Bictegravir/Emtricitabine/Tenofovir Alafenamide in a Multicentre Cohort: Real-Life Experience From Spain.

BACKGROUND: The evaluation of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) in clinical trials has shown high rates of virological suppression but information about its use in real-life settings is scarce. OBJECTIVE: To evaluate the effectiveness, safety, durability, and predictive variables of therapeutic failure of BIC/FTC/TAF in a real-life cohort. METHODS: This observational, retrospective, multicentered cohort study included treatment-naive (TN) and treatment-experienced (TE) adult patients living with HIV (PLWH) who started treatment with BIC/FTC/TAF from January 1, 2019, to January 31, 2022. Treatment effectiveness (based on intention-to-treat [ITT], modified ITT [mITT], and on-treatment [OT]), tolerability, and safety were evaluated in all patients who started BIC/FTC/TAF antiretroviral therapy. RESULTS: We included a total of 505 PLWH of whom 79 (16.6%) were TN and 426 (83.4%) were TE. Patients were followed up for a median (interquartile range [IQR]) of 19.6 (9.6-27.3) months, and 76% and 56% of PLWH reached month 6 and month 12 of treatment, respectively. Rates of TN PLWH with HIV-RNA <50 copies/mL in the OT, mITT, and ITT groups were 94%, 80%, and 62%, respectively, after 12 months of BIC/FTC/TAF treatment. Rates of TE PLWH with HIV-RNA <50 copies/mL were 91%, 88%, and 75% at month 12. The multivariate analysis revealed that neither age, sex, CD4 cell count <200 cells/µL, or viral load >100 000 copies/mL were associated with therapeutic failure. CONCLUSION AND RELEVANCE: Our real-life data showed that BIC/FTC/TAF is effective and safe for use in the treatment of both TN and TE patients in clinical practice.

Aprotinin treatment against SARS-CoV-2: A randomized phase III study to evaluate the safety and efficacy of a pan-protease inhibitor for moderate COVID-19.

BACKGROUND: SARS-CoV-2 virus requires host proteases to cleave its spike protein to bind to its ACE2 target through a two-step furin-mediated entry mechanism. Aprotinin is a broad-spectrum protease inhibitor that has been employed as antiviral drug for other human respiratory viruses. Also, it has important anti-inflammatory properties for inhibiting the innate immunity contact system. METHODS: This was a multicentre, double-blind, randomized trial performed in four Spanish hospitals comparing standard treatment versus standard treatment + aprotinin for patients with COVID-19 between 20 May 2020 and 20 October 2021. The primary efficacy outcomes were length of hospital stay and ICU admission. The secondary endpoints were each of the primary efficacy outcomes and a composite of oxygen therapy, analytical parameters and death. Safety outcomes included adverse reactions to treatment during a 30-day follow-up period. Treatment was given for 11 days or till discharge. RESULTS: With almost identical analytical profiles, significant differences were observed in treatment time, which was 2 days lower in the aprotinin group (p = .002), and length of hospital admission, which was 5 days shorter in the aprotinin group (p = .003). The incidence of discharge was 2.19 times higher (HR: 2.188 [1.182-4.047]) in the aprotinin group than in the placebo group (p = .013). In addition, the aprotinin-treated group required less oxygen therapy and had no adverse reactions or side effects. CONCLUSION: Inhaled aprotinin may improve standard treatment and clinical outcomes in hospitalized patients with COVID-19, resulting in a shorter treatment time and hospitalization compared with the placebo group. The administration of aprotinin was safe.

Impact of interferon-free therapies in HIV/HCV co-infected patients on real clinical practice: results from a multicenter region-wide cohort study (2014-2018).

