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HCV infection poses a global health threat, with significant morbidity and mortality. This study examines HCV trends in a large Italian region from 2015 to 2022, considering demographic changes, evolving clinical profiles, treatment regimens and outcomes, including the impact of the COVID-19 pandemic. This multicentre retrospective study analysed demographics, clinical histories and risk factors in 6882 HCV patients. The study spanned before and after the direct-acting antiviral (DAA) era, and the COVID-19 period, focusing on treatment outcomes (SVR12, non-SVR12 and patients lost to follow-up). Statistical methods included ANOVA, multinomial logistic regression, Kruskal-Wallis test and chi-square analysis, and were conducted adhering to the intention-to-treat (ITT) principle. The cohort, mainly Italian males (average age 58.88), showed Genotype 1 dominance (56.6%) and a high SVR12 rate (97.5%). The pandemic increased follow-up losses, yet SVR12 rates remained stable, influenced by factors like age, gender, cirrhosis and comorbidities. Despite COVID-19 challenges, the region sustained high SVR12 rates in HCV care, emphasising the importance of sustained efforts in HCV care. Continuous screening and targeted interventions in high-risk populations are crucial for achieving WHO elimination targets. The study highlights the resilience of HCV care during the pandemic and provides insights for future public health strategies.
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OBJECTIVES: To explore the effectiveness and durability of integrase strand transfer inhibitor (INSTI)-based regimens in pre-treated subjects. METHODS: Treatment-experienced individuals starting an INSTI-based regimen during 2012-2019 were selected from the INTEGRATE collaborative study. The time to virological failure [VF: one measurement of viral load (VL) ≥ 1000 copies/mL or two ≥ 50 copies/ml or one VL measurement ≥ 50 copies/mL followed by treatment change] and to INSTI discontinuation were evaluated. RESULTS: Of 13 560 treatments analysed, 4284 were from INSTI-naïve, non-viraemic (IN-NV) individuals, 1465 were from INSTI-naïve, viraemic (IN-V) individuals, 6016 were from INSTI-experienced, non-viraemic (IE-NV) individuals and 1795 were from INSTI-experienced, viraemic (IE-V) individuals. Major INSTI drug resistance mutations (DRMs) were previously detected in 4/519 (0.8%) IN-NV, 3/394 (0.8%) IN-V, 7/1510 (0.5%) IE-NV and 25/935 (2.7%) IE-V individuals. The 1-year estimated probabilities of VF were 3.1% [95% confidence interval (CI): 2.5-3.8] in IN-NV, 18.4% (95% CI: 15.8-21.2) in IN-V, 4.2% (95% CI: 3.6-4.9) in IE-NV and 23.9% (95% CI: 20.9-26.9) in IE-V subjects. The 1-year estimated probabilities of INSTI discontinuation were 12.1% (95% CI: 11.1-13.0) in IN-NV, 19.6% (95% CI: 17.5-21.6) in IN-V, 10.8% (95% CI: 10.0-11.6) in IE-NV and 21.7% (95% CI: 19.7-23.5) in IE-V subjects. CONCLUSIONS: Both VF and INSTI discontinuation occur at substantial rates in viraemic subjects. Detection of DRMs in a proportion of INSTI-experienced individuals makes INSTI resistance testing mandatory after failure.
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Infecciones por VIH , Inhibidores de Integrasa VIH , Integrasa de VIH , Farmacorresistencia Viral , Europa (Continente) , Infecciones por VIH/tratamiento farmacológico , Integrasa de VIH/genética , Inhibidores de Integrasa VIH/farmacología , Inhibidores de Integrasa VIH/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Humanos , Integrasas/uso terapéutico , Oxazinas/uso terapéutico , Carga ViralRESUMEN
BACKGROUND: INSTIs have become a pillar of first-line ART. Real-world data are needed to assess their effectiveness in routine care. OBJECTIVES: We analysed ART-naive patients who started INSTI-based regimens in 2012-19 whose data were collected by INTEGRATE, a European collaborative study including seven national cohorts. METHODS: Kaplan-Meier analyses assessed time to virological failure (VF), defined as one viral load (VL) ≥1000 copies/mL, two consecutive VLs ≥50 copies/mL, or one VL ≥50 copies/mL followed by treatment change after ≥24 weeks of follow-up, and time to INSTIs discontinuation (INSTI-DC) for any reason. Factors associated with VF and INSTI-DC were explored by logistic regression analysis. RESULTS: Of 2976 regimens started, 1901 (63.9%) contained dolutegravir, 631 (21.2%) elvitegravir and 444 (14.9%) raltegravir. The 1 year estimated probabilities of VF and INSTI-DC were 5.6% (95% CI 4.5-6.7) and 16.2% (95% CI 14.9-17.6), respectively, and were higher for raltegravir versus both elvitegravir and dolutegravir. A baseline VL ≥100 000 copies/mL [adjusted HR (aHR) 2.17, 95% CI 1.55-3.04, P < 0.001] increased the risk of VF, while a pre-treatment CD4 count ≥200 cells/mm3 reduced the risk (aHR 0.52, 95% CI 0.37-0.74, P < 0.001). Predictors of INSTI-DC included use of raltegravir versus dolutegravir (aHR 3.03, 95% CI 2.34-3.92, P < 0.001), use of >3 drugs versus 3 drugs (aHR 2.73, 95% CI 1.55-4.79, P < 0.001) and starting ART following availability of dolutegravir (aHR 0.64, 95% CI 0.48-0.83, P = 0.001). Major INSTI mutations indicative of transmitted drug resistance occurred in 2/1114 (0.2%) individuals. CONCLUSIONS: This large multi-cohort study indicates high effectiveness of elvitegravir- or dolutegravir-based first-line ART in routine practice across Europe.
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Infecciones por VIH , Inhibidores de Integrasa VIH , Estudios de Cohortes , Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/farmacología , Inhibidores de Integrasa VIH/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Humanos , Integrasas , Oxazinas , Piridonas , Raltegravir Potásico/uso terapéuticoRESUMEN
BACKGROUND: Antiretroviral drug resistance mutations remain a major cause of treatment failure. OBJECTIVES: To evaluate the impact of NRTI resistance mutations on virological effectiveness of elvitegravir-containing regimens. MATERIALS AND METHODS: We selected treatment-experienced HIV-1-infected patients starting elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF), with at least one protease/reverse transcriptase genotype available before switching and at least one HIV-1 RNA viral load (VL) measurement during follow-up. The primary endpoint was virological failure (VF), defined as one VL value of ≥1000 copies/mL or two consecutive VL values of >50 copies/mL. RESULTS: We included 264 ART regimens: 75.6% male, median (IQR) age 47 years (39-53), 7 years (3-16) of HIV infection, nadir CD4+ 247 cells/mm3 (105-361), 81.5% with VL ≤50 copies/mL and 11.7% with at least one NRTI mutation at baseline. Eleven (5.2%) VFs occurred in virologically suppressed patients versus eight (15.1%) in viraemic patients. The estimated probability of VF at 48 weeks with versus without any NRTI mutation was 7.4% (95% CI 2.3-12.5) versus 3.8% (2.1-5.5) in virologically suppressed patients and 66.7% (39.5-93.9) versus 11.2% (6.5-15.9) (P<0.001) in viraemic patients. The only predictor of VF was time on therapy (per 1 year more, adjusted HR 1.14, 95% CI 1.02-1.27, P=0.024) in viraemic patients. CONCLUSIONS: A switch to E/C/F/TDF or E/C/F/TAF is safe for virologically suppressed patients without documented NRTI resistance, but not recommended in viraemic patients with a history of NRTI resistance. Although we did not detect a detrimental effect of past NRTI resistance in virologically suppressed patients, a fully active regimen remains preferred in this setting due to possible rebound of drug-resistant virus in the long term.
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Antirretrovirales/uso terapéutico , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Quinolonas/uso terapéutico , Adulto , Terapia Antirretroviral Altamente Activa , Estudios de Cohortes , Bases de Datos Factuales , Quimioterapia Combinada , Femenino , VIH-1/efectos de los fármacos , Humanos , Italia , Masculino , Persona de Mediana Edad , Mutación , Resultado del Tratamiento , Carga Viral/efectos de los fármacosRESUMEN
Acanthamoeba spp. is a free-living amoeba, frequently involved in keratitis by contact lens in immunocompetent hosts. Anecdotal reports associate Acanthamoeba spp. as a cause of severe granulomatous encephalitis in immunocompromised and, less frequently, in immunocompetent subjects. Data regarding clinical and therapeutic management are scanty and no defined therapeutic guidelines are available. We describe an unusual case of non-granulomatous Acanthamoeba cerebellitis in an immunocompetent adult male, with abrupt onset of neurological impairment, subtle hemorrhagic infarction at magnetic resonance imaging, and initial suspicion of cerebellar neoplasm. Histopathological findings of excised cerebellar mass revealed the presence of necrosis and inflammation with structure resembling amoebic trophozoites, but without granulomas. Polymerase chain reaction from cerebellar tissue was positive for Acanthamoeba T4 genotype. Due to gastrointestinal intolerance to miltefosine, the patient was treated with long-term course of fluconazole and trimethoprim/sulphamethoxazole, obtaining complete clinical and neuroradiological resolution.
