Italian Observational study on the outcome of Atazanavir/ritonavir-based ARV therapies (SIMIT 001 Study) : final data S.Lo Caputo, F. Mazzotta, A. Chirianni, F. Maggiolo, A. Antinori, A. Castagna, C. Torti, R. Cauda, P. Bonfanti, M. Galli, A. Gori, R. Scaggiante, A. D’Arminio Monforte and SIMIT 001 Study Team XIV Congresso Nazionale SIMIT, 8-11 novembre Catania

Discolosure Slide Dr. Sergio Lo Caputo have received consultancy and/or speakers’ fees from Abbott, Bristol Myers Squibb, Gilead Sciences, Janssen and Merck Sharp & Dohme

SIMIT 001 Study  Observational studies enable to collect useful data about the management antiretroviral drugs with information that come from clinical practice and complete those received from registrative studies and randomized trials  SIMIT (Italian Society of Infectious Diseases) planned and set up an observational study on HIV positive patients starting ATV/r-including cART.  In this study SIMIT involved also clinical centers that do not take part to clinical trials with the aim of spreading the culture of appropriate data collection and of the cohort studies participation Rationale and aim of the study

Study design Observational cohort study retrospective: data collection for patients starting from January 2009 to June 2011 prospective: data collection for patients taking ATV/r-based therapy from June 2011 Study period: 3 years SIMIT 001 Study  HIV infection  Age >18 years  ATV/r based HAART from at least 2 months  Patients initiating ATV/r-including regimen as first line treatment or  Patients on virological suppressed ART initiating their first ATV/r- including regimen as switching strategy Inclusion Criteria

Secondary Objective(s) - to evaluate the frequency and predictors of therapy discontinuation - to observe and describe long term immunological efficacy - to observe and describe resistance profile of isolates from patients failing an ATV/r-based regimen - to observe and describe long term treatment safety and tolerability Primary Objective To evaluate the frequency and predictors of virological failure (VF) in naïve or virologically suppressed patients in long term ATV/r-based cART SIMIT 001 Study

Methods Data from patients initiating ATV/r–based regimens, both naïve and experienced, were collected until Oct 2014 in an electronic database. Data included:  demographics (age, sex, ethnicity, risk factors for HIV),  HIV-related variables (CDC Stage, nadir CD4 and HIV-RNA, CD4 and HIV-RNA from starting ATV/r-based regimens, all cART drugs)  HBV and HCV status,  clinical events and discontinuation Evaluation of predictors of discontinuation and predictors of virological failure (defined as the first of two consecutive VL >50/ml after at least 6 months of therapy) with two multivariate Cox analyses.

Results Patients enrolled in the study : 653 Patients evaluated : 494 median follow up 33,6 months (QR 14,7-43,5) %

Antiretroviral regimens NRTI backbone % %

N%N%N% Age median (IQR) 42,445,143,9 Sex 26274,721577,637776,3 Male Ethnicity 18685,724688,843287,4 Caucasian Risk HIV 2411,96123,38518,4 IVDU Homosexual 7135,37327,914431,1 Heterosexual 10049,812346,922348,2 Unknow/other 2210,1207,2428,5 HBsAg 146, Positive HCV ab 3616, Positive naive on ART total Baseline characteristics of the study population-1

naive on ART total N%N%N% CDC Class C 3616, ,5 HIV-RNA cp/ml CD4/mmc < ,5155,55711, ,712746,923648,6 > ,812947,619339,7 Baseline characteristics of the study population-2

Virological failure

Discontinuation

Discontinuation for AE 51 (10,3%) grade I-II Deaths causes (6 patients): Intestinal cancer, Burkitt’s lymphoma, Acute pulmonary embolism, HCC, SNC lymphoma, lung cancer %

Conclusions  cART including ATV/r has proved to be safe and virologically effective in naïve patients and simplification regimens over a long term follow-up  According to clinical management very few variables seem to significantly affect persistence and efficacy of ATV/r based cART  Our data confirm the efficacy and good tolerability of ATV/r based cART in a wide variety of patients

SIMIT 001 Study Team 5 29 centers Andrea AntinoriIRCCS L. Spallanzani - Roma Massimo ArlottiOspedale Infermi - Rimini Orlando ArmignaccoOspedale Belcolle - Viterbo Giampiero CarosiSpedali Civili - Brescia Roberto CaudaPoliclinico A. Gemelli - Roma Antonio ChirianniOspedale Cotugno - Napoli Ercole ConciaPoliclinico G. B. Rossi - Verona Antonella D'Arminio MonforteOspedale San Paolo - Milano Pietro Di GregorioAzienda Ospedaliera Cannizzaro - Catania Gaetano FiliceIRCCS Policlinico San Matteo - Pavia Massimo GalliAzienda Ospedaliera L. Sacco - Milano Andrea GoriAzienda Ospedaliera San Gerardo - Monza Adriano LazzarinFondazione San Raffaele del Monte Tabor - Milano Francesco LeonciniAzienda Ospedaliero-Universitaria Careggi - Firenze Roberto LuzzatiAzienda Ospedaliera Ospedali Riuniti di Trieste Franco MaggioloOspedali Riuniti di Bergamo Filippo MatarazzoOspedale Monsignor Di Liegro - Gaeta Francesco MazzottaOspedale Santa Maria Annunziata - Firenze Gabriella PaganoOspedale San Martino - Genova Giustino ParrutiOspedale di Pescara Enzo RaiseOsp.SS. Giovanni e Paolo, Azienda ULSS 12 veneziana Roberto RinaldiAzienda Ospedaliera di Padova Evangelista SagnelliAzienda Osp. Sant'Anna e San Sebastiano - Caserta Irene SchlachtOspedale Niguarda Cà Granda - Milano Lucina TitonePoliclinico Paolo Giaccone - Palermo Mario TotiOspedale Misericordia - Grosseto Anna OraniOspedale Manzoni - Lecco Giovanni TodaroAzienda Ospedaliera Papardo - Messina Paola MeravigliaAzienda Ospedaliera L. Sacco - Milano Tiziana QuirinoA.O. Ospedale di Circolo di Busto Arsizio