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1.
J Infect Dis ; 215(4): 606-613, 2017 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-28011921

RESUMEN

Background: Previous studies have shown that the durability of serological response is impaired in successfully vaccinated human immunodeficiency virus-1 (HIV-1) positive subjects after receiving 2 doses of inactivated hepatitis A virus (HAV) vaccine. We evaluated whether 3 doses compared with 2 doses of HAV vaccine could improve the long-term seroprotection for this susceptible group. Methods: Antibody persistence among HIV-positive men who have sex with men aged 18-40 years who had received 2 or 3 doses of HAV vaccine according to a 0-6- or a 0-1-6-month schedule was evaluated biannually for 5 consecutive years in this prospective, nonrandomized cohort study. Results: At the end of 5 years, seroprotection persisted in 79% (146/185) versus 76% (85/110) and 94% (146/155) versus 88% (84/95) of the 3- versus 2-dose primary responders by intention-to-treat and per-protocol analyses, respectively (P > .05). Throughout the 5 years, the geometric mean concentrations of anti-HAV immunoglobulin G (IgG) were significantly higher for the 3-dose than the 2-dose group. In the multivariable analysis, a 3-dose regimen compared with a 2-dose regimen (odds ratio = 3.36; 95% confidence interval = 1.14-9.93) was independently associated with sustained seroprotection. Conclusions: Three doses versus 2 doses of HAV vaccine improve the durability of immune responses in terms of higher concentrations of specific IgG, which take longer to decay to subthreshold levels.


Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Vacunas contra la Hepatitis A/administración & dosificación , Adolescente , Adulto , Recuento de Linfocito CD4 , Relación Dosis-Respuesta Inmunológica , Estudios de Seguimiento , Infecciones por VIH/inmunología , Hepatitis A/prevención & control , Anticuerpos de Hepatitis A/sangre , Humanos , Inmunización Secundaria , Inmunoglobulina G/sangre , Estudios Longitudinales , Masculino , Análisis Multivariante , Estudios Prospectivos , ARN Viral/aislamiento & purificación , Factores de Tiempo , Vacunación , Vacunas de Productos Inactivados/administración & dosificación , Carga Viral , Adulto Joven
2.
Clin Infect Dis ; 58(11): 1625-33, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24599769

RESUMEN

BACKGROUND: Superinfection with hepatitis D virus (HDV) may increase the risk for hepatitis flares and chronic hepatic complications in patients with chronic hepatitis B virus (HBV) infection. This retrospective observational study aimed to examine the incidence of and factors associated with recent HDV superinfection among individuals coinfected with human immunodeficiency virus (HIV) and HBV. METHOD: Anti-HDV immunoglobulin G (IgG) was sequentially determined in 375 HIV/HBV-coinfected patients to estimate the HDV incidence between 1992 and 2012. Plasma HDV and HBV loads and HBV surface antigen (HBsAg) levels were determined for the HDV seroconverters. A nested case-control study was conducted to identify the associated factors with HDV seroconversion. Phylogenetic analysis was performed using HDV sequences amplified from HDV seroconverters and HDV-seropositive patients at baseline. RESULTS: During 1762.4 person-years of follow-up [PYFU], 16 patients seroconverted for HDV, with an overall incidence rate of 9.07 per 1000 PYFU, which increased from 0 in 1992-2001, to 3.91 in 2002-2006, to 13.26 per 1000 PYFU in 2007-2012 (P < .05). Recent HDV infection was associated with elevated aminotransferase and bilirubin levels and elevated rapid plasma reagin titers. Of the 12 patients with HDV viremia, 2 were infected with genotype 2 and 10 with genotype 4. HBsAg levels remained elevated despite a significant decline of plasma HBV DNA load with combination antiretroviral therapy that contained lamivudine and/or tenofovir. CONCLUSIONS: Our findings show that the incidence of recent HDV infection in HIV/HBV-coinfected patients increased significantly from 1992-2001 to 2007-2011, and was associated with hepatitis flares and syphilis.


Asunto(s)
Infecciones por VIH/complicaciones , Hepatitis B Crónica/complicaciones , Hepatitis D/epidemiología , Virus de la Hepatitis Delta/aislamiento & purificación , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , ADN Viral/aislamiento & purificación , Femenino , Anticuerpos Antihepatitis/sangre , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/aislamiento & purificación , Virus de la Hepatitis Delta/clasificación , Virus de la Hepatitis Delta/inmunología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Filogenia , Plasma/virología , ARN Viral/genética , ARN Viral/aislamiento & purificación , Estudios Retrospectivos , Factores de Riesgo , Análisis de Secuencia de ADN , Carga Viral
3.
J Infect Chemother ; 20(8): 465-70, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24855915

RESUMEN

OBJECTIVES: The study aimed to investigate the incidence of and associated factors with skin rashes among HIV-infected Taiwanese patients who received once-daily darunavir (DRV) boosted by ritonavir (RTV) (800/100 mg) plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs). METHODS: We reviewed the medical records of HIV-infected patients who switched to once-daily DRV/RTV-containing regimens between January 2012 and November 2013. Patients who switched from 2 NRTIs plus non-NRTI (nNRTI) or other protease inhibitor (PI) to 2 NRTIs plus PIs other than DRV were chosen as comparators. RESULTS: During the study period, 238 patients who switched to once-daily DRV/RTV-containing regimens (Group A) and 178 patients who switched from 2 NRTIs plus nNRTI or other PI to 2 NRTIs plus PI other than DRV/RTV (Group B) were included. There were no differences between Groups A and B in most of the baseline characteristics. Compared with Group B in which 7 (3.9%) developed rashes after switch to PI other than DRV, 26 patients (10.9%) in Group A developed rashes after a median interval of 14 days of starting DRV/RTV-containing regimens (P = 0.009). In multivariate analysis, patients with a history of rashes related to the previous nNRTI-containing regimens before starting DRV/RTV-containing regimens were more likely to develop rashes with an adjusted odds ratio of 3.53 (95% confidence interval, 1.45-8.62). CONCLUSIONS: Once-daily regimens containing DRV/RTV is associated with a higher rate of adverse cutaneous reactions than other PI-containing regimens in HIV-infected Taiwanese, especially in those who have a history of rashes to nNRTI-containing regimens before switch to DRV/RTV-containing regimens.


Asunto(s)
Antirretrovirales/efectos adversos , Exantema/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Sulfonamidas/efectos adversos , Adulto , Antirretrovirales/administración & dosificación , Antirretrovirales/uso terapéutico , Darunavir , Exantema/etiología , Femenino , Infecciones por VIH/complicaