RESUMO
Organ transplant recipients with hepatitis E virus (HEV) infection bears high risk to develop chronic hepatitis, which is generally associated with immunosuppressive therapies. This study aimed to identify the incidence and predictors of de novo HEV infection in patients after receiving transplantation. We performed a large retrospective study to investigate the prevalence of anti-HEV at baseline, incidence of de novo HEV infection after transplantation, and the risk factors of HEV infection among patients with liver transplant in China. A total of 407 liver transplant recipients were examined for the presence of anti-HEV immunoglobulin G, IgM antibodies, and HEV RNA in serum. Basal indexes in individuals with evidence of post-transplant HEV infection were compared with those without evidence of that, and risk factors associated with HEV infection were assessed. The prevalence of anti-HEV at pretransplant in liver transplant recipients was 25.8% (105/407). Serum-negative conversion occurred in 34 (32.38%) of 105 liver transplant patients. Sixty-five out of 302 patients had de novo HEV infection after transplantation, with a cumulative incidence of 42.74% during follow-up. After transplantation, HEV infection was associated with liver failure (p = 0.012), hypoproteinemia (p = 0.030) and higher level of r-glutamyl transferase (GGT) (p = 0.022) before transplantation. Graft rejection (OR = 0.075; p = 0.045) was negatively associated with serum-negative conversion in patients who had positive anti-HEV antibody before transplantation. The incidence of de novo HEV infection after transplantation were higher in China. Liver failure, hypoproteinemia, and GGT elevation may be associated with HEV infection after liver transplantation. This study suggests that prevention and control of HEV infection after liver transplantation should be paid attention in patients bearing these risk factors.
Assuntos
Anticorpos Anti-Hepatite , Vírus da Hepatite E , Hepatite E , Imunoglobulina M , Transplante de Fígado , Humanos , Hepatite E/epidemiologia , Transplante de Fígado/efeitos adversos , Masculino , Feminino , Fatores de Risco , Pessoa de Meia-Idade , Incidência , Estudos Retrospectivos , Adulto , China/epidemiologia , Anticorpos Anti-Hepatite/sangue , Vírus da Hepatite E/imunologia , Imunoglobulina M/sangue , RNA Viral/sangue , Imunoglobulina G/sangue , Transplantados/estatística & dados numéricos , Adulto Jovem , Idoso , Adolescente , PrevalênciaRESUMO
During antiretroviral therapy (ART), most people living with HIV-1 have undetectable HIV-1 RNA in their plasma. However, they occasionally present with new or progressive neurologic deficits and detectable HIV-1 RNA in the cerebrospinal fluid (CSF), a condition defined as neurosymptomatic HIV-1 CSF escape (NSE). We explored the source of neuropathogenesis and HIV-1 RNA in the CSF during NSE by characterizing HIV-1 populations and inflammatory biomarkers in CSF from 25 individuals with NSE. HIV-1 populations in the CSF were uniformly drug resistant and adapted to replication in CD4+ T cells, but differed greatly in genetic diversity, with some having low levels of diversity similar to those observed during untreated primary infection and others having high levels like those during untreated chronic infection. Higher diversity in the CSF during NSE was associated with greater CNS inflammation. Finally, optimization of ART regimen was associated with viral suppression and improvement of neurologic symptoms. These results are consistent with CNS inflammation and neurologic injury during NSE being driven by replication of partially drug-resistant virus in CNS CD4+ T cells. This is unlike nonsuppressible viremia in the plasma during ART, which typically lacks clinical consequences and is generated by virus expression without replication.
Assuntos
Linfócitos T CD4-Positivos , Infecções por HIV , HIV-1 , RNA Viral , Replicação Viral , Humanos , HIV-1/imunologia , Masculino , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/líquido cefalorraquidiano , Infecções por HIV/virologia , Infecções por HIV/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Adulto , RNA Viral/líquido cefalorraquidiano , RNA Viral/sangue , Pessoa de Meia-Idade , Inflamação/imunologia , Inflamação/líquido cefalorraquidianoRESUMO
BACKGROUND: People with HIV-1 often have chronic inflammation leading to severe non-AIDS morbidity and mortality. The AIDS Clinical Trials Group Study A5314 sought to lower inflammation with low-dose methotrexate (LDMTX). The primary study outcomes were reported previously but here we present the impact of LDMTX on multiple measures of HIV-1 persistence. METHODS: A5314 was a phase 2 randomized, double-blind, multicenter trial in 176 adult people with HIV-1 on virally suppressive antiretroviral therapy. LDMTX (5-15 mg/wk) was administered for 24 weeks with an additional 12 weeks of participant follow-up. The current analyses of HIV-1 persistence were restricted to 60 participants (30 LDMTX and 30 placebo) randomly selected from the total population. Plasma HIV-1 RNA, total HIV-1 DNA, and cell-associated HIV-1 RNA (CA HIV-1 RNA) were measured by sensitive quantitative PCR assays. RESULTS: LDMTX treatment had no significant effect on sensitive measures of plasma HIV-1 RNA, HIV-1 DNA, CA HIV-1 RNA, or CA HIV-1 RNA/DNA ratio at any time point or from baseline to week 24. As observed in the main study, absolute peripheral CD4+ and CD8+ T-cell numbers decreased from baseline to week 24 among the 30 participants receiving LDMTX compared with placebo (median decrease of -31.5 CD4+ T cells/µL, -83.5 CD8+ T cells/µL). CONCLUSIONS: LDMTX had no significant effect on any measure of HIV-1 persistence in plasma or peripheral blood mononuclear cells. Further studies are needed to determine whether other immunosuppressive and/or immunoreductive interventions are safe and capable of affecting HIV-1 persistence.
