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1.
AIDS Behav ; 28(3): 907-911, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37792228

RESUMO

Aim was to investigate the propensity to switch to long-acting injectable HIV pre-exposure prophylaxis (PrEP) with cabotegravir among oral PrEP-experienced men who have sex with men. Out of 377 PrEP users, 325 (86.2%) were interested (would like = 210) or considering (would consider = 115) switch to long-acting PrEP. At multivariable analysis, the odds ratio of interest in long-acting PrEP in non-adherent vs. adherent individuals to oral PrEP was 5.03 (95%CI = 1.73-14.61,p = 0.003) and of consideration 1.63 (95%CI = 0.51-5.23,p = 0.410). We observed very high propensity to switch to long-acting PrEP, particularly among non-adherent users. Rapid availability of long-acting PrEP might address unmet needs of PrEP users in Italy.


Assuntos
Fármacos Anti-HIV , Dicetopiperazinas , Infecções por HIV , Profilaxia Pré-Exposição , Piridonas , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Itália/epidemiologia
2.
Eur J Clin Microbiol Infect Dis ; 42(11): 1383-1387, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37723323

RESUMO

Management of COVID-19 patients experiencing persisting respiratory failure despite corticosteroids remains challenging. Data on high-dose intravenous anakinra (HD-ANK) in this context are lacking. We aimed to investigate the impact of HD-ANK on mortality in COVID-19 patients progressing to non-invasive ventilation (NIV) while receiving corticosteroids. We retrospectively analyzed the impact of HD-ANK on 28-day mortality in individuals hospitalized with COVID-19 necessitating NIV after corticosteroid initiation. A total of 256 patients were identified: 146 received standard-of-care only (SOC), and 110 received HD-ANK+SOC. The groups were well-balanced at baseline. In-hospital mortality at 28 days did not differ between the two groups. HD-ANK is not beneficial in patients with severe COVID-19 deteriorating despite corticosteroids.

3.
New Microbiol ; 46(3): 296-302, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37747475

RESUMO

The impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on patients with pre-existing chronic liver diseases (CLD) remains elusive. The aim of this study was to investigate the in-hospital mortality in patients hospitalized for Coronavirus disease of 2019 (COVID-19) with CLD (CLD group) compared to those without CLD (non-CLD group). We performed a retrospective cohort study including patients with confirmed SARS-CoV-2 infection, hospitalized at San Raffaele Hospital (Milan), stratified according to the presence or absence of CLD. A propensity score was estimated and used to match the two groups by age, gender, body mass index, type 2 diabetes mellitus, and hypertension. Predictors of mortality were assessed using univariate and multivariate logistic regression model. Among 1210 patients with COVID-19, 41 (3.4%) were included in the CLD group and 1169 (96.6%) in the non-CLD group. Using a propensity score, we matched 41 patients in the CLD group with 123 in the non-CLD group. At admission, patients in the CLD group had worse liver function, lower platelets count, and lower c-reactive protein levels. By multivariate analysis, the CLD group showed a higher risk of death: OR 4.04 (95% CI 1.29-12.70; p= 0.017). Our study showed that COVID-19 with chronic liver diseases has a higher risk of mortality during hospitalization.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Hepatopatias , Humanos , Centros de Atenção Terciária , SARS-CoV-2 , Estudos Retrospectivos , Itália/epidemiologia , Hepatopatias/epidemiologia
4.
Virol J ; 17(1): 103, 2020 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-32660499

