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5. Genotypic testing on HIV-1 DNA as a tool to assess HIV-1 co-receptor usage in clinical practice: results from the DIVA study group

Author

Svicher, V., Alteri, C., Montano, M., Nori, A., D’Arrigo, R., Andreoni, M., Angarano, G., Antinori, A., Antonelli, G., Allice, T., Bagnarelli, P., Baldanti, F., Bertoli, A., Borderi, M., Boeri, E., Bon, I., Bruzzone, B., Barresi, R., Calderisi, S., Callegaro, A. P., Capobianchi, M. R., Gargiulo, F., Castelli, F., Cauda, R., Ceccherini-Silberstein, F., Clementi, M., Chirianni, A., Colafigli, M., D’Arminio Monforte, A., De Luca, A., Di Biagio, A., Di Nicuolo, G., Di Perri, G., Di Santo, F., Fadda, G., Galli, M., Gennari, W., Ghisetti, V., Costantini, A., Gori, A., Gulminetti, R., Leoncini, F., Maffongelli, G., Maggiolo, F., Maserati, R., Mazzotta, F., Meini, G., Micheli, V., Monno, L., Mussini, C., Nozza, S., Paolucci, S., Palù, G., Parisi, S., Parruti, G., Pignataro, A. R., Quirino, T., Re, M. C., Rizzardini, G., Sanguinetti, M., Santangelo, R., Scaggiante, R., Sterrantino, G., Turriziani, O., Vatteroni, M. L., Viscoli, C., Vullo, V., Zazzi, M., Lazzarin, A., and Perno, C. F.

Published
2014
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7. A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

Author

PProsperi MC, Di Giambenedetto S, Fanti I, Meini G, Bruzzone B, Callegaro A, Penco G, Bagnarelli P, Micheli V, Paolini E, Di Biagio A, Ghisetti V, Di Pietro M, Zazzi M, De Luca A, Giacometti A, Butini L, del Gobbo R, Menzo S, Tacconi D, Corbelli G, Zanussi S, Monno L, Punzi G, Maggiolo F, CALZA, LEONARDO, RE, MARIA CARLA, Pristerà R, Turconi P, Mandas A, Tini S, Carnevale G, Amadio G, Sighinolfi L, Zuccati G, Morfini M, Manetti R, Galli L, Bartalesi F, Colao G, Tosti A, Setti M, Trezzi M, Orani A, Pardelli R, De Gennaro M, Chiodera A, Scalzini A, Palvarini L, Almi P, Todaro G, Gianotti N, Cicconi P, Rusconi S, Gismondo MR, Biondi ML, Capetti A, Meraviglia P, Boeri E, Pecorari M, Mussini C, Santirocchi M, Brustia D, Ravanini P, Dal Bello F, Romano N, Mancuso S, Calzetti C, Maserati R, Baldanti F, Francisci D, Parruti G, Polilli E, Sacchini D, Martinelli C, Consolini R, Vatteroni L, Vivarelli A, Nerli A, Lenzi L, Magnani G, Ortolani P, Andreoni M, Palamara G, Fimiani C, Palmisano L, Antinori A, Vullo V, Turriziani O, Perno CF, Montano M, Cenderello G, Gonnelli A, Romano L, Palumbo M, Bonora S, Delle Foglie P, Rossi C, Poletti F, Mondino V, Malena M, Lattuada E., PProsperi MC, Di Giambenedetto S, Fanti I, Meini G, Bruzzone B, Callegaro A, Penco G, Bagnarelli P, Micheli V, Paolini E, Di Biagio A, Ghisetti V, Di Pietro M, Zazzi M, De Luca A, Giacometti A, Butini L, del Gobbo R, Menzo S, Tacconi D, Corbelli G, Zanussi S, Monno L, Punzi G, Maggiolo F, Calza L, Re MC, Pristerà R, Turconi P, Mandas A, Tini S, Carnevale G, Amadio G, Sighinolfi L, Zuccati G, Morfini M, Manetti R, Galli L, Bartalesi F, Colao G, Tosti A, Setti M, Trezzi M, Orani A, Pardelli R, De Gennaro M, Chiodera A, Scalzini A, Palvarini L, Almi P, Todaro G, Gianotti N, Cicconi P, Rusconi S, Gismondo MR, Biondi ML, Capetti A, Meraviglia P, Boeri E, Pecorari M, Mussini C, Santirocchi M, Brustia D, Ravanini P, Dal Bello F, Romano N, Mancuso S, Calzetti C, Maserati R, Baldanti F, Francisci D, Parruti G, Polilli E, Sacchini D, Martinelli C, Consolini R, Vatteroni L, Vivarelli A, Nerli A, Lenzi L, Magnani G, Ortolani P, Andreoni M, Palamara G, Fimiani C, Palmisano L, Antinori A, Vullo V, Turriziani O, Perno CF, Montano M, Cenderello G, Gonnelli A, Romano L, Palumbo M, Bonora S, Delle Foglie P, Rossi C, Poletti F, Mondino V, Malena M, Lattuada E., Prosperi, M, Di Giambenedetto, S, Fanti, I, Meini, G, Bruzzone, B, Callegaro, A, Penco, G, Bagnarelli, P, Micheli, V, Paolini, E, Di Biagio, A, Ghisetti, V, Di Pietro, M, Zazzi, M, De Luca, A, and Mancuso, S