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Acanthamoeba/aislamiento & purificación , Amebiasis/diagnóstico , Antiprotozoarios/uso terapéutico , Cerebelo/parasitología , Encefalitis/diagnóstico , Adulto , Amebiasis/complicaciones , República Dominicana/etnología , Encefalitis/parasitología , Fluconazol/uso terapéutico , Humanos , Italia , Masculino , Reacción en Cadena de la Polimerasa , Resultado del Tratamiento , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoRESUMEN
Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration > 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r.
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COVID-19 , Pacientes Ambulatorios , Humanos , Anciano , Estudios Retrospectivos , SARS-CoV-2 , Italia/epidemiologíaRESUMEN
OBJECTIVES: The aim of this study was to evaluate the impact of resistance mutations on efficacy of dolutegravir-based two-drug regimens (2DR). METHODS: Virologically suppressed patients with HIV-1 switching to dolutegravir + lamivudine or rilpivirine or to a dolutegravir-based three-drug regimen (3DR) with pre-baseline genotype were selected. Virological failure (VF) was defined as one HIV-RNA viral load (VL) >200 cps/mL or two consecutive VL >50 cps/mL; treatment failure (TF) was defined as VF or treatment discontinuation (TD). Resistance was defined as at least low-level resistance to at least one drug of the current regimen. Propensity score matching was used to conduct adjusted analyses within a competing risks framework. RESULTS: A total of 971 dolutegravir-based regimens were selected: 339 (34.9%) 2DR and 632 (65.1%) 3DR. The adjusted cumulative 48-week incidence of VF was 4.2% (90% CI 3.1%-5.3%) with 2DR and 4.7% (90% CI 3.5%-5.8%) with 3DR. The cumulative 48-week incidence of TF was 15.8% (90% CI 13.9%-17.9%) with 2DR and 24.5% (90% CI 22.2%-27.0%) with 3DR. For VF, the estimated hazard ratio (HR) for 2DR vs. 3DR was 1.02 (90% CI: 0.78-1.34), with evidence of effect modification by low-level resistance (HR 3.96, 90% CI: 2.10-7.46). The estimated HR of TF for 2DR vs. 3DR was 0.54 (90% CI: 0.48-0.60). The 48-week cumulative incidence of TD was 11.7% (8.7%, 14.6%) in 2DR and 19.6% (16.9%, 22.4%) in 3DR. CONCLUSIONS: Dolutegravir-based 2DR showed high virological efficacy and durability; however, past resistance increased the risk of VF, but not of TD or TF.
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Fármacos Anti-VIH , Infecciones por VIH , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Estudios de Cohortes , Infecciones por VIH/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos , Humanos , Lamivudine/uso terapéutico , Mutación , Oxazinas , Piperazinas , Piridonas , Rilpivirina/uso terapéuticoRESUMEN
Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia. Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia. Design, Setting, and Participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible. Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations. Main Outcomes and Measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2 ratio <150 mm Hg) or death within 30 days from randomization. Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04). Conclusions and Relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04716556.
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COVID-19/terapia , Mortalidad Hospitalaria , Hospitalización , Inmunización Pasiva , Plasma , Insuficiencia Respiratoria , Anciano , COVID-19/complicaciones , COVID-19/mortalidad , Progresión de la Enfermedad , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Nivel de Atención , Sueroterapia para COVID-19RESUMEN
INTRODUCTION: Long-term comparative immunologic response to 13-valent pneumococcal conjugate vaccine (PCV13) versus 23-valent polysaccharide vaccine (PPV23) among HIV-infected adults has not yet been investigated. METHODS: In this prospective pilot study, we quantified in HIV-positive adults serotype-specific IgG concentrations of the 12 pneumococcal serotypes shared by both vaccines 5 years after vaccination with two doses of PCV13 8 weeks apart (group 1) or one dose of PPV23 (group 2) and compared them with those assessed prior to vaccination (BL) and after 1 year (T1). Comparison of immunogenicity was based on geometric mean concentration (GMC), proportion of individuals with ≥ twofold increase from BL in specific antibody concentration against ≥ 2 serotypes and percentage of individuals with serotype-specific IgG ≥ 0.35 µg/ml, ≥ 1 µg/ml and ≥ individual serotype-specific correlates of protection. RESULTS: We included 91 subjects (median CD4+ 650 cells/µl, > 90% with HIV-RNA < 50 copies/ml); patients in groups 1 (n = 42) and 2 (n = 49) were homogeneous for the main characteristics. GMCs were significantly higher in the PCV13 group than in the PPV23 group for serotype 19F (p = 0.003). Both vaccines revealed higher significant GMCs to most serotypes compared with BL, i.e., eight in group 1 vs. seven in group 2. With respect to T1, GMCs decreased significantly in the PCV13 group for eight vs. ten serotypes in the PPV23 group. More participants in the PCV13 group had ≥ 2 increase from BL in antibody levels to ≥ 2 serotypes compared with the PPV23 group (78.6% vs. 59.2%, p = 0.042). Overall, the percentage of subjects with serotype-specific IgG ≥ 0.35 µg/ml, ≥ 1 µg/ml and ≥ individual serotype-specific correlates of protection was similar between groups. CONCLUSION: In this study with HIV-positive adults with a favorable viro-immunologic profile, both vaccines were shown to achieve a long-term durable serologic response. We found minor differences in immunogenicity between the two vaccines, which favored PCV13 over PPV23 5 years after immunization. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02123433.