Assuntos
Infecções por HIV , HIV-1 , Metotrexato , RNA Viral , Humanos , Metotrexato/uso terapêutico , Metotrexato/administração & dosagem , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Adulto , Masculino , Feminino , RNA Viral/sangue , Método Duplo-Cego , Pessoa de Meia-Idade , DNA Viral/sangue , Carga Viral/efeitos dos fármacos , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Contagem de Linfócito CD4RESUMO
OBJECTIVE: In the hepatitis C virus (HCV) diagnostic algorithm, an anti-HCV screening test is recommended first. In countries with low HCV prevalence, anti-HCV testing can often give false-positive results. This may lead to unnecessary retesting, increased costs, and psychological stress for patients. METHODS: In this study, the most appropriate S/Co (signal-cutoff) value to predict HCV viremia in anti-HCV test(+) individuals was determined, and the effect of genotype differences was evaluated. Of the 96,515 anti-HCV tests performed between 2020 and 2023, 934 were reactive. A total of 332 retests and 65 patients without HCV-ribonucleic acid (RNA) analysis were excluded. Demographic data were calculated for 537 patients, and 130 patients were included in the study. RESULTS: The average age of 537 patients was 55±18 years, and 57.1% were women. The anti-HCV positivity rate was 0.62% (602/96,515), and the actual anti-HCV positivity rate was 0.13% (130/96,515). Anti-HCV levels were higher in HCV-RNA(+) patients than in HCV-RNA-negative individuals (p<0.0001) (Table 1). Receiver operating characteristic curve analysis identified the optimal S/Co value to be 10.86 to identify true positive cases. Sensitivity was 96.1%, specificity was 61.2%, positive predictive value (PPV) was 44.2%, and negative predictive value (NPV) was 98% (Figure 2). A total of 107 (82.3%) of the patients were identified as GT1, and the most common subtype was GT1b (n=100). CONCLUSION: If anti-HCV S/Co is ≥10.86, direct HCV RNA testing may be recommended; However, the possibility of false positivity should be considered in patients with a S/Co value below 10.86.
Assuntos
Genótipo , Hepacivirus , Anticorpos Anti-Hepatite C , Hepatite C , Valor Preditivo dos Testes , RNA Viral , Viremia , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Hepacivirus/genética , RNA Viral/sangue , RNA Viral/análise , Anticorpos Anti-Hepatite C/sangue , Hepatite C/genética , Hepatite C/sangue , Adulto , Idoso , Sensibilidade e EspecificidadeRESUMO
Recent studies indicate that treatment of chronic hepatitis D virus (HDV) with either pegylated interferon (IFN)λ or pegylated IFNα monotherapy leads to a dramatic decline in HDV RNA. Herein, we investigated the innate antiviral efficacy of IFNλ and IFNα in humanized mice that lack an adaptive immune response. Humanized mice were either co-infected with hepatitis B virus (HBV) and HDV simultaneously, or HDV infection was performed subsequent to HBV infection (i.e., superinfected). After steady viral replication was achieved, mice received either IFNλ (n = 6) or IFNα (n = 7) for 12 (or 13) weeks. Pretreatment median levels of serum HBV DNA (8.8 [IQR:0.2] log IU/ml), HDV RNA (9.8 [0.5] log IU/ml), HBsAg (4.0 [0.4] log IU/ml) and human albumin, hAlb (6.9 [0.1] log ng/mL) were similar between mice treated with IFNα or IFNλ and between those coinfected versus superinfected. Compared to mice treated with IFNλ, mice treated with IFNα had a significantly greater decline in HBV, HDV, and HBsAg levels. In conclusion, IFNα induces stronger inhibition of HBV and HDV than IFNλ in humanized mice that lack an adaptive immune response. Further studies are needed to assess the respective role of the combined innate-and adaptive-immune systems in the treatment of HBV and HDV with IFNα and IFNλ.
