Suchergebnisse

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

The life‐long antiretroviral treatment of HIV‐1 infection requires effective and well tolerated medications complemented by high rates of adherence in order to achieve viral suppression, immunologic reconstitution and to prevent the development of resistance. Single‐tablet regimens (STRs), combining a full antiretroviral regimen in one tablet taken once daily, have been designed to achieve high adherence and better long‐term outcomes. "STRike" is the first cohort study, describing the use of various STRs in routine clinical practice in Germany. In this observational cohort study 800 participants will be included in 4 treatment arms, treated with the STRs of TDF/FTC/EFV (a retrospective and prospective arm), TDF/FTC/RPV or TDF/FTC/COBI/EVG after regulatory approval. Patients are followed for at least two years, and reasons for choice of medications and treatment satisfaction will be collected, in addition to safety, demographic, effectiveness data. To date 344 patients on TDF/FTC/EFV and 123 patients on TDF/FTC/RPV are being followed. In general, the spectrum of patients in the study reflects the German HIV‐1 infected population with regards to gender (88%/89% male), age (median 40/38 years of age) and mode of infection (71%/63% MSM). However, patients starting TDF/FTC/RPV are less progressed in their disease according to their CDC stage compared with patients on TDF/FTC/EFV (74.5% stage "A" vs. 53.2%). Patients starting TDF/FTC/RPV show less comorbidities (54% vs. 82%) with a spectrum different from patients on TDF/FTC/EFV. Pre‐existing neuropsychiatric comorbidities are relatively more common (10% more) among patients starting TDF/FTC/RPV than TDF/FTC/EFV. The decision to use an STR is mostly driven by patient preference to start with a more convenient ART regimen (56%) or to simplify their current ART regimen (75%). STRs aim to make treatment of HIV more convenient, more efficacious and more durable and by that allowing for earlier initiation of treatment. Different STRs may meet the requirements of distinct patient populations. TDF/FTC/RPV in this early review of our data, is utilized by younger patients with fewer overall comorbidities, but is selected more frequently for patients with pre‐existing neuropsychiatric comorbidities presumably to avoid the known neuropsychiatric complications of TDF/FTC/EFV. TDF/FTC/RPV appears to fit into the concept of early HIV treatment initiation as recommended by national and international guidelines.image

Different diagnostic parameters may affect the tropism prediction reliability. The impact of usage of FPR cut‐offs<20%, use of viral RNA versus proviral DNA samples, single versus triple amplification, and presence of MVC resistance mutations on tropism prediction at baseline were analysed on 101 patients receiving maraviroc (MVC) and correlated with their clinical outcome. This was a non‐interventional, retrospective study. 82 RNA and 54 DNA samples from the 101 patients receiving MVC were obtained. The V3 region was sequenced and the tropism predicted using the geno2pheno[coreceptor] and T‐CUP tools with FPR cut‐offs of 5%, 7.5%, 10%, 15% and 20%. Additionally, 27/82 RNA and 28/54 DNA samples were analysed in triplicate and 34/82 samples with the ESTA assay. The influence of 16 MVC resistance mutations on clinical outcome was studied. The genotypic susceptibility score (GSS) of the concomitant drugs was mapped to numerical values: susceptible to 1 (or 0.5 for NRTIs), intermediate to 0.5 (0.25 for NRTIs) and resistant to 0. Detection of baseline R5 viruses in RNA (by geno2pheno[coreceptor] and T‐CUP) or DNA (by T‐CUP) samples correlated with MVC‐treatment success. Both tools performed very similarly, with PPVs close to 90%, even with FPR cut‐offs as low as 5%. The use of triple amplification did not improve the prediction value but reduced the number of patients elegible for MVC treatment. No influence of the GSS or MVC resistance mutations on the clinical outcome was detected. Genotypic tropism testing from viral RNA and proviral DNA using the geno2pheno[coreceptor] and T‐CUP systems is valid to select candidates for MVC treatment. Our data suggest that the use of FPR cut‐offs of 5–7.5% and single amplification from RNA or DNA would assure a safe administration of MVC without excluding many patients who could benefit from this potent antiretroviral drug.

Publisher's version (útgefin grein) ; Objectives There are currently few data on the long‐term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. Methods The EuroSIDA cohort was divided into three groups: those starting RAL‐based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression. Results The RAL cohort included 1470 individuals [with 4058 person‐years of follow‐up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non‐AIDS‐related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95–1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37–2.61). In intention‐to‐treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84–1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90–1.61) and 0.83 (95% CI 0.70–0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47–1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65–1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53–1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76–1.72 for RALvs. CONC). Conclusions We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups. ; EuroSIDA was supported by the European Union's Seventh Framework Programme for research, technological development and demonstration under EuroCoord grant agreement no. 260694. Current support includes unrestricted grants from Bristol‐Myers Squibb, Gilead, GlaxoSmithKline LLC, Janssen R&D, Merck and Co. Inc. and Pfizer Inc. The participation of centres from Switzerland was supported by The Swiss National Science Foundation (Grant 108787). The study is also supported by a grant (grant number DNRF126) from the Danish National Research Foundation. ; Peer Reviewed