Effectiveness and safety of dual therapy with rilpivirine and boosted darunavir in treatment-experienced patients with advanced HIV infection: a preliminary 24 week analysis (RIDAR study).

BACKGROUND: The objective was to analyze the effectiveness and safety of dual therapy with rilpivirine plus boosted-darunavir (RPV + bDRV) in real-life patients. METHODS: Observational, retrospective, multi-center study in HIV+ patients who had received RPV + bDRV for 24 weeks to optimize/simplify their previous antiretroviral treatment. We determined the percentage of patients without virologic failure (2 consecutive viral loads > 50 copies/mL) at 24 weeks of treatment. RESULTS: The study included 161 patients from 15 hospitals with median age of 49 years; 29.3% had previous AIDS stage and median CD4+ lymphocyte nadir of 170 cells/uL. They had been diagnosed with HIV for a median of 17 years and had received 14 years of ART, with five previous treatment combinations, and 36.6% had a history of virological failure. The reasons for the switch were simplification/optimization (49.7%), toxicity/intolerance (17.4%), or inadequate effectiveness of previous ART (10.6%). Baseline VL of 50-1000 copies/mL was recorded in 25.5% of the patients. In the"intention-to-treat" analysis at 24 weeks, 87.6% of 161 patients continued the study treatment without virologic failure criteria. In the "on treatment" analysis (excluding patients who discontinued treatment with dual therapy for any reason other than virologic failure) the efficacy was 94.6% (141/149 patients). CONCLUSIONS: Dual therapy with RPV + DRVb proved to be effective and safe in patients with advanced HIV infection, long exposure to ART, low CD4 nadir, previous virologic failure, and/or history of ineffective ART.

Interferon-free therapy for treating hepatitis C virus in difficult-to-treat HIV-coinfected patients.

BACKGROUND/AIMS: Data regarding the use of all-oral direct-acting antivirals in HIV/hepatitis C virus (HCV)-coinfected patients with advanced liver fibrosis are required, because they are generally under-represented in clinical trials. This study sought to evaluate the use of these drugs in a cohort of coinfected patients, mostly with factors that have previously been recognized as predictors of treatment failure. METHODS: COINFECOVA-2 is an observational, multicenter study conducted in Eastern Spain. Data of all HIV/HCV-coinfected patients treated with direct-acting antiviral under real-life conditions were retrospectively collected, and factors associated with treatment success or safety were analysed. RESULTS: Among 515 included patients, 96% were on antiretroviral therapy and 89.5% had an HIV-RNA less than 50 copies/ml. HCV genotype (G) distribution was 47% G-1a, 20% G-4, 14.4% G-1b, and 12.8% G-3. Patients with cirrhosis were 54.2%, and 46% failed to prior HCV-therapies. Overall, 92.8% patients (95% confidence interval: 90.2-94.9) achieved sustained virologic response (SVR12). Cirrhosis was the only factor associated with treatment failure, and SVR12 rate was significantly lower in patients with liver stiffness at least 21 kPa. Adverse events were reported in 36.7%, but only two patients (0.4%) discontinued treatment because of adverse events. The bivariate analysis showed an association between ribavirin use and an increased risk of adverse events (odds ratio 2.84; 95% confidence interval: 1.95-4.1; P ≤ 0.0001). CONCLUSION: This heterogeneous cohort of coinfected patients showed a high rate of SVR12. Among cirrhotic patients, those with a liver stiffness at least 21 kPa had a higher probability of treatment failure. Ribavirin use seems to increase the appearance of adverse events.

Telaprevir or boceprevir in HIV/HCV-1 co-infected patients in a real-life setting. Interim analysis (24 weeks). COINFECOVA-SEICV study.

INTRODUCTION: In general, HIV co-infected patients included in clinical trials evaluating the hepatitis C virus (HCV) therapy with telaprevir (TVR) or boceprevir (BOC) with advanced fibrosis, are scarce. We analyze data concerning the use of these drugs in a real-life clinical setting with patients affected by a more advanced degree of fibrosis in a Spanish cohort. METHODS: We evaluated safety and efficacy in an interim analysis encompassing the first 24 weeks of triple therapy with peginterferon (alfa-2a or alfa-2b), ribavirin and TVR or BOC in an observational, multicentre study. HIV/HCV genotype 1 co-infected patients beginning therapy from January 2012 to July 2013 were included. RESULTS: Enrolled patients were 155 (144 patients on TVR and 11 on BOC), average age was 47 years, 83% were male. With respect to HCV treatment, 44% were naïve, 13% relapsers, 17% partial responders, 21% null responders, and in seven patients, the previous response was unknown. All but three (98%) were under antiretroviral therapy (ART) (other than reverse transcriptase inhibitors, the backbone was raltegravir 43%, atazanavir 35%, and etravirine 28%). Median HCV-RNA at baseline was 6.1 log10, 54% were cirrhotic and 38% F3. At week 4, 93% of patients continued on therapy, 81% at w12, and 73% at w24. Virological failure was observed more frequently in: cirrhotic patients (19% [95% CI, 11-27]) vs F3 (12% [CI, 4-20]); patients with TT allele of the IL28B polymorphism (40% [CI, 18-61]) vs CT (21% [CI, 12-31]), or CC (2,2% [CI, -2-6]); previous null responders (37.5% [CI, 21-54]) vs partial responders (15.4% [CI, 1-29]), naïve (13% [CI, 5-21]) or relapsers (0% [CI, 0-0]); and in patients with a genotype subtype 1a (23.6% [CI, 57-76]) vs 1b (8.1% [CI, -1-17]). Overall, 17% had virological failure and in 8% treatment was discontinued due to adverse events. Severe adverse events occurred in 30 patients (19%). Haematologic disorders were the most common type including severe anaemia in 12 (7.7%) patients. Erythropoietin was employed in 41 patients (26.4%) and 11 (7.1%) received blood transfusions. Nineteen patients (12.2%) were treated with G-CSF, and 17 (11%) with thrombopoietin-receptor agonists. Five patients died (3.2%), three due to hepatic decompensation, one due to pneumonia and one due to pulmonary hypertension. CONCLUSIONS: In a real-life setting, therapy against HCV in co-infected patients with advanced liver fibrosis shows high virologic success at 24 weeks. However, frequent haematologic disorders are observed and a close monitoring and an intensive therapy are needed to optimize the results.

