Body mass index does not impact on molecular response rate of chronic myeloid leukaemia patients treated frontline with second generation tyrosine kinase inhibitors.

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Clinical relevance of silent red blood cell autoantibodies.

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Impact of transmitted drug resistance in naïve-patients starting 2 NRTI plus a boosted protease-inhibitor (PI) or integrase-inhibitor (INSTI).

Background The role of transmitted drug resistance (TDR) in predicting outcomes of initial antiretroviral therapy including PI or INSTI has not been fully explored. Methods From the ARCA database we selected adult naïve HIV-1 infected patients starting first-line 3-drugs therapy including INSTI or PI, from 1/2008 to 6/2016, with baseline resistance genotype and at least 1 HIV-1 RNA during follow up. TDR was defined as the detection of at least one mutation among those included in the WHO-recommended SDRM list (Bennett 2009). The primary endopoints were: virological failure (VF, defined as an HIV-RNA, VL, > 200 copies/ml after week 24) and treatment failure (TF, defined as VF or treatment change for any reason). Survival analysis was used to investigate predictors of TF and VF. Results 1147 pts were analyzed: 1031 (89.9%) treated with PI and 116 (10.1%) with INSTI. Baseline characteristics are shown in table. In the PI-group baseline VL was higher while CD4+ cells count was lower than in INSTI. Overall TDR were 4.7% for NRTI, 4.4% NNRTI, 1.5% PI without significant differences between groups. During a median observation time of 57 wks (IQR 26-107) TF occurred in 771 treatments in PI-group, with an estimated probability at 48 wks of 36% (CI 34.5-37.5) and in 46 in INSTI-group with an estimated probability at 48 wks of 31% (26.2-35.8); during a median observation time of 55 wks (26-107) VF occurred in 161 treatments in PI-group, with an estimated probability at 48 wks of 12% (10.8-13.1) and in 11 in INSTI-group with an estimated probability at 48 wks of 12% (8.5-15.5). After adjusting for gender, nationality, TDF/FTC use and viral subtype, independent predictor of VF was AZT/3TC use (vs other backbones HR 3.8, CI 95% 2.2-6.3, p<0.001); adjusting for nationality and viral subtype, independent predictors of TF were geographic area (Southern vs Northern Italy, HR 0.8, 0.6-0.9, p=0.04), baseline VL (+ 1 log10 HR 1.1, 1.0-1.2, p=0.03) and AZT/3TC (versus other backbones HR 2.1, 1.5-2.8, p=<0.001). Third drug class was not associated with VF or TF. In the INSTI-group, but not in the PI-group, the presence of any NRTI TDR was predictor of VF (HR 7.1, 1.8-28.2, p=0.005) after adjusting for nadir CD4 cells count and TF (HR 2.7, 1.1-7.0, p=0.03). Among patients in the INSTI-group with VF, 3 presented NRTI TDR (2 M41L and 1 M184V). In the PI-group, adjusting for gender, nationality, geographic area, viral subtype, TDF/FTC use, baseline and nadir CD4 cells count, independent predictor of VF was AZT/3TC use (HR 3.4, 1.8-6.2, p<0.001); adjusting for nationality and viral subtype, independent predictor of TF was AZT/3TC use (vs other backbones HR 2.3, 1.7-3.1, p<0.001). Conclusions PI and INSTI based first-line regimens show high efficacy in the real practice; despite the low incidence of TDR, our data support the need of pre-treatment genotyping to optimize therapy in patients starting INSTI-therapy. Further studies are required to confirm our suggestions

Use of efavirenz or atazanavir/ritonavir is associated with better clinical outcomes of HAART compared to other protease inhibitors: routine evidence from the Italian MASTER Cohort.

Randomized trials and observational cohorts reported higher rates of virological suppression after highly active antiretroviral therapy (HAART) including efavirenz (EFV), compared with boosted protease inhibitors (PIs). Correlations with immunological and clinical outcomes are unclear. Patients of the Italian MASTER cohort who started HAART from 2000 to 2010 were selected. Outstanding outcome (composite outcome for success (COS)) was introduced. We evaluated predictors of COS (no AIDS plus CD4+ count &gt;500/ mm3 plus HIV-RNA &lt;500 copies/mL) and of eight single outcomes either at month 6 or at year 3. Multivariable logistic regression was conducted. There were 6259 patients selected. Patients on EFV (43%) were younger, had greater CD4+ count, presented with AIDS less frequently, and more were Italians. At year 3, 90% of patients had HIV RNA &lt;500 copies/mL, but only 41.4% were prescribed EFV, vs. 34.1% prescribed boosted PIs achieved COS (p &lt;0.0001). At multivariable analysis, patients on lopinavir/ritonavir had an odds ratio of 0.70 for COS at year 3 (p &lt;0.0001). Foreign origin and positive hepatitis C virus-Ab were independently associated with worse outcome (OR 0.54, p &lt;0.0001 and OR 0.70, p 0.01, respectively). Patients on boosted PIs developed AIDS more frequently either at month 6 (13.8% vs. 7.6%, p &lt;0.0001) or at year 3 (17.1% vs. 13.8%, p &lt;0.0001). At year 3, deaths of patients starting EFV were 3%, vs. 5% on boosted PIs (p 0.008). In this study, naïve patients on EFV performed better than those on boosted PIs after adjustment for imbalances at baseline. Even when virological control is achieved, COS is relatively rare. Hepatitis C virus-positive patients and those of foreign origin are at risk of not obtaining COS. Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved

Risk of Severe Non AIDS Events Is Increased among Patients Unable to Increase their CD4+ T-Cell Counts >200+/μl Despite Effective HAART

Immunological non-response (INR) despite virological suppression is associated with AIDS-defining events/death (ADE). Little is known about its association with serious non-AIDS-defining events (nADE)

Trends and correlates of HIV-1 resistance among subjects failing an antiretroviral treatment over the 2003-2012 decade in Italy

BACKGROUND: Despite a substantial reduction in virological failures following introduction of new potent antiretroviral therapies in the latest years, drug resistance remains a limitation for the control of HIV-1 infection. We evaluated trends and correlates of resistance in treatment failing patients in a comprehensive database over a time period of relevant changes in prescription attitudes and treatment guidelines. METHODS: We analyzed 6,796 HIV-1 pol sequences from 49 centres stored in the Italian ARCA database during the 2003-2012 period. Patients (n = 5,246) with viremia > 200 copies/mL received a genotypic test while on treatment. Mutations were identified from IAS-USA 2013 tables. Class resistance was evaluated according to antiretroviral regimens in use at failure. Time trends and correlates of resistance were analyzed by Cochran-Armitage test and logistic regression models. RESULTS: The use of NRTI backbone regimens slightly decreased from 99.7% in 2003-2004 to 97.4% in 2010-2012. NNRTI-based combinations dropped from 46.7% to 24.1%. PI-containing regimens rose from 56.6% to 81.7%, with an increase of boosted PI from 36.5% to 68.9% overtime. In the same reference periods, Resistance to NRTIs, NNRTIs and PIs declined from 79.1% to 40.8%, from 77.8% to 53.8% and from 59.8% to 18.9%, respectively (p < .0001 for all comparisons). Dual NRTI + NNRTI and NRTI + PI resistance decreased from 56.4% to 33.3% and from 36.1% to 10.5%, respectively. Reduced risk of resistance over time periods was confirmed by a multivariate analysis. CONCLUSIONS: Mutations associated with NRTIs, NNRTIs and PIs at treatment failure declined overtime regardless of specific class combinations and epidemiological characteristics of treated population. This is likely due to the improvement of HIV treatment, including both last generation drug combinations and prescription guidelines

Comparative determination of HIV-1 co-receptor tropism by Enhanced Sensitivity Trofile, gp120 V3-loop RNA and DNA genotyping

BACKGROUND: Trofile is the prospectively validated HIV-1 tropism assay. Its use is limited by high costs, long turn-around time, and inability to test patients with very low or undetectable viremia. We aimed at assessing the efficiency of population genotypic assays based on gp120 V3-loop sequencing for the determination of tropism in plasma viral RNA and in whole-blood viral DNA. Contemporary and follow-up plasma and whole-blood samples from patients undergoing tropism testing via the enhanced sensitivity Trofile (ESTA) were collected. Clinical and clonal geno2pheno[coreceptor] (G2P) models at 10% and at optimised 5.7% false positive rate cutoff were evaluated using viral DNA and RNA samples, compared against each other and ESTA, using Cohen's kappa, phylogenetic analysis, and area under the receiver operating characteristic (AUROC). RESULTS: Both clinical and clonal G2P (with different false positive rates) showed good performances in predicting the ESTA outcome (for V3 RNA-based clinical G2P at 10% false positive rate AUROC = 0.83, sensitivity = 90%, specificity = 75%). The rate of agreement between DNA- and RNA-based clinical G2P was fair (kappa = 0.74, p < 0.0001), and DNA-based clinical G2P accurately predicted the plasma ESTA (AUROC = 0.86). Significant differences in the viral populations were detected when comparing inter/intra patient diversity of viral DNA with RNA sequences. CONCLUSIONS: Plasma HIV RNA or whole-blood HIV DNA V3-loop sequencing interpreted with clinical G2P is cheap and can be a good surrogate for ESTA. Although there may be differences among viral RNA and DNA populations in the same host, DNA-based G2P may be used as an indication of viral tropism in patients with undetectable plasma viremia