RESUMO

BACKGROUND: Notwithstanding the efforts of direct-acting antivirals (DAAs) for the treatment of chronically infected hepatitis C virus (HCV) patients, concerns exist regarding the emergence of resistance-associated substitutions (RAS) related to therapy failure. Sanger sequencing is still the reference technique used for the detection of RAS and it detects viral variants present up to 15%, meaning that minority variants are undetectable, using this technique. To date, many studies are focused on the analysis of the impact of HCV low variants using next-generation sequencing (NGS) techniques, but the importance of these minority variants is still debated, and importantly, a common data analysis method is still not defined. METHODS: Serum samples from four patients failing DAAs therapy were collected at baseline and failure, and amplification of NS3, NS5A and NS5B genes was performed on each sample. The genes amplified were sequenced using Sanger and NGS Illumina sequencing and the data generated were analyzed with different approaches. Three different NGS data analysis methods, two homemade in silico pipeline and one commercially available certified user-friendly software, were used to detect low-level variants. RESULTS: The NGS approach allowed to infer also very-low level virus variants. Moreover, data processing allowed to generate high accuracy data which results in reduction in the error rates for each single sequence polymorphism. The results improved the detection of low-level viral variants in the HCV quasispecies of the analyzed patients, and in one patient a low-level RAS related to treatment failure was identified. Importantly, the results obtained from only two out of the three data analysis strategies were in complete agreement in terms of both detection and frequency of RAS. CONCLUSIONS: These results highlight the need to find a robust NGS data analysis method to standardize NGS results for a better comprehension of the clinical role of low-level HCV variants. Based on the extreme importance of data analysis approaches for wet-data interpretation, a detailed description of the used pipelines and further standardization of the in silico analysis could allow increasing diagnostic laboratory networking to unleash true potentials of NGS.


Assuntos
Antivirais/uso terapêutico , Variação Genética , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Proteínas não Estruturais Virais/genética , Idoso , Substituição de Aminoácidos , Coinfecção/virologia , Simulação por Computador , Análise de Dados , Genótipo , Hepatite C Crônica/sangue , Hepatite C Crônica/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Software , Falha de Tratamento , Proteínas não Estruturais Virais/classificação
5.
Infection ; 48(4): 553-558, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32430647

RESUMO

To assess the HIV -1subtypes distribution in HIV-1 positive migrants living in Milan we studied 77 HIV-1 patients followed at the San Raffaele Hospital of Milan. Twenty subjects were born in Europe, 43 in the Americas, 10 in Africa and 4 in Asia. Unsafe heterosexual activity prevailed in migrants born in Africa and male homosexuality in those born in European, American and Asian countries (p = 0.05). The phylogeny showed that 38/77 (49.3%) subjects carried HIV-B subtype while the remaining strains were classified as not pure HIV-1 B subtypes 13/77 (16.9%) or recombinant forms 26/77 (33.8%). Female gender more frequently showed HIV-1 non-B strains and rarely HIV-1 B subtypes (12/39, 30.8% vs. 3/38, 7.9%, p = 0.02). Transmitted drug resistance was identified in 10/77 (13%) patients predominately with B subtype. Our data underscore a large heterogeneity in HIV-1 subtypes and a large proportion of recombinant forms.


Assuntos
Emigrantes e Imigrantes , Infecções por HIV/epidemiologia , HIV-1/isolamento & purificação , Adulto , Cidades/epidemiologia , Feminino , Infecções por HIV/classificação , Infecções por HIV/virologia , HIV-1/classificação , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Filogenia , Adulto Jovem
6.
Epidemiol Infect ; 148: e19, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32019634

RESUMO

Human immunodeficiency virus-1 (HIV-1) is characterised by a vast genetic diversity classified into distinct phylogenetic strains and recombinant forms. We describe the HIV-1 molecular epidemiology and evolution of 129 consecutive HIV-1 positive migrants living in Milan (northern Italy). Polymerase gene sequences of 116 HIV-1 subtype-B positive patients were aligned with HIV-1 reference sequences (https://www.ncbi.nlm.nih.gov/) by using MAFFT alignment and edited by using Bioedit software. A maximum likelihood (ML) phylogenetic tree was performed by MEGA7 and was visualised by using FigTree v1.4.3. Of 129 migrants, 35 were born in Europe (28 in Eastern Europe), 70 in the Americas (67 in South America), 15 in Africa and nine in Asia; 76.4% were men who have sex with men (MSM). The serotype HIV-1-B prevailed (89.9%), followed by -C, -F1, -D and -A. Compared with 116 HIV-B patients, the 13 with HIV-non-B showed lower Nadir of CD4+ cell/mmc (P = 0.043), more frequently had sub Saharan origin (38.5 vs. 1.72%, P = 0.0001) and less frequently were MSM (40 vs. 74.5%, P = 0.02). The ML phylogenetic tree of the 116 HIV-1 subtype-B positive patients showed 13 statistically supported nodes (bootstrap > 70%). Most of the sequences included in these nodes have been isolated from male patients from the Americas and the most common risk factor was MSM. The low number of HIV-1 non-B subtype patients did not allow to perform this analysis. These results suggest a shift of HIV-1 prevention projects' focus and a continuous monitoring of HIV-1 molecular epidemiology among entry populations. Prevention efforts based on HIV molecular epidemiology may improve public health surveillance setting.


