RESUMO
OBJECTIVE: Large inter-individual variability in the pharmacokinetics of rilpivirine and cabotegravir has been reported in the first weeks after starting long-acting injectable (LAI) therapy. Here, we assessed the distribution of rilpivirine and cabotegravir trough concentrations in people with HIV (PWH) on long-term LAI treatment. METHODS: Adult PWH treated with LAI for at least 32 weeks with an assessment of drug plasma trough concentrations were considered. The proportion of rilpivirine and cabotegravir plasma trough concentrations below four-times the protein-adjusted concentrations required for 90% inhibition of viral replication (4×PA-IC90) was estimated. RESULTS: Sixty-seven PWH were identified. LAI treatment duration was 216â±â80 weeks (range 32-320 weeks). Cabotegravir concentrations were associated with lower inter-individual variability compared with rilpivirine (45% versus 84%; Pâ<â0.05). No differences were found in rilpivirine (160â±â118 versus 189â±â81 ng/mL; Pâ=â0.430) and cabotegravir (1758â±â807 versus 1969â±â802 ng/mL; Pâ=â0.416) trough concentrations in males (nâ=â55) versus females (nâ=â12). A non-significant trend for lower cabotegravir concentrations was found in PWH with a body mass index >30 kg/m2 (nâ=â9) versus non-obese participants (1916â±â905 versus 1606â±â576 ng/mL; Pâ=â0.131). Three out of the 67 PWH had at least one drug concentration <4×PA-IC90: 100% of PWH had undetectable HIV viral load. CONCLUSIONS: At steady state, optimal systemic exposure of cabotegravir and rilpivirine was found in most PWH; cabotegravir trough concentrations were associated with lower inter-individual variability compared with rilpivirine. The study was not powered to assess the contribution of sex and/or body weight on LAI exposure due to the small number of females and obese PWH included.
Assuntos
Fármacos Anti-HIV , Dicetopiperazinas , Infecções por HIV , Piridonas , Rilpivirina , Humanos , Rilpivirina/farmacocinética , Rilpivirina/administração & dosagem , Rilpivirina/uso terapêutico , Rilpivirina/sangue , Masculino , Feminino , Infecções por HIV/tratamento farmacológico , Pessoa de Meia-Idade , Adulto , Piridonas/farmacocinética , Piridonas/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/uso terapêutico , Idoso , Injeções , Carga Viral/efeitos dos fármacosRESUMO
The association between human papillomavirus (HPV) and other sexually transmitted infections (STIs) in anal lesions still remains unclear. Aim of the study was to evaluate the prevalence of simultaneous infection of HPV and Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis in individuals screened for HPV anal infection. A total of 507 anal samples were tested for both anal HPV and STIs: 16% resulted positive for one or more non-HPV STIs. Specifically, C. trachomatis, M. genitalium, and N. gonorrhoeae were detected in 8%, 5%, and 4% of cases, respectively. Two groups were considered, including a positive STI group and a negative STI group. The prevalence of HPV was similar in patients in both groups: high risk (HR)-HPV and low risk (LR)-HPV were 67% and 53% versus 62% (p = 0.361) and 54% (p = 0.864) of patients, respectively. However, HPV 16, 18, 35, 51, 59, and 69 were significantly more frequent in patients tested positive for other STIs versus HPV infection alone (p < 0.05). No significant differences between the two groups were observed in vaccination coverage, 28% versus 32% (p = 0.463), and HIV status, 86% versus 84% (p = 0.658). The study shows that the overall HPV status is not directly correlated to other STIs in the investigated population, except for certain HPV types, including HR-HPV 16, reinforcing the urge for a greater vaccination coverage.
Assuntos
Coinfecção , Infecções por Papillomavirus , Infecções Sexualmente Transmissíveis , Humanos , Feminino , Prevalência , Adulto , Masculino , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Pessoa de Meia-Idade , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/virologia , Adulto Jovem , Coinfecção/epidemiologia , Coinfecção/virologia , Adolescente , Canal Anal/virologia , Canal Anal/microbiologia , Mycoplasma genitalium/isolamento & purificação , Papillomaviridae/isolamento & purificação , Papillomaviridae/genética , Papillomaviridae/classificação , Idoso , Chlamydia trachomatis/isolamento & purificação , Gonorreia/epidemiologia , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/microbiologia , Trichomonas vaginalis/isolamento & purificação , Infecções por Mycoplasma/epidemiologia , Neisseria gonorrhoeae/isolamento & purificaçãoRESUMO
Human papillomavirus (HPV) is the most common sexually transmitted infection, linked to several types of lesions. HPV, specifically HPV 16, accounts for most of anal cancer cases. In this study, we evaluated the proportion of samples tested positive for HPV and characterized genotypes distribution in anal specimens collected from individuals at risk of anal HPV infection attending from 2018 to 2022 a large Infectious Diseases Department in Italy. The presence of HPV DNA was investigated through a commercial kit detecting 12 HR-HPV, 8 probable/possible HR-HPV, and 8 LR-HPV genotypes. Among 1514 samples, 84% (1266/1514) resulted positive for any type of HPV. The prevalence of high-risk HPV types remained high during all the years of the study period, from 2018 to 2022, ranging from 65% to 73%. Most of HR-HPV, LR-HPV and HPV 16 positive samples were collected from men >45 years. HPV 16 was also the most frequent type in men and women. We did not observe significant variations between years in detection of HR-HPV, instead of LR-HPV, that significantly decreased. In conclusion, the high prevalence of oncogenic HPV genotypes underlines the necessity of clear anal HPV screening guidelines and, along with frequent HR-HPV coinfections, reinforces the urge to intensify the anti-HPV vaccination campaign.
