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1. Potential benefit of dolutegravir once daily: efficacy and safety

Author

Fantauzzi A, Turriziani O, and Mezzaroma I

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Alessandra Fantauzzi,1 Ombretta Turriziani,2 Ivano Mezzaroma11Department of Clinical Medicine, 2Department of Molecular Medicine, Sapienza, University of Rome, Rome, ItalyAbstract: The viral integrase enzyme has recently emerged as a primary alternative target to block HIV-1 replication, and integrase inhibitors are considered a pivotal new class of antiretroviral drugs. Dolutegravir is an investigational next-generation integrase inhibitor showing some novel and intriguing characteristics, ie, it has a favorable pharmacokinetic profile with a prolonged intracellular half-life, rendering feasible once-daily dosing without the need for ritonavir boosting and without regard to meals. Moreover, dolutegravir is primarily metabolized via uridine diphosphate glucuronosyltranferase 1A1, with a minor component of the cytochrome P450 3A4 isoform, thereby limiting drug–drug interactions. Furthermore, its metabolic profile enables coadministration with most of the other available antiretroviral agents without dose adjustment. Recent findings also demonstrate that dolutegravir has significant activity against HIV-1 isolates with resistance mutations associated with raltegravir and/or elvitegravir. The attributes of once-daily administration and the potential to treat integrase inhibitor-resistant viruses make dolutegravir an interesting and promising investigational drug. In this review, the main concerns about the efficacy and safety of dolutegravir as well as its resistance profile are explored by analysis of currently available data from preclinical and clinical studies.Keywords: antiretroviral drugs, HIV-1 integrase, integrase inhibitors, dolutegravir, once daily

Published
2013

12. External quality assessment of HIV-1 DNA quantification assays used in the clinical setting in Italy

Author

Vicenti, I., Dragoni, F., Giannini, A., Casabianca, A., Lombardi, F., Di Sante, L., Turriziani, O., Racca, S., Paolucci, S., Lai, A., Bon, I., Abbate, I., Rozera, G., Belmonti, S., Scutari, R., Alteri, C., Saladini, F., Zazzi, M., Orlandi, C., Magnani, M., Di Giambenedetto, S., Longo, R., Menzo, S., Di Carlo, D., Mazzuti, L., Ardemagni, A., Clementi, M., Baldanti, F., Giardina, F., Bergna, A., Balotta, C., Bertoldi, A., Capobianchi, M. R., Ceccherini-Silberstein, F., Antonello, M., Perno, C. F., Andreoni, M., Lombardi F. (ORCID:0000-0001-5757-8346), Paolucci S., Lai A., Magnani M., Di Giambenedetto S. (ORCID:0000-0001-6990-5076), Longo R., Ardemagni A., Clementi M., Vicenti, I., Dragoni, F., Giannini, A., Casabianca, A., Lombardi, F., Di Sante, L., Turriziani, O., Racca, S., Paolucci, S., Lai, A., Bon, I., Abbate, I., Rozera, G., Belmonti, S., Scutari, R., Alteri, C., Saladini, F., Zazzi, M., Orlandi, C., Magnani, M., Di Giambenedetto, S., Longo, R., Menzo, S., Di Carlo, D., Mazzuti, L., Ardemagni, A., Clementi, M., Baldanti, F., Giardina, F., Bergna, A., Balotta, C., Bertoldi, A., Capobianchi, M. R., Ceccherini-Silberstein, F., Antonello, M., Perno, C. F., Andreoni, M., Lombardi F. (ORCID:0000-0001-5757-8346), Paolucci S., Lai A., Magnani M., Di Giambenedetto S. (ORCID:0000-0001-6990-5076), Longo R., Ardemagni A., and Clementi M.

Abstract

Total cell-associated HIV-1 DNA is a surrogate marker of the HIV-1 reservoir, however, certified systems for its quantification are not available. The Italian HIV DNA Network was launched to validate HIV-1 DNA quantification methods in use at University and Hospital labs. A quality control panel including HIV-1 DNA standards, reconstructed blood samples (RBSs) and DNA from different HIV-1 subtypes was blindly tested by 12 participating labs by quantitative real-time PCR (n = 6), droplet digital PCR (n = 3) or both (n = 3). The median 95% hit rate was 4.6 (3.7–5.5) copies per test and linearity in the tested range was excellent (R2 = 1.000 [1.000–1.000]). The median values obtained across labs were 3,370 (2,287–4,245), 445 (299–498), 59 (40–81) and 7 (6–11) HIV-1 DNA copies, for the 3,584, 448, 56 and 7-copy standards, respectively. With RBSs, measured values were within twofold with respect to the median in two thirds of cases. HIV-1 subtypes were missed (CRF01_AE by 3 labs) or underestimated by > 1 log (subtypes A, C, D, F by one lab; CRF01_AE by one lab; CRF02_AG by one lab). The overall performance was excellent with HIV-1 DNA standards, however detection of different HIV-1 subtypes must be improved.

Published
2022

14. 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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16. High HIV-1 diversity in immigrants resident in Italy (2008–2017)

Author

Maggiorella M. T., Sanarico N., Brindicci G., Monno L., Santoro C. R., Coppola N., Cuomo N., Azzurri A., Cesario F., Luciani F., El-Hamad I., D'Ettorre G., Turriziani O., Mazzuti L., Poggi A., Vichi F., Mariabelli E., Surace L., Berardelli G., Picconi O., Cenci A., Sernicola L., Rovetto C., Fulgenzi D., Belli R., Salvi E., Zeo P. D., Borsetti A., Ridolfi B., Losappio R., Zoboli F., Schietroma I., Cella E., Angeletti S., Ciccozzi M., D'Amato S., Ensoli B., Butto S., Angarano G., Babudieri S., Scheri G. C., Lichtner M., Martini S., Mazzella A., Romano N., Pansera A., Pontali E., Raddi A., Starnini G., Dell'Isola S., Maggiorella, M. T., Sanarico, N., Brindicci, G., Monno, L., Santoro, C. R., Coppola, N., Cuomo, N., Azzurri, A., Cesario, F., Luciani, F., El-Hamad, I., D'Ettorre, G., Turriziani, O., Mazzuti, L., Poggi, A., Vichi, F., Mariabelli, E., Surace, L., Berardelli, G., Picconi, O., Cenci, A., Sernicola, L., Rovetto, C., Fulgenzi, D., Belli, R., Salvi, E., Zeo, P. D., Borsetti, A., Ridolfi, B., Losappio, R., Zoboli, F., Schietroma, I., Cella, E., Angeletti, S., Ciccozzi, M., D'Amato, S., Ensoli, B., Butto, S., Angarano, G., Babudieri, S., Scheri, G. C., Lichtner, M., Martini, S., Mazzella, A., Romano, N., Pansera, A., Pontali, E., Raddi, A., Starnini, G., and Dell'Isola, S.