Assuntos
Emigrantes e Imigrantes , Variação Genética , Genótipo , Infecções por HIV/epidemiologia , HIV-1/classificação , HIV-1/genética , Adulto , Feminino , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Filogenia , Análise de Sequência de DNA , Sorogrupo , Inquéritos e Questionários , Adulto Jovem
7.
J Med Virol ; 91(11): 1937-1943, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31286527

RESUMO

OBJECTIVE: To describe the trajectories of the homeostatic model assessment for insulin resistance (HOMA-IR) index in a cohort of HIV-1 infected patients during their first-line antiretroviral (ART) regimen. METHODS: Retrospective analysis of naïve patients who started ART from 2007 at the Infectious Diseases Unit of the San Raffaele Hospital, Milan. We included patients treated with two nucleoside reverse transcriptase inhibitors (NRTIs, tenofovir, abacavir, lamivudine or emtricitabine), and one anchor drug (ritonavir-boosted protease inhibitor [PI/r], non-NRTI [NNRTI], or integrase strand transfer inhibitor [InSTI]), and with HOMA-IR assessed both before and after the start of ART. Univariate and multivariate mixed linear models estimated HOMA-IR changes during ART. RESULTS: Among 618 patients included in the study, 218 received InSTI-, 210 PI/r-, and 190 NNRTI-based regimens. Median follow-up was 27.4 (16.3-41.2) months. Adjusted mean change in HOMA-IR index was significantly higher (P = .041) in patients treated with InSTI-based regimens [0.160 (95% CI: 0.003-0.321) units per year] compared with NNRTI-based regimens [-0.005 (95% CI: -0.184-0.074) units per year]; no difference was observed between patients treated with NNRTI- and PI/r-based regimens or between INSTI-based and PI/r-based regimens. CONCLUSION: InSTI-based first-line ARTs were independently associated with greater increases in HOMA-IR index.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Homeostase , Resistência à Insulina , Adulto , Terapia Antirretroviral de Alta Atividade , Feminino , Infecções por HIV/complicações , Inibidores da Protease de HIV/uso terapêutico , Humanos , Inibidores de Integrase/uso terapêutico , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/uso terapêutico , Carga Viral
8.
Virol J ; 15(1): 144, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30227876

RESUMO

BACKGROUND: We evaluated the frequency of naturally occurring resistance associated substitutions (RASs) and their characteristic of polymorphic or non-polymorphic amino acid change to direct acting antivirals (DAAs) in NS5b HCV subtypes 1a and 1b according to different geographic origin of isolates. METHODS: Using a public database we retrieved 738 worldwide NS5b sequences (for which was available the geographic origin) from HCV genotype (G)1 infected patients naive to DAAs. NS5b sequences clustering with G1a were more conserved in regard of RASs than G1b isolates, (14% vs 57% RASs, P < 0.0001). RESULTS: In G1a, RASs were differently distributed between isolates from Europe (24%) and USA, (12%) P = 0.0186. In particular, 421 V associated with resistance to non-nucleoside inhibitor beclabuvir was polymorphic in Europe and USA, being detected in 24% and 11% of sequences, respectively, P = 0.0140. In G1b, RASs were found in 45% of sequences from Europe, in 54% of isolates from USA and in 70% of sequences from Asia (P = 0.0051). The 316 N polymorphism was detected in 54% of Asian isolates and at lower frequency, in 28% of isolates from USA and in 20% of European sequences (P < 0.0001). CONCLUSIONS: In conclusion, a higher prevalence of RASs in G1b respect to G1a was found and a geographical distribution of RASs and polymorphic aa changes was observed in G1a as well in G1b. The clinical and therapeutic impact of the geographic distribution of RASs to polymerase inhibitors remains to be established, particularly in patients with virologic failure to DAAs and/or advanced liver disease.


