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OBJECTIVE: To evaluate the prevalence and characteristics of concurrent bacterial sexually transmitted infections (bSTIs) among individuals with mpox. DESIGN: Prospective cohort study of participants aged 18âyears or older with confirmed mpox conducted in Rio de Janeiro, Brazil. This cross-sectional analysis include only participants who underwent bSTI testing at baseline between June 2022 and January 2024. METHODS: Participants were offered testing for chlamydia/gonorrhea (NAAT, anorectal swabs) and syphilis (active diagnosis if VDRL ≥ 1/8). Baseline prevalence of bSTIs was calculated, and participant characteristics were described based on bSTI diagnosis (yes/no). Chi-squared/Fisher's tests were used for qualitative variables, and the Wilcoxon rank-sum test for quantitative variables. RESULTS: Out of 634 enrolled participants, 538 (84.9%) were tested for STIs and included in this analysis, mostly cisgender men, aged 30-39âyears with post-secondary education. Overall prevalence of concurrent bSTI was 37.3%, mainly syphilis, followed by chlamydia and gonorrhea. Half of the participants had HIV coinfection, and one-third were on PrEP. Concurrent bSTI diagnosis at the time of mpox assessment was associated with being aged 30-39âyears, self-identifying as cisgender men, having HIV-positive status, reporting proctitis symptoms and reporting any STI in the past 12âmonths. CONCLUSIONS: Our data reveals a notable prevalence of concurrent STIs among participants with confirmed mpox at a prominent infectious diseases' referral center in Rio de Janeiro, Brazil. These findings underscore the importance of integrating mpox into the differential diagnosis of anogenital manifestations and to promote combination prevention strategies within sexual health care services.
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OBJECTIVES: This study aimed to analyze characteristics of mpox hospitalization in a Brazilian cohort, further exploring the impact of HIV on mpox-related outcomes and hospitalization. DESIGN: We conducted a descriptive analysis, comparing characteristics of individuals diagnosed with mpox according to hospitalization and HIV status, and described the mpox cases among those living with HIV. METHODS: This was a single-center, prospective cohort study conducted at a major infectious diseases referral center in Rio de Janeiro, Brazil, that enrolled participants older than 18âyears of age diagnosed with mpox. Information was collected on standardized forms, including data on sociodemographic, behavioral, clinical and laboratory characteristics. For comparisons, we used chi-squared, Fisher's exact and the Moods median tests whenever appropriate. RESULTS: From June to December, 2022, we enrolled 418 individuals diagnosed with mpox, of whom 52% were people with HIV (PWH). PWH presented more frequently with fever, anogenital lesions and proctitis. The overall hospitalization rate was 10.5% ( n â=â43), especially for pain control. Among hospitalized participants, PWH had more proctitis and required invasive support. Mpox severity was related to poor HIV continuum of care outcomes and low CD4 + cell counts. All deaths ( n â=â2) occurred in PWH with CD4 + less than 50âcells/µl. CONCLUSION: HIV-related immunosuppression likely impacts mpox clinical outcomes. This is of special concern in settings of poor adherence and late presentation to care related to socioeconomic inequalities, such as Brazil. The HIV continuum of care must be taken into account when responding to the mpox outbreak.
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Infecções por HIV , Mpox , Proctite , Humanos , Brasil/epidemiologia , Estudos Prospectivos , Infecções por HIV/complicações , Terapia de Imunossupressão , HospitalizaçãoRESUMO
The role of liver stiffness measurement (LSM) after sustained virological response (SVR) in HCV patients treated by direct-acting antivirals (DAAs) remains unclear. We aimed to evaluate LSM regression value after SVR and to identify risk factors associated with liver related complications (LRC) or death. This retrospective study analyzed patients with LSM ≥ 10 kPa with LSM by transient elastography pre-DAAs and post-SVR. Patients with previous hepatic decompensation were excluded. Medical records were reviewed to identify primary outcomes. Kaplan-Meier curves and time-to-event Cox proportional-hazard models were performed. 456 patients [65% female, 62 years (IQR 57-68)] were included. During a follow-up of 2.3 years (IQR 1.6-2.7), 28 patients developed 37 outcomes [rate = 29.0 (95% CI 20.0-42.0) per 1000 person-years]. The cumulative incidence of outcomes was significantly lower in patients who regressed LSM ≥ 20% [3.4% (95% CI 1.8-7.0) vs. 9.0% (5.5-14.5), p = 0.028]. In a multivariate Cox-model [HR(95% CI)], male gender [HR = 3.00 (1.30-6.95), p = 0.010], baseline albumin < 3.5 mg/dL [HR = 4.49 (1.95-10.34), p < 0.001] and baseline unfavorable Baveno-VI [HR = 4.72 (1.32-16.83), p = 0.017] were independently associated and LSM regression ≥ 20% after SVR had a trend to reduce the risk of LRC or death [HR = 0.45 (0.21-1.02), p = 0.058]. The use of simple parameters before DAAs and repetition of LSM post-SVR can identify patients with different risks for severe outcome after HCV eradication.