Subjects
0301 basic medicine, Male, Latin Americans, Immigration, Human immunodeficiency virus (HIV), lcsh:Medicine, HIV Infections, Drug resistance, medicine.disease_cause, Antiretroviral Therapy, Highly Active, Cluster Analysis, HIV Infection, lcsh:Science, Phylogeny, media_common, Recombination, Genetic, Multidisciplinary, Geography, virus diseases, High HIV-1 diversity in immigrants, Middle Aged, Italy, Medicine, Infectious diseases, Female, Human, Adult, Tuberculosis, media_common.quotation_subject, Science, 030106 microbiology, Emigrants and Immigrants, Article, 03 medical and health sciences, Population screening, Drug Resistance, Viral, medicine, Humans, Hepatitis, Cluster Analysi, lcsh:R, Genetic Variation, Emigrants and Immigrant, medicine.disease, Antiretroviral therapy, 030104 developmental biology, Mutation, HIV-1, lcsh:Q, Demography, Diversity (politics)
Abstract

The proportion of new diagnoses of HIV infection in immigrants residing in Italy raised from 11% in 1992 to 29.7% in 2018. To investigate the HIV clades circulating in this community a retrospective study was performed in 557 HIV-infected immigrants living in 12 Italian cities. Immigrants originated from East-Europe and Central-Asia (11.7%), North Africa and Middle East (7.3%), South and South-East Asia (7.2%), Latin America and the Caribbean (14.4%), and sub-Saharan Africa (59.4%). More than 87% of immigrants were on antiretroviral therapy (ART), although 26.6% of them were viremic. A 22.0% of immigrants had hepatitis (HBV and/or HCV) and/or tuberculosis. HIV phylogenetic analysis on sequences from 192 immigrants showed the presence of clades B (23.4%), G (16.1%), C (10.4%), A1 (9.4%), F1 (5.2%), D (1.6%) and Circulating Recombinant Forms (CRFs) (33.9%). CRF02_AG represented 72.3% of the total CRFs. Clusters between immigrants and Italian natives were also present. Drug resistance mutations to NRTI, NNRTI, and PI drug classes occurred in 29.1% of ART-treated and in 12.9% of ART-naïve individuals. These data highlight the need for tailored public health interventions in immigrants to avoid spreading in Italy of HIV genetic forms and ART-resistant variants, as well as HIV co-morbidities.

Published
2020

19. Prevalence of acquired resistance mutations in a large cohort of perinatally infected HIV-1 patients

Author

Ungaro, R., Taramasso, L., Bruzzone, B., Vicenti, I., Galli, L., Borghi, V., Francisci, D., Pecorari, M., Zoncada, A., Callegaro, A. P., Paolini, E., Monno, L., Bonora, S., Di Biagio, A., ARCA Study Group, Giacometti, A., Butini, L., del Gobbo, R., Bagnarelli, P., Tacconi, D., Corbelli, G., Zanussi, S., Punzi, G., Maggiolo, F., Calza, L., Carla Re, M., Pristera, R., Turconi, P., Mandas, A., Tini, S., Amadio, G., Sighinolfi, L., Corsi, P., Di Pietro, M., Colao, G., Tosti, A., Setti, M., Cenderello, G., Trezzi, M., Orani, A., Arcidiacono, I., Degiuli, A., De Gennaro, M., Chiodera, A., Scalzini, A., Palvarini, L., Todaro, G., Rusconi, S., Gismondo, M. R., Micheli, V., Biondi, M. L., Capetti, A., Meraviglia, P., Boeri, E., Mussini, C., Soria, A., Vecchi, L., Santirocchi, M., Brustia, D., Ravanini, P., Dal Bello, F., Romano, N., Mancuso, S., Calzetti, C., Maserati, R., Filice, G., Baldanti, F., Parruti, G., Polilli, E., Sacchini, D., Martinelli, C., Consolini, R., Vatteroni, L., Vivarelli, A., Nerli, A., Lenzi, L., Magnani, G., Ortolani, P., Andreoni, M., Fimiani, C., Palmisano, L., Di Giambenedetto, S., Vullo, V., Turriziani, O., Montano, M., Antinori, A., Zaccarelli, M., Dentone, C., Gonnelli, A., De Luca, A., Palumbo, M., Ghisetti, V., Delle Foglie, P., Rossi, C., Mondino, V., Malena, M., Grossi, P., Seminari, E., Poletti, F., Ungaro R., Taramasso L., Bruzzone B., Vicenti I., Galli L., Borghi V., Francisci D., Pecorari M., Zoncada A., Callegaro A.P., Paolini E., Monno L., Bonora S., Di Biagio A., Giacometti A., Butini L., del Gobbo R., Bagnarelli P., Tacconi D., Corbelli G., Zanussi S., Punzi G., Maggiolo F., Calza L., Carla Re M., Pristera R., Turconi P., Mandas A., Tini S., Amadio G., Sighinolfi L., Corsi P., Di Pietro M., Colao G., Tosti A., Setti M., Cenderello G., Trezzi M., Orani A., Arcidiacono I., Degiuli A., De Gennaro M., Chiodera A., Scalzini A., Palvarini L., Todaro G., Rusconi S., Gismondo M.R., Micheli V., Biondi M.L., Capetti A., Meraviglia P., Boeri E., Mussini C., Soria A., Vecchi L., Santirocchi M., Brustia D., Ravanini P., Dal Bello F., Romano N., Mancuso S., Calzetti C., Maserati R., Filice G., Baldanti F., Parruti G., Polilli E., Sacchini D., Martinelli C., Consolini R., Vatteroni L., Vivarelli A., Nerli A., Lenzi L., Magnani G., Ortolani P., Andreoni M., Fimiani C., Palmisano L., Di Giambenedetto S., Vullo V., Turriziani O., Montano M., Antinori A., Zaccarelli M., Dentone C., Gonnelli A., De Luca A., Palumbo M., Ghisetti V., Delle Foglie P., Rossi C., Mondino V., Malena M., Grossi P., Seminari E., and Poletti F.

Subjects
Male, antiretroviral treatment, Infectious Disease Transmission, genotype, Human immunodeficiency virus (HIV), Drug Resistance, HIV Infections, Drug resistance, medicine.disease_cause, Retrospective Studie, Genotype, pol Gene Products, Human Immunodeficiency Viru, Prevalence, Medicine, Vertical, HIV Infection, Viral, pol Gene Products, Young adult, General Medicine, Infectious Diseases, Italy, Mutation (genetic algorithm), Female, Human Immunodeficiency Virus, Human, Microbiology (medical), Adult, Settore MED/17 - Malattie Infettive, Adolescent, Anti-HIV Agents, Young Adult, Acquired resistance, Drug Resistance, Viral, Humans, vertical HIV transmission, HIV-1, Mutation, Retrospective Studies, pol Gene Products, Human Immunodeficiency Virus, Infectious Disease Transmission, Vertical, HIV perinatally infection, business.industry, Anti-HIV Agent, Retrospective cohort study, Virology, Large cohort, business
Published
2019

21. New indolylarylsulfone non-nucleoside reverse transcriptase inhibitors show low nanomolar inhibition of single and double HIV-1 mutant strains

Author

Nalli, M., Armijos Rivera, J. I., Masci, Domiziana, Coluccia, A., Badia, R., Riveira-Munoz, E., Brambilla, Alberto, Cinquina, E., Turriziani, O., Falasca, F., Catalano, M., Limatola, Carlo, Este, J. A., Maga, G., Silvestri, R., Crespan, E., La Regina, Giuseppe, Masci D. (ORCID:0000-0002-5615-5111), Brambilla A., Limatola C., La Regina G., Nalli, M., Armijos Rivera, J. I., Masci, Domiziana, Coluccia, A., Badia, R., Riveira-Munoz, E., Brambilla, Alberto, Cinquina, E., Turriziani, O., Falasca, F., Catalano, M., Limatola, Carlo, Este, J. A., Maga, G., Silvestri, R., Crespan, E., La Regina, Giuseppe, Masci D. (ORCID:0000-0002-5615-5111), Brambilla A., Limatola C., and La Regina G.