Assuntos
Farmacorresistência Viral , Genótipo , Hepatite C/virologia , Mutação de Sentido Incorreto , Filogeografia , Polimorfismo Genético , Proteínas não Estruturais Virais/genética , Ásia/epidemiologia , Europa (Continente)/epidemiologia , Hepatite C/epidemiologia , Humanos , Epidemiologia Molecular , Prevalência , Estados Unidos/epidemiologia
9.
J Antimicrob Chemother ; 72(3): 812-815, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-27999010

RESUMO

Objectives: To evaluate the plasma trough concentrations ( C trough ) of dolutegravir and rilpivirine used in combination with simeprevir and sofosbuvir in HIV/hepatitis C virus (HCV)-coinfected patients with liver cirrhosis. Virological efficacy and safety of both ART and anti-HCV therapy were assessed. Patients and methods: A prospective observational study in HIV/HCV-coinfected patients with liver cirrhosis on ART with dolutegravir plus rilpivirine and treated with simeprevir plus sofosbuvir (±ribavirin) was conducted. Dolutegravir, rilpivirine, GS-331007 (sofosbuvir metabolite) and simeprevir C trough were evaluated with a validated HPLC method at anti-HCV treatment baseline and weeks 2 and 4. Geometric means were calculated to summarize C trough values. Results: Twelve patients were evaluated: 75% were males and the median (IQR) age was 53 (53-55) years. All patients were Child-Pugh stage A, except one who was stage B. The geometric mean (95% CI) of C trough of rilpivirine and dolutegravir did not change between baseline and week 4 ( P = 0.654 and P = 0.268, respectively), with corresponding overall values of 135 (102-177) and 1357 (970-1897) ng/mL. The overall geometric mean (95% CI) of GS-331007 and simeprevir C trough was 370 (268-512) and 2537 (1569-4101) ng/mL, respectively, without significant variation between weeks 2 and 4 ( P = 0.643 and P = 0.179, respectively). All patients completed anti-HCV treatment, achieving sustained virological response. All but two patients maintained undetectable HIV-RNA up to post-treatment week 24. Conclusions: Dolutegravir and rilpivirine C trough appeared not to be affected by concomitant treatment with simeprevir plus sofosbuvir in these HIV/HCV-coinfected patients with liver cirrhosis, supporting the use of this antiretroviral regimen in this setting.


Assuntos
Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Cirrose Hepática/complicações , Rilpivirina/farmacocinética , Simeprevir/farmacocinética , Sofosbuvir/farmacocinética , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Quimioterapia Combinada , Feminino , Genótipo , Infecções por HIV/complicações , Hepacivirus/fisiologia , Hepatite C Crônica/complicações , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Cirrose Hepática/virologia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Estudos Prospectivos , Piridonas , RNA Viral/sangue , Rilpivirina/administração & dosagem , Rilpivirina/uso terapêutico , Simeprevir/administração & dosagem , Simeprevir/uso terapêutico , Sofosbuvir/administração & dosagem , Sofosbuvir/uso terapêutico , Carga Viral
10.
Oncology ; 93(6): 395-400, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28918424