Assuntos
Infecções por Papillomavirus , Masculino , Humanos , Feminino , Prevalência , Infecções por Papillomavirus/epidemiologia , Papillomavirus Humano 16 , Itália/epidemiologia , GenótipoRESUMO
OBJECTIVE: Preliminary evidence shows that concomitant administration of valproic acid can reduce the exposure to dolutegravir with limited clinical impacts. Here, we describe a male living with HIV who experienced a drastic reduction in dolutegravir trough concentrations a few weeks after starting valproic acid treatment as identified by therapeutic drug monitoring. Concomitantly, pharmacists recommended a supplementation of magnesium to improve insomnia. CASE REPORT: A 62-year-old man with HIV on antiretroviral therapy with dolutegravir and lamivudine recently added valproic acid to clonazepam and sertraline to treat severe sleep disturbances. An 84% reduction in dolutegravir trough concentrations was observed compared with the previous outpatient visit (418 versus 2714 ng/mL), with values close to the minimum effective drug concentration (300 ng/mL). Considering this, we strongly discourage the use of magnesium. CONCLUSIONS: We are confident that our findings can contribute to a better understanding of the clinical problems that infectious disease physicians encounter in their daily management of people with HIV and how therapeutic drug monitoring may add value in this context. This case also highlights the importance of multidisciplinary services for the optimal management of polypharmacy in people with HIV.
Assuntos
Interações Medicamentosas , Monitoramento de Medicamentos , Infecções por HIV , Compostos Heterocíclicos com 3 Anéis , Oxazinas , Piperazinas , Piridonas , Ácido Valproico , Humanos , Masculino , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Piridonas/uso terapêutico , Piridonas/farmacocinética , Piperazinas/uso terapêutico , Pessoa de Meia-Idade , Ácido Valproico/uso terapêutico , Infecções por HIV/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Inibidores de Integrase de HIV/uso terapêutico , Inibidores de Integrase de HIV/farmacocinética , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacocinéticaRESUMO
BACKGROUND: Carbamazepine (CBZ) is an antiseizure medication known to induce the expression of cytochrome P4503A metabolic enzymes. Here, we describe a man living with HIV who underwent several changes in the daily dose of CBZ, which resulted in different induction effects on darunavir trough concentrations. METHODS: A 59-year-old man with HIV, successfully undergoing maintenance antiretroviral treatment with darunavir/cobicistat once daily (combined with raltegravir), was prescribed CBZ for recurrent trigeminal neuralgia. Over subsequent months, the patient underwent various changes in the doses (from 200 to 800 mg/d) and trough concentrations (from 3.6 to 18.0 mg/L) of CBZ, guided by clinical response to trigeminal neuralgia. RESULTS: A highly significant inverse association was observed between darunavir trough concentration and both CBZ dose or trough concentration (coefficient of determination >0.75, P < 0.0001). Ultimately, the darunavir dose was increased to 600 mg twice daily with ritonavir and dolutegravir to ensure optimal antiretroviral coverage, anticipating potential further uptitration of CBZ doses. CONCLUSIONS: The impact of CBZ on boosted darunavir exposure seemed to be dose- and concentration-dependent. The management of such drug-drug interactions in daily practice was facilitated through therapeutic drug monitoring. This case underscores the importance of a multidisciplinary approach that incorporates both antiretroviral and nonantiretroviral comedications contributing to the optimal management of polypharmacy in individuals living with HIV.