Abstract

We designed and synthesized 21 new indolylarylsulfones (IASs) as new HIV-1 NNRTIs. Among these, IAS 12 exhibited a remarkable antiviral activity against single and double mutants (K103N EC50 = <0.7 nM; Y181C EC50 = <0.7 nM; Y188L EC50 = 21.3 nM; K103N–Y181C EC50 = 6.2 nM), resulting equally or more active than previuosly reported IAS 6 and some approved anti-HIV-1 drugs. Docking and molecular dynamics simulations of compound 12 in complex with WT, Y181C, Y188L, K103N and K103N–Y181C RTs clarified a general binding mode that was consistent with biological results. Kinetic experiments disclosed that derivative 12 preferentially binds WT and K103N–Y181C RTs to binary and ternary complexes, respectively.

Published
2020

22. The Synergistic Effect of Time of Exposure, Distance and No Use of Personal Protective Equipment in the Determination of SARS-CoV-2 Infection: Results of a Contact Tracing Follow-Up Study in Healthcare Workers

Author

La Torre, G., Marte, M., Previte, C. M., Barone, L. C., Picchioni, F., Chiappetta, M., Faticoni, A., Marotta, D., Mazzalai, E., Barletta, V. I., Kibi, S., Cammalleri, V., Dorelli, B., Giffi, M., Pocino, R. N., Massetti, A. P., Fimiani, C., Turriziani, O., Romano, F., Antonelli, G., Deales, A., Mastroianni, C. M., Vasaturo, F., Rossi, N., D'Ambrogio, M. G., Calogero, C., Falasconi, G., Mazza, S., Limongi, A., Drago, G., Del Parco, F., Nicoli, F., Colazingari, V., Renzi, S., Celani, M., Buzatu, A., Andreski, A., Koteva, M., Mazza, E., Morgante, L., Masi, P., Bruccoleri, G., La Penna, V., Casertano, F., Vespa, G., Vannozzi, A., Attardo, I., Candeloro, C., Apuzzo, D., Terzo, D., Olbes, A., Addari, S., Cinti, N. A., Bolettieri, A., Campanella, G., Silvestri, G., Sorrentino, A., Taibi, C., Ponzi, B., Marceline, N. K., Colelli, C., Cupelloni, L., Festucci, S., Bellenzier, C., Ribezzo, G., Fabbri, S., Tenore, G., Pacheco, R. M. V., Caprini, D., Andreacchio, S., Antico, R., Catherine, S. M., Pepe, P., Ricci, D., D'Intino, P., Chiaravallotti, S., Napolitano, D., Panarello, C., Galbera, M., Iobbi, N., Lomartire, F., and Inchingolo, V.

Subjects
safety, Infectious Disease Transmission, Patient-to-Professional, Health Personnel, Health, Toxicology and Mutagenesis, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), education, Article, contact tracing, synergism, Environmental health, time of exposure, Health care, Humans, Medicine, COVID-19, cistance, personal protective equipment, SARS-CoV-2, female, follow-up studies, health personnel, humans, infectious disease transmission, patient-to-professional, middle aged, pandemics, distance, Pandemics, Personal protective equipment, Univariate analysis, business.industry, Proportional hazards model, Hazard ratio, Public Health, Environmental and Occupational Health, Follow up studies, virus diseases, Middle Aged, Female, business, Contact tracing, Follow-Up Studies
Abstract

The aim of this study is to assess the effect of contact time, contact distance and the use of personal protective equipment on the determination of SARS-CoV-2 infection in healthcare workers (HCWs). This study consists of an analysis of data gathered for safety reasons at the Sapienza Teaching Hospital Policlinico Umberto I in Rome through the surveillance system that was put into place after the worsening of the COVID-19 pandemic. The studied subjects consist of HCWs who were put under health surveillance, i.e., all employees who were in contact with subjects who were confirmed to have tested positive for SARS-CoV-2. The HCWs under surveillance were monitored for a period encompassing ten days after the date of contact, during which they undertook nasopharyngeal swab tests analysed through RT-PCR (RealStar® SARS-CoV-2 Altona Diagnostic–Germany). Descriptive and univariate analyses have been undertaken, considering the following as risk factors: (a) no personal protective equipment use (PPE), (b) Distance &lt, 1 m between the positive and contact persons, (c) contact time &gt, 15′. Finally, a Cox regression and an analysis of the level of synergism between factors, as specified by Rothman, were carried out. We analysed data from 1273 HCWs. Of these HCWs, 799 (62.8%) were females, with a sample average age of 47.8 years. Thirty-nine (3.1%) tested positive during surveillance. The overall incidence rate was 0.4 per 100 person-days. Time elapsed from the last exposure and a positive RT-PCR result ranged from 2 to 17 days (mean = 7, median = 6 days). In the univariate analysis, a distance &lt, 1 m and a contact time &gt, 15′ proved to be risk factors for the SARS-CoV-2 infection, with a hazard ratio (HR) of 2.62 (95% CI: 1.11–6.19) and 3.59 (95% IC: 1.57–8.21), respectively. The synergism analysis found the highest synergism between the “no PPE use” x “Contact time”. The synergy index S remains strongly positive also in the analysis of the factors “no PPE use” x “Distance” and “Time of contact” x “Distance”. This study confirms the absolute need to implement safety protocols during the pandemic and to use the correct PPE within health facilities in order to prevent SARS-CoV-2 infection. The analysis shows that among the factors considered (contact time and distance, no use of PPE), there is a strong synergistic effect.

Published
2021

24. Sperm cryopreservation during the SARS-CoV-2 pandemic

Author

Paoli, D., primary, Pallotti, F., additional, Nigro, G., additional, Aureli, A., additional, Perlorca, A., additional, Mazzuti, L., additional, Di Carlo, D., additional, Turriziani, O., additional, Lenzi, A., additional, and Lombardo, F., additional

Published
2020
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28. Lymphomagenic properties of a HIV p17 variant derived from a splenic marginal zone lymphoma occurred in a HIV-infected patient

Author

Caccuri, F, Muraro, E, Gloghini, A, Turriziani, O, Riminucci, M, Giagulli, C, Mastorci, K, Fae, DA, Fiorentini, S, Caruso, A, Carbone, A, Dolcetti, R, Caccuri, F, Muraro, E, Gloghini, A, Turriziani, O, Riminucci, M, Giagulli, C, Mastorci, K, Fae, DA, Fiorentini, S, Caruso, A, Carbone, A, and Dolcetti, R

Abstract

Despite antiretroviral therapy, HIV+ individuals still have increased risk to develop lymphomas, including marginal zone lymphomas, suggesting that factors other than HIV-related immunosuppression are probably acting as lymphomagenic factors in the HIV setting. The possible pathogenic involvement of HIV p17 protein variants was investigated in a particularly informative case of HIV-related splenic marginal zone lymphoma, which was negative for oncogenic virus infections, thus allowing us to assess the possible direct contribution of these HIV-encoded proteins to lymphomagenesis. The presence of p17 protein was analyzed by immunohistochemistry in lymphoma tissue. Recombinant p17 protein derived from the dominant sequence detected in plasma and lymphoma biopsy was characterized for B-cell proliferation, clonogenicity in soft agar, in vitro tube formation and wound healing. Intracellular signaling was investigated by immunoblotting. HIV p17 protein was detected in reactive lymphoid follicles but not within lymphoma cells. An identical dominant variant p17 sequence, p17-Lyrm, carrying a 117 to 118 Ala-Ala insertion was detected in both plasma and lymphoma tissue. Recombinant p17-Lyrm enhanced B-cell proliferation and clonogenicity promoted the formation of capillary-like structures and enhanced endothelial cell migration. Unlike reference p17, the p17-Lyrm variant enhanced the activation of Akt and ERK, critical kinases in lymphomagenesis. p17-Lyrm clonogenic activity was dependent on the activation of Akt but not of ERK1/2. These results indicated that HIV p17 variants with distinct molecular signatures and functional properties may accumulate in lymphoid tissues of HIV-infected individuals where they may act as a local stimulus promoting the development of lymphomas.