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is increasingly prevalent in people living with HIV. Systemic inflammation is a prognostic factor requiring validation in HIV-associated HCC. AIMS: Using a multi-centre database of consecutive HCC cases, we investigated the prognostic role of a panel of inflammatory markers, including neutrophil to lymphocyte ratio (NLR), using univariate and multivariate survival analyses. RESULTS: Fifty-nine patients with HIV-associated HCC secondary to hepatitis C (69%) or B virus infection (32%) were identified. The median survival was 22 months. A raised NLR independently predicted patients' survival and was correlated with advanced Barcelona Clinic Liver Cancer stage (p = 0.003) and poor performance status (p < 0.001) but not with HIV RNA or CD4 counts. CONCLUSION: Systemic inflammation, as measured by NLR, is a prognostic determinant associated with adverse pathological features of malignancy, but not coexisting HIV infection, suggesting a tumour-promoting role of the innate immune response that warrants further investigation in mechanistic studies.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Infecções por HIV/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Síndrome de Resposta Inflamatória Sistêmica/patologia , Adulto , Idoso , Feminino , Infecções por HIV/virologia , Humanos , Linfócitos/patologia , Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Neutrófilos/virologia , Prognóstico , Análise de Sobrevida , Síndrome de Resposta Inflamatória Sistêmica/virologia
11.
Arch Virol ; 162(8): 2271-2277, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28421367

RESUMO

The presence of naturally occurring resistance-associated substitutions (RASs) in the HCV-protease domain has been poorly investigated in the liver, the main site of HCV replication. We evaluated the natural resistance of the virus to NS3 protease inhibitors in liver tissue and plasma samples taken from HCV-infected patients. RASs were investigated by means of viral population sequencing in liver tissue samples from 18 HCV-infected patients harbouring genotype 1a or genotype 1b; plasma samples from 12 of these patients were also available for virological investigation. A discordant genotype was found in two of the 12 patients (16.6%) who provided samples from both compartments. Sequence analysis of the NS3 protease domain showed the presence of RASs in four of the 18 liver tissue samples (22.2%), two of which showed cross-resistance to protease inhibitors in clinical use or phase 2-3 trials. The analysis of the 12 paired tissues and plasma samples excluded the presence of RASs in the plasma compartment. The dominance of discordant genotypes in the paired liver and plasma samples of some HCV-infected patients suggests mixed infection possibly leading to the selective advantage of different genotype in the two compartments. The presence of RASs at intra-hepatic level is not uncommon and may lead to the early emergence of cross-resistant strains.


Assuntos
Farmacorresistência Viral/genética , Hepacivirus/genética , Hepatite C Crônica/virologia , Inibidores de Proteases/farmacologia , Proteínas não Estruturais Virais/genética , Adulto , Idoso , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Humanos , Itália , Fígado/patologia , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Plasma/virologia , Análise de Sequência de DNA
12.
New Microbiol ; 40(1): 53-55, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28072886

RESUMO

The genetic analysis of THE natural protease inhibitors (PI) resistance of HCV genotype (GT)1 involves subtypes 1a and 1b. NS3 protease domain was sequentially analysed in 10 HIV/HCV GT1-coinfected individuals naïve to HCV treatment. Analysis at different time points showed that 2/3 GT1b patients were infected by a GT1a clade1 during follow-up. In one patient a switch from clade1 to clade2 and in one other patient a switch from clade2 to clade1 was revealed. Four out of ten patients had resistance-associated substitutions (RASs) at baseline. The dynamics of the dominant infecting subtype suggests the presence of mixed infection in some patients.


Assuntos
Infecções por HIV/complicações , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Proteínas não Estruturais Virais/metabolismo , Antivirais/farmacologia , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Genótipo , Hepacivirus/metabolismo , Humanos , Filogenia , Carga Viral , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/genética
13.
New Microbiol ; 39(2): 110-3, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-27196548