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Hepatite C Crônica/complicações , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Antivirais/uso terapêutico , Coinfecção , Técnicas de Imagem por Elasticidade , Feminino , Genótipo , Hepacivirus/genética , Hepatite B/complicações , Hepatite B/virologia , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Incidência , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Masculino , Avaliação de Resultados da Assistência ao Paciente , Estudos Retrospectivos , Fatores de Risco , Resposta Viral Sustentada , Resultado do TratamentoRESUMO
Cryptococcal meningitis is a several disease common in late stage of HIV infection. Detection of cryptococcal antigen (CrAg) is an important for early diagnosis of this invasive mycosis. The pre-emptive treatment for isolated antigenemia prevents the onset of meningoencephalitis. Screening CrAg in patients with low CD4 count is cost-effective in countries with prevalence of antigenemia above 3%. However, in Brazil, the number of prevalence studies on cryptococcosis and HIV is insufficient. The objective of this study is to estimate the prevalence of CrAg and describe clinical characteristics from a cohort of patients followed at a reference center in Brazil. CrAg screening was performed in 89 inpatients with CD4 count ≤200 cells/mm3 or WHO stage III/IV from the National Institute of Infecttious Disease, Rio de Janeiro. Patients with isolated antigenemia received pre-emptive therapy with fluconazole and patients with meningoencephalitis were treated with Amphotericin B. Individuals were followed up for 12 months. Prevalence of serum CrAg was 11.23%, cryptococcal meningoencephalitis 6.74% and isolated antigenemia 4.81%. None of the patients with isolated antigenemia developed meningoencephalitis during the follow up. Signs and symptoms of meningoencephalitis were unspecific or absent. Our study suggests the need of CrAg screening in Brazil and highlights that lumbar puncture is mandatory in all individuals CrAg positive to exclude asymptomatic meningoencephalitis.
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Criptococose/complicações , Infecções por HIV/complicações , Adulto , Antígenos de Fungos/sangue , Brasil/epidemiologia , Criptococose/epidemiologia , Criptococose/imunologia , Criptococose/mortalidade , Cryptococcus/imunologia , Feminino , Seguimentos , Humanos , Masculino , Meningite Criptocócica/líquido cefalorraquidiano , Meningite Criptocócica/complicações , Meningite Criptocócica/epidemiologia , Meningite Criptocócica/imunologia , Pessoa de Meia-Idade , Prevalência , Tuberculose/complicações , Tuberculose/mortalidadeRESUMO
In Brazil, hepatitis C treatment has been evolving significantly with the licensing of direct-acting antivirals (DAAs). However, viral determinants (amino acid substitutions in hepatitis C virus (HCV) genome and infective genotype) associated with host factors (hepatic condition and prior HCV therapy) might limit the achievement of sustained virologic response (SVR). Here, we described two case reports in which the occurrence of HCV NS5A mutations A30K (subtype 3a) and Y93N (subtype 1a) might have influenced daclatasvir (DCV)/sofosbuvir (SOF) combined therapy non-response. Despite high response rates for DAA combined therapies in Brazil, these case reports stated the importance of an investigation about how to manage a DAA treatment failure since a combination of factors, especially the occurrence of resistance substitutions, could impact a rescue therapy with new available antivirals in clinical routine.