Assuntos
Carbamazepina , Darunavir , Interações Medicamentosas , Infecções por HIV , Humanos , Darunavir/uso terapêutico , Darunavir/farmacocinética , Masculino , Pessoa de Meia-Idade , Carbamazepina/uso terapêutico , Carbamazepina/farmacocinética , Infecções por HIV/tratamento farmacológico , Neuralgia do Trigêmeo/tratamento farmacológico , Ritonavir/uso terapêutico , Ritonavir/administração & dosagem , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/administração & dosagem , Piridonas/farmacocinética , Piridonas/uso terapêutico , Piridonas/sangue , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Piperazinas/uso terapêutico , Piperazinas/farmacocinética , Oxazinas/uso terapêutico , Oxazinas/farmacocinética , Relação Dose-Resposta a Droga , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/administração & dosagem , Monitoramento de Medicamentos/métodosRESUMO
Thromboprophylaxis/anticoagulation treatment is often required in hospitalized COVID-19 patients. We aimed to estimate the prevalence of major bleeding events in hospitalized COVID-19 patients. This was a retrospective observational study including all COVID-19 hospitalized patients ≥18 years of age at one reference center in northern Italy. The crude prevalence (between February 2020-2022) of major bleeding events was estimated as the number of major bleeding episodes divided by patients at risk. Uni- and multivariable Cox models were built to assess factors potentially associated with major bleeding events. Twenty-nine (0.98%) out of 2,945 COVID-19 patients experienced a major bleeding event [prevalence of 0.55% (95%CI 0.37-0.79)], of which five were fatal. Patients who experienced a major bleeding event were older [78 years (72-84 IQR) vs. 67 years (55-78 IQR), p-value < 0.001] and more frequently exposed to anti-aggregating therapy (44.8% vs. 20.0%, p-value 0.002) when compared to those who did not. In the multivariable Cox model, age [per 1 year more AHR 1.05 (CI95% 1.02-1.09)] was independently associated with an increased risk of major bleeding events. A strict monitoring of older hospitalized COVID-19 patients is warranted due to the risk of major bleeding events.
Assuntos
COVID-19 , Hemorragia , Hospitalização , Humanos , COVID-19/complicações , Estudos Retrospectivos , Idoso , Masculino , Feminino , Hemorragia/epidemiologia , Hemorragia/etiologia , Itália/epidemiologia , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , Fatores de Risco , Prevalência , SARS-CoV-2 , Fatores Etários , Modelos de Riscos ProporcionaisRESUMO
In 2022, many monkeypox (MPX) outbreaks have been documented in countries where MPX was not endemic. It spread all around the world, especially in European Union and United States. While MPX is classically considered to be transmitted through close contact with lesions, the hypothesis of sexual transmission has been proposed. This study considered a total of 49 patients suspected for MPX that were also tested for other sexually transmitted infections (STIs), including Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis. The data from coinfected patients suggested that MPXV and STIs might share the same route of inoculum, corroborating the hypothesis of possible sexual transmission for the emerging poxvirus. And like any other STI, MPX should be considered without stigmatization.
Assuntos
Infecções por Chlamydia , Gonorreia , Mpox , Saúde Sexual , Infecções Sexualmente Transmissíveis , Humanos , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Mpox/diagnóstico , Mpox/epidemiologia , Infecções por Chlamydia/epidemiologia , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Chlamydia trachomatis , Neisseria gonorrhoeae , PrevalênciaRESUMO
Real-life comparisons of dolutegravir/rilpivirine (DTG/RPV) and DTG/lamivudine (3TC) regimens in people living with human immunodeficiency virus (PLWHIV) who switched from a standard three-drug regimen based on nonnucleoside reverse transcriptase inhibitors (NNRTIs) are missing. This study aimed to compare DTG/3TC and DTG/RPV in virologically suppressed patients (HIV-RNA < 50 copies/mL) coming from any NNRTI-based regimen in terms of discontinuation due to virologic failure (VF) discontinuation rates due to all causes, and adverse events. As a secondary outcome, we evaluated the difference in creatinine, total cholesterol, CD4, and triglycerides from baseline to weeks 48 after the switch. Of the 415 PLWHs included in the study, 278 (66.9%) switched to DTG/3TC, and 137 (33.1%) switched to DTG/RPV. Overall, 48 PLWHs (11.6%) discontinued the treatment:38 with DTG/3TC and 10 with DTG/RPV with similar discontinuation rates: 5.01 × 100 py (95% confidence interval [CI] 3.64-6.94) and 4.66 × 100 py (95% CI 2.51-8.67), respectively. The most common reason for discontinuation was toxicity (26 patients, 22/278 [7.9%] in the DTG/3TC group and 4/137 [2.9%] in the DTG/RPV group), mainly neurologic toxicity (never above grade 2). We found no differences in discontinuation rates due to treatment adverse events. Two study participants experienced virological failure in the DTG/3TC arm. We observed no significant difference in CD4 cell counts, lipid parameters, or renal function between the two groups at 48 weeks. This study demonstrated that, in clinical practice, a two-drug regimen with DTG/3TC or DTG/RPV is characterized by a low discontinuation rate and VF in virologically suppressed PLWHs switched from an NNRTI-based three antiretroviral drugs regimen.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Lamivudina/efeitos adversos , Inibidores da Transcriptase Reversa/efeitos adversos , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Estudos Retrospectivos , Rilpivirina/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/efeitos adversosRESUMO
