Impact of HCV treatment with Direct-Acting Antivirals on glucose levels in diabetic HIV/HCV co-infected patients in the ICONA and HepaICONA ...
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Impact of HCV treatment with Direct-Acting Antivirals
on glucose levels in diabetic HIV/HCV co-infected patients in the
ICONA and HepaICONA cohorts
I. Mastrorosa1, P. Lorenzini1, A. Cozzi-Lepri2, M. Puoti3, R. Rossotti3, G. Marchetti4, G. Orofino5, L.
Sighinolfi6, A. Raimondi7, A. d'Arminio Monforte4, A. Antinori1, A. De Luca8
on behalf of the Icona/HepaIcona Foundation Study Group
1. Clinical Department, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy. 2. Institute for Global Health, University College London, United Kingdom. 3. Unit of Infectipus Diseases - ASST
GOM Niguarda, Milan, Italy. 4. Clinic of Infectious and Tropical Diseases, University of Milan, ASST Santi Paolo e Carlo, Milan , Italy. 5. 1st Division of Infectious Diseases Amedeo di Savoia Hospital, Torino, Italy.
6. Infectious Diseases Unit, Azienda Ospedaliero-Universitaria di Ferrara, Ferrara, Italy. 7. Clinic of Infectious Diseases, AOU Policlinico di Modena, Modena, Italy. 8. Infectious Diseases
Unit, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy.
Disclosures
Dr. I. Mastrorosa has no financial relationships to disclose.
Funding
ICONA Foundation is supported by unrestricted grants from Gilead Science,
Janssen, MSD and ViiV Healthcare.
10th ITALIAN CONFERENCE ON AIDS AND ANTIVIRAL REASERCH May 22-24,2018 - Rome, Italy
BACKGROUND
❖Chronic HCV infection has been associated with a number of extrahepatic
manifestations and comorbidities, including diabetes mellitus.
❖Prior to interferon (IFN)-free HCV therapies, treatment of HCV in diabetic
patients was partially contraindicated since IFN could induce a diabetic
decompensation.
❖Now that direct-acting antivirals (DAA) offers high cure rates within few
weeks of treatment, it is of major importance to determine whether
therapeutic HCV eradication has an effect on non-liver-related morbidity.
White DL, et al. J Hepatol. 2008.
De Luca A., at al. J Acquir Immune Defic Syndr. 2017.
10th ITALIAN CONFERENCE ON AIDS AND ANTIVIRAL REASERCH May 22-24,2018 - Rome, Italy
BACKGROUND
❖Some large observational studies found that treatment response in
HIV/HCV co-infected patients was associated with a significant decrease in
the risk of diabetes.
Kovari H, et al. Clin Infect Dis. 2017.
Berenguer J, et al. Hepatology 2017.
❖Data on the impact of HCV treatment in HIV/HCV co-infected patients
with known diabetes are lacking.
10th ITALIAN CONFERENCE ON AIDS AND ANTIVIRAL REASERCH May 22-24,2018 - Rome, ItalyAIM
We conducted a longitudinal analysis to explore if
the HCV treatment with DAA had an impact on
glucose levels in diabetic patients enrolled in the
ICONA and HepaICONA study cohorts
10th ITALIAN CONFERENCE ON AIDS AND ANTIVIRAL REASERCH May 22-24,2018 - Rome, ItalyMETHODS
Study Population
We included in the analysis any HIV/HCV co-infected patients enrolled in
the ICONA and HepaICONA study cohorts who have:
➢ started DAA treatment
➢ had a diagnosis of diabetes mellitus, at or before DAA initiation
➢ had fasting glucose levels measurement, before and after DAA
completion.
10th ITALIAN CONFERENCE ON AIDS AND ANTIVIRAL REASERCH May 22-24,2018 - Rome, ItalyMETHODS
Definitions
Diabetes mellitus was defined by at least one of the following criteria:
I. Diagnosis of diabetes mellitus as reported by the treating clinician
II. Use of antidiabetic drugs (insulin or oral hypoglycemic agents)
III. At least a single fasting blood glucose level > 125 mg/dL.
American Diabetes Association (ADA), guidelines 2017
Successful DAA treatment was defined by HCV RNA not detected 12 weeks
(SVR12) after the end of treatment (EOT).