Assuntos
Antivirais , Modelos Animais de Doenças , Vírus da Hepatite B , Vírus Delta da Hepatite , Interferon-alfa , Animais , Camundongos , Interferon-alfa/uso terapêutico , Interferon-alfa/farmacologia , Antivirais/uso terapêutico , Antivirais/farmacologia , Vírus Delta da Hepatite/efeitos dos fármacos , Humanos , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/imunologia , Replicação Viral/efeitos dos fármacos , Hepatite D Crônica/tratamento farmacológico , Hepatite D Crônica/virologia , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Interferons , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Hepatite B/imunologia , Hepatite D/tratamento farmacológico , Hepatite D/virologia , Hepatite D/imunologia , RNA Viral/sangue , DNA Viral/sangue , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Carga Viral/efeitos dos fármacosAssuntos
Anticorpos Neutralizantes , Doadores de Sangue , RNA Viral , Febre do Nilo Ocidental , Vírus do Nilo Ocidental , Humanos , Vírus do Nilo Ocidental/imunologia , RNA Viral/sangue , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Masculino , Feminino , Febre do Nilo Ocidental/sangue , Anticorpos Antivirais/sangue , Adulto , Pessoa de Meia-IdadeRESUMO
To understand the roles of acute-phase viral dynamics and host immune responses in post-acute sequelae of SARS-CoV-2 infection (PASC), we enrolled 136 participants within 5 days of their first positive SARS-CoV-2 real-time PCR test. Participants self-collected up to 21 nasal specimens within the first 28 days post-symptom onset; interviewer-administered questionnaires and blood samples were collected at enrollment, days 9, 14, 21, 28, and month 4 and 8 post-symptom onset. Defining PASC as the presence of any COVID-associated symptom at their 4-month visit, we compared viral markers (quantity and duration of nasal viral RNA load, infectious viral load, and plasma N-antigen level) and host immune markers (IL-6, IL-10, TNF-α, IFN-α, IFN-γ, MCP, IP-10, and Spike IgG) over the acute period. Compared to those who fully recovered, those reporting PASC demonstrated significantly higher maximum levels of SARS-CoV-2 RNA and N-antigen, burden of RNA and infectious viral shedding, and lower Spike-specific IgG levels within 9 days post-illness onset. No significant differences were identified among a panel of host immune markers. Our results suggest early viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC, highlighting the importance of understanding early biological markers in the natural history of PASC.
Assuntos
Biomarcadores , COVID-19 , RNA Viral , SARS-CoV-2 , Carga Viral , Humanos , COVID-19/imunologia , COVID-19/virologia , COVID-19/sangue , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Masculino , Feminino , Adulto , Biomarcadores/sangue , RNA Viral/sangue , Pessoa de Meia-Idade , Síndrome de COVID-19 Pós-Aguda , Idoso , Citocinas/sangue , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologiaRESUMO
ABSTRACTRat hepatitis E virus (ratHEV) is an emerging cause of acute hepatitis of zoonotic origin. Since seroprevalence studies are scarce, at-risk groups are almost unknown. Because blood-borne infections frequently occur in people with drug use, who are particularly vulnerable to infection due to lack of housing and homelessness, this population constitutes a priority in which ratHEV infection should be evaluated. Therefore, the aim of this study was to evaluate the ratHEV seroprevalence and RNA detection rate in drug users as a potential at-risk population. We designed a retrospective study involving individuals that attended drug rehabilitation centres. Exposure to ratHEV was assessed by specific antibody detection using ELISA and dot blot (DB) assay and the presence of active infection by ratHEV RNA detection using RT-qPCR. Three-hundred and forty-one individuals were included, the most of them being men (67.7%) with an average age of 45 years. A total of 17 individuals showed specific IgG antibodies against ratHEV (4.6%; 95% CI; 3.1%-7.9%). One case of active ratHEV infection was identified (0.3%; 95% CI: 0.1%-1.8%). This was a 57-year-old homeless woman with limited financial resources, who had active cocaine and heroin use via parenteral route. In conclusion, we identified a potential exposure to ratHEV among drug users. Targeted studies in drug users with proper control groups are necessary to evaluate high-risk populations and transmission routes more accurately.
Assuntos
Usuários de Drogas , Vírus da Hepatite E , Hepatite E , Humanos , Pessoa de Meia-Idade , Hepatite E/epidemiologia , Hepatite E/virologia , Hepatite E/veterinária , Masculino , Feminino , Estudos Soroepidemiológicos , Adulto , Estudos Retrospectivos , Vírus da Hepatite E/imunologia , Vírus da Hepatite E/genética , Vírus da Hepatite E/isolamento & purificação , RNA Viral/sangue , Anticorpos Anti-Hepatite/sangue , Animais , Imunoglobulina G/sangue , Adulto Jovem , RatosRESUMO
BACKGROUND: To delineate the levels of serum Hepatitis B virus (HBV) RNA in patients with HBV-related hepatocellular carcinoma (HCC) and study comparisons with those of individuals afflicted with cirrhosis. METHODS: Adult patients diagnosed with HBV-related cirrhosis or HCC (initial diagnosis) were enrolled in the cross-sectional study. Serum HBV DNA level was quantified through a real-time polymerase chain reaction assay with a lower limit of quantification (LLQ) of 20 IU/ml. Additionally, serum HBV RNA was quantified employing RNA real-time fluorescence thermostatic amplification detection technology with LLQ of 100 copies/ml. Propensity score matching (PSM) was conducted to ensure balance in between-group confounders. RESULTS: A total of 187 patients (47 with HCC and 140 with cirrhosis) were recruited, among whom 140 (74.9%) had undergone antiviral therapy prior to their inclusion, with varying durations. Serum HBV RNA was detectable in 89.4% of HCC patients at the time of carcinoma diagnosis. After PSM, individuals with HCC exhibited significantly elevated levels of serum HBV DNA and HBV RNA compared to those with cirrhosis (median lgHBV RNA 3.1 vs 2.0 copies/ml, P = 0.001). Subgroup analysis, including 38 patients who exhibited ultrasensitive HBV DNA negativity, revealed similar results (median lgHBV RNA 3.0 vs 0.0 copies/ml, P < 0.001). CONCLUSIONS: Serum HBV RNA levels were significantly higher in HBV-related HCC patients compared to cirrhotic patients. The presence of serum HBV RNA positivity or elevated levels was associated with the onset of HCC.