OBJECTIVES AND DESIGN: Using pol sequences obtained for routine resistance testing, we characterised the molecular patterns of HIV-1 transmission and factors associated with being part of a transmission cluster among individuals who in 2008-2014 presented with primary HIV-1 infection (PHI) at 11 urban centres across Italy. METHODS: Pol sequences were obtained by Sanger sequencing. Transmission clusters were identified by phylogenetic analysis (maximum likelihood method, confirmed by Bayesian analysis). Multivariable logistic regression explored factors associated with a participant being part of a transmission cluster. RESULTS: The PHI cohort comprised 186 participants (159/186, 85.5% males) with median age 44 years, median CD4 count 464 cells/mm3 and median plasma HIV-1 RNA 5.6 log10 copies/mL. Drug resistance associated mutations were found in 16/186 (8.6%). A diversity of non-B subtypes accounted for 60/186 (32.3%) of all infections. A total of 17 transmission clusters were identified, including 44/186 (23.7%) participants. Each cluster comprised 2-6 sequences. Non-B subtypes accounted for seven clusters and 22/44 (50%) of clustered sequences. In multivariable logistic regression analysis, factors associated with being part of a transmission cluster comprised harbouring a non-B subtype (adjusted OR (adjOR) 2.28; 95% CI 1.03 to 5.05; p=0.04) and showing a lower plasma HIV-1 RNA (adjOR 0.80, 95% CI 0.64 to 0.99; p=0.04). CONCLUSIONS: There was a large contribution of diverse non-B subtypes to transmission clusters among people presenting with acute or recent HIV-1 infection in this cohort, illustrating the evolving dynamics of the HIV-1 epidemic in Italy, where subtype B previously dominated.
Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Masculino , Humanos , Adulto , Feminino , HIV-1/genética , Filogenia , Teorema de Bayes , Infecções por HIV/epidemiologia , Itália/epidemiologia , RNA , Genótipo , Epidemiologia Molecular , Análise por ConglomeradosRESUMO
PURPOSE: This multicenter observational study was done to evaluate risk factors related to the development of BSI in patients admitted to ICU for COVID-19. METHODS: All patients with COVID-19 admitted in two COVID-19 dedicated ICUs in two different hospital between 02-2020 and 02-2021 were recruited. RESULT: 537 patients were included of whom 265 (49.3%) experienced at least one BSI. Patients who developed bacteremia had a higher SOFA score [10 (8-12) vs 9 (7-10), p < 0.001], had been intubated more frequently [95.8% vs 75%, p < 0.001] and for a median longer time [16 days (9-25) vs 8 days (5-14), p < 0.001]. Patients with BSI had a median longer ICU stay [18 days (12-31.5) vs 9 days (5-15), p < 0.001] and higher mortality [54% vs 42.3%, p < 0.001] than those who did not develop it. Development of BSI resulted in a higher SOFA score [aHR 1.08 (95% CI 1.03-1.12)] and a higher Charlson score [csAHR 1.15 (95% CI 1.05-1.25)]. CONCLUSION: A high SOFA score and a high Charlson score resulted associated with BSI's development. Conversely, immunosuppressive therapy like steroids and tocilizumab, has no role in increasing the risk of bacteremia.
Assuntos
Bacteriemia , COVID-19 , Humanos , Estudos de Coortes , COVID-19/complicações , COVID-19/epidemiologia , Bacteriemia/epidemiologia , Unidades de Terapia Intensiva , Fatores de Risco , Estudos RetrospectivosRESUMO
BACKGROUND: The aim of this study was to investigate whether switching from a ritonavir-boosted PI-based regimen to a dolutegravir-based regimen improved the atherogenic properties of LDL particles in patients with HIV. METHODS: This was a substudy of the NEAT022 study (ClinicalTrials.gov NCT02098837). Adults with HIV with a Framingham score >10% or aged >50â years and being treated with a stable boosted PI-based regimen were randomized to either switch to dolutegravir or continue with boosted PI. At baseline and Week 48, we assessed atherogenic LDL properties: LDL particle size and phenotype (A, intermediate, B), oxidized LDL (ox-LDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity. RESULTS: Eighty-six participants (dolutegravir 44; PI 42) were included. Participants had a median (IQR) age of 54 (51-57) years and 79.1% were male. In the dolutegravir arm, after 48â weeks, we observed: (1) an increase in LDL size [median 1.65â Å (IQR -0.60 to 4.20); Pâ=â0.007], correlated with the decrease in triglyceride concentration [Spearman correlationâ=â-0.352 (Pâ=â0.001)], with a corresponding decrease of subjects with atherogenic LDL phenotype B (36.4% to 20.5%; Pâ=â0.039); (2) a decrease in Lp-PLA2 activity [median 1.39â µmol/min/mL (IQR -2.3 to 0.54); Pâ=â0.002]; and (3) a decrease in ox-LDL [median 14â U/L (IQR -102 to 13); Pâ=â0.006]. In the PI arm, none of these favourable lipid modifications was observed. CONCLUSIONS: Forty-eight weeks after switching from a PI-based to a dolutegravir-based regimen, patients with Framingham score >10% or aged >50â years showed improvement of several atherogenic lipid features, including LDL particle phenotype, ox-LDL and Lp-PLA2.