RESUMO

We determined the diagnostic accuracy and optimal cut off of three indirect fibrosis biomarkers (APRI, FIB-4, Forns) compared with liver stiffness (LS) for the detection of liver cirrhosis in HIV/HCV-coinfected patients. An observational retrospective study on HIV/HCV-coinfected patients with concomitant LS measurement and APRI, FIB-4 and Forns was performed. The presence of liver cirrhosis was defined as a LS ≥13 KPa. The diagnostic accuracy and optimal cut-off values, compared with LS categorization (<13 vs ≥13 KPa), were determined by receiver operating characteristics (ROC) curves. The study sample included 646 patients. The area-under-the ROC curve (95% confidence interval) for the detection of liver cirrhosis were 0.84 (0.81-0.88), 0.87 (0.84-0.91) and 0.87 (0.84-0.90) for APRI, FIB-4 and Forns, respectively. According to the optimal cut off values for liver cirrhosis (≥0.97 for APRI, ≥2.02 for FIB-4 and ≥7.8 for Forns), 80%, 80% and 82% of subjects were correctly classified by the three indirect fibrosis biomarkers, respectively. Misclassifications were mostly due to false positive cases. The study suggests that indirect fibrosis biomarkers can help clinicians to exclude liver cirrhosis in the management of HIV/HCV co-infected patients, reducing the frequency of more expensive or invasive assessments.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Infecções por HIV/complicações , Hepatite C/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Biomarcadores/sangue , Coinfecção , Feminino , Hepacivirus , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
14.
Microorganisms ; 12(6)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38930529

RESUMO

The emergence of new SARS-CoV-2 variants can affect vaccine efficacy, laboratory diagnosis and the therapies already available, triggering interest in the search for antiviral agents for SARS-CoV-2 infections. Ribavirin (RBV) is a broad-spectrum antiviral with demonstrated in vitro activity against multiple viruses, including SARS-CoV-2. This retrospective study evaluated the dynamics and viral clearance of SARS-CoV-2 in hospitalised adult participants (PTs) with COVID-19 pneumonia who received an RBV aerosol within a compassionate use study. The impact of RBV on the clinical outcome and the mutational profile of SARS-CoV-2 was also assessed. The median RNA values measured in nine PTs included in this study decreased from baseline to discharge (at BL, threshold cycle (Ct) = 22.4, IQR 19.84-5.07; at discharge, Ct = 27.92, IQR 26.43-36.11), with a significant decline in the Ct value evaluated by Friedman rank ANOVA analysis, p = 0.032. Seven out of nine PTs experienced a clinical improvement, while two PTs deceased during hospitalisation. In PTs with a favourable outcome, the virus clearance rate at discharge was 28.6%. The cumulative clearance rate was 71.4% within 14 days from discharge. A mutational pattern after RBV was detected in three out of five PTs in whom whole-genome sequencing was available. Our findings suggest that RBV limits SARS-CoV-2 replication, possibly resulting in a favourable clinical outcome. Ribavirin may also contribute to the mutational spectrum of SARS-CoV-2.

15.
Liver Int ; 33(7): 1113-20, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23534616

RESUMO

BACKGROUND & AIMS: HIV-monoinfected patients are susceptible to liver injury by different factors and may develop liver fibrosis, which requires adequate clinical management in terms of therapy and disease monitoring. We aimed to evaluate the presence of liver fibrosis identified by transient elastography (TE), its relationships with indirect biochemical markers [the aspartate aminotransferase/platelet ratio index (APRI), the Forns index and FIB-4] and its predictive factors in HIV-monoinfected patients receiving antiretroviral therapy (ART). METHODS: Seventy-two HIV-monoinfected patients underwent TE and were evaluated using APRI, Forns and FIB-4. The clinical, immunological, virological and other biochemical characteristics were evaluated at the time of TE, together with their history of ART. RESULTS: Seven patients (10%) had liver stiffness (LS) values predicting cirrhosis, and 12 (17%) had values predicting significant or advanced fibrosis. Higher indirect biochemical scores of liver fibrosis were significantly associated with higher LS values [APRI rs  = 0.4296 (P < 0.001); Forns rs  = 0.4754 (P < 0.001); FIB-4 rs  = 0.285 (P = 0.015)]. At multivariable analysis, APRI (ß = 2.7405; P = 0.036), Forns (ß = 1.4174; P = 0.029) and triglyceride levels (ß = 1.3028; P = 0.007) were independently associated with LS. CONCLUSIONS: Indirect fibrosis biomarkers may increase the probability to detect liver injury enhancing a specific diagnostic workup and so contribute to improving the clinical management of HIV-monoinfected patients with clinically suspected liver disease.


