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Introduction Proven resistance against HIV drugs, either by phenotyping or genotyping is a rare event in clinical trials. The overall assumption of drug resistance disappearing is additionally driven by the recommendations to screen for transmitted drug resistance, leading to large numbers of examinations with relatively low rates of resistance. Goal of our analysis was to assess if drug resistance in treatment failure is also decreasing outside of clinical trials. Materials and Methods The MIB database at timepoint of analysis consists of data from 2876 HIV infected patients. Besides various laboratory parameters, clinical data and treatment history is included. HIV-1 protease and reverse transcriptase sequences were analyzed using the HIV-GRADE drug resistance algorithm. As in only a small number of patients genotypic resistance testing for integrase inhibitors was performed, mainly due to reimbursement reasons, it was assumed that failing treatment on a previous integrase inhibitor containing regimen is equate to resistance. Results Of the 2876 patients in the database, 220 had a treatment change due to treatment failure between 2009 and 2012, a genotypic resistance testing at an appropriate timepoint of maximum four weeks before treatment change and a treatment duration of at least six months before treatment failure. In 2009, 61% of patients showed no drug resistance while 39% showed resistance against one or more drug classes (two or more drug classes: 19.5%; three or more drug classes: 2.4%, four drug classes 2.4%). In 2012, no resistance was found in 52% of patients while resistance against three or more drug classes was found in nearly 14% of patients (one or more: 48%; two or more 23%; four classes: 4.5%). Conclusions Treatment failure with viral load sufficiently high for drug resistance testing was not frequently observed in our database. Nevertheless, treatment failure was often associated with drug resistance against at least one drug class. With more use of the newer drug classes, resistance against those new classes will become more common and rates of multiclass resistance will be increasing. [ABSTRACT FROM AUTHOR]

Introduction Acute hepatitis C virus (HCV) infection has emerged as a major cause of morbidity in the HIV-infected population. Most guidelines recommend early treatment with pegylated interferon and ribavirin due to higher cure rates. The impact of acute HCV and its treatment on the outcome of the HIV-infected population is unknown. With new treatment options for HCV, early treatment of acute HCV has to be questioned. Here, we report a long-term analysis on patients with acute HCV. Methods Retrospective analysis from an outpatient clinic from Berlin. All patients with the diagnosis of acute HCV according to The European AIDS Treatment Network (NEAT) criteria were included in the database at their date of HCV diagnosis and followed-up until the last medical contact. Demographic data was taken from the medical file. A fibrosis estimation was performed using transient elastography (Fibroscan(®). A Fibroscan value above 7 kPa was considered as significant fibrosis, above 12.4 kPa as liver cirrhosis. The following outcomes were documented: (a) liver-related: hepatic decompensation, cirrhosis, hepatocellular carcinoma. (b) non-liver-related: death, myocardial infarction, AIDS-defining event, psychiatric hospitalisation. Results A total of 207 cases of acute HCV infection in HIV-infected patients were diagnosed between May 2002 and September 2013. All patients were male and declared homosexual contacts as their risk factor for having acquired HIV. The mean age was 39 years, 162 patients (78%) were on antiretroviral treatment, and the median CD4 cell count was 593/mm3 (IQR 443-749). At HCV diagnosis, the highest median alanine aminotransferase (ALT) level was 408 IU/mL (159-871), the HCV viral load was 800,000 IU/mL (45x103-2.8x106). 22 cases (11%) cleared their infection spontaneously, 161 (77%) underwent interferon-based treatment. Of those treated, 58% had a sustained virological response. 36 cases of HCV reinfection were documented. All patients were followed-up over an interval of 806 patient-years. The median liver stiffness was 5.3 kPa (4-7) after a median interval of 34 months. 33 patients developed significant fibrosis, and 11 patients (6%) developed cirrhosis. Nine (5%) patients died during follow-up, and 11 developed non-liver-related endpoints. All but one deceased patients had interferon-based treatment. Conclusions Severe hepatic disease and death rarely occurs in a highly treated HCV population. As interferon-based treatment may induce side effects, it is from now on justified to await new HCV treatment options. [ABSTRACT FROM AUTHOR]

Purpose of the study HIV-1-infected patients have elevated levels of immune activation and systemic inflammatory markers which are partially strong predictors of disease progression or are associated with increased cardiovascular risk. The dependency of anti-retroviral treatment (ART), the usage of NNRTI or PI-based and the application of non-nuc regimens is analysed here on the basis of a dataset (Chronic Inflammation Dependency on TREatment: CIDRE cohort) from 1500 patients in Berlin. Methods In a retrospective analysis we compared relative CD4+ cell counts, viral load, relative CD8+CD38+DR-and CD3+DR+cells, concentration of high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) in therapy-naïve or treated patients dependent on usage or non-usage of NUCs, PI or NNRTI. Statistics were performed with R (R Core Team; 2012; R: A language and environment for statistical computing) using Wilcoxon rank sum test in two-sided analysis. Summary of results As to expect, ART-naïve patients (n=190) had significantly higher viral loads and lower CD4+cell counts (p: both<0.05) and showed higher activation levels than treated patient (CD8+CD38+DR- and CD3+DR+both<0.05). But no significant difference was calculated for hsCRP or IL-6. Nuc-sparing regimen (n=46) did not show any distinction compared to nuc-containing therapies (n=1249) for the analysed parameters. Significant differences were detected for PI-regimen (n=711) with lower CD4+ cell counts and higher activation (CD8+38+DR-, CD3+DR+) and IL-6 (p: all<0.05) but not for hsCRP (p=0.39). The opposite was true for NNRTI-based therapies (n=445) with higher CD4+ cell percentages and lower activation and inflammation markers (p: all<0.05) and as well no difference in hsCRP (p=0.97) compared with all other treated patients. Conclusions The lack of differences between therapy-naïve patients and patients on ART for inflammation markers may be due to the relative good immunological state of the first group, which could be one of the reasons why they are not treated so far. The number of nuc-sparing regimen is perhaps too low and too undifferentiated to find diverse inflammation states. Although the differences in activation status can be attributed to different treatment strata, there is no clear explanation for this outcome. A possible reason could be a pre-selection bias either for NNRTI-based or PI-based regimens. Additional data is acquired to perform longitudinal analysis to gain further insight. [ABSTRACT FROM AUTHOR]

7-11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK [ABSTRACT FROM AUTHOR]