Assuntos
Fármacos Anti-HIV , Aterosclerose , Infecções por HIV , Lipoproteínas LDL , 1-Alquil-2-acetilglicerofosfocolina Esterase/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis , Humanos , Lipoproteínas LDL/metabolismo , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Inibidores de Proteases/uso terapêutico , PiridonasRESUMO
BACKGROUND: To compare differences in the probability of COVID-19-related death between native Italians and immigrants hospitalised with COVID-19. METHODS: This retrospective study of prospectively collected data was conducted at the ASST Fatebenefratelli-Sacco Hospital in Milan, Italy, between 21 February and 31 November 2020. Uni- and multivariable Cox proportional hazard models were used to assess the impact of the patients' origin on the probability of COVID-19-related death. RESULTS: The study population consisted of 1,179 COVID-19 patients: 921 Italians (78.1%) and 258 immigrants (21.9%) who came from Latin America (99, 38%), Asia (72, 28%), Africa (50, 19%) and central/eastern Europe (37, 14%). The Italians were significantly older than the immigrants (median age 70 years, interquartile range (IQR) 58-79 vs 51 years, IQR 41-60; p < 0.001), and more frequently had one or more co-morbidities (79.1% vs 53.9%; p < 0.001). Mortality was significantly greater among the Italians than the immigrants as a whole (26.6% vs 12.8%; p < 0.001), and significantly greater among the immigrants from Latin America than among those from Asia, Africa or central/eastern Europe (21% vs 8%, 6% and 8%; p = 0.016). Univariable analysis showed that the risk of COVID-19-related death was lower among the immigrants (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.30-0.63; p < 0.0001], but the risk of Latin American immigrants did not significantly differ from that of the Italians (HR 0.74, 95% CI 0.47-1.15; p = 0.183). However, after adjusting for potential confounders, multivariable analysis showed that there was no difference in the risk of death between the immigrants and the Italians (adjusted HR [aHR] 1.04, 95% CI 0.70-1.55; p = 0.831), but being of Latin American origin was independently associated with an increased risk of death (aHR 1.95, 95% CI 1.17-3.23; p = 0.010). CONCLUSIONS: Mortality was lower among the immigrants hospitalised with COVID-19 than among their Italian counterparts, but this difference disappeared after adjusting for confounders. However, the increased risk of death among immigrants of Latin American origin suggests that COVID-19 information and prevention initiatives need to be strengthened in this sub-population.
Assuntos
COVID-19 , Emigrantes e Imigrantes , Idoso , Hospitais , Humanos , Itália/epidemiologia , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , SARS-CoV-2RESUMO
Anal and urethral samples from confirmed cases of monkeypox were screened for monkeypox virus (MPXV) by real-time PCR. Isolation of the virus was subsequently attempted in cell culture. Actively-replicating virus was demonstrated in 13 of 18 and 11 of 15 PCR-positive anal and urethral swabs, respectively, collected within 7 days from symptoms onset. Two asymptomatic secondary cases had detectable MPXV genetic material in urethral secretion and for one, MPXV was successfully isolated, supporting a potential MPXV sexual transmission hypothesis.
Assuntos
Líquidos Corporais , Mpox , Animais , Humanos , Mpox/diagnóstico , Monkeypox virus , Técnicas de Amplificação de Ácido Nucleico , Reação em Cadeia da PolimeraseRESUMO
BackgroundAdequate identification and testing of people at risk for HIV is fundamental for the HIV care continuum. A key strategy to improve timely testing is HIV indicator condition (IC) guided testing.AimTo evaluate the uptake of HIV testing recommendations in HIV IC-specific guidelines in European countries.MethodsBetween 2019 and 2021, European HIV experts reviewed guideline databases to identify all national guidelines of 62 HIV ICs. The proportion of HIV IC guidelines recommending HIV testing was reported, stratified by subgroup (HIV IC, country, eastern/western Europe, achievement of 90-90-90 goals and medical specialty).ResultsOf 30 invited European countries, 15 participated. A total of 791 HIV IC guidelines were identified: median 47 (IQR: 38-68) per country. Association with HIV was reported in 69% (545/791) of the guidelines, and 46% (366/791) recommended HIV testing, while 42% (101/242) of the AIDS-defining conditions recommended HIV testing. HIV testing recommendations were observed more frequently in guidelines in eastern (53%) than western (42%) European countries and in countries yet to achieve the 90-90-90 goals (52%) compared to those that had (38%). The medical specialties internal medicine, neurology/neurosurgery, ophthalmology, pulmonology and gynaecology/obstetrics had an HIV testing recommendation uptake below the 46% average. None of the 62 HIV ICs, countries or medical specialties had 100% accurate testing recommendation coverage in all their available HIV IC guidelines.ConclusionFewer than half the HIV IC guidelines recommended HIV testing. This signals an insufficient adoption of this recommendation in non-HIV specialty guidelines across Europe.
