Is HCV elimination among persons living with HIV feasible? Data from the NoCo study in the setting of the ICONA cohort

Background and aims: Whether the HCV test-and-treat strategy impacted on the rate of new HCV infections among PLWH in Italy is unknown. Methods: Prospective study of PLWH in the ICONA network. At baseline, PLWH were tested for HCV-Ab; HCV-RNA (if HCV-Ab positive) and, if positive, treated with DAA. SVR12 indicated eradication. Seroconversions and re-infections were evaluated yearly in HCV-Ab neg and HCV-RNA neg at first screening. We estimated the following: HCV seroconversions, incidence of HCV reinfections, and access to DAA and SVR12 rates tighter with factors associated with each outcome. Data were analysed by Cox regression, Poisson regression and logistic regression models. Results: Sixteen thousand seven hundred and forty-three PLWH were included; 27.3% HCV-Ab positive; of these, 39.3% HCV-RNA positive. HCV seroconversion incidence: .48/100 PYFU (95% CI: .36-.65); re-infections incidence: 1.40/100 PYFU (95% CI: .91-2.04). The risk factor for HCV re-infection was young age: aIRR 1.85, 95% CI: 1.17-2.95) per 10 years younger. 86.4% of HCV viremic in follow-up started DAA. PWID vs. heterosexuals (aHR .75, 95% CI .62-.90), HIV-RNA >50 copies/mL (aHR .70, 95% CI .56-.87), HCV genotype other than G1, G2, G3, G4 or with multiple/missing HCV genotype and post-COVID-19 calendar periods were associated with lower DAA access. 922/965 (95.5%) PLWH achieved SVR12. We estimated 72% reduction of chance to achieve SVR12 in PLWH with a CD4 count <200/mm3 (vs. CD4 ≥200/mm3 aOR .18, 95% CI: .07-.46). 95.5% of DAA-treated individuals eradicated HCV, but they represent only 53.2% of HCV viremic PLWH and 66.4% of those in follow-up. HCV-RNA positivity by year decreased from 41.7% in 2017 to 11.7% in 2022. Conclusions: The screening-and-treat campaign implemented in Italy, even if only partially effective, resulted in a dramatic drop in HCV circulation in our cohort

Determinants of worse liver‐related outcome according to HDV infection among HBsAg positive persons living with HIV: Data from the ICONA cohort

Objectives: We aimed to study hepatitis D virus (HDV) prevalence and risk of progression to severe liver-related events (SLRE) in HBsAg positive people living with HIV (PLWH) in Italy; role of HDV-RNA copy levels, HCV coinfection and nadir CD4 counts were also investigated.Methods: People living with HIV (PLWH) from Italian Foundation cohort Naive antiretrovirals (ICONA) with available HBsAg and HDV Ab were enrolled. HBsAg, HDV Ab, HDV-RNA and HDV genotypes were tested. Primary end-point: time from first HDV screening to Severe Liver Related Events (SLRE: decompensated cirrhosis, liver transplantation, HCC). Fine-grey regression models were used to evaluate the association of HDV Ab, HDV-RNA, HDV/HCV coinfection, CD4 nadir and outcome. Secondary end-points: time to SLRE or death; HDV Ab and HDV-RNA prevalence.Results: A total of 152/809 (18.8%) HBsAg positive PLWH showed HDV Ab reactivity; 63/93 (67.7%) were HDV-RNA positive. Being male, persons who inject drugs (PWID), HCV Ab positive, with FIB-4 > 3.25 were independent factors of HDV Ab positivity. In a median follow-up of 5 years, 37 PLWH (4.1% at 5-year) developed SLRE and 97 (12.0%) reached the SLRE or death end-point. HDV-RNA positive (independently from HDV-RNA copy level) PLWH had a 4.6-fold (95%CI 2.0-10.5) higher risk of SLRE than HDV negatives. PLWH positive for both HCV Ab and HDV Ab showed the highest independent risk of SLRE (ASHR: 11.9, 95%CI: 4.6-30.9 vs. HCV neg/HDV neg). Nadir CD4 < 200/mL was associated with SLRE (ASHR: 3.9, 95% 1.0-14.5).Conclusions: One-fifth of the HBsAg positive PLWH harbour HDV infection, and are at high risk of progression to advanced liver disease. HCV contributes to worse outcomes. This population needs urgently effective treatments

Serum interleukin-6 levels are increased in HIV-infected patients that develop autoimmune disease during long-term follow-up