Switching to raltegravir in virologically suppressed in HIV-1-infected patients: a retrospective, multicenter, descriptive study.

OBJECTIVES: To describe the efficacy and tolerability of switching to raltegravir (RAL) in virologically suppressed HIV-1-infected patients during routine clinical practice. METHODS: A total number of 263 subjects (189 men, median age 48.1 years) with HIV-1 RNA < 50 copies/mL for ≥ 6 months were switched to RAL (400 mg b.i.d). Reasons for change were toxicity (49.0%), drug interactions (6.1%) or convenience (28.6%) (switch from subcutaneous to oral treatment 22.4%, improvement of posology 3.4%). Patients were followed up to 24 months after switching to RAL. Primary end-points were tolerability and virological failure defined as two consecutive measures of HIV-1 RNA > 50 copies/mL. RESULTS: After a median of 12.4 months (range 2.8-26.4 months), virological failure was observed in 6 (2.3%) patients (2.2 per 100 person-years [95%CI 0.9-4.6]), while AIDS occurred in 1, drug discontinuation in 4, 3 patients died and 10 were lost to follow-up. The median CD4+ T cell count increased from 460 cells/mm3 to 508.6 cells/mm3 (P < 0.001). CONCLUSIONS: Switching to RAL in clinical practice was mainly driven by toxicity, convenience or interactions, they were well tolerated and secured virologic suppression in the vast majority of patients.

Tigecycline: a new treatment choice against Acinetobacter baumannii.

Acinetobacter baumannii (AB) is a gram-negative organism that has emerged recently as a major cause of nosocomial infections, because of the extent of its antimicrobial resistance and its persistence in the hospital environment, where intensive care units are the place of greatest risk for acquiring AB. There is no treatment of choice for AB and it's treatment is based on clinical experience and in vitro susceptibility testing. Also, nowadays Acinetobacter resistance to carbapenems is common and isolates resistant to colistin and polymyxin B have been reported. Tigecycline, the 9-tert-butyl-glycylamido derivative of minocycline, exhibits a broad-spectrum of activity against numerous pathogens, including AB and several reports place it among the antimicrobials with lower MIC for AB. Tigecycline overcomes the two major mechanisms of resistance to tetracyclines (ribosomal protection and efflux), but tigecycline resistance emerging during therapy has been reported. Tigecycline efficacy has been demonstrated in clinical studies in skin and skin structure infections and in complicated intra-abdominal infections but, although it seems a good alternative for the treatment of AB infections, there is few evidence about its use in these cases and more clinical experience and adequate trials are needed. The present review shows the recent patents related to treatment by tigecycline in different AB infections.

Adherence, quality of life, and general satisfaction with co-formulated zidovudine, lamivudine, and abacavir on antiretroviral-experienced patients.

PURPOSE: The main objective of the study was to evaluate patients' adherence to a fixed dose combination containing abacavir, zidovudine, and lamivudine (TZV) and to evaluate whether TZV might improve general satisfaction and quality of life (QOL) with anti-HIV treatment. METHOD: Patients with viral load (VL) <400 copies switched their antiretroviral therapy to TZV. Adherence was assessed by patient self-report and medication accountability at week 24. General satisfaction was evaluated with 10-point Visual Analog Scale (VAS) at baseline and week 24. QOL was assessed with MOS-HIV questionnaire at baseline and weeks 12 and 24. Biochemical and hematological parameters were evaluated for safety reasons. RESULTS: A total of 224 patients were included in the study. Overall, 81% (intent to treat [ITT]) and 98% (per protocol [PP]) of patients reported an adherence >95%, reaching 75% and 100% among the intravenous drug user population by ITT and PP analysis, respectively. General satisfaction was significantly higher at week 24 (90 +/- 14 vs. 53 +/- 26) in both ITT and PP populations (p<.0001). There were no statistically significant differences in QOL. Total cholesterol and triglycerides levels decreased significantly at week 24 compared to baseline (p<.05). CONCLUSION: Patients who switched to TZV showed an increase in general satisfaction and high levels of adherence.