Assuntos
Infecções por HIV , Medicina , Feminino , Gravidez , Humanos , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Europa (Continente)/epidemiologia , Europa Oriental , Teste de HIVRESUMO
Diagnosis and management of infectious diseases (ID) at the emergency department (ED) are challenging due to the peculiar setting and the available diagnostic tools. The involvement of an ID consultant has been described to improve clinical outcomes and antimicrobial stewardship (AMS) programs. An online survey was sent to 100 Italian Departments of Infectious Diseases affiliated with the Italian Society of Infectious Diseases and Tropical Medicine (SIMIT). The primary objective of our study was to describe the characteristics of ID services in Italian EDs to identify possible challenges and shortcomings and provide tips to improve the management of patients. Secondary objectives included the evaluation of diagnostic capability and the management of patients with suspected or confirmed ID. Seventy-six out of the 100 SIMIT centers, 32 (42.1%) of which were teaching hospitals, answered the survey. In 62 (82.7%) centers, consultations were performed by the IDs specialist on call. In 29 (38.2%) centers, there was a formal AMS program, and 32 (42.7%) had protocols for antibiotic use in the ED. Microbiological tests to be performed before starting antibiotic treatment in the ED were clearly defined in 44 (57.9%) hospitals. This survey highlighted several challenges in the current organization of ID consultations in Italian EDs.
Assuntos
Doenças Transmissíveis , Humanos , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/epidemiologia , Serviço Hospitalar de Emergência , Antibacterianos/uso terapêutico , Encaminhamento e Consulta , Itália/epidemiologia , Hospitais de EnsinoRESUMO
OBJECTIVES: We aimed to assess the frequency of ICU-acquired bloodstream infections in coronavirus disease 2019 patients. DESIGN: Retrospective observational study. SETTING: The emergency expansion of an ICU from eight general beds to 30 coronavirus disease 2019 beds. PARTICIPANTS: Patients with coronavirus disease 2019 admitted to the ICU of Luigi Sacco Hospital (Milan, Italy) for greater than or equal to 48 hours between February 21, 2020, and April 30, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The frequency of bloodstream infections per 1,000 days of ICU stay was calculated in 89 coronavirus disease 2019 patients, and the cumulative probability of bloodstream infection was estimated using death and ICU discharge as competing events. Sixty patients (67.4%) experienced at least one of the 93 recorded episodes of bloodstream infection, a frequency of 87 per 1,000 days of ICU stay (95% CI, 67-112).The patients who experienced a bloodstream infection had a higher Sequential Organ Failure Assessment score upon ICU admission (9.5; interquartile range, 8-12 vs 8, interquartile range, 5-10; p = 0.042), a longer median ICU stay (15 d; interquartile range, 11-23 vs 8, interquartile range, 5-12; p < 0.001), and more frequently required invasive mechanical ventilation (98.3% vs 82.8%; p = 0.013) than those who did not. The median time from ICU admission to the first bloodstream infection episode was 10 days. Gram-positive bacteria accounted for 74 episodes (79.6%), with Enterococcus species being the most prevalent (53 episodes, 55.8%). Thirty-two isolates (27.3%) showed multidrug resistance. CONCLUSIONS: Coronavirus disease 2019 seemed to increase the frequency of bloodstream infections (particularly Enterococcus-related bloodstream infection) after ICU admission. This may have been due to enteric involvement in patients with severe coronavirus disease 2019 and/or limitations in controlling the patient-to-patient transmission of infectious agents in extremely challenging circumstances.
