A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

<p>Abstract</p> <p>Background</p> <p>HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed.</p> <p>Methods</p> <p>We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90^thday after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure.</p> <p>Results</p> <p>The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards.</p> <p>Conclusions</p> <p>GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.</p

Late presenters among persons with a new HIV diagnosis in Italy, 2010-2011

Background: In Western Europe, about 50% of newly diagnosed HIV-positive individuals are diagnosed at a late stage disease and enter in care late (i.e. with a CD4 count 64350 \u3bcL/\u3bcL). The aim of the present study is to analyze the characteristics and the factors associated with being diagnosed late or at an advanced stage of disease among persons with a new HIV diagnosis in Italy, in the period 2010-2011. Methods. We used individual data on new HIV diagnoses reported by the HIV surveillance system in 2010 and in 2011. Persons with CD4 64350 cells/\u3bcL or diagnosed with AIDS (regardless of the CD4 cell count) were defined as late presenters (LP); persons with CD4 64 200 cells/\u3bcL or AIDS (regardless of the CD4 cell count) were defined as presenting with advanced HIV disease (AHD). Results: Of the 7,300 new diagnoses reported in 2010-2011 by the included regions, 55.2% were LP; among these, 37.9% was diagnosed with AIDS. Persons presenting with AHD were 37.8%.The median age of LP was 40 years (IQR 33-48), significantly higher (p &lt; 0.001) than that of non-LP (35 years); 73.9% were males; 30.7% were non-nationals. The median age of AHD was 42 years (IQR 35-50), 74.5% were males; 31.1% were non-nationals.The proportion of LP among IDUs was 59.8%, among heterosexuals (HET) 61.1% and among MSM 44.3%. The proportion of AHD among IDUs was 43.6%, among HET 43.2% and among MSM 27.4%.Factors significantly associated with being LP were: age older than 50 years (OR = 4.6 [95% CI 3.8-5.6]); having been diagnosed in Southern Italy (Southern vs Northern Italy OR = 1.5 [95% CI 1.3-1.7]) having been diagnosed in Central Italy (Central vs Northern Italy OR = 1.3 [95% CI 1.1-1.6]); being HET (HET vs MSM, OR = 1.7 [95% CI 1.5-2.0]), being non-national (Non-national vs Italian, OR 1.7 (95% CI 1.5-2.0); being IDU (IDU vs MSM, OR = 1.6 [95% CI 1.2-2.1]). The same factors were significantly associated with being AHD. Conclusions: Older people, people diagnosed in Central and Southern Italy, non nationals, and persons who acquired the infection through injecting drug use or heterosexual contact showed a higher risk of being diagnosed late. A more active offer of HIV testing and targeted interventions focussed on these populations are needed to optimize early access to care and treatment. \ua9 2013 Camoni et al.; licensee BioMed Central Ltd

Rules-based HIV-1 genotypic resistance interpretation systems predict 8 week and 24 week virological antiretroviral treatment outcome and benefit from drug potency weighting.

Objectives To test retrospectively the ability of four freely available rules-based expert systems to predict short- and medium-term virological outcome following an antiretroviral treatment switch in pre-treated HIV-1 patients. Methods The HIV-1 genotype interpretation systems (GISs) HIVdb, ANRS, Rega and AntiRetroScan were tested for their accuracy in predicting response to highly active antiretroviral therapy using 8 week (n\u200a=\u200a765) and 24 week (n\u200a=\u200a634) follow-up standardized treatment change episodes extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) database. A genotypic sensitivity score (GSS) was derived for each genotype\u2013treatment pair for the different GISs and tested as a predictor of virological treatment outcome by univariable and multivariable logistic regression as well as by receiver operating characteristic curve analysis. The two systems implementing drug potency weights (AntiRetroScan and Rega) were evaluated with and without this correction factor. Results All four GSSs were strong predictors of virological treatment outcome at both 8 and 24 weeks after adjusting for baseline viro-immunological parameters and previous drug exposure (odds ratios ranging from 2.04 to 2.43 per 1 unit GSS increase; P\u200a<\u200a0.001 for all the systems). The accuracy of AntiRetroScan and Rega was significantly increased by drug potency weighting with respect to the unweighted versions (P\u200a 64\u200a0.001). HIVdb and ANRS also increased their performance with the same drug potency weighting adopted by AntiRetroScan and Rega, respectively (P\u200a<\u200a0.001 for both analyses). Conclusions Currently available GISs are valuable tools for assisting antiretroviral treatment choices. Drug potency weighting can increase the accuracy of all systems