10th ITALIAN CONFERENCE ON AIDS AND ANTIVIRAL REASERCH May 22-24,2018 - Rome, ItalyMETHODS
Statistical Analysis
✓ Paired Wilcoxon test was used for statistical comparisons of glucose levels
from baseline to 6 and 12 months.
✓ Piecewise linear mixed models with random intercept/slope were fitted to
analyse the slope of glucose levels comparing periods before and after
DAA therapy start.
✓ Multivariable model was adjusted for main potential confounding factors
(demographic, clinical, treatment-related).
10th ITALIAN CONFERENCE ON AIDS AND ANTIVIRAL REASERCH May 22-24,2018 - Rome, ItalyRESULTS
Main Characteristics of Study Population
(n=185)
Gender, n. % M 159 86.0%
Stiffness, kPa, n. % 200 127 68.7%
Lenght of HCV therapy, n. % 8 weeks 7 3.8%
missing 5 2.7%
12 weeks 95 51.4%
CD4 current, cell/mm3, n. % 0-350 49 26.5%
24 weeks 83 44.9%
351-500 26 14.1%
Type of DAA, n. % sofosbuvir 12 6.5%
>500 105 56.8%
sof+daclatasvir 50 27.5%
missing 5 2.7%
sof+velpatasvir 7 3.8%
HIV-RNA, copies/mL, n. % ≤40 171 92.4%
sof+ledipasvir 67 36.2%
>40 12 6.5%
other 49 26.5%
missing 2 1.1%
Ribavirin use, n. % no 76 41.1%
cART change for DAA use, n. % No 118 63.8%
yes 109 58.9%
Yes 67 36.2%
Genotype 3, n. % yes 47 25.4%
Type of cART regimen, n. % NRTI+NNRTI 34 18.7%
no 134 72.4%
NRTI+bPI 31 17.0%
missing 4 2.2%
NRTI+INSTI 67 36.8%
Blood glucose, mg/dL,
NUCs-sparing 25 13.7%
median (IQR) 122 100-155
Other 25 13.7%
10th ITALIAN CONFERENCE ON AIDS AND ANTIVIRAL REASERCH May 22-24,2018 - Rome, ItalyRESULTS
Changes in Glucose Levels
n=127* Baseline 6 months p-value 12 months p-value
Glucose levels, mg/dL
median (IQR) 130 (100-157) 119 (95-148) 0.031 114 (90-143) 0.004
Change respect to baseline, mg/dL
median (IQR) -6 (-34; 10) -11 (-36; 12)
*patients with glucose level measurements 6 and 12 months after baseline
10th ITALIAN CONFERENCE ON AIDS AND ANTIVIRAL REASERCH May 22-24,2018 - Rome, ItalyRESULTS
Univariable Beta 95% CI p-value
Slope before
DAA starting 0.008 0.006 0.009CONCLUSIONS
➢ Based on these preliminary data, DAA treatment seemed to have a
beneficial effect on glucose levels, in HIV/HCV co-infected patients with
diabetes.
➢ This finding underscores the need to accelerate DAA treatment in
individuals affected by this comorbid condition.
➢ Longer follow up is required to confirm this observation and to better
investigate the real impact of HCV eradication on glucose metabolism in
HIV/HCV co-infected population.
