviruses ; 22(4): 321-9, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16623634

RESUMEN

Using a multicenter, cross-sectional, observation study, the long-term safety, metabolic profile, and viral efficacy of nevirapine (NVP)-based approaches in HIV-1-infected patients treated for at least 2 years were assessed. For 4 months, all consecutive HIV-1-infected patients who had been receiving an NVP-containing regimen for at least 2 years were recruited. A total of 613 patients were included with a median follow-up period of 43 months (IQR: 31-51). At baseline, 24.5% (150 patients) were treatment naive, 41.5% (254 patients) switched for simplification purposes, and 34% (209 patients) were failing HAART. Increases by five times or more in AST/ALT values were observed in fewer than 2% of patients. Only 5.7% of all adverse events reported during the investigation were attributable to NVP. The percentage of patients with normal HDL cholesterol levels rose from 17.7% at baseline to 35.4% at the last visit. At the latest time point available for analysis, 76% of naive and 74% of those who had switched had HIV-1 RNA loads of <50 copies/ml, while 59% of salvage patients achieved this level of viral suppression. Factors associated with viral suppression at the latest visit were adequate adherence (OR: 2.58, 95% CI: 0.85-7.78, p < 0.001), first-line treatment (OR: 3.02, 95% CI: 1.52-6.00, p = 0.002), and baseline CD4 cells >400 cells/microl (OR: 2.34, 95% CI: 1.22-4.47, p = 0.010). Exposure to nevirapine for up to 4 years is safe. Liver toxicity is infrequent and generally mild. HDL cholesterol levels consistently increase over time and viral suppression is maintained.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Nevirapina/uso terapéutico , Adulto , Fármacos Anti-VIH/efectos adversos , Recuento de Linfocito CD4 , Distribución de Chi-Cuadrado , HDL-Colesterol/sangre , Ensayos Clínicos como Asunto , Estudios Cruzados , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Nevirapina/efectos adversos , ARN Viral/sangre , Factores de Tiempo , Resultado del Tratamiento , Carga Viral
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