Assuntos
COVID-19/microbiologia , Enterococcus/isolamento & purificação , Infecções por Bactérias Gram-Positivas/microbiologia , Tempo de Internação/estatística & dados numéricos , Sepse/microbiologia , Adulto , Idoso , COVID-19/epidemiologia , Estado Terminal , Feminino , Infecções por Bactérias Gram-Positivas/epidemiologia , Humanos , Unidades de Terapia Intensiva , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sepse/epidemiologia , Resultado do TratamentoRESUMO
Biological sex could affect the natural history of severe acute respiratory syndrome coronavirus 2 infection. We enrolled all COVID-19 patients admitted to two COVID-19 hospitals in Milan in a prospective observational study. The primary outcome was death during the study period and the secondary outcome was critical disease at hospital admission. The association(s) between clinically relevant, noncollinear variables, and the primary outcome was assessed with uni- and multivariable Logistic regression models. A total of 520 patients were hospitalized of whom 349 (67%) were males with a median age 61 (interquartile range: 50-72). A higher proportion of males presented critically ill when compared to females (30.1% vs. 18.7%, p < .046). Death occurred in 86 (24.6%) males and 27 (15.8%) females (p = .024). In multivariable analysis age (per 10 years more) (adjusted odds ratio [AOR]: 1.83 [95% confidence interval {CI}: 1.42-2.35], p < .0001), obesity (AOR: 2.17 [95% CI: 1.10-4.31], p = .026), critical disease at hospital admission (AOR 6.34 [95% CI: 3.50-11.48], p < .0001) were independently associated to higher odds of death whereas gender was not. In conclusion, a higher proportion of males presented critically ill at hospital admission. Age, critical disease at hospital admission, obesity, anemia, D-dimer, estimated glomerular filtration rate, lactate dehydrogenase, and creatine kinase predicted death in hospitalized COVID-19 patients.
Assuntos
COVID-19/mortalidade , Estado Terminal/epidemiologia , Razão de Masculinidade , Fatores Etários , Idoso , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2 , Fatores SexuaisRESUMO
As it has been shown that lopinavir (LPV) and hydroxychloroquine (HCQ) have in vitro activity against coronaviruses, they were used to treat COVID-19 during the first wave of the epidemic in Lombardy, Italy. To compare the rate of clinical improvement between those who started LPV/ritonavir (LPV/r)+HCQ within 5 days of symptom onset (early treatment, ET) and those who started later (delayed treatment, DT). This was a retrospective intent-to-treat analysis of the hospitalized patients who started LPV/r + HCQ between 21 February and 20 March 2020. The association between the timing of treatment and the probability of 30-day mortality was assessed using univariable and multivariable logistic models. The study involved 172 patients: 43 (25%) in the ET and 129 (75%) in the DT group. The rate of clinical improvement increased over time to 73.3% on day 30, without any significant difference between the two groups (Gray's test P = .213). After adjusting for potentially relevant clinical variables, there was no significant association between the timing of the start of treatment and the probability of 30-day mortality (adjusted odds ratio [aOR] ET vs DT = 1.45, 95% confidence interval 0.50-4.19). Eight percent of the patients discontinued the treatment becausebecause of severe gastrointestinal disorders attributable to LPV/r. The timing of the start of LPV/r + HCQ treatment does not seem to affect the clinical course of hospitalized patients with COVID-19. Together with the severe adverse events attributable to LPV/r, this raises concerns about the benefit of using this combination to treat COVID-19.
Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Hidroxicloroquina/uso terapêutico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Idoso , Combinação de Medicamentos , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: We aimed to assess the overall cardiovascular and metabolic effect of the switch to three different single tablet regimens (STRs) [tenofovir alafenamide/emtricitabine/rilpivirine (TAF/FTC/RPV), TAF/FTC/elvitegravir/cobi (TAF/FTC/EVG/cobi) and ABC/lamivudine/dolutegravir (ABC/3TC/DTG)] in a cohort of people living with HIV/AIDS (PLWH) under effective ART. METHODS: All PLWH aged above 18 years on antiretroviral treatment with an HIV-RNA < 50 cp/mL at the time of the switch to TAF/FTC/RPV, TAF/FTC/EVG/cobi and ABC/3TC/DTG were retrospectively included in the analysis. Framingham risk score modification after 12 months from the switch such as lipid profile and body weight modification were assessed. The change from baseline to 12 months in mean cardiovascular risk and body weight in each of the STR's group were assessed by means of Wilcoxon signed-rank test whereas a mixed regression model was used to assess variation in lipid levels. RESULTS: Five-hundred and sixty PLWH were switched to an STR regimen of whom 170 (30.4%) to TAF/FTC/EVG/cobi, 191 (34.1%) to TAF/FTC/RPV and 199 (35.5%) to ABC/3TC/DTG. No difference in the Framingham cardiovascular risk score was observed after 12 