Published
2019

31. ACKNOWLEDGEMENT OF REVIEWERS

Author

Adams, NG, Adekambi, T, Afeltra, J, Aguado, J, Aires de Sousa, M, Akiyoshi, K, Al Hasan, M, Ala-Kokko, T, Albert, M, Alfandari, S, Allen, D, Allerberger, F, Almyroudis, N, Alp, E, Amin, R, Anderson-Berry, A, Andes, DR, Andremont, A, Andreu, A, Angelakis, M, Antachopoulos, C, Antoniadou, A, Arabatzis, M, Arlet, G, Arnez, M, Arnold, C, Asensio, A, Asseray, N, Ausiello, C, Avni, T, Ayling, R, Baddour, L, Baguelin, M, Bányai, K, Barbour, A, Basco, LK, Bauer, D, Bayston, R, Beall, B, Becker, K, Behr, M, Bejon, P, Belliot, G, Benito-Fernandez, J, Benjamin, D, Benschop, K, Berencsi, G, Bergeron, MG, Bernard, K, Berner, R, Beyersmann, J, Bille, J, Bizzini, A, Bjarnsholt, T, Blanc, D, Blanco, J, Blot, S, Bohnert, J, Boillat, N, Bonomo, R, Bonten, M, Bordon, JM, Borel, N, Boschiroli, ML, Bosilkovski, M, Bosso, JA, Botelho-Nevers, E, Bou, G, Bretagne, S, Brouqui, P, Brun-Buisson, C, Brunetto, M, Bucher, H, Buchheidt, D, Buckling, A, Bulpa, P, Cambau, E, Canducci, F, Cantón, R, Capobianchi, M, Carattoli, A, Carcopino, X, Cardona-Castro, N, Carling, PC, Carrat, F, Castilla, J, Castilletti, C, Cavaco, L, Cavallo, R, Ceccherini-Silberstein, F, Centrón, D, Chappuis, F, Charrel, R, Chen, M, Chevaliez, S, Chezzi, C, Chomel, B, Chowers, M, Chryssanthou, E, Ciammaruconi, A, Ciccozzi, M, Cid, J, Ciofu, O, Cisneros, D, Ciufolini, MG, Clark, C, Clarke, SC, Clayton, R, Clementi, M, Clemons, K, Cloeckaert, Ael, Cloud, J, Coenye, T, Cohen Bacri, S, Cohen, R, Coia, J, Colombo, A, Colson, P, Concerse, P, Cordonnier, C, Cormican, M, Cornaglia, G, Cornely, O, Costa, S, Cots, F, Craxi, A, Creti, R, Crnich, C, Cuenca Estrella, M, Cusi, MG, d'Ettorre, G, da Cruz Lamas, C, Daikos, G, Dannaoui, E, De Barbeyrac, B, De Grazia, S, de Jager, C, de Lamballerie, X, de Marco, F, del Palacio, A, Delpeyroux, F, Denamur, E, Denis, O, Depaquit, J, Deplano, A, Desenclos, J-C, Desjeux, P, Deutch, S, Di Luca, D, Dianzani, F, Diep, B, Diestra, K, Dignani, C, Dimopoulos, G, Divizia, M, Doi, Y, Dornbusch, HJ, Dotis, J, Drancourt, M, Drevinek, P, Dromer, F, Dryden, M, Dubreuil, L, Dubus, J-C, Dumitrescu, O, Dumke, R, DuPont, H, Edelstein, M, Eggimann, P, Eis-Huebinger, A-M, El Atrouni, WI, Entenza, J, Ergonul, O, Espinel-Ingroff, A, Esteban, J, Etienne, J, Fan, X-G, Fenollar, F, Ferrante, P, Ferrieri, P, Ferry, T, Feuchtinger, T, Finegold, S, Fingerle, V, Fitch, M, Fitzgerald, R, Flori, P, Fluit, A, Fontana, R, Fournier, PE, François, M, Francois, P, Freedman, DO, Friedrich, A, Gallego, L, Gallinella, G, Gangneux, J-P, Gannon, V, Garbarg-Chenon, A, Garbino, J, Garnacho-Montero, J, Gatermann, Soeren, Gautret, P, Gentile, G, Gerlich, W, Ghannoum, M, Ghebremedhin, B, Ghigo, E, Giamarellos-Bourboulis, E, Girgis, R, Giske, C, Glupczynski, Y, Gnarpe, J, Gomez-Barrena, E, Gorwitz, RJ, Gosselin, R, Goubau, P, Gould, E, Gradel, K, Gray, J, Gregson, D, Greub, G, Grijalva, CG, Groll, A, Groschup, M, Gutiérrez, J, Hackam, DG, Hall, WA, Hallett, R, Hansen, S, Harbarth, S, Harf-Monteil, C, Hasanjani, Roushan MR, Hasler, P, Hatchette, T, Hauser, P, He, Q, Hedges, A, Helbig, J, Hennequin, C, Herrmann, B, Hezode, C, Higgins, P, Hoesli, I, Hoiby, N, Hope, W, Houvinen, P, Hsu, LY, Huard, R, Humphreys, H, Icardi, M, Imoehl, M, Ivanova, K, Iwamoto, T, Izopet, J, Jackson, Y, Jacobsen, K, Jang, TN, Jasir, A, Jaulhac, B, Jaureguy, F, Jefferies, JM, Jehl, F, Johnstone, J, Joly-Guillou, M-L, Jonas, M, Jones, M, Joukhadar, C, Kahl, B, Kaier, K, Kaiser, L, Kato, H, Katragkou, A, Kearns, A, Kern, W, Kerr, K, Kessin, R, Kibbler, C, Kimberlin, D, Kittang, B, Klaassen, C, Kluytmans, J, Ko, W-C, Koh, W-J, Kostrzewa, M, Kourbeti, I, Krause, R, Krcmery, V, Krizova, P, Kuijper, E, Kullberg, B-J, Kumar, G, Kunin, CM, La Scola, B, Lagging, M, Lagrou, K, Lamagni, T, Landini, P, Landman, D, Larsen, A, Lass-Floerl, C, Laupland, K, Lavigne, JP, Leblebicioglu, H, Lee, B, Lee, CH, Leggat, P, Lehours, P, Leibovici, Lonard, Leon, L, Leonard, N, Leone, M, Lescure, X, Lesprit, P, Levy, PY, Lew, D, Lexau, CA, Li, S-Y, Li, W, Lieberman, D, Lina, B, Lina, G, Lindsay, JA, Livermore, D, Lorente, L, Lortholary, O, Lucet, J-C, Lund, B, Lütticken, R, MacLeod, C, Madhi, S, Maertens, J, Maggi, F, Maiden, M, Maillard, J-Y, Maira-Litran, T, Maltezou, H, Manian, FA, Mantadakis, E, Maragakis, L, Marcelin, A-G, Marchaim, D, Marchetti, O, Marcos, M, Markotic, A, Martina, B, Martínez, J, Martinez, J-L, Marty, F, Maurin, M, McGee, L, Mediannikov, O, Meersseman, W, Megraud, F, Meletiadis, J, Mellmann, A, Meyer, E, Meyer, W, Meylan, P, Michalopoulos, A, Micol, R, Midulla, F, Mikami, Y, Miller, RF, Miragaia, M, Miriagou, V, Mitchell, TJ, Miyakis, S, Mokrousov, I, Monecke, S, Mönkemüller, K, Monno, L, Monod, M, Morales, G, Moriarty, F, Morosini, I, Mortensen, E, Mubarak, K, Mueller, B, Mühlemann, K, Muñoz Bellido, JL, Murray, P, Muscillo, M, Mylotte, J, Naessens, A, Nagy, E, Nahm, MH, Nassif, X, Navarro, D, Navarro, F, Neofytos, D, Nes, I, Ní Eidhin, D, Nicolle, L, Niederman, MS, Nigro, G, Nimmo, G, Nordmann, P, Nougairède, A, Novais, A, Nygard, K, Oliveira, D, Orth, D, Ortiz, JR, Osherov, N, Österblad, M, Ostrosky-Zeichner, L, Pagano, L, Palamara, AT, Pallares, R, Panagopoulou, P, Pandey, P, Panepinto, J, Pappas, G, Parkins, M, Parola, P, Pasqualotto, A, Pasteran, F, Paul, M, Pawlotsky, J-M, Peeters, M, Peixe, L, Pepin, J, Peralta, G, Pereyre, S, Perfect, JR, Petinaki, E, Petric, M, Pettigrew, M, Pfaller, M, Philipp, M, Phillips, G, Pichichero, M, Pierangeli, A, Pierard, D, Pigrau, C, Pilishvili, T, Pinto, F, Pistello, M, Pitout, J, Poirel, L, Poli, G, Poppert, S, Posfay-Barbe, K, Pothier, P, Poxton, I, Poyart, C, Pozzetto, B, Pujol, M, Pulcini, C, Punyadeera, C, Ramirez, M, Ranque, S, Raoult, D, Rasigade, J-P, Re, MC, Reilly, JS, Reinert, R, Renaud, B, Rice, L, Rich, S, Richet, H, Rigouts, L, Riva, E, Rizzo, C, Robotham, J, Rodicio, MR, Rodriguez, J, Rodriguez-Bano, J, Rogier, C, Roilides, E, Rolain, J-M, Rooijakkers, S, Rooney, P, Rossi, F, Rotimi, V, Rottman, M, Roux, V, Ruhe, J, Russo, G, Sadowy, E, Sagel, U, Said, SI, Saijo, M, Sak, B, Sa-Leao, R, Sanders, EAM, Sanguinetti, M, Sarrazin, C, Savelkoul, P, Scheifele, D, Schmidt, W-P, Schønheyder, H, Schönrich, G, Schrenzel, J, Schubert, S, Schwarz, K, Schwarz, S, Sefton, A, Segondy, M, Seifert, H, Seng, P, Senneville, E, Sexton, D, Shafer, RW, Shalit, I, Shankar, N, Shata, TM, Shields, J, Sibley, C, Sicinschi, L, Siljander, T, Simitsopoulou, M, Simoons-Smit, AM, Sissoko, D, Sjögren, J, Skiada, A, Skoczynska, A, Skov, R, Slack, M, Sogaard, M, Sola, C, Soriano, A, Sotto, A, Sougakoff, W, Souli, M, Spelberg, B, Spelman, D, Spiliopoulou, I, Springer, B, Stefani, S, Stein, A, Steinbach, WJ, Steinbakk, M, Strakova, L, Strenger, V, Sturm, P, Sullivan, P, Sutton, D, Symmons, D, Tacconelli, E, Tamalet, C, Tang, JW, Tang, Y-W, Tattevin, P, Thibault, V, Thomsen, RW, Thuny, F, Tong, S, Torres, C, Townsend, R, Tristan, A, Trouillet, J-L, Tsai, H-C, Tsitsopoulos, P, Tuerlinckx, D, Tulkens, P, Tumbarello, M, Tureen, J, Turnidge, JD, Turriziani, O, Tutuian, R, Uçkay, I, Upton, M, Vabret, A, Vamvakas, EC, van den Boom, D, Van Eldere, J, van Leeuwen, W, van Strijp, J, Van Veen, S, Vandamme, P, Vandenesch, F, Vayssier, M, Velin, D, Venditti, M, Venter, M, Venuti, A, Vergnaud, G, Verheij, T, Verhofstede, C, Viscoli, C, Vizza, CD, Vogel, U, Waller, A, Wang, YF, Warn, P, Warris, A, Wauters, G, Weidmann, M, Weill, F-X, Weinberger, M, Welch, D, Wellinghausen, N, Wheat, J, Widmer, A, Wild, F, Willems, R, Willinger, B, Winstanley, C, Witte, W, Wolff, M, Wong, F, Wootton, M, Wyllie, D, Xu, W, Yamamoto, S, Yaron, S, Yildirim, I, Zaoutis, T, Zazzi, M, Zbinden, R, Zehender, Gianguglielmo G, Zemlickova, H, Zerbini, ML, Zhang, L, Zhang, Y, Zhao, Y-D, Zhu, Z, and Zimmerli, W