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Farmacorresistência Viral/genética , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Proteínas não Estruturais Virais/genética , Idoso , Antivirais/farmacologia , Carbamatos , Feminino , Humanos , Imidazóis/farmacologia , Masculino , Mutação , Pirrolidinas , Sofosbuvir/farmacologia , Falha de Tratamento , Valina/análogos & derivadosRESUMO
The selection of viral strains with resistance-associated substitutions at hepatitis C virus (HCV) NS5A and NS5B genes is considered one of the limiting factors for achieving sustained virologic response (SVR) to combination of direct-acting antivirals daclatasvir (DCV) and sofosbuvir (SOF). Since 2015, this interferon-free regimen has been available in Brazilian clinical routine for treating mono- and HCV/HIV-coinfected patients chronically infected with genotypes 1 and 3. Our aim was to assess SVR rate for Brazilian patients chronically infected with genotypes 1 and 3 after DCV/SOF therapy and the frequency of baseline RASs in HCV NS5A and NS5B genes. Serum samples were collected from 107 monoinfected patients and 25 HCV/HIV co-infected patients before antiviral therapy with DCV/SOF. Genetic diversity of NS5A and NS5B genes was assessed by direct nucleotide sequencing. Overall, SVR rate was 95.4% (126/132), and treatment failure occurred in five monoinfected and one HCV/HIV co-infected patient. NS5A RASs frequency was higher for HCV/HIV patients (28%) than monoinfected patients (16.8%). No difference was evidenced between mono- and HCV/HIV-coinfected groups (15% vs. 16%) regarding NS5B gene. Genotype (GT) 1b strains had significantly more baseline substitutions in NS5A (31.6%) than GT 1a and 3a. At least one primary NS5A RAS described in literature at loci 28, 30, 31 or 93 was identified in HCV GTs 1 strains for both groups. As for NS5B, RASs at positions 159 and 316 was observed only in GT 1b strains. This study highlighted that SVR rate in clinical routine in Brazil was similar to randomized clinical trials (89-98%). Our research provided genetic data about the circulation of resistant variants in Brazil. Despite its presence, most of identified baseline mutations did not negatively impact treatment outcome. Genetic diversity of circulating strains suggested that most of the Brazilian HCV chronic carriers are susceptible to new therapeutic regimens including recently approved DAAs.
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Farmacorresistência Viral/genética , Variação Genética , Hepacivirus/genética , Hepatite C , Imidazóis/administração & dosagem , Mutação , Sofosbuvir/administração & dosagem , Proteínas não Estruturais Virais/genética , Idoso , Brasil , Carbamatos , Farmacorresistência Viral/efeitos dos fármacos , Feminino , Genótipo , Hepatite C/tratamento farmacológico , Hepatite C/genética , Humanos , Masculino , Pessoa de Meia-Idade , Pirrolidinas , RNA Viral/genética , Análise de Sequência de RNA , Valina/análogos & derivadosRESUMO
BACKGROUND AND AIM: Few studies have evaluated sustained virological response (SVR) rates by direct-acting agents (DAAs) and liver stiffness measurement (LSM) changing post-SVR in limited-resource settings. We aimed to describe the effectiveness of DAAs for hepatitis C virus treatment and to assess the changing of LSM post-SVR. METHODS: This retrospective study analyzed data of consecutive hepatitis C virus-infected patients treated by DAAs from 2015 to 2017 in two tertiary centers in Brazil. SVR rates were reported by intention-to-treat and per-protocol analyses. LSM by transient elastography performed before treatment and post-SVR was compared, and logistic regression models were performed. RESULTS: Six hundred seventy-one patients (63% female, 62 years [55-68], 89% genotype 1, 8% HIV co-infected, and 64% with cirrhosis) were included. Most patients were treated by sofosbuvir/daclatasvir ± ribavirin (74%) and sofosbuvir/simeprevir ± ribavirin (21%). SVR rates (95% confidence interval [CI]) were 94.6% (92.7-96.1) and 97.8% (96.4-98.7) for intention-to-treat and per-protocol analyses, respectively. The leading adverse event was anemia (9.6% [95% CI 7.6-12.1]). Pretreatment and post-SVR12 LSM were available in 400 patients. LSM had significantly decreased after SVR (13.6 kPa [interquartile range, 10.0-21.6] vs 10.2 kPa [7.0-17.6], P < 0.001). A total of 167 patients (42%) decreased at least 30% of LSM post-SVR. The absence of type 2 diabetes (odds ratio = 1.52 [95% CI 1.05-2.21], P = 0.028) and presence of platelet count ≥ 150 × 109 /mm3 (odds ratio = 1.75 [1.23-2.50], P = 0.002) were independently associated with a significant LSM regression (≥ 30%) post-SVR. CONCLUSION: DAAs were highly effective and safe, and LSM significantly decreased after SVR in a real-life cohort in Brazil. The absence of type 2 diabetes and presence of high platelet count were independently associated with LSM decrease post-SVR.