10th ITALIAN CONFERENCE ON AIDS AND ANTIVIRAL REASERCH May 22-24,2018 - Rome, ItalyIcona Foundation Study Group BOARD OF DIRECTORS: A d’Arminio Monforte (President), A Antinori, A Castagna, F Castelli, R Cauda, G Di Perri, M Galli, R Iardino, G Ippolito, A Lazzarin, GC Marchetti, CF Perno, G Rezza, F von Schloesser, P Viale. SCIENTIFIC SECRETARY: A d’Arminio Monforte, A Antinori, A Castagna, F Ceccherini-Silberstein, A Cozzi-Lepri, E Girardi, S Lo Caputo, C Mussini, M Puoti, CF Perno. STEERING COMMITTEE: M Andreoni, A Antinori, C Balotta, A Bandera, P Bonfanti, S Bonora, M Borderi, A Calcagno, L Calza, A Capetti, MR Capobianchi, A Castagna, F Ceccherini-Silberstein, A Cingolani, P Cinque, A Cozzi-Lepri, A d’Arminio Monforte, A De Luca, A Di Biagio, E Girardi, N Gianotti, A Gori, G Guaraldi, G Lapadula, M Lichtner, S Lo Caputo, G Madeddu, F Maggiolo, G Marchetti, S Marcotullio, L Monno, C Mussini, S Nozza, M Puoti, E Quiros Roldan, R Rossotti, S Rusconi, MM Santoro, A Saracino, M Zaccarelli. STATISTICAL AND MONITORING TEAM: A Cozzi-Lepri, I Fanti, L Galli, P Lorenzini, A Rodano’, M Macchia, A Tavelli. BIOLOGICAL BANK INMI: F Carletti, S Carrara, A Di Caro, S Graziano, F Petrone, G Prota, S Quartu, S Truffa. PARTICIPATING PHYSICIANS AND CENTERS: Italy A Giacometti, A Costantini, V Barocci (Ancona); G Angarano, L Monno, C Santoro (Bari); F Maggiolo, C Suardi (Bergamo); P Viale, V Donati, G Verucchi (Bologna); F Castelnuovo, C Minardi, E Quiros Roldan (Brescia); B Menzaghi, C Abeli (Busto Arsizio); B Cacopardo, B Celesia (Catania); J Vecchiet, K Falasca (Chieti); L Sighinolfi, D Segala (Ferrara); P Blanc, F Vichi (Firenze); G Cassola, C Viscoli, A Alessandrini, N Bobbio, G Mazzarello (Genova); M Lichtner, I Pozzetto (Latina); P Bonfanti, C Molteni (Lecco); A Chiodera, P Milini (Macerata); G Nunnari, G Pellicanò (Messina); A d’Arminio Monforte, M Galli, A Lazzarin, G Rizzardini, M Puoti, A Castagna, F Bai, MC Moioli, R Piolini, AL Ridolfo, S Salpietro, C Tincati, (Milano); C Mussini, C Puzzolante (Modena); GM Migliorino, G Lapadula (Monza); V Sangiovanni, G Borgia, V Esposito, F Di Martino, I Gentile, L Maddaloni (Napoli); AM Cattelan, S Marinello (Padova); A Cascio, C Colomba (Palermo); F Baldelli, E Schiaroli (Perugia); G Parruti, F Sozio (Pescara); G Magnani, MA Ursitti (Reggio Emilia); M Andreoni, A Antinori, R Cauda, A Cristaudo, V Vullo, R Acinapura, G Baldin, M Capozzi, S Cicalini, A Cingolani, M Rivano Capparucia, G Iaiani, A Latini, I Mastrorosa, MM Plazzi, S Savinelli, A Vergori (Roma); M Cecchetto, F Viviani (Rovigo); G Madeddu, P Bagella (Sassari); A De Luca, B Rossetti (Siena); A Franco, R Fontana Del Vecchio (Siracusa); D Francisci, C Di Giuli (Terni); P Caramello, G Di Perri, S Bonora, GC Orofino, M Sciandra (Torino); M Bassetti, A Londero (Udine); G Pellizzer, V Manfrin (Vicenza); G Starnini, A Ialungo (Viterbo).
HepaIcona Study Group A Costantini (Ancona); L Monno, A Saracino, G Bruno (Bari); F Maggiolo, C Suardi (Bergamo); G Verucchi, L Badia (Bologna); F Castelnuovo, C Minardi (Brescia); B Menzaghi, C Abeli (Busto Arsizio); L Sighinolfi, D Segala (Ferrara); P Blanc, V Vichi (Firenze); G Cassola, C Viscoli, A Alessandrini, N Bobbio, G Mazzarello (Genova); C Matroianni, R Marocco (Latina); P Bonfanti, I Caramma (Lecco); A Chiodera, M Maracci (Macerata); A d'Arminio Monforte, M Galli, A Lazzarin, M Puoti, A Castagna, F Bai, MC Moioli, L Milazzo, C Uberti-Foppa (Milano); C Mussini, C Puzzolante (Modena); A Gori, G Lapadula (Monza); V Esposito, G Borgia, A Maddaloni, I Gentile (Napoli); A Cascio, M Trizzino (Palermo); F Baldelli, C Pallotto (Perugia); G Parruti, F Sozio (Pescara); G Magnani, M Ursitti (Reggio Emilia); A Antinori, V Vullo, G Taliani, R Acinapura, A Vergori, I Mastrorosa, MM Plazzi, P Zuccalà, M Rivano Capparucia (Roma); G Madeddu, P Bagella (Sassari); A De Luca, B Rossetti (Siena) P Caramello, GC Orofino (Torino).
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