Assuntos
Carcinoma Hepatocelular , Vírus da Hepatite B , Cirrose Hepática , Neoplasias Hepáticas , Pontuação de Propensão , RNA Viral , Humanos , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Cirrose Hepática/virologia , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Estudos Transversais , RNA Viral/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , DNA Viral/sangue , Adulto , Idoso , Hepatite B Crônica/complicações , Hepatite B Crônica/virologia , Hepatite B Crônica/sangueRESUMO
Coinfections with human pegivirus 1 (HPgV-1) are common in chronic hepatitis C virus (HCV) patients. However, little is known about whether HPgV-1 is affected by direct-acting antivirals during HCV treatment. Metagenomic analysis and reverse transcriptase-quantitative PCR (RT-qPCR) were performed on RNA from the plasma of 88 selected chronic HCV patients undergoing medical treatment. Twenty (23%) of these HCV patients had HPgV-1 coinfections and were followed by RT-qPCR during treatment and follow-up to investigate HPgV-1 RNA titers. Recovered sequences could be assembled to complete HPgV-1 genomes, and most formed a genotype 2 subclade. All HPgV-1 viral genomic regions were under negative purifying selection. Glecaprevir/pibrentasvir treatment in five patients did not consistently lower the genome titers of HPgV-1. In contrast, a one log10 drop of HPgV-1 titers at week 2 was observed in 10 patients during treatment with sofosbuvir-containing regimens, sustained to the end of treatment (EOT) and in two cases decreasing to below the detection limit of the assay. For the five patients treated with ledipasvir/sofosbuvir with the inclusion of pegylated interferon, titers decreased to below the detection limit at week 2 and remained undetectable to EOT. Subsequently, the HPgV-1 titer rebounded to pretreatment levels for all patients. In conclusion, we found that HCV treatment regimens that included the polymerase inhibitor sofosbuvir resulted in decreases in HPgV-1 titers, and the addition of pegylated interferon increased the effect on patients with coinfections. This points to the high specificity of protease and NS5A inhibitors toward HCV and the more broad-spectrum activity of sofosbuvir and especially pegylated interferon. IMPORTANCE: Human pegivirus 1 coinfections are common in hepatitis C virus (HCV) patients, persisting for years. However, little is known about how pegivirus coinfections are affected by treatment with pangenotypic direct-acting antivirals (DAAs) against HCV. We identified human pegivirus by metagenomic analysis of chronic HCV patients undergoing protease, NS5A, and polymerase inhibitor treatment, in some patients with the addition of pegylated interferon, and followed viral kinetics of both viruses to investigate treatment effects. Only during HCV DAA treatment regimens that included the more broad-spectrum drug sofosbuvir could we detect a consistent decline in pegivirus titers that, however, rebounded to pretreatment levels after treatment cessation. The addition of pegylated interferon gave the highest effect with pegivirus titers decreasing to below the assay detection limit, but without clearance. These results reveal the limited effect of frontline HCV drugs on the closest related human virus, but sofosbuvir appeared to have the potential to be repurposed for other viral diseases.
Assuntos
Antivirais , Benzimidazóis , Coinfecção , Infecções por Flaviviridae , Hepatite C Crônica , Pegivirus , Sofosbuvir , Humanos , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Benzimidazóis/uso terapêutico , Sofosbuvir/uso terapêutico , Pegivirus/efeitos dos fármacos , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Masculino , Infecções por Flaviviridae/tratamento farmacológico , Infecções por Flaviviridae/virologia , Feminino , Genótipo , Quinoxalinas/uso terapêutico , Pessoa de Meia-Idade , Pirrolidinas , Sulfonamidas/uso terapêutico , RNA Viral/sangue , RNA Viral/genética , Hepacivirus/genética , Hepacivirus/efeitos dos fármacos , Genoma Viral , Adulto , Idoso , Carga Viral/efeitos dos fármacos , Metagenômica , Ciclopropanos , Ácidos Aminoisobutíricos , Filogenia , Combinação de MedicamentosRESUMO
BACKGROUNDWe evaluated the safety and viral rebound, after analytical treatment interruption (ATI), of vedolizumab and ART in recent HIV-1 infection. We used this model to analyze the effect of α4ß7 on the HIV-1 reservoir size.METHODSParticipants started ART with monthly vedolizumab infusions, and ATI was performed at week 24. Biopsies were obtained from ileum and cecum at baseline and week 24. Vedolizumab levels, HIV-1 reservoir, flow cytometry, and cell-sorting and antibody competition experiments were assayed.RESULTSVedolizumab was safe and well tolerated. No participant achieved undetectable viremia off ART 24 weeks after ATI. Only a modest effect on the time to achieve more than 1,000 HIV-1 RNA copies/mL and the proportion of participants off ART was observed, being higher in the vedolizumab group compared with historical controls. Just before ATI, α4ß7 expression was associated with HIV-1 DNA and RNA in peripheral blood and with PD1 and TIGIT levels. Importantly, a complete blocking of α4ß7 was observed on peripheral CD4+ T cells but not in gut (ileum and cecum), where α4ß7 blockade and vedolizumab levels were inversely associated with HIV-1 DNA.CONCLUSIONOur findings support α4ß7 as an important determinant in HIV-1 reservoir size, suggesting the complete α4ß7 blockade in tissue as a promising tool for HIV-cure combination strategies.TRIAL REGISTRATIONClinicalTrials.gov NCT03577782.FUNDINGThis work was supported by the Instituto de Salud Carlos III (Fondo Europeo de Desarrollo Regional, "a way to make Europe," research contracts FI17/00186 and FI19/00083 and research projects PI18/01532, PI19/01127, PI22/01796), Conserjería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía (research projects P20/00906), the Red Temática de Investigación Cooperativa en SIDA (RD16/0025/0020), and the Spanish National Research Council.