Subjects
Oncology, Male, Adult, Anti-HIV Agents, Cohort Studies, Drug Therapy, Combination, Female, HIV Infections, HIV-1, Humans, Middle Aged, Proportional Hazards Models, Treatment Failure, Viral Load, 0302 clinical medicine, ANTIRETROVIRAL THERAPY, Medicine, HIV Infection, 030212 general & internal medicine, 0303 health sciences, Health Policy, 3. Good health, Computer Science Applications, Censoring (clinical trials), Cohort, Combination, lcsh:R858-859.7, Viral load, Human, Research Article, Cart, medicine.medical_specialty, antiretroviral therapy, Health Informatics, Settore MED/17 - MALATTIE INFETTIVE, lcsh:Computer applications to medicine. Medical informatics, 03 medical and health sciences, Drug Therapy, Internal medicine, Survival analysis, 030306 microbiology, business.industry, Proportional hazards model, ANTIRETROVIRAL DRUGS, Anti-HIV Agent, HIV, GENOTYPES, Discontinuation, Regimen, Immunology, Proportional Hazards Model, Cohort Studie, business
Abstract

Background 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. Methods 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 90th day 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. Results 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. Conclusions 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.

Published
2011
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8. A new species of otoplanid (Plathelminthes: Rhabditophora: Otoplanidae) from Sicily, Italy.

Author

Lanfranchi, A., Meini, G., and Melai, M.

Abstract

A new species, Philosyrtis aegusae sp. nov., collected in the ‘Otoplanen-Zone’ of the sands of western Sicily, is described. The specimens show the typical morphological peculiarities of the subfamily Parotoplaninae (‘Turbellaria’: Otoplanidae), but differ clearly from the species already described. The body length of the sexually mature animals reaches 0.9–1.1 mm and they appear to belong to the genus Philosyrtis because of the general arrangement of testes and germo-vitellaria, and of the sclerotic apparatus. The vesicula granulorum is clearly distinct from the sclerotic apparatus unlike the other ten species belonging to the same genus. The male copulatory organ consists of a dorsal group of 7–8 spines similar in shape and length (33–40 mm), and a ventral group of at least 6 long thin spines with curved pointed tips. The new species differs from the already described species above all in its body dimensions, the shorter path of the vitellaries and especially the characteristics of the male sclerotic apparatus. [ABSTRACT FROM PUBLISHER]

Published
2011
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9. Postbursoplana parafibulata sp. nov.: A new flatworm from the Ligurian Sea (Plathelminthes, Rhabditophora, Otoplanidae).

Author

LANFRANCHI, A., MELAI, M., and MEINI, G.