Assuntos
Biomarcadores/metabolismo , Técnicas de Imagem por Elasticidade/métodos , Infecções por HIV/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Fatores Etários , Antirretrovirais/uso terapêutico , Aspartato Aminotransferases/sangue , Plaquetas/metabolismo , Colesterol/sangue , Infecções por HIV/tratamento farmacológico , Humanos
16.
Front Oncol ; 13: 1242741, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38115904

RESUMO

The use and choice of the best systemic treatment is gaining increasing interest in people living with HIV (PLWH) because hepatocellular carcinoma (HCC) represents an increasing cause of morbidity and mortality in this setting and most HCCs are diagnosed in the advanced stage. Ten years ago, the multi-kinase inhibitor lenvatinib was approved in the first-line setting. However, to date, no data on the efficacy and tolerability of lenvatinib in PLWH from clinical trials and real-life studies are available. Case 1 was a gentleman with hepatitis B virus-related cirrhosis who underwent orthotopic liver transplantation for HCC and developed peritoneal metastasis several years later. Lenvatinib treatment was selected at HCC recurrence. This participant maintained undetectable HIV viremia and a relatively preserved immune status during 6 months of systemic treatment with lenvatinib. After 6 months, he discontinued lenvatinib for progression of the disease (growing of peritoneal metastasis) and uncontrolled hypertension. Case 2 was a gentleman with hepatitis C-genotype 1a-related cirrhosis who experienced unresectable recurrences after radiofrequency thermal ablation of the tumor. At the first recurrence, HCC was treated with six cycles of trans-catheter arterial chemoembolization; at the second recurrence, the participant underwent trans-catheter arterial radioembolization; and at the third recurrence, he received lenvatinib. A week after the start of lenvatinib, the participant had liver decompensation and discontinued therapy. The presently reported cases showed low tolerability of systemic therapy with lenvatinib in PLWH. Cumulative data are necessary to define the position of lenvatinib in this setting.

17.
AIDS Res Hum Retroviruses ; 39(4): 204-210, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36511389

RESUMO

Menopause is a high-risk period for osteoporosis, which may be exacerbated by HIV and/or antiretroviral therapy (ART). Our goal was to study the impact of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on bone mineral density (BMD) in peri- and early postmenopausal women living with HIV. This is a randomized international multicenter study of an early versus delayed (48-week) switch. BMD was measured by dual energy X-ray absorptiometry scan. Thirty-four women were enrolled: 19 in the immediate and 15 in the delayed switch arm from September 2017 to April 2019; 30 completed the 96-week protocol. The study closed for futility during the COVID-19 pandemic. The median (intraquartile range [IQR]) age was 51 years (47, 53), with a median (IQR) of 16.5 years (14, 23) since HIV diagnosis, median (IQR) 14 years (11, 20) of ART, and mean 8.6 years TDF. At enrollment, TDF was used in combination with a boosted protease inhibitor (n = 7), a non-nucleoside reverse transcriptase inhibitor (n = 13), an integrase inhibitor (n = 11), or more than one ART class (n = 3). The median (95% confidence interval [CI]) percentage change in BMD at the lumbar spine from 0 to 48 weeks in the immediate switch group was 1.97% (-1.15 to 5.49) compared with a median (95% CI) decrease of 2.32% (-5.11 to 0.19) in the delayed arm. The median (95% CI) percentage change in BMD from 0 to 96 weeks was 2.33% (0-4.51) in the immediate arm compared with 0.70% (-3.19 to 2.47) in the delayed arm. We demonstrated a trend to increased BMD at the lumbar spine after a switch from TDF to TAF in peri- and early postmenopausal women living with HIV. Clinical Trials.gov: NCT02815566.