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Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente , Idoso , Anemia/induzido quimicamente , Antivirais/efeitos adversos , Quimioterapia Combinada , Técnicas de Imagem por Elasticidade/métodos , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/diagnóstico por imagem , Hepatite C Crônica/virologia , Humanos , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resposta Viral Sustentada , Carga ViralRESUMO
INTRODUCTION: Non-alcoholic fatty liver disease is characterized by the presence of hepatic steatosis and can be associated with fibrosis progression, development of cirrhosis and liver-related complications. Data on the prevalence of liver fibrosis and steatosis in HIV patients remain contradictory in resource-limited settings. We aimed to describe the prevalence and factors associated with liver fibrosis and steatosis in patients with HIV mono-infection under long-term antiretroviral therapy (ART) in Rio de Janeiro, Brazil. METHODS: Clinical assessment, fasting blood collection and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by transient elastography were performed on the same day for this cross-sectional study (PROSPEC-HIV study; NCT02542020). Patients with viral hepatitis co-infection, ART-naïve or missing data were excluded. Liver fibrosis and steatosis were defined by LSM ≥ 8.0 kPa and CAP ≥ 248 dB/m respectively. HIV history, cumulative and current ART regimens were evaluated. Multivariate logistic regression models adjusted for age and gender were performed. RESULTS: In total, 395 patients (60% female; median age of 45 (IQR, 35 to 52) years, body mass index = 25.7 (23.2 to 29.4) kg/m2 , alanine aminotransferase = 30 (23 to 42) IU/L, duration of ART for 7 (4 to 14) years) were included. LSM and CAP were reliable in 93% (n = 367) and 87% (n = 344) respectively. The prevalence of fibrosis and steatosis were 9% (95% confidence interval (CI), 7 to 13) and 35% (95% CI, 30 to 40) respectively. The following factors were associated with fibrosis (odds ratio (OR) (95% CI)): older age (per 10 years; 1.80 (1.27 to 2.55); p = 0.001) and CD4+ count <200 cells/mm3 (7.80 (2.09 to 29.09), p = 0.002). Type 2 diabetes had a trend towards the presence of liver fibrosis (2.67 (0.96 to 7.46), p = 0.061). Central obesity (10.74 (4.40 to 26.20), p < 0.001), type 2 diabetes (9.74 (3.15 to 30.10), p < 0.001), dyslipidaemia (2.61 (1.35 to 5.05), p = 0.003) and metabolic syndrome (4.28 (2.45 to 7.46), p < 0.001) were associated with steatosis. A dominant backbone ART regimen of zidovudine (AZT), d4T, ddI or ddC was associated with steatosis (1.90 (1.07 to 3.38), p = 0.028) independently of metabolic features. CONCLUSION: Integrated strategies for preventing non-communicable diseases in people with HIV mono-infection are necessary to decrease the burden of liver diseases. Clinical Trial Number: NCT02542020.