Background: Elevated IL-6 levels have been associated with both autoimmune diseases and treated HIV-seropositive (HIV+) subjects. However, few data on classic and trans-signaling IL-6 in autoimmune thyroid diseases and HIV+ subjects developing autoimmune disorders are currently available. Materials and methods: A total of 102 patients were included in the study. They were subdivided into two groups. Group A consisted in 51 HIV+ patients, who were followed-up for a period of five years in search of possible occurrence of autoimmune diseases. Ten of them, treated with antiretroviral therapy (ART), developed an autoimmune disorder, namely Hashimoto's thyroiditis, and psoriasis. Group B consisted in 51 patients affected by Hashimoto's thyroiditis (HT). Serum levels of the free form of IL-6 were analyzed by ELISA in all patients and for HIV+ patients at the beginning of the follow-up, before initiation of ART. Results: Mean serum levels of IL-6 were similar in Group A and in Group B. In Group B, IL-6 levels showed a 5.8% increase compared with assay minimum detectable dose corresponding to 1% of full serum IL-6 level. However, serum levels of free IL-6 were increased in those HIV+ patients who developed autoimmune disorders (5.8 ± 2.8 pg/ml) and in these patients, the highest levels of free IL-6 correlated with age and CD4 cellular counts. Conclusions: The present study indicates a correlation between serum free IL-6 levels and the occurrence of autoimmune disease in HIV+ population, treated with ART during a long-term follow-up. The increased levels of serum free IL-6 were observed before ART treatment was initiated, indicating that IL-6 measurement in such patients may represent an early predictor of development of autoimmune disease

Switching from TDF to TAF or dual therapy (DT)-based regimens in HIV-infected individuals with viral load <= 50 copies/ml: does eGFR matter?

reserved98noOur aim was to evaluate the association between recent eGFR values and risk of switching from TDF to TAF or dual therapy (DT) in real life. HIV-positive patients achieving HIV-RNA ≤50 copies/mL for the first time after starting a TDF-based regimen were included. Kaplan–Meier (KM) curves and Cox regression models were used to estimate the time from TDF to switch to TAF or DT. 1486 participants were included: median (IQR) age 36 (30–42) years; baseline CKD-EPI eGFR 99.92 (86.47–111.4) mL/min/1.73m2. We observed a consistently higher proportion of people with HIV-RNA ≤50 copies/mL who switched from TDF to TAF rather than to DT. By competing risk analysis, at 2 years from baseline, the probability of switching was 3.5% (95% CI 2.6–4.7%) to DT and 46.7% (42.8–48.5%) to TAF. A significantly higher probability of switching to TAF was found for patients receiving INSTI at baseline versus NNRTIs and PI/b [KM, 65.6% (61.7–69.4%) vs. 4.0% (1.8–6.1%) and 59.9% (52.7–67.2%), respectively; P &lt; 0.0001]. eGFR &lt;60 mL/min/1.73m2 both as time-fixed covariate at baseline or as current value was associated with a higher risk of switching to DT [aHR 6.68 (2.69–16.60) and 8.18 (3.54–18.90); P &lt; 0.001] but not to TAF-based cART [aHR 0.94 (0.39–2.31), P = 0.897; and 1.19 (0.60–2.38), P = 0.617]. Counter to our original hypothesis, current eGFR is used by clinicians to guide switches to DT but does not appear to be a key determinant for switching to TAF.mixedA Vergori, R Gagliardini, N Gianotti, A Gori, M Lichtner, A Saracino, A De Vito, A Cascio, A Di Biagio, A d'Arminio Monforte, A Antinori, A Cozzi-Lepri on behalf of the ICONA Foundation Study Network, A. Giacometti, A. Costantini, V. Barocci; G. Angarano, L. Monno, E. Milano; F. Maggiolo, C. Suardi ; P. Viale, V. Donati, G. Verucchi ; F. Castelnuovo, C. Minardi, E. Quiros Roldan ; B. Menzaghi, C. Abeli ; L. Chessa, F. Pes ; B. Cacopardo, B. Celesia ; J. Vecchiet, K. Falasca (Chieti); A. Pan, S. Lorenzotti ; L. Sighinolfi; Daniela Segala ; P. Blanc, F. Vichi ; G. Cassola, M. Bassetti, A. Alessandrini, N. Bobbio, G. Mazzarello ; M. Lichtner, L. Fondaco (Latina); P. Bonfanti, C. Molteni ; A. Chiodera, P. Milini ; G. Nunnari, G. Pellicanò ; A. d’Arminio Monforte, M. Galli, A. Lazzarin, G. Rizzardini, M. Puoti, A. Castagna, E.S. Cannizzo, M.C. Moioli, R. Piolini, D. Bernacchia, A. Poli, C. Tincati, C. Mussini, C. Puzzolante ; C. Migliorino, G. Lapadula ; V. Sangiovanni, G. Borgia, V. Esposito, G. Di Flumeri, I. Gentile, V. Rizzo ; A.M. Cattelan, S. Marinello ; A. Cascio, C. Colomba ; D. Francisci, E. Schiaroli; G. Parruti, F. Sozio ; C. Lazzaretti, R. Corsini ; M. Andreoni, A. Antinori, R. Cauda, A. Cristaudo, V. Vullo, R. Acinapura, S. Lamonica, M. Capozzi, A. Mondi, A. Cingolani, M. Rivano Capparuccia, G. Iaiani, A. Latini, G. Onnelli, M.M. Plazzi, G. De Girolamo, A. Vergori; M. Cecchetto, F. Viviani; G. Madeddu, A. De Vito ; B. Rossetti, F. Montagnani ; A. Franco, R. Fontana Del Vecchio ; C.Di Giuli; P. Caramello, G. Di Perri, S. Bonora, G.C. Orofino, M. Sciandra; C. Tascini, A. Londer; V. Manfrin, G. Battagin ; G. Starnini, A. IalungoVergori, A; Gagliardini, R; Gianotti, N; Gori, A; Lichtner, M; Saracino, A; De Vito, A; Cascio, A; Di Biagio, A; d'Arminio Monforte, A; Antinori, A; Cozzi-Lepri on behalf of the ICONA Foundation Study Network, A; Giacometti, A.; Costantini, A.; Barocci, V.; Angarano, G.; Monno, L.; Milano, E.; C. Suardi, F. Maggiolo; Viale, P.; Donati, V.; Verucchi, G.; Castelnuovo, F.; Minardi, C.; Quiros Roldan, E.; C. Abeli, B. Menzaghi; F. Pes, L. Chessa; B. Celesia, B. Cacopardo; K. Falasca (Chieti), J. Vecchiet; S. Lorenzotti, A. Pan; Sighinolfi, L.; Segala, Daniela; F. Vichi, P. Blanc; Cassola, G.; Bassetti, M.; Alessandrini, A.; Bobbio, N.; Mazzarello, G.; L. Fondaco (Latina), M. Lichtner; C. Molteni, P. Bonfanti; P. Milini, A. Chiodera; G. Pellicanò, G. Nunnari; d’Arminio Monforte, A.; Galli, M.; Lazzarin, A.; Rizzardini, G.; Puoti, M.; Castagna, A.; Cannizzo, E. S.; Moioli, M. C.; Piolini, R.; Bernacchia, D.; Poli, A.; Tincati, C.; Mussini, C.; Puzzolante, C.; G. Lapadula, C. Migliorino; Sangiovanni, V.; Borgia, G.; Esposito, V.; Di Flumeri, G.; Gentile, I.; Rizzo, V.; S. Marinello, A. M. Cattelan; C. Colomba, A. Cascio; E. Schiaroli, D. Francisci; F. Sozio, G. Parruti; R. Corsini, C. Lazzaretti; Andreoni, M.; Antinori, A.; Cauda, R.; Cristaudo, A.; Vullo, V.; Acinapura, R.; Lamonica, S.; Capozzi, M.; Mondi, A.; Cingolani, A.; Rivano Capparuccia, M.; Iaiani, G.; Latini, A.; Onnelli, G.; Plazzi, M. M.; De Girolamo, G.; Vergori, A.; F. Viviani, M. Cecchetto; A. De Vito, G. Madeddu; F. Montagnani, B. Rossetti; R. Fontana Del Vecchio, A. Franco; Di Giuli, C.; Caramello, P.; Di Perri, G.; Bonora, S.; Orofino, G. C.; Sciandra, M.; A. Londer, C. Tascini; G. Battagin, V. Manfrin; A. Ialungo, G. Starnin