Assuntos
Fármacos Anti-HIV , COVID-19 , Infecções por HIV , Humanos , Feminino , Pessoa de Meia-Idade , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Densidade Óssea , Fármacos Anti-HIV/efeitos adversos , Tenofovir/efeitos adversos , Pandemias , Perimenopausa , Adenina/farmacologia , Envelhecimento
18.
Cancers (Basel) ; 15(6)2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36980538

RESUMO

BACKGROUND AND AIMS: To address the overall survival (OS) and recurrence (RE) in people living with HIV (PLWH) treated with invasive therapy (IT) for hepatocellular carcinoma (HCC). METHODS: This is a retrospective cohort study on 41 PLWH with HCC receiving IT, defined as liver resection (LR), orthotopic liver transplantation (OLT), radiofrequency thermo-ablation (RFTA) trans arterial chemo, or radioembolization (CRE). OS and RE were investigated by Kaplan-Meier curves. The Cox proportional hazard regression model was used for multivariate analyses. RESULTS: Recurrence occurred in 46.3% PLWH; in 36.7% of participants at 2 years and in 52% at 5 years from HCC diagnosis; it was less frequent in males, p = 0.036. Overall, 2- and 5-year survival after HCC diagnosis was 72% and 48%, respectively. Two-and five-year survival was 100% and 90.9%, respectively, in PLWH receiving OLT, compared to other IT (60.9% and 30.6%, respectively) log-rank p = 0.0006. Two- and five-year survival in participants with no-RE was 70.5% and 54.6%, respectively, and 73.7% and 42.1% among RE, respectively, log-rank p = 0.7772. By multivariate analysis, AFP at values < 28.8 ng/mL, at HCC diagnosis, was the only factor predicting survival. CONCLUSIONS: Fifty percent of PLWH survived five years after HCC diagnosis; 90.9% among OLT patients. Recurrence after IT was observed in 46% of HCC/PLWH. AFP cut-off levels of 28.8 ng/mL were the only independent variable associated with survival.

19.
Nutrients ; 15(22)2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-38004121

RESUMO

Older individuals face an elevated risk of developing geriatric syndromes when confronted with acute stressors like COVID-19. We assessed the connection between in-hospital delirium, malnutrition, and frailty in a cohort of COVID-19 survivors. Patients aged ≥65, hospitalized in a tertiary hospital in Milan for SARS-CoV-2 pneumonia, were enrolled and screened for in-hospital delirium with the 4 'A's Test (4AT) performed twice daily (morning and evening) during hospital stay. Malnutrition was assessed with the malnutrition universal screening tool (MUST) at hospital admission and with the mini-nutritional assessment short-form (MNA-SF) one month after hospital discharge. Frailty was computed with the frailty index one month after hospital discharge. Fifty patients (median age 78.5, 56% male) were enrolled. At hospital admission, 10% were malnourished. The 13 patients (26%) who developed delirium were frailer (7 vs. 4), experienced a higher in-hospital mortality (5 vs. 3), and were more malnourished one month after discharge (3 of the 4 patients with delirium vs. 6 of the 28 patients without delirium who presented at follow up). The 4AT scores correlated with the MNA-SF scores (r = -0.55, p = 0.006) and frailty (r = 0.35, p = 0.001). Frailty also correlated with MUST (r = 0.3, p = 0.04), MNA-SF (r = -0.42, p = 0.02), and hospitalization length (r = 0.44, p = 0.001). Delirium, malnutrition, and frailty are correlated in COVID-19 survivors. Screening for these geriatric syndromes should be incorporated in routine clinical practice.


Assuntos
COVID-19 , Delírio , Fragilidade , Desnutrição , Humanos , Masculino , Idoso , Feminino , Estudos Prospectivos , COVID-19/complicações , SARS-CoV-2 , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Desnutrição/etiologia , Hospitalização , Avaliação Nutricional , Delírio/epidemiologia , Delírio/etiologia , Avaliação Geriátrica , Estado Nutricional
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