Published
2011
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32. Lack of association of Chlamydia pneumoniae with cardiovascular diseases in virologically suppressed HIV patients

Author

Sessa, R., Di Pietro, M., Filardo, S., Bressan, A., LAURA MAZZUTI, Serafino, S., Fantauzzi, A., and Turriziani, O.

Subjects
Male, Anti-HIV Agents, Cardiovascular Diseases, c. pneumoniae, cardiovascular diseases, hiv, real-time pcr, Humans, Female, HIV Infections, Chlamydophila pneumoniae, Middle Aged, Chlamydophila Infections, Lipids, Aged, CD4 Lymphocyte Count
Abstract

Cardiovascular disease (CVD) is a major public health problem in developed countries with over 17 million deaths per year. In the last decade, several infectious agents rather than any single pathogen, including Chlamydia pneumoniae and human immunodeficiency virus (HIV), have been shown to contribute to the development of atherosclerosis and subsequent cardiovascular events by inducing systemic inflammation and/or acting directly on the vascular wall. For the first time, we evaluated C. pneumonia DNA in peripheral blood mononuclear cells from HIV patients by real-time polymerase chain reaction in order to shed light on C. pneumonia as a co-factor with HIV in the development of CVDs. C. pneumonia DNA was not detected in our virologically suppressed HIV patients (37 copies/mL). This finding may be related to high CD4+T cell count (500 cells/μl) found in HIV patients suggesting functional cell-mediated immunity as a fundamental mechanism for the clearance of chlamydial infection in this population. Larger studies are needed to confirm this hypothesis.

Published
2017

34. Genotypic resistance profiles associated with virological failure to darunavir-containing regimens: a cross-sectional analysis

Author

Sterrantino, G, Zaccarelli, M, Colao, G, Baldanti, F, Di Giambenedetto, S, Carli, T, Maggiolo, F, Zazzi, M, Giacometti, A, Butini, L, Del Gobbo, R, Bagnarelli, P, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Callegaro, A, Calza, L, Re, MC, Pristera, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, di Biagio, A, Penco, G, Trezzi, M, Orani, A, Pardelli, R, Arcidiacono, I, Degiuli, A, de Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Cicconi, P, Rusconi, S, Gismondo, MR, Micheli, V, Biondi ML, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Gerardo, AO, Santirocchi, M, Brustia, D, Maggiore, AO, Ravanini, P, Bello, FD, Romano, N, MANCUSO, Salvatrice, Calzetti, C, Maserati, R, Filice, G, 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, di Giambenedetto, S, Colafigli, M, Vullo, V, Turriziani, O, Montano, M, Antinori, A, Dentone, C, Gonnelli, A, de Luca, A, Palumbo, M, Ghisetti, V, Bonora, S, Foglie, PD, Rossi, C, Mondino, V, Malena, M, Grossi, P, Seminari, E, Poletti, F., Sterrantino, G, Zaccarelli, M, Colao, G, Baldanti, F, Di Giambenedetto, S, Carli, T, Maggiolo, F, Zazzi, M, Giacometti, A, Butini, L, Del Gobbo, R, Bagnarelli, P, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Callegaro, A, Calza, L, Re, MC, Pristera, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, di Biagio, A, Penco, G, Trezzi, M, Orani, A, Pardelli, R, Arcidiacono, I, Degiuli, A, de Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Cicconi, P, Rusconi, S, Gismondo, MR, Micheli, V, Biondi ML, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Gerardo, AO, Santirocchi, M, Brustia, D, Maggiore, AO, Ravanini, P, Bello, FD, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, 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, di Giambenedetto, S, Colafigli, M, Vullo, V, Turriziani, O, Montano, M, Antinori, A, Dentone, C, Gonnelli, A, de Luca, A, Palumbo, M, Ghisetti, V, Bonora, S, Foglie, PD, Rossi, C, Mondino, V, Malena, M, Grossi, P, Seminari, E, and Poletti, F