Assuntos
Anticorpos Monoclonais Humanizados , Infecções por HIV , HIV-1 , Carga Viral , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Linfócitos T CD4-Positivos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Íleo/metabolismo , Íleo/virologia , Integrinas/metabolismo , RNA Viral/sangue , Carga Viral/efeitos dos fármacosRESUMO
BACKGROUND: The ongoing, observational BICSTaR (BICtegravir Single Tablet Regimen) cohort study is evaluating real-world effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV across 14 countries over 24 months. We present 12-month data from the BICSTaR Asia cohort. METHODS: Data were pooled from retrospective and prospective cohorts of antiretroviral therapy (ART)-naïve (hereafter, TN) and ART-experienced (hereafter, TE) people with HIV (aged ≥21 years) receiving B/F/TAF in routine clinical care in the Republic of Korea, Singapore, and Taiwan. Analyses included effectiveness (primary endpoint: HIV-1 RNA <50 copies/ml, missing = excluded analysis), CD4 count, CD4/CD8 ratio, safety, treatment persistence, and patient-reported outcomes (prospective group). RESULTS: The analysis population included 328 participants (80 retrospective, 248 prospective; 65 TN, 263 TE). Participants were predominantly male (96.9% TN, 93.2% TE) with ≥1 comorbidity (52.3% TN, 57.8% TE); median age (years) was 31 (TN) and 42 (TE). Following 12 months of B/F/TAF, HIV-1 RNA was <50 copies/ml in 98.2% (54/55) of TN and 97.0% (227/234) of TE participants. Median (Q1, Q3) CD4 cell count increased by +187 (119, 291) cells/µl in the TN group (p < 0.001) and remained stable (+8 [-91, 110] cells/µl) in the TE group. B/F/TAF persistence was high in the prospective group, with 1/34 (2.9%) TN and 5/214 (2.3%) TE participants discontinuing treatment within 12 months. Drug-related adverse events occurred in 5.8% (19/328) of participants, leading to treatment discontinuation in 0.6% (2/328). CONCLUSIONS: Real-world evidence from BICSTaR supports the effectiveness, safety and tolerability of B/F/TAF in people with HIV in Asia.
Assuntos
Fármacos Anti-HIV , Emtricitabina , Infecções por HIV , HIV-1 , Piridonas , Tenofovir , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Masculino , Feminino , Adulto , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Emtricitabina/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Estudos Retrospectivos , Pessoa de Meia-Idade , Estudos Prospectivos , Piridonas/uso terapêutico , Resultado do Tratamento , Contagem de Linfócito CD4 , HIV-1/efeitos dos fármacos , HIV-1/genética , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Piperazinas/uso terapêutico , Adenina/análogos & derivados , Adenina/uso terapêutico , Adenina/efeitos adversos , Alanina/uso terapêutico , Alanina/análogos & derivados , Combinação de Medicamentos , Carga Viral/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Singapura/epidemiologia , Amidas/uso terapêutico , Taiwan , Estudos de Coortes , RNA Viral/sangueRESUMO
BACKGROUND: The rapid start of antiretroviral therapy (RSA) model initiates antiretroviral therapy (ART) as soon as possible after a new or preliminary diagnosis of HIV, in advance of HIV-1 RNA and other baseline laboratory testing. This observational study aims to determine if RSA with a single tablet regimen of bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) is an effective regimen for achieving viral suppression and accepted by patients at the time of diagnosis. METHODS: Adults newly or preliminarily diagnosed with HIV were enrolled from October 2018 through September 2021. Real world advantage, measured in days between clinical milestones and time to virologic suppression, associated with B/F/TAF RSA was compared to historical controls. RESULTS: All Study RSA participants (n = 45) accepted treatment at their first visit and 43(95.6%) achieved virologic suppression by week 48. Study RSA participants had a significantly shorter time (median 32 days) from diagnosis to ART initiation and virologic suppression, in comparison to historical controls (median 181 days) (n = 42). Qualitative feedback from study RSA participants showed high acceptance positive response to RSA. CONCLUSIONS: RSA is feasible and well accepted by patients in a real-world community-based clinic setting. Promoting RSA in community-based clinics is an important tool in ending the HIV epidemic.