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BACKGROUND: Two-drug regimens are increasingly used in clinical practice as switch strategies. We compared the efficacy and safety of two dolutegravir (DTG)-based dual therapies: DTG plus lamivudine (3TC group) versus DTG plus rilpivirine (RPV group). METHODS: In a multicentre cohort of virologically suppressed (HIV RNA <50 copies/ml) HIV+ patients switching to DTG+3TC or DTG+RPV we analysed the incidence of virological failures (VF) and treatment discontinuations (TD), as well as their predictors. RESULTS: We analysed 416 patients, 229 in the 3TC group and 187 in the RPV group. The 3TC group, during 344.4 person-years of follow-up (PYFU), had 10 VF without the emergence of resistance mutations, while 30 patients discontinued the regimen. In the RPV group, during 371.0 PYFU, there were 5 VF (1 developed non-nucleoside reverse transcriptase inhibitor mutations Y181C and E138Q) and 13 TD. The estimated probability of remaining free from VF at 48 weeks showed no significant difference between groups (log-rank 0.172). We found a higher risk of VF in patients with peak viral load >500,000 copies/ml in both treatment groups (log-rank P=0.004 in each group). The estimated probability of remaining in the study regimen at week 48 was 89.0% with DTG+3TC and 96.1% with DTG+RPV (log-rank 0.015). After adjusting for potential confounders, treatment group was not associated with TD. A significant decrease in total cholesterol was observed at week 48 in both groups while renal function remained unchanged. CONCLUSIONS: DTG+RPV and DTG+3TC were compared in populations with different characteristics in clinical practice: both regimens showed good effectiveness and improved lipid profile.
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Quimioterapia Combinada , Infecciones por VIH/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos , Lamivudine , Rilpivirina , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Colesterol/sangre , Estudios de Cohortes , Femenino , VIH-1 , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Humanos , Lamivudine/administración & dosificación , Lamivudine/uso terapéutico , Masculino , Persona de Mediana Edad , Oxazinas , Piperazinas , Piridonas , Rilpivirina/administración & dosificación , Rilpivirina/uso terapéutico , Carga ViralRESUMEN
Kaposi sarcoma (KS) remains a relevant malignancy in human immunodeficiency virus (HIV)-infected patients with a non-standardized management; despite past suggestions that ritonavir-boosted protease inhibitor (bPI)-based regimens could be preferable, no combination antiretroviral therapy (cART) regimen was demonstrated to outperform the others and the impact of new drugs, drug classes or paradigms was never investigated nor proven better than previous therapeutic regimes. In order to do this, we retrospectively collected data regarding HIV-infected patients with a diagnosis of KS last seen in six Italian centers after 1 January 2013. A total of 104 KS cases in 99 patients was analyzed for 945.34 patient-year follow-up (PYFU). Twenty-six patients had visceral localizations. Thirty-three patients were treated with chemotherapy, four with electrochemotherapy, and 12 with α-interferon (α-IFN). At censor, 22% received a bPI-based, 14% a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based, and 28% an integrase inhibitor (INI)-based standard cART, 24% a less drug regimen and 12% a mega-cART. Twelve recurrence episodes were observed in seven patients for an incidence of 1.27 per 100 PYFU. Two patients with no evidence of recurrence episodes died for other reasons. In our experience, KS recurrence episodes were infrequent. Despite the increasing use of new antiretroviral drug classes and new treatment paradigms, no excess of recurrence episodes was observed in patients receiving such cART regimens.