Subjects
Male, Time Factors, Cross-sectional study, Human immunodeficiency virus (HIV), Drug Resistance, HIV Infections, Drug resistance, medicine.disease_cause, Cohort Studies, Antiretroviral Therapy, Highly Active, Ritonavir-boosted darunavir, Genotype, HIV Infection, Treatment Failure, Viral, Genotypic resistance, Darunavir, Sulfonamides, General Medicine, Middle Aged, Virological failure, Infectious Diseases, Female, Human, medicine.drug, Adult, Microbiology (medical), Logistic Model, Time Factor, Antiretroviral Therapy, Settore MED/17 - MALATTIE INFETTIVE, Sulfonamide, Drug Resistance, Viral, medicine, Humans, Highly Active, Protease inhibitors, Cross-Sectional Studies, HIV Protease Inhibitors, HIV-1, Logistic Models, Mutation, HIV Protease Inhibitor, Cross-Sectional Studie, business.industry, Antiretroviral therapy, Virology, Protease inhibitor, Cohort Studie, business
Abstract

Introduction: This study aimed at defining protease (PR) resistance mutations associated with darunavir (DRV) failure and PR resistance evolution at DRV failure in a large database of treatment-experienced human immunodeficiency virus (HIV) patients. Results: Overall, 1,104 patients were included: 118 (10.7%) failed at a median observation time of 16 months. The mean number of PR mutations at baseline was 2.7, but it was higher in patients who subsequently failed DRV. In addition, the number of PR mutations increased at failure. The increase in the mean number of mutations was completely related to mutations considered to be associated with DRV resistance following the indications of the main DRV clinical trials. Discussion The higher statistical difference at baseline between failing versus non-failing patients was observed for the V32I and I84V mutations. At DRV failure, the major increase was still observed for V32I; I54L, V11I, T74P and I50V also increased. Despite the increment in the mean number of mutations per patient between baseline and failure, in 21 patients (17.8%) at baseline and 36 (30.5%) at failure, no PR mutation was detected. Conclusion: The HIV-DB interpretation algorithm identified few patients with full DRV resistance at baseline and few patients developed full resistance at DRV failure, indicating that complete resistance to DRV is uncommon. © Springer-Verlag 2011.

Published
2012

35. No pol mutation is associated independently with the lack of immune recovery in patients infected with HIV and failing antiretroviral therapy

Author

Gianotti, N1, Galli, L, Zazzi, M, Ghisetti, V, Bonora, S, Micheli, V, Meraviglia, P, Corsi, P, Bruzzone, B, Menzo, S, Di Giambenedetto, S, De Luca, A, Filice, G, Penco, G, Castagna, A, Collaborators Giacometti A, ARCA database i. n. i. t. i. a. t. i. v. e., Butini, L, del Gobbo, R, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Maggiolo, F, Callegaro, A, Calza, L, Re, Mc, Pristerà, R, Turconi, P, Mandas, A, Tini, S, Carnevale, G, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, 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, 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, Vincenzo, Turriziani, O, Perno, Cf, Montano, M, Cenderello, G, Gonnelli, A, Romano, L, Palumbo, M, Delle Foglie, P, Rossi, C, Poletti, F, Mondino, V, Malena, M, Lattuada, E., Gianotti, N, Galli, L, Zazzi, M, Ghisetti, V, Bonora, S, Micheli, V, Meraviglia, P, Corsi, P, Bruzzone, B, Menzo, S, Di Giambenedetto, S, De Luca, A, Filice, G, Penco, G, Castagna, A, Mancuso, S, Gianotti N, Galli L, Zazzi M, Ghisetti V, Bonora S, Micheli V, Meraviglia P, Corsi P, Bruzzone B, Menzo S, Di Giambenedetto S, De Luca A, Filice G, Penco G, Castagna A, Giacometti A, Butini L, del Gobbo R, Tacconi D, Corbelli G, Zanussi S, Monno L, Punzi G, Maggiolo F, Callegaro A, Calza L, Re MC, Pristerà R, Turconi P, Mandas A, Tini S, Carnevale G, Paolini E, Amadio G, Sighinolfi L, Zuccati G, Morfini M, Manetti R, Di Pietro M, Bartalesi F, Colao G, Tosti A, Di Biagio A, Setti M, Trezzi M, Orani A, Pardelli R, De Gennaro M, Chiodera A, Scalzini A, Palvarini L, Almi P, Todaro G, Cicconi P, Rusconi S, Gismondo MR, Biondi ML, Capetti A, 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, Delle Foglie P, Rossi C, Poletti F, Mondino V, Malena M, Lattuada E., Gianotti, Nicola, Galli, Laura, Zazzi, Maurizio, Ghisetti, Valeria, Bonora, Stefano, Micheli, Valeria, Meraviglia, Paola, Corsi, Paola, Bruzzone, Bianca, Menzo, Stefano, Di Giambenedetto, Simona, De Luca, Andrea, Filice, Gaetano, Penco, Giovanni, and Castagna, Antonella

Subjects
Male, HIV Infections, Drug resistance, Logistic regression, Resistance to nucleoside reverse transcriptase inhibitor, CD4+ T-lymphocyte, Retrospective Studie, Immunopathology, Antiretroviral Therapy, Highly Active, Resistance to non-nucleoside reverse transcriptase inhibitor, genetics, Resistance to protease inhibitor, HIV Infection, resistance to nucleoside reverse transcriptase inhibitors, Viral, Sida, resistance to protease inhibitors, biology, Reverse-transcriptase inhibitor, Viral Load, Genes, pol, drug therapy/immunology/virology, Reverse Transcriptase Inhibitor, Infectious Diseases, Treatment Outcome, resistance to non-nucleoside reverse transcriptase inhibitors, Reverse Transcriptase Inhibitors, Female, Viral load, medicine.drug, Human, pol, Anti-HIV Agents, Antiretroviral Therapy, Viremia, Infectious Disease, Settore MED/17 - MALATTIE INFETTIVE, pharmacology/therapeutic use, Acquired immunodeficiency syndrome (AIDS), Virology, Drug Resistance, Viral, medicine, Humans, Highly Active, Retrospective Studies, pharmacology/therapeutic use, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Drug Resistance, genetics, Female, Genes, pol, HIV Infections, drug therapy/immunology/virology, HIV-1, drug effects/enzymology/genetics, Humans, Male, Mutation, Retrospective Studies, Reverse Transcriptase Inhibitors, therapeutic use, Treatment Outcome, Viral Load, drug resistance, Anti-HIV Agent, biology.organism_classification, medicine.disease, CD4 Lymphocyte Count, Genes, drug effects/enzymology/genetics, therapeutic use, Mutation, CD4+ T-lymphocytes, HIV-1
Abstract