BACKGROUND: Here, we assess the efficacy and safety of direct antiviral agents (DAAs) in a real-world cohort of co-infected individuals, and evaluate the consistency between clinical practice and guideline recommendations. METHODS: Multicenter, prospective cohort study of HIV/HCV co-infected patients followed-up in nine sites in Spain. All patients with detectable HCV-RNA naive to second-generation DAAs were enrolled. The primary endpoint was the assessment of sustained virological response at week 12 (SVR12). We performed intention-to-treat (ITT), per-protocol (PP), and multivariable analyses to identify factors associated with therapeutic failure. We compared the DAAs we administered to available guideline recommendations. Schemes not perfectly adjusted to the recommendations were defined as sub-optimal. RESULTS: Overall, 316 patients (82.1% male) received a total of 330 treatments. Of these, 43.9% were cirrhotic and 40.6% were treatment-experienced. In the ITT and PP analyses, SVR12 was achieved in 90.9% [95% confidence interval (CI) 87.3-93.6] and 93.7% (95% CI 90.5-95.6), respectively. Only alcohol abuse [odds ratio (OR): 0.33; 95% CI 0.138-0.789, P = 0.013] and a higher basal bilirubin level (OR: 0.595; 95% CI 0.416-0.851, P = 0.004) were independently associated to therapeutic failure. A progressive decrease in the proportion of sub-optimal treatments was observed over time, from 75% in 2014 to 0% in 2018. Being treated with a sub-optimal regimen was not associated with failure. CONCLUSION: Despite numerous difficulties in treatment access and in adaptation to the changing guidelines, we detected no differences among the DAAs used, nor did we detect a lower efficacy when the chosen treatment was not optimal.

Does fibrosis really regress in HIV/hepatitis C virus co-infected patients after treatment with direct antiviral agents?

OBJECTIVE: To evaluate the progression of liver stiffness after treatment with direct antiviral agents (DAAs), to identify predictive factors of fibrosis regression and to analyze the changes of scores AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) after treatment. DESIGN: Multicenter prospective cohort study of HIV/HCV co-infected patients conducted within the GECMEI cohort, Spain. METHODS: Individuals were eligible if they were willing to start DAAs and underwent two transient elastographies: at baseline and after the end of treatment (EOT). All patients with detectable HCV RNA naïve to DAAs were consecutively enrolled from nine medical hospitals. Liver stiffness results were categorized in four Metavir stages (F1: <7.1; F2 : 7.1--9.5; F3 : 9.5--2.4; F4: >12.4 kPa). The APRI and FIB-4 scores were calculated at baseline, EOT and 12 weeks after EOT. RESULTS: One hundred and seventy-eight patients were examined throughout a follow-up of 16.3 months (IQR: 12.5-25). The median of liver stiffness decrease was 2.6 kPa (IQR: 0-6.3). A greater improvement was observed in F3-F4 compared with F1-F2, (6.4 vs. 0.91 kPa, P < 0.001; P = 0.001, respectively). A decline between baseline and EOT measures was observed in APRI and FIB-4 (P < 0.001). Sustained virological response (SVR12) achievement was the only predictor of fibrosis regression [OR:17.4 (95% CI: 1.8-164.6; P = 0.013)]. CONCLUSION: Most patients experienced a significant reduction of liver stiffness and APRI and FIB-4 scores. This improvement was greater in those with advanced liver disease. SVR12 was the only predictor of fibrosis regression. The significance of this reduction is unclear and could reflect a decline in inflammation rather than true fibrosis regression.

Efectividad del tratamiento con agentes antivirales directos en pacientes con coinfección por VHC y VIH. Estudio de cohorte multicéntrico / Effectiveness of direct-acting antiviral therapy in patients with a HCV/HIV coinfection. A multicenter cohort study