Assuntos
Fármacos Anti-HIV , Emtricitabina , Infecções por HIV , Tenofovir , Humanos , Infecções por HIV/tratamento farmacológico , Projetos Piloto , Masculino , Feminino , Adulto , Tenofovir/uso terapêutico , Tenofovir/administração & dosagem , Tenofovir/análogos & derivados , Pessoa de Meia-Idade , Fármacos Anti-HIV/uso terapêutico , Emtricitabina/uso terapêutico , Emtricitabina/administração & dosagem , Alanina/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , HIV-1/efeitos dos fármacos , Piperazinas/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Carga Viral/efeitos dos fármacos , Amidas/uso terapêutico , RNA Viral/sangue , PiridonasRESUMO
Optimal timing for intubating patients with coronavirus disease 2019 (COVID-19) has been debated throughout the pandemic. Early use of high-flow nasal cannula (HFNC) can help reduce the need for intubation, but delay can result in poorer outcomes. This study examines trends in laboratory parameters and serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA levels of patients with COVID-19 in relation to HFNC failure. Patients requiring HFNC within three days of hospitalization between July 1 and September 30, 2021 were enrolled. The primary outcome was HFNC failure (early failure ≤Day 3; late failure ≥Day 4), defined as transfer to intensive care just before/after intubation or in-hospital death. We examined changes in laboratory markers and SARS-CoV2-RNAemia on Days 1, 4, and 7, together with demographic data, oxygenation status, and therapeutic agents. We conducted a univariate logistic regression with the explanatory variables defined as 10% change rate in each laboratory marker from Day 1 to 4. We utilized the log-rank test to assess the differences in HFNC failure rates, stratified based on the presence of SARS-CoV2 RNAemia. Among 122 patients, 17 (13.9%) experienced HFNC failure (early: n = 6, late: n = 11). Seventy-five patients (61.5%) showed an initial SpO2/FiO2 ratio ≤243, equivalent to PaO2/FiO2 ratio ≤200, and the initial SpO2/FiO2 ratio was significantly lower in the failure group (184 vs. 218, p = 0.018). Among the laboratory markers, a 10% increase from Day 1 to 4 of lactate dehydrogenase (LDH) and interleukin (IL)-6 was associated with late failure (Odds ratio [OR]: 1.42, 95% confidence interval [CI]: 1.09-1.89 and OR: 1.04, 95%CI: 1.00-1.19, respectively). Furthermore, in patients with persistent RNAemia on Day 4 or 7, the risk of late HFNC failure was significantly higher (Log-rank test, p<0.01). In conclusion, upward trends in LDH and IL-6 levels and the persistent RNAemia even after treatment were associated with HFNC failure.
Assuntos
Biomarcadores , COVID-19 , Oxigenoterapia , RNA Viral , SARS-CoV-2 , Humanos , COVID-19/terapia , COVID-19/sangue , COVID-19/virologia , Masculino , Feminino , Biomarcadores/sangue , Pessoa de Meia-Idade , RNA Viral/sangue , Oxigenoterapia/métodos , Idoso , L-Lactato Desidrogenase/sangue , Falha de Tratamento , Resultado do Tratamento , CânulaRESUMO
Hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg) have been reported to reflect the transcriptional activity of covalently closed circular HBV DNA. We retrospectively investigated the proportions of quantifiable serum HBV RNA and immunoassay for total antigen including complex via pretreatment-hepatitis B core-related antigen (iTACT-HBcrAg) in chronic hepatitis B patients negative for hepatitis B e antigen (HBeAg) and/or with hepatitis B surface antigen (HBsAg) seroclearance. This study included 246 HBeAg-negative HBV-infected patients, who comprised 13 with liver cirrhosis (LC, the LC group), 118 chronic hepatitis (CH, the CH group), and 115 inactive carriers (IC, the IC group), and 44 patients with HBsAg seroclearance. iTACT-HBcrAg and HBV RNA levels were determined using stored serum samples. Higher proportions of the patients had quantifiable iTACT-HBcrAg than HBV RNA in all groups of HBeAg-negative patients (iTACT-HBcrAg: 84.6%, 90.7%, 35.7%, HBV RNA: 23.1%, 26.3%, 14.8%, for the LC, CH, IC groups). With HBsAg seroclearance (HBsAg <0.05 IU/mL), the proportions of quantifiable samples for HBV RNA were also lower than iTACT-HBcrAg (0% for HBV RNA). Thus, iTACT-HBcrAg was more often detectable than circulating HBV RNA in this study population. Further long-term prospective evaluation of iTACT-HBcrAg is desirable for its utilization in clinical practice.