months from the switch in each of the STR's groups. No significant overtime variation in mean total cholesterol levels from baseline to 12 months was observed for PLWH switched to ABC/3TC/DTG [200 (SD 38) mg/dl vs 201 (SD 35) mg/dl; p = 0.610] whereas a significant increment was observed in PLWH switched to TAF/FTC/EVG/cobi [192 (SD 34) mg/dl vs 208 (SD 40) mg/dl; p < 0.0001] and TAF/FTC/RPV [187 (SD 34) mg/dl vs 195 (SD 35) mg/dl; p = 0.027]. In addition, a significant variation in the mean body weight from baseline to 12 months was observed in PLWH switched to TAF/FTC/EVG/cobi [72.2 (SD 13.5) kilograms vs 74.6 (SD 14.3) kilograms; p < 0.0001] and TAF/FTC/RPV [73.4 (SD 11.6) kilograms vs 75.6 (SD 11.8) kilograms; p < 0.0001] whereas no difference was observed in those switched to ABC/3TC/DTG [71.5 (SD 12.8) kilograms vs 72.1 (SD 12.6) kilograms; p = 0.478]. CONCLUSION: No difference in the cardiovascular risk after 1 year from the switch to these STRs were observed. PLWH switched to TAF/FTC/EVG/cobi and TAF/FTC/RPV showed an increase in total cholesterol levels and body weight 12 months after the switch.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Combinação Emtricitabina, Rilpivirina e Tenofovir/uso terapêutico , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Lamivudina/uso terapêutico , Oxazinas/uso terapêutico , Piperazinas/uso terapêutico , Piridonas/uso terapêutico , Adulto , Fármacos Anti-HIV/metabolismo , Peso Corporal/efeitos dos fármacos , Estudos de Coortes , Didesoxinucleosídeos/metabolismo , Combinação de Medicamentos , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/metabolismo , Combinação Emtricitabina, Rilpivirina e Tenofovir/metabolismo , Feminino , Fatores de Risco de Doenças Cardíacas , Compostos Heterocíclicos com 3 Anéis/metabolismo , Humanos , Itália/epidemiologia , Lamivudina/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Oxazinas/metabolismo , Piperazinas/metabolismo , Piridonas/metabolismo , Estudos Retrospectivos , Comprimidos/uso terapêuticoRESUMO
BACKGROUND: Confirmed COVID-19 cases have been registered in more than 200 countries, and as of July 28, 2020, over 16 million cases have been reported to the World Health Organization. This study was conducted during the epidemic peak of COVID-19 in Italy. The early identification of individuals with suspected COVID-19 is critical in immediately quarantining such individuals. Although surveys are widely used for identifying COVID-19 cases, outcomes, and associated risks, no validated epidemiological tool exists for surveying SARS-CoV-2 infection in the general population. OBJECTIVE: We evaluated the capability of self-reported symptoms in discriminating COVID-19 to identify individuals who need to undergo instrumental measurements. We defined and validated a method for identifying a cutoff score. METHODS: Our study is phase II of the EPICOVID19 Italian national survey, which launched in April 2020 and included a convenience sample of 201,121 adults who completed the EPICOVID19 questionnaire. The Phase II questionnaire, which focused on the results of nasopharyngeal swab (NPS) and serological tests, was mailed to all subjects who previously underwent NPS tests. RESULTS: Of 2703 subjects who completed the Phase II questionnaire, 694 (25.7%) were NPS positive. Of the 472 subjects who underwent the immunoglobulin G (IgG) test and 421 who underwent the immunoglobulin M test, 22.9% (108/472) and 11.6% (49/421) tested positive, respectively. Compared to NPS-negative subjects, NPS-positive subjects had a higher incidence of fever (421/694, 60.7% vs 391/2009, 19.5%; P<.001), loss of taste and smell (365/694, 52.6% vs 239/2009, 11.9%; P<.001), and cough (352/694, 50.7% vs 580/2009, 28.9%; P<.001). With regard to subjects who underwent serological tests, IgG-positive subjects had a higher incidence of fever (65/108, 60.2% vs 43/364, 11.8%; P<.001) and pain in muscles/bones/joints (73/108, 67.6% vs 71/364, 19.5%; P<.001) than IgG-negative subjects. An analysis of self-reported COVID-19 symptom items revealed a 1-factor solution, the EPICOVID19 diagnostic scale. The following optimal scores were identified: 1.03 for respiratory problems, 1.07 for chest pain, 0.97 for loss of taste and smell 0.97, and 1.05 for tachycardia (ie, heart palpitations). These were the most important symptoms. For adults aged 18-84 years, the cutoff score was 2.56 (sensitivity: 76.56%; specificity: 68.24%) for NPS-positive subjects and 2.59 (sensitivity: 80.37%; specificity: 80.17%) for IgG-positive subjects. For subjects aged ≥60 years, the cutoff score was 1.28, and accuracy based on the presence of IgG antibodies improved (sensitivity: 88.00%; specificity: 89.58%). CONCLUSIONS: We developed a short diagnostic scale to detect subjects with symptoms that were potentially associated with COVID-19 from a wide population. Our results support the potential of self-reported symptoms in identifying individuals who require immediate clinical evaluations. Although these results come from the Italian pandemic period, this short diagnostic scale could be optimized and tested as a screening tool for future similar pandemics.