Introducción: la eficacia de los agentes antivirales directos (AAD) ha quedado demostrada en ensayos clínicos tanto en mono como en coinfectados. Nuestro objetivo es analizar la efectividad y toxicidad de este tratamiento en vida real en pacientes con coinfección por VIH y VHC así como determinar variables asociadas a una evolución desfavorable. Métodos: estudio ambispectivo multicéntrico en una cohorte de pacientes coinfectados. Los datos fueron recogidos en ocho centros de Castilla-La Mancha entre 2014 y 2016. Se realizó un análisis por intención de tratamiento en el que cualquier pérdida de seguimiento, abandono de tratamiento o toxicidad terapéutica se consideró fracaso. Resultados: se estudiaron 229 pacientes con una mediana de edad de 49,6 años con predominio masculino (83%). Menos de un 10% presentaba carga viral (CV) detectable para el VIH. El genotipo de VHC más prevalente fue el 1 (65,1%). Un 50% tenía hepatopatía en grado de cirrosis. El 65% presentaba más de 800.000 copias/ml de CV de VHC. La respuesta viral sostenida (RVS) se alcanzó globalmente en el 91,7%. La estrategia de AAD más utilizada fue sofosbuvir/ ledipasvir. Un 52% de las pautas incluyeron ribavirina. El 65,9% completó pautas de 12 semanas y un 30%, de 24 semanas. Hubo 19 fracasos terapéuticos. No existen diferencias entre las distintas estrategias de AAD utilizadas. No se observó ningún factor predictor independiente de RVS. Conclusiones: el tratamiento del VHC en pacientes coinfectados presenta tasas de RVS muy elevadas también en vida real. La toxicidad es excepcional. No hemos identificado factores predictores específicos de evolución desfavorable (AU)

ntroduction: The effectiveness of direct-acting antiviral (DAA) agents has been demonstrated in clinical trials both in patients with mono and coinfections. The goal of the study was to analyze the effectiveness and toxicity of this therapy in real-life patients with a HIV/HCV coinfection and to identify variables that are associated with an unfavorable outcome. Methods: This was a multicenter ambispective study in a cohort of coinfected patients. Data were collected from eight centers in Castilla-La Mancha from 2014 to 2016. An intent-to-treat analysis was performed and any loss to follow-up, treatment withdrawal or toxicity was considered as a failure. Results: A total of 229 patients were included with a median age of 49.6 years and the majority were male (83%). Fewer than 10% had a detectable HIV-related viral load (VL). The most prevalent HCV genotype was 1 (65.1%). Fifty percent had cirrhotic liver disease and 65% had over 800,000 copies/ml of HCV VL. The global sustained viral response (SVR) was reached by 91.7% of cases. The most commonly used DAA regimen was sofosbuvir/ledipasvir. Ribavirin was included in 52% of regimens, 65.9% of cases completed 12-week regimens and 30% completed 24-week schemes. There were 19 therapy failures. No differences were observed between the various DAA strategies used. No independent predictor was found for SVR. Conclusions: HCV treatment in coinfected patients is highly successful in terms of SVR rate in the real-life setting and toxicity is exceptional. We identified no specific predictors of an unfavorable outcome (AU)

Effectiveness of direct-acting antiviral therapy in patients with a HCV/HIV coinfection. A multicenter cohort study.

INTRODUCTION: The effectiveness of direct-acting antiviral (DAA) agents has been demonstrated in clinical trials both in patients with mono and coinfections. The goal of the study was to analyze the effectiveness and toxicity of this therapy in real-life patients with a HIV/HCV coinfection and to identify variables that are associated with an unfavorable outcome. METHODS: This was a multicenter ambispective study in a cohort of coinfected patients. Data were collected from eight centers in Castilla-La Mancha from 2014 to 2016. An intent-to-treat analysis was performed and any loss to follow-up, treatment withdrawal or toxicity was considered as a failure. RESULTS: A total of 229 patients were included with a median age of 49.6 years and the majority were male (83%). Fewer than 10% had a detectable HIV-related viral load (VL). The most prevalent HCV genotype was 1 (65.1%). Fifty percent had cirrhotic liver disease and 65% had over 800,000 copies/ml of HCV VL. The global sustained viral response (SVR) was reached by 91.7% of cases. The most commonly used DAA regimen was sofosbuvir/ledipasvir. Ribavirin was included in 52% of regimens, 65.9% of cases completed 12-week regimens and 30% completed 24-week schemes. There were 19 therapy failures. No differences were observed between the various DAA strategies used. No independent predictor was found for SVR. CONCLUSIONS: HCV treatment in coinfected patients is highly successful in terms of SVR rate in the real-life setting and toxicity is exceptional. We identified no specific predictors of an unfavorable outcome.