Assuntos
Antígenos do Núcleo do Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Vírus da Hepatite B , Hepatite B Crônica , RNA Viral , Humanos , Hepatite B Crônica/virologia , Hepatite B Crônica/sangue , Masculino , Feminino , Antígenos de Superfície da Hepatite B/sangue , RNA Viral/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/isolamento & purificação , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Idoso , Imunoensaio/métodosRESUMO
OBJECTIVES: Patients with haematologic malignancies (HM) COVID-19 have more severe disease, with increased risk of mortality. Therefore, this study aimed to evaluate the effect of SARS-CoV-2 RNAemia and the specific humoral immune responses on the clinical outcomes of patients with HM and COVID-19. METHODS: Interferon-α/γ (IFN-α/IFN-γ) serum levels, neutralizing antibodies and RNAemia at COVID-19 diagnosis, and persistent RNAemia during the follow-up were evaluated. RESULTS: Overall, 63 (58.9%) out of 107 patients had RNAemia, which was persistent in 26 (41.3%) patients. RNAemia at diagnosis and persistent RNAemia were associated with the need for high-flow nasal oxygen therapy during admission. Persistent RNAemia, age >70 years, and CURB-65 score ≥2 in patients with pneumonia were associated with increased 90-day mortality (P = 0.009, P = 0.030 and P = 0.001, respectively). The 90-day overall survival was lower (P = 0.006) in patients with persistent RNAemia. In addition, dexamethasone administration was associated with a COVID-19 episode with persistent RNAemia. CONCLUSION: Our results suggest that in patients with HM, RNAemia at the time of COVID-19 diagnosis and during the follow-up can be used to stratify patients with HM according to their clinical evolution and to guide clinical decisions tailored to the specific needs of each patient.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Neoplasias Hematológicas , RNA Viral , SARS-CoV-2 , Humanos , COVID-19/complicações , COVID-19/imunologia , Masculino , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/imunologia , Idoso , Pessoa de Meia-Idade , RNA Viral/sangue , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Interferon gama/sangue , Interferon-alfa/uso terapêutico , Idoso de 80 Anos ou mais , Adulto , Dexametasona/uso terapêutico , Dexametasona/administração & dosagemRESUMO
This study assesses the prevalence of hepatitis D virus (HDV) in people living with HIV (PLWHIV) in Greece. Given the compounding effects of HDV and hepatitis B (HBV) on liver disease progression, as well as the emergence of new therapeutic options such as bulevirtide, understanding regional disparities and the epidemiological impact of such co-infections is vital. A cross-sectional analysis was conducted utilizing 696 serum samples from PLWHIV attending five major university hospitals. The methodology included HDV antibody detection by ELISA and HDV RNA confirmation. Of the 30 HBsAg-positive samples analyzed, the study population was primarily male (93%), with a median age of 54 years. Participants had been on antiretroviral therapy for a median of 10 years, and the median CD4 count was 738 (539-1006) copies/mL. Additional serological findings revealed a 7% prevalence of hepatitis C virus (HCV) IgG antibodies and a 55% prevalence of hepatitis A virus (HAV) IgG antibodies. Seroreactivity for syphilis (RPR/VDRL/TPHA positive) was identified in 33% of the participants. The results indicated a low HDV prevalence, with only one individual (3%) testing positive for anti-HDV IgG antibodies and none for HDV RNA. This indicates a lower prevalence of HDV among PLWHIV with chronic HBV in Greece compared to global data.
Assuntos
Coinfecção , Infecções por HIV , Anticorpos Anti-Hepatite , Hepatite D , Vírus Delta da Hepatite , Humanos , Estudos Transversais , Masculino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Hepatite D/epidemiologia , Feminino , Pessoa de Meia-Idade , Projetos Piloto , Grécia/epidemiologia , Vírus Delta da Hepatite/imunologia , Vírus Delta da Hepatite/genética , Adulto , Prevalência , Coinfecção/epidemiologia , Coinfecção/virologia , Anticorpos Anti-Hepatite/sangue , Idoso , RNA Viral/sangue , Estudos SoroepidemiológicosRESUMO
BACKGROUND: Cabotegravir plus rilpivirine (CAB + RPV) is a guideline-recommended long-acting (LA) injectable regimen for the maintenance of human immunodeficiency virus-1 (HIV-1) virologic suppression. This post hoc analysis summarizes CAB + RPV LA results by baseline body mass index (BMI) category among phase 3/3b trial participants. METHODS: Data from CAB + RPV-naive participants receiving every 4 or 8 week dosing in FLAIR, ATLAS, and ATLAS-2M were pooled through week 48. Data beyond week 48 were summarized by study (FLAIR through week 96 and ATLAS-2M through week 152). HIV-1 RNA <50 and ≥50â copies/mL, confirmed virologic failure (CVF; 2 consecutive HIV-1 RNA ≥200â copies/mL), safety and tolerability, and plasma CAB and RPV trough concentrations were evaluated by baseline BMI (<30â kg/m2, lower; ≥30â kg/m2, higher). RESULTS: Among 1245 CAB + RPV LA participants, 213 (17%) had a baseline BMI ≥30â kg/m2. At week 48, 92% versus 93% of participants with lower versus higher BMI had HIV-1 RNA <50â copies/mL, respectively. Including data beyond week 48, 18 participants had CVF; those in the higher BMI group (n = 8) all had at least 1 other baseline factor associated with CVF (archived RPV resistance-associated mutations or HIV-1 subtype A6/A1). Safety and pharmacokinetic profiles were comparable between BMI categories. CONCLUSIONS: CAB + RPV LA was efficacious and well tolerated, regardless of baseline BMI category. CLINICAL TRIALS REGISTRATION: NCT02938520, NCT02951052, and NCT03299049.
Assuntos
Fármacos Anti-HIV , Índice de Massa Corporal , Infecções por HIV , HIV-1 , Piridonas , Rilpivirina , Humanos , Rilpivirina/farmacocinética , Rilpivirina/uso terapêutico , Rilpivirina/administração & dosagem , Rilpivirina/efeitos adversos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Masculino , HIV-1/efeitos dos fármacos , Feminino , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Adulto , Pessoa de Meia-Idade , Piridonas/farmacocinética , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Carga Viral/efeitos dos fármacos , RNA Viral/sangue , Resultado do Tratamento , Quimioterapia Combinada , DicetopiperazinasRESUMO
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the world and can lead to severe complications in immunocompromised individuals. HEV is primarily transmitted through eating pork, which has led to an increased in anti-HEV IgG seropositivity in the general population of Europe in particular. However, it can also be transmitted intravenously, such as through transfusions. The growing evidence of HEV contamination of blood products and documented cases of transmission have given rise to practice changes and blood product screening of HEV in many European countries. This review covers the abundant European literature and focuses on the most recent data pertaining to the prevalence of HEV RNA positivity and IgG seropositivity in the North American general population and in blood products from Canada and the United States. Currently, Health Canada and the Food and Drug Administration do not require testing of HEV in blood products. For this reason, awareness among blood product prescribers about the possibility of HEV transmission through blood products is crucial. However, we also demonstrate that the province of Quebec has a prevalence of anti-HEV and HEV RNA positivity similar to some European countries. In light of this, we believe that HEV RNA blood donation screening be reevaluated with the availability of more cost-effective assays.