An investigation was undertaken to determine whether specific pol mutations hinder long-term immune recovery regardless of virological response. In total, 826 patients with >50 HIV RNA copies/ml, who underwent genotypic resistance testing between 1 January 2000 and 31 December 2003 after >3 years of antiretroviral treatment, and were followed up for >3 years after genotypic resistance testing, were analyzed retrospectively. The outcome of the study was the lack of immune recovery after >3 years of follow-up, defined as a slope by linear regression 50 copies/ml divided by the number of HIV RNA measurements during follow-up. Logistic regression was used for univariable and multivariable analysis. Median (Q1, Q3) values at baseline were the following: age 40 (37, 45) years, years on antiretroviral therapy 4.45 (3.65, 5.47), HIV RNA 3.91 (3.39, 4.53) log 10 copies/ml, CD4+ T-cell 358 (211, 524)/μl. After 3.13 years of follow-up, 375 patients (45.4%) showed a lack of immune recovery. The risk of lack of immune recovery increased independently with increasing baseline CD4+ counts (OR=1.104 per 50-cell increase, 95% CI=1.069-1.142, P

Published
2011

37. C-C chemokines, IL-16, and soluble antiviral factor activity are increased in cloned T cells from subjects with long-term nonprogressive HIV infection

Author

Enrico Scala, D Offizi, G., Rosso, R., Turriziani, O., Ferrara, R., Mazzone, A. M., Antonelli, G., Aiuti, F., and Paganelli, R.

Subjects
Immunology, Immunology and Allergy
Abstract

A combination of three beta, or C-C, chemokines, as well as IL-16, have been shown to inhibit HIV replication in vitro. Cellular antiviral factor is a more potent agent, and acts on all HIV strains. All are mainly, but not exclusively, produced by CD8+ T cells, both in HIV+ and healthy subjects. We studied the production of these HIV-suppressive factors in patients with HIV infection at different stages of disease. No difference in production by PBMC stimulated with PHA has been observed in asymptomatic HIV+, long-term nonprogressors (LTnP), and AIDS patients. When T cell line supernatants from these three groups were studied, no significant difference was found for C-C chemokines or IL-16 production, and viral suppression. However, T cell clones from LTnP secreted higher levels of all three chemokines, IL-16, and exerted a stronger inhibition on HIV replication. CD8+ clones showed a higher production than CD4+ clones. These clones were able to produce all antiviral factors irrespective of the secretion of type 1 or type 2 cytokines. The antiviral activities were not correlated, implying that viral suppression did not depend solely on C-C chemokines or IL-16. We postulate that all factors are needed to prevent HIV disease progression.

Published
1997

40. Performance of genotypic tropism testing on proviral DNAin clinical practice: results from the DIVA Study Group

Author

Svicher, V, Alteri, C, Montano, M, 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, Callegaro, Ap, Capobianchi, Mr, Carosi, G, 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 Pietro, M, Di Santo, F, Fabeni, L, Fadda, G, Galli, M, Gennari, W, Ghisetti, V, Giacometti, A, Gori, C, Gori, A, Gulminetti, R, Leoncini, F, Maffongelli, G, Maggiolo, F, Manca, G, Gargiulo, F, Martinelli, C, Maserati, R, Mazzotta, F, Meini, G, Micheli, V, Monno, L, Mussini, C, Narciso, P, Nozza, S, Paolucci, S, Pal, G, Parisi, S, Parruti, G, Pignataro, Ar, Pollicita, M, Quirino, T, Re, Mc, Rizzardini, G, Santangelo, R, Scaggiante, R, Sterrantino, G, Turriziani, O, Vatteroni, Ml, Vecchi, L, Viscoli, Claudio, Vullo, V, Zazzi, M, Lazzarini, A, and Perno, Cf

Subjects
HIV, Proviral DNA, Tropism
Published
2012

41. Evolution of transmitted HIV-1 drug resistance in HIV-1-infected patients in Italy from 2000 to 2010

Author

Colafigli, M, Torti, Carlo, Trecarichi, Em, Albini, Laura, Rosi, A, Micheli, V, Manca, Nino, Penco, G, Bruzzone, B, Punzi, G, Corsi, P, Parruti, G, Bagnarelli, P, Monno, L, Gonnelli, A, Cauda, R, Di Giambenedetto, S, Arca, Ucsc, Collaborators: Fabbiani M, Brescia HIV resistance study g. r. o. u. p. s., Sidella, L, Mondi, A, Farina, S, D'Avino, A, Fanti, I, Doino, M, Prosperi, M, Gargiulo, F, Benini, A, Paraninfo, G, QUIROS ROLDAN, Maria Eugenia, Castelnuovo, F, Carosi, Giampiero, Scalzini, A, Castelli, Francesco, Giacometti, A, Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Maggiolo, F, Callegaro, A, Calza, L, Carla, M, Pristera, R, Turconi, P, Mandas, A, Tini, S, Carnevale, G, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Galli, L, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, 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, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, Sm, Filice, G, Baldanti, F, Francisci, D, 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, Romano, L, Palumbo, M, Ghisetti, V, Bonora, S, Delle Foglie, P, Rossi, C, Poletti, F, Mondino, V, Malena, M, and Lattuada, E.

Published
2012

42. Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study

Author

Prosperi, Mc1, Mackie, N, Di Giambenedetto, S, Zazzi, M, Camacho, R, Fanti, I, Torti, C, Sönnerborg, A, Kaiser, R, Codoñer, Fm, Van Laethem, K, Bansi, L, van de Vijver DA, Geretti, Am, De Luca, A, Giacometti A, SEHERE c. o. n. s. o. r. t. i. u. m., Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Maggiolo, F, Callegaro, A, Calza, L, Carla Re, M, Pristerà, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, d'Arminio Monforte, A, Cicconi, P, Rusconi, S, Gismondo, Mr, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Bello, Fd, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Dionisio, D, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, Fadda, G, Vullo, Vincenzo, Turriziani, O, Montano, M, Cenderello, G, Gonnelli, A, Palumbo, M, Ghisetti, V, Bonora, S, Foglie, Pd, Rossi, C, Grossi, P, Seminari, E, Poletti, F, Mondino, V, Malena, M, Lattuada, E, Lengauer, T, Däumer, M, Hoffmann, D, Schülter, E, Müller, C, Oette, M, Reuter, S, Esser, S, Fätkenheuer, G, Rockstroh, J, Incardona, F, Rosen Zvi, M, Clotet, B, Thalme, A, Svedhem, V, Bratt, G, Gargiulo, F, Lapadula, G, Manca, N, Paraninfo, G, Quiros Roldan, E, Carosi, G, Castelnuovo, F, Vandamme, Am, Van Wijngaerden, E, Ainsworth, J, Anderson, J, Babiker, A, Dunn, D, Easterbrook, P, Fisher, M, Gazzard, B, Garrett, N, Gilson, R, Gompels, M, Hill, T, Johnson, M, Leen, C, Orkin, C, Phillips, A, Pillay, D, Porter, K, Post, F, Sabin, C, Sadiq, T, Schwenk, A, Walsh, J, Delpech, V, Palfreeman, A, Glabay, A, Lynch, J, Hand, J, de Souza, C, Perry, N, Tilbury, S, Churchill, D, Nelson, M, Waxman, M, Mandalia, S, Kall, M, Korat, H, Taylor, C, Ibrahim, F, Campbell, L, James, L, Brima, N, Williams, I, Youle, M, Lampe, F, Smith, C, Grabowska, H, Chaloner, C, Puradiredja, Di, Weber, J, Ramzan, F, Carder, M, Wilson, A, Dooley, D, Asboe, D, Pozniak, A, Cameron, S, Cane, P, Chadwick, D, Clark, D, Collins, S, Lazarus, L, Dolling, D, Fearnhill, E, Castro, H, Coughlin, K, Zuckerman, M, Booth, C, Goldberg, D, Hale, A, Kaye, S, Kellam, P, Leigh Brown, A, Smit, E, Templeton, K, Tilston, P, Tong, W, Zhang, H, Ushiro Lumb, I, Oliver, T, Bibby, D, Mitchell, S, Mbisa, T, Wildfire, A, Tandy, R, Shepherd, J, Maclean, A, Bennett, D, Hopkins, M, Garcia Diaz, A, Kirk, S, Sloot, P. M., Virology, Prosperi, M, Mackie, N, di Giambenedetto, S, Zazzi, M, Camacho, R, Fanti, I, Torti, C, Sönnerborg, A, Kaiser, R, Codoñer, F, van laethem, K, Bansi, L, van de Vijver, D, Geretti, A, de luca, A, and Mancuso, S