HBcAb Positivity Increases the Risk of Severe Hepatic Fibrosis Development in HIV/HCV-Positive Subjects From the ICONA Italian Cohort of HIV-Infected Patients

The aim of this study was to investigate the impact of anti-HBc (HBcAb) positivity on the progression of liver fibrosis (Fibrosis-4 score &gt;3.25) in the Italian cohort of HIV-infected individuals na\uefve to antiretroviral treatment (ICONA)

Long-acting injectable antiretrovirals for HIV treatment in the ICONA cohort: physicians’ and nurses’ points of view

Background: Implementation level of long-acting injectable agents cabotegravir/rilpivirine (LAI CAB/RPV) for human immunodeficiency virus (HIV) treatment in Italy is still not known. The aim of this study is to identify the status of implementation of LAI CAB-RPV and its barriers. Materials and methods: A cross-sectional online survey was conducted among infectious diseases (ID) physicians and nurses belonging to the ICONA network in Italy. Three validate 4-items measures were used: Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM) and Feasibility of Intervention Measure (FIM). Results: Out of 61 ICONA centres, 38 (62%) completed the survey: 57.9% were academic centres, 42.1% were hospital-based. In total, 104 respondents were ID physicians (57.4%), 77 were nurses (42.5%); 4.5% of all PWH followed at the 38 centres started LAI CAB/RPV at time of study. Centres taking care of &gt;1000 PWH reported 95% application of procedures for LA implementation, higher than other centres (P = 0.009). Mean score of AIM was (16.0, standard deviation, SD, 3.3), of IAM (16.0, SD 3.0) and FIM (16.0, SD 2.9). A linear correlation was found between AIM and the number of people with HIV who started LAI CAB/RPV (25-50 versus &lt;25, coefficient of correlation [b] 2.57, 95%CI 0.91-4.60, P = 0.004), academic versus hospital-based centres (b -1.59, 95%CI -2.76-0.110044, P = 0.007) and the absence of preliminary systematic assessment of staff (b -1.98, 95%CI -3.31-0.65, P = 0.004). Implementation barriers were not significantly different according to the number of PWH/centre. Conclusions: LAI CAB/RPV implementation was low, with a great variability according to centre size. Tailored and centre-specific interventions to address barriers and to optimize the LA treatment implementation should be designed