Subjects
PLATYHELMINTHES, MARINE worms, WORMS
Abstract

A new species, Postbursoplana parafibulata sp. nov., is described from lower interstitial habitats of the Upper Tuscan sea coast (Ligurian Sea). The specimens display the typical collar-shaped pharynx, perpendicularly positioned, of the subfamily Parotoplaninae (“Turbellaria”, Otoplanidae). The sexually mature animals are 1.2-1.4 mm in length, and appear to belong to the genus Postbursoplana because of the general arrangement of testes and germo-vitellaria, and of the sclerotic apparatus characteristics. Their male copulatory organ consists of 10 spines differentiated in five groups with variable shape and length (52-73 μm). P. parafibulata sp. nov. differs from the already described species above all for the body dimensions and the characteristics of the sclerotic male apparatus. The new species appears more similar to P. fibulata collected in the Mediterranean Sea. [ABSTRACT FROM AUTHOR]

Published
2010
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10. Is there a relationship between HIV tropism and historical genotypic resistance in treatment-experienced patients?

Author

Zaccarelli, M, Sterrantino, G, Francisci, D, Di Biagio, A, Di Giambenedetto, S, De Luca, A, Punzi, G, Bruzzone, B, Meini, G, and Zazzi, M

Subjects
HEALTH outcome assessment, HIV protease inhibitors, GENOTYPES, HIV infections, VIRAL tropism
Abstract

Purpose of the study Since X4/DM HIV-1 tropism is associated with poorer prognosis and worse response to treatment, the aim of this study was to assess whether X4/DM HIV-1 tropism is also related with a higher accumulation of resistance in patients experiencing treatment failure. Methods HIV protease (PR) and reverse transcriptase (RT) resistance mutations and tropism test results were extracted from a national database. Viral tropism data included enhanced sensitivity Trofile assay (ESTA) and geno2pheno results at 10% false positive rate. Historical resistance mutations (HRM) for PI, NRTI and NNRTI, detected in all genotypic tests performed during patient treatment history, were selected according to IAS-USA indications. Summary of results Overall, 1280 patients were included: males 65%, median age 45 years (IQR: 40-50), median CD4 nadir 116 (IQR: 34-272), median past regimens 7 (IQR: 3-12), median previous NRTI used 5 (IQR: 4-7), median previous NNRTI used 1 (IQR 1-2) and median previous PI used 3 (IQR 1-5). HIV tropism was assessed by ESTA in 271 patients (21.2%) and by geno2pheno in 1009 patients (78.8%). Four hundred and fifteen patients (32.4%) carried X4/DM virus and 321 (25.1%) had ≥1 HRM for each antiretroviral class. The mean number of HRM was higher in patients harboring X4/DM virus than in patients harboring R5 virus (5.1±6.4 vs. 4.3±5.9, p = 0.02 at ANOVA test). X4/DM strains also harbored a higher mean number of PI-related HRM (1.8±2.8 vs. 1.5±2.6, p = 0.003) and NNRTI-related HRM (1.2±1.6 vs. 0.9±1.4, p = 0.001), but not of NRTI-related HRM (2.2±2.6 vs. 2.0±2.6). At logistic regression, patients with HRM for all the 3 classes had a significant higher risk of also harboring X4/DM virus (OR: 1.6, 95% CI: 1.0-2.4, p = 0.04). Moreover, X4/DM virus was found to be associated with previous use of NNRTI-containing regimens (OR: 1.4, 95% CI: 1.1-1-9, p = 0.03) and lower CD4 nadir (OR: 0.9, 95% CI: 0.9-1.0, p = 0.001, per 50-CD4 increase). The analysis was adjusted by number of genotypic tests, number of treatment lines, age and HV subtype. Single mutations significantly associated with X4/DM tropism were: for PI, V32I and L76V; for NRTI: M41L, K70R, L74V and T215Y and for NNRTI: E138G and V179T. Conclusions Our data suggest that X4/DM tropism is associated with accumulation of resistance mutations during treatment history. X4/DM tropism is also confirmed to be a marker of a more compromised clinical and immune-virological condition. [ABSTRACT FROM AUTHOR]

Published
2012
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