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.

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.

[Incidence of pneumonia in HIV-infected patients in the highly active antiretroviral therapy era]. / Incidencia de neumonía en pacientes infectados por el virus de la inmunodeficiencia humana en la era del tratamiento antirretroviral de gran actividad.

BACKGROUND AND OBJECTIVE: There is scant data comparing the incidence of pneumonia in the community and in the human immunodeficiency virus (HIV) population in highly active antiretroviral therapy (HAART) era. PATIENTS AND METHOD: Prospective study during 18 months. Data were obtained by the means of the electronic clinical record. Incidence rate was compared between HIV positive and negative patients. RESULTS: There were 529 pneumonia episodes in global population (n = 220,000), 1.6 cases/1000 person-year. HIV-infected patients (n = 170) suffered 12 episodes of pneumonia; 46 cases/1000 person-year (relative risk = 29.3, 95% confidence interval, 16.34-51.4; p < 0.01). HIV infected patients with pneumonia have a lower CD4 count (mean 434 versus 230 cells/ml; p = 0.04), higher viral load (4.1 versus 3.2 log copies/ml; p = 0.07) and received antiretroviral treatment in a similar proportion compared to HIV without pneumonia (62 versus a 66.7%, p = 0.5). CONCLUSIONS: Pneumonia in HIV infected patients may be about 30 times more frequent than general population in HAART era. Prevention measures should be reinforced.