Assuntos
Doadores de Sangue , Seleção do Doador , Vírus da Hepatite E , Hepatite E , Humanos , Hepatite E/epidemiologia , Hepatite E/diagnóstico , Hepatite E/transmissão , Canadá/epidemiologia , Estados Unidos/epidemiologia , Vírus da Hepatite E/isolamento & purificação , Vírus da Hepatite E/imunologia , Seleção do Doador/métodos , RNA Viral/sangue , Programas de Rastreamento/métodos , Prevalência , Anticorpos Anti-Hepatite/sangue , Segurança do Sangue , Imunoglobulina G/sangue , Doação de SangueRESUMO
BACKGROUND: Data characterising the long-term use and safety of emtricitabine plus tenofovir disoproxil fumarate as daily oral pre-exposure prophylaxis (PrEP) are scarce and there are uncertainties regarding the value of routine HIV-1 RNA testing during oral PrEP follow-up. METHODS: The DISCOVER trial was a randomised, controlled, phase 3 trial in which cisgender men and transgender women aged 18 years and older with a high likelihood of acquiring HIV were recruited from 94 clinics in Europe and North America and randomly assigned to receive either emtricitabine plus tenofovir disoproxil fumarate (200/25 mg) tablets daily, with matched placebo tablets, or emtricitabine plus tenofovir alafenamide (200/300 mg) tablets daily, with matched placebo tablets, for at least 96 weeks. After completion of the trial, participants were offered enrolment in this 48-week open-label extension study of emtricitabine plus tenofovir alafenamide. In participants diagnosed with HIV during the randomised and open-label phases of the study, we characterised HIV-1 test results and measured HIV-1 RNA viral load retrospectively when available. Adherence based on tenofovir diphosphate concentrations in dried blood spots and genotypic resistance were assessed in participants diagnosed with HIV. Safety assessments included adverse events, laboratory parameters, and, in a subset of participants, bone mineral density. HIV-1 incidence in participants initially randomly assigned to receive emtricitabine plus tenofovir alafenamide was estimated using a Poisson distribution. Changes from baseline in safety endpoints were described in participants assigned to received emtricitabine plus tenofovir alafenamide and in those who switched from emtricitabine plus tenofovir disoproxil fumarate during the open-label phase. This trial is registered with ClinicalTrials.gov, NCT02842086, and is ongoing. FINDINGS: Between Sept 13, 2016, and June 30, 2017, 5399 participants were enrolled and randomly assigned in DISCOVER. 2699 were assigned to receive emtricitabine plus tenofovir disoproxil fumarate and 2700 were assigned to receive emtricitabine plus tenofovir alafenamide, of whom 2693 and 2694, respectively, received at least one dose of study drug. 2115 (79%) assigned to emtricitabine plus tenofovir disoproxil fumarate switched to emtricitabine plus tenofovir alafenamide in the open-label phase, and 2070 (77%) continued with emtricitabine plus tenofovir alafenamide in the open-label phase. As of data cutoff (Dec 10, 2020), after 15 817 person-years of follow-up, 27 new HIV-1 diagnoses were observed across the total study period, with three occurring during the open-label phase. In participants who were initially assigned to emtricitabine plus tenofovir alafenamide, the incidence was 0·13 per 100 person-years (95% CI 0·061-0·23; ten of 2670). Stored plasma samples were available for 23 of 27 participants, including 22 with incident infection. In four (17%) of 23 participants, retrospective testing detected HIV-1 RNA before serological HIV-1 test positivity; one was a suspected baseline infection. Of the three incident cases, all three were non-adherent to PrEP and none developed drug resistance. Among participants taking emtricitabine plus tenofovir alafenamide for up to 144 weeks, markers of glomerular filtration and proximal renal tubule dysfunction (ß2-microglobulin to creatinine ratio and retinol-binding protein to creatinine ratio) improved or remained stable at 144 weeks compared with baseline, bone mineral density in hip and lumbar spine increased or remained stable from baseline to week 144 (n=191), cholesterol and glucose concentrations remained stable, and median bodyweight increased by less than 1 kg per year. In participants who switched from emtricitabine plus tenofovir disoproxil fumarate during the open-label phase (2115 [79%] of 2693), markers of glomerular filtration and proximal renal tubule dysfunction improved or remained stable, bone mineral density increased, cholesterol concentrations increased, glucose concentrations were similar, and median bodyweight increased more compared with those who remained on emtricitabine and tenofovir alafenamide. INTERPRETATION: Routine HIV-1 RNA testing for follow-up of individuals on daily oral PrEP provides modest additional clinical benefit. Long-term use of emtricitabine and tenofovir alafenamide as daily oral PrEP is safe and well tolerated and can be an especially appropriate choice for people with bone or renal morbidities. FUNDING: Gilead Sciences.