Subjects
Male, Drug Resistance, HIV Infections, Drug resistance, Cohort Studies, 0302 clinical medicine, Genotype, HIV Infection, Pharmacology (medical), 030212 general & internal medicine, Viral, 0303 health sciences, Proteolytic enzymes, Genotypic testing, HIV, Viral load, Adult, Anti-HIV Agents, CD4 Lymphocyte Count, Europe, Female, HIV-1, Humans, RNA, Viral, Viral Proteins, Drug Resistance, Viral, Mutation, Missense, Viral Load, Pharmacology, Infectious Diseases, 3. Good health, Cohort, Cohort study, Human, Microbiology (medical), Biology, Settore MED/17 - MALATTIE INFETTIVE, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Viral Protein, 030306 microbiology, Anti-HIV Agent, Virology, Reverse transcriptase, Regimen, genotypic testing, viral load, Immunology, Mutation, RNA, Missense, Cohort Studie
Abstract

Background and objectives: Guidelines indicate a plasma HIV-1 RNA load of 500-1000 copies/mL as the minimal threshold for antiretroviral drug resistance testing. Resistance testing at lower viral load levels may be useful to guide timely treatment switches, although data on the clinical utility of this remain limited. We report here the influence of viral load levels on the probability of detecting drug resistance mutations (DRMs) and other mutations by routine genotypic testing in a large multicentre European cohort, with a focus on tests performed at a viral load

Published
2011

44. Low rate of virological failure and maintenance of susceptibility to HIV-1 protease inhibitors with first-line lopinavir/ritonavir-based antiretroviral treatment in clinical practice

Author

Prosperi, Mc1, Zazzi, M, Punzi, G, Monno, L, Colao, G, Corsi, P, Di Giambenedetto, S, Meini, G, Ghisetti, V, Bonora, S, Pecorari, M, Gismondo, Mr, Bagnarelli, P, Carli, T, De Luca, A, Collaborators Giacometti A, ARCA Collaborative G. r. o. u. p., Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Maggiolo, F, Callegaro, A, Calza, L, Re, Mc, Raffaele, P, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Galli, L, Di Pietro, M, Bartalesi, F, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Monforte, Ad, Cicconi, P, Rusconi, S, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Dionisio, D, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, Vullo, Vincenzo, Turriziani, O, Montano, M, Cenderello, G, Gonnelli, A, Palumbo, M, Delle Foglie, P, Rossi, C, Poletti, F, Mondino, V, Malena, M, and Lattuada, E.

Published
2010

45. 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, Ap, Capobianchi, Mr, Gargiulo, F, Castelli, F, Cauda, Roberto, Ceccherini Silberstein, F, Clementi, M, Chirianni, A, Colafigli, Manuela, D'Arminio Monforte, A, De Luca, Andrea, 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, Ar, Quirino, T, Re, Mc, Rizzardini, G, Sanguinetti, Maurizio, Santangelo, Rosaria, Scaggiante, R, Sterrantino, G, Turriziani, O, Vatteroni, Ml, Viscoli, C, Vullo, V, Zazzi, M, Lazzarin, A, Perno, Cf, Cauda, Roberto (ORCID:0000-0002-1498-4229), De Luca, Andrea (ORCID:0000-0002-8311-6935), Sanguinetti, Maurizio (ORCID:0000-0002-9780-7059), Santangelo, Rosaria (ORCID:0000-0002-8056-218X), 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, Ap, Capobianchi, Mr, Gargiulo, F, Castelli, F, Cauda, Roberto, Ceccherini Silberstein, F, Clementi, M, Chirianni, A, Colafigli, Manuela, D'Arminio Monforte, A, De Luca, Andrea, 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, Ar, Quirino, T, Re, Mc, Rizzardini, G, Sanguinetti, Maurizio, Santangelo, Rosaria, Scaggiante, R, Sterrantino, G, Turriziani, O, Vatteroni, Ml, Viscoli, C, Vullo, V, Zazzi, M, Lazzarin, A, Perno, Cf, Cauda, Roberto (ORCID:0000-0002-1498-4229), De Luca, Andrea (ORCID:0000-0002-8311-6935), Sanguinetti, Maurizio (ORCID:0000-0002-9780-7059), and Santangelo, Rosaria (ORCID:0000-0002-8056-218X)

Abstract

We have developed a sequencing assay for determining the usage of the genotypic HIV-1 co-receptor using peripheral blood mononuclear cell (PBMC) DNA in virologically suppressed HIV-1 infected patients. Our specific aims were to (1) evaluate the efficiency of V3 sequences in B versus non-B subtypes, (2) compare the efficiency of V3 sequences and tropism prediction using whole blood and PBMCs for DNA extraction, (3) compare the efficiency of V3 sequences and tropism prediction using a single versus a triplicate round of amplification.

Published
2014

47. P-glycoprotein expression affects the intracellular concentration and antiviral activity of the protease inhibitor saquinavir in a T cell line

Author

Maffeo, A., Bellomi, F., Solimeo, I., Bambacioni, F., CAROLINA SCAGNOLARI, Pisa, F., Dupuis, M. L., Cianfriglia, M., Antonelli, G., and Turriziani, O.

Subjects
T-Lymphocytes, protease inhibitors, Biological Transport, hiv, HIV Protease Inhibitors, p-glycoprotein, Cell Line, Gene Expression Regulation, Humans, ATP-Binding Cassette Transporters, ATP Binding Cassette Transporter, Subfamily B, Member 1, RNA, Messenger, Cells, Cultured, Saquinavir
Abstract

A number of ATP-binding cassette proteins, which function as cellular efflux pumps, are known to be expressed on the membranes of human cells, including CD4-positive lymphocytes. It has also been shown recently that most anti-HIV protease inhibitors (PIs) are first-rate substrates of one of these membrane transporters, P-glycoprotein (Pgp). These findings raise the question of whether Pgp expression could influence HIV replication and/or affect the action of PIs. To gain new insight into this, initially unexpected, phenomenon, a study was undertaken with the aims of investigating whether treatment with saquinavir (SQV) induces Pgp expression in primary or transformed human T cell lines and, primarily, establishing whether Pgp expression could modify both the uptake of SQV and its antiviral action. Pgp expression, mainly measured by reverse transcription-PCR, was found to be variably detectable in healthy individuals, and short or prolonged SQV treatment was unable to induce or increase the expression of Pgp in a lymphoblastoid cell line or in primary lymphocytes derived from these individuals. However, further experiments, performed in a cell line with high Pgp expression (CEM(VBL100) cells) and its parental cell line (CEM cells), demonstrated that over-expression of Pgp reduces the uptake of SQV This result is consistent with the finding that CEM(VBL100) cells are less sensitive to the antiviral activity of SQV, the ID50 value (100 microM) being significantly higher than the corresponding value in parental CEM cells (4 microM).

Published
2004

48. 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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