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Técnicas de Imagem por Elasticidade , Infecções por HIV/complicações , Infecções por HIV/patologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Adulto , Idoso , Brasil/epidemiologia , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , HIV , Infecções por HIV/epidemiologia , Humanos , Cirrose Hepática/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de RiscoRESUMO
INTRODUCTION AND AIM: Approximately 650,000 people in Brazil have chronic hepatitis C virus (HCV) infection. We evaluated the safety and efficacy of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) plus dasabuvir (DSV) with/without ribavirin (RBV) in an openlabel multicenter phase 3b trial in treatment-naive or interferon (IFN) treatment-experienced Brazilian patients with advanced hepatic fibrosis (METAVIR F3/4) and HCV genotype (GT) 1 infection. MATERIAL AND METHODS: All patients received coformulated OBV/PTV/r daily + DSV twice daily (3-DAA). GT1a-infected patients received 3-DAA plus RBV for 12 weeks, except for prior pegIFN/RBV nonresponders with cirrhosis who were treated for 24 weeks. GT1b-infected patients received 3-DAA alone (F3) or in combination with RBV (F4) for 12 weeks. The primary endpoint was sustained virologic response (HCV RNA < 15 IU/mL) at post-treatment Week 12 (SVR12). RESULTS: The study enrolled 222 patients, 214 achieved an SVR12 (96.4%; 95% CI, 93.1-98.2%), one GT1a-infected patient experienced virologic breakthrough, six (5 GT1a) relapsed, and one was lost to follow-up. SVR12 was achieved in 111/ 112 (99.1%) GT1b-infected patients, including 42/43 (97.7%) noncirrhotic, and 69/69 (100%) cirrhotic patients; and in 103/110 (93.6%) GT1a-infected patients, including 44/46 (95.7%) noncirrhotic and 59/64 (92.2%) cirrhotic patients. Overall there was a low rate of serious adverse events (n = 6, 2.7%). One patient experienced a treatment-related serious adverse event and one patient discontinued treatment because of an adverse event. DISCUSSION: The results confirm that the 3-DAA regimen with/without RBV is well tolerated and had a favorable safety profile and is efficacious in GT1-infected patients with advanced fibrosis (METAVIR F3/4).
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Anilidas/administração & dosagem , Antivirais/administração & dosagem , Carbamatos/administração & dosagem , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Compostos Macrocíclicos/administração & dosagem , Ribavirina/administração & dosagem , Ritonavir/administração & dosagem , Sulfonamidas/administração & dosagem , Uracila/análogos & derivados , 2-Naftilamina , Adulto , Idoso , Anilidas/efeitos adversos , Antivirais/efeitos adversos , Brasil , Carbamatos/efeitos adversos , Ciclopropanos , Combinação de Medicamentos , Farmacorresistência Viral , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/virologia , Humanos , Lactamas Macrocíclicas , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologia , Compostos Macrocíclicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prolina/análogos & derivados , RNA Viral/sangue , RNA Viral/genética , Ribavirina/efeitos adversos , Ritonavir/efeitos adversos , Sulfonamidas/efeitos adversos , Resposta Viral Sustentada , Fatores de Tempo , Resultado do Tratamento , Uracila/administração & dosagem , Uracila/efeitos adversos , Valina , Carga ViralRESUMO
Diabetes mellitus (DM) is a major cause of morbidity worldwide and a known factor leading to increased risk of death, especially in conjunction with other risk factors. In this study, we evaluated the prevalence of DM among HIV-infected patients and its association with overall mortality. All HIV-infected patients 18 years or older who were followed in the Instituto Nacional de Infectologia Evandro Chagas (INI) cohort from January 1991 to December 2011 were included. Time-updated covariables included DM status, calendar year, combination antiretroviral therapy (cART), and CD4 cell counts. Fixed demographic covariables included gender and age at entry. Poisson models were used to calculate mortality rate ratios (RR) with robust variances. Among the 4,871 patients included, 1,192 (24.4%) died (mortality rate = 4.72/100 person-years [PY]; 95% confidence interval [CI] = 4.46-5.00). Death rates were significantly higher among those presenting with DM compared with those who did not (6.16/100 vs. 4.61/100 PY, respectively. p = 0.001). In the final model, DM was significantly associated with mortality (RR = 1.74; 95% CI = 1.57-1.94; p < 0.001). When the analysis was restricted to those on cART or the period post-1996, the association between DM and mortality was even stronger (RR = 2.17; 95% CI = 1.91-2.46; p < 0.001 and RR = 1.95; 95% CI = 1.75-2.18; p < 0.001, respectively). Among the major groups of cause of deaths (CODs), the proportion of AIDS-related conditions in patients with DM was lower (74.27% vs. 58.93%, respectively; p < 0.001); whereas in non-AIDS-related conditions, nonimmunodeficiency-related causes (22.44% vs. 34.82%, respectively; p = 0.004) were more common in patients with DM. In conclusion, DM was associated with increased mortality rates even after controlling for HIV-related variables associated to this outcome. Differences in the underlying CODs were identified, reinforcing the necessity to assess and treat comorbidities such as DM in HIV-infected patients.