Evolution of major non-HIV-related comorbidities in HIV-infected patients in the Italian Cohort of Individuals, Naïve for Antiretrovirals (ICONA) Foundation Study cohort in the period 2004–2014

Objectives: The management of HIV disease is complicated by the incidence of a new spectrum of comorbid noncommunicable diseases (NCDs). It is important to document changes in the prevalence of NCDs over time. The aim of the study was to describe the impact of ageing on HIV markers and on the prevalence of NCDs in people living with HIV (PLWHIV) in the Italian Cohort of Individuals, Naïve for Antiretrovirals (ICONA) seen for care in 2004-2014. Methods: Analyses were conducted separately for a closed cohort (same people seen at both times) and an open cohort (all people under follow-up). We used the χ2 test for categorical factors and the Wilcoxon test for quantitative factors to compare profiles over time. Results: The closed cohort included 1517 participants and the open cohort 3668 under follow-up in 2004 and 6679 in 2014. The median age of the open cohort was 41 [interquartile range (IQR) 37-46] years in 2004 and 44 (IQR 36-52) years in 2014. Analysis of the closed cohort showed an increase in the prevalence of some NCDs [the prevalence of dyslipidaemia increased from 75% in 2004 to 91% in 2014, that of hypertension from 67 to 84%, and that of cardiovascular disease (CVD) from 18 to 32%] and a decrease in renal function (5% with eGFR < 60 mL/min per 1.73 m2 in 2004 versus 30% in 2014); the percentage of people in the high-risk group for the Framingham CHD score more than tripled (from 13 to 45%). Results in the open cohort were similar. Conclusions: The burden of NCDs in our PLWHIV population markedly worsened over a 10-year time-span, which is likely to be a result of the effects of both ageing and HIV infection as well as their interaction. Special attention must be given to the management and prevention of NCDs

Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort

156INTRODUCTION: Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. METHODS: We performed a multicentre, observational study including all antiretroviral therapy (ART)-naïve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan-Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. RESULTS: About 1679 individuals (932 ART-naïve, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-naïve (2.1%) and TE (1.7%) patients. In ART-naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC-based triple-therapies, aHR = 3.56, p = 0.012 for tenofovir-based) and for toxicity (aHR = 5.26, p = 0.030 for ABC-based, aHR = 6.60, p = 0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. CONCLUSIONS: In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practicenonenoneMondi A.; Cozzi-Lepri A.; Tavelli A.; Rusconi S.; Vichi F.; Ceccherini-Silberstein F.; Calcagno A.; De Luca A.; Maggiolo F.; Marchetti G.; Antinori A.; d'Arminio Monforte A.; Andreoni M.; Castagna A.; Castelli F.; Cauda R.; Di Perri G.; Galli M.; Iardino R.; Ippolito G.; azzarin A.; Rezza G.; von Schloesser F.; Viale P.; Ceccherini-Silberstein F.; Cozzi-Lepri A.; Girardi E.; Lo Caputo S.; Mussini C.; Puoti M.; Perno C.F.; Balotta C.; Bandera A.; Bonora S.; Borderi M.; Capetti A.; Capobianchi M.R.; Cicalini S.; Cingolani A.; Cinque P.; Di Biagio A.; Gianotti N.; Gori A.; Guaraldi G.; Lapadula G.; Lichtner M.; Madeddu G.; Maggiolo F.; Monno L.; Nozza S.; Quiros Roldan E.; Rossotti R.; Rusconi S.; Santoro M.M.; aracino A.; Sarmati L.; Fanti I.; Galli L.; Lorenzini P.; Rodano' A.; Macchia M.; Tavelli A.; Carletti F.; Carrara S.; Di Caro A.; Graziano S.; Petrone F.; Prota G.; Quartu S.; Truffa S.; Giacometti I.A.; Costantini A.; Barocci V.; Angarano G.; Fabrizio C.; Suardi C.; i V.; Verucchi G.; Castelnuovo F.; Minardi C.; Menzaghi B.; Abeli C.; Cacopardo B.; Celesia B.; Vecchiet J.; Falasca K.; Pan A.; Lorenzotti S.; Sighinolfi L.; Segala D.; Blanc P.; Cassola G.; Viscoli C.; lessandrini A.; Bobbio N.; Mazzarello G.; Pozzetto I.; Bonfanti P.; Molteni C.; Chiodera A.; Milini P.; Nunnari G.; Pellicano G.; Rizzardini G.; Bai F.; Moioli M.C.; Piolini R.; Ridolfo A.L.; Salpietro S.; Tincati C.; Puzzolante C.; Migliorino C.; Sangiovanni V.; Borgia G.; Esposito V.; Di Martino F.; Gentile I.; Maddaloni L.; Cattelan A.M.; Marinello S.; Cascio A.; Colomba C.; Baldelli F.; Schiaroli E.; Parruti G.; Sozio F.; Magnani G.; Ursitti M.A.; Cristaudo A.; Vullo V.; Acinapura R.; Baldin G.; Capozzi M.; Rivano Capparucia M.; Iaiani G.; atini A.; Mastrorosa I.; Plazzi M.M.; Savinelli S.; Vergori A.; Cecchetto M.; Viviani F.; Bagella P.; Rossetti B.; Fontana Del Vecchio R.; Francisci D.; Di Giuli C.; Caramello P.; Orofino G.C.; Sciandra M.; Bassetti M.; ondero A.; Pellizzer G.; Manfrin V.; Starnini G.; alungo A.Mondi, A.; Cozzi-Lepri, A.; Tavelli, A.; Rusconi, S.; Vichi, F.; Ceccherini-Silberstein, F.; Calcagno, A.; De Luca, A.; Maggiolo, F.; Marchetti, G.; Antinori, A.; d'Arminio Monforte, A.; Andreoni, M.; Castagna, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Azzarin, A.; Rezza, G.; von Schloesser, F.; Viale, P.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; Girardi, E.; Lo Caputo, S.; Mussini, C.; Puoti, M.; Perno, C. F.; Balotta, C.; Bandera, A.; Bonora, S.; Borderi, M.; Capetti, A.; Capobianchi, M. R.; Cicalini, S.; Cingolani, A.; Cinque, P.; Di Biagio, A.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Madeddu, G.; Maggiolo, F.; Monno, L.; Nozza, S.; Quiros Roldan, E.; Rossotti, R.; Rusconi, S.; Santoro, M. M.; Aracino, A.; Sarmati, L.; Fanti, I.; Galli, L.; Lorenzini, P.; Rodano', A.; Macchia, M.; Tavelli, A.; Carletti, F.; Carrara, S.; Di Caro, A.; Graziano, S.; Petrone, F.; Prota, G.; Quartu, S.; Truffa, S.; Giacometti, I. A.; Costantini, A.; Barocci, V.; Angarano, G.; Fabrizio, C.; Suardi, C.; I, V.; Verucchi, G.; Castelnuovo, F.; Minardi, C.; Menzaghi, B.; Abeli, C.; Cacopardo, B.; Celesia, B.; Vecchiet, J.; Falasca, K.; Pan, A.; Lorenzotti, S.; Sighinolfi, L.; Segala, D.; Blanc, P.; Cassola, G.; Viscoli, C.; Lessandrini, A.; Bobbio, N.; Mazzarello, G.; Pozzetto, I.; Bonfanti, P.; Molteni, C.; Chiodera, A.; Milini, P.; Nunnari, G.; Pellicano, G.; Rizzardini, G.; Bai, F.; Moioli, M. C.; Piolini, R.; Ridolfo, A. L.; Salpietro, S.; Tincati, C.; Puzzolante, C.; Migliorino, C.; Sangiovanni, V.; Borgia, G.; Esposito, V.; Di Martino, F.; Gentile, I.; Maddaloni, L.; Cattelan, A. M.; Marinello, S.; Cascio, A.; Colomba, C.; Baldelli, F.; Schiaroli, E.; Parruti, G.; Sozio, F.; Magnani, G.; Ursitti, M. A.; Cristaudo, A.; Vullo, V.; Acinapura, R.; Baldin, G.; Capozzi, M.; Rivano Capparucia, M.; Iaiani, G.; Atini, A.; Mastrorosa, I.; Plazzi, M. M.; Savinelli, S.; Vergori, A.; Cecchetto, M.; Viviani, F.; Bagella, P.; Rossetti, B.; Fontana Del Vecchio, R.; Francisci, D.; Di Giuli, C.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Bassetti, M.; Ondero, A.; Pellizzer, G.; Manfrin, V.; Starnini, G.; Alungo, A

Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort

Introduction: Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. Methods: We performed a multicentre, observational study including all antiretroviral therapy (ART)-na\uefve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Na\uefve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan\u2013Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. Results: About 1679 individuals (932 ART-na\uefve, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-na\uefve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-na\uefve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-na\uefve (2.1%) and TE (1.7%) patients. In ART-na\uefve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH)&nbsp;=&nbsp;3.38, p&nbsp;=&nbsp;0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH&nbsp;=&nbsp;3.30, p&nbsp;=&nbsp;0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR)&nbsp;=&nbsp;2.50, p&nbsp;=&nbsp;0.037 for ABC-based triple-therapies, aHR&nbsp;=&nbsp;3.56, p&nbsp;=&nbsp;0.012 for tenofovir-based) and for toxicity (aHR&nbsp;=&nbsp;5.26, p&nbsp;=&nbsp;0.030 for ABC-based, aHR&nbsp;=&nbsp;6.60, p&nbsp;=&nbsp;0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART na\uefve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. Conclusions: In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-na\uefve as well as in treated individuals reassures on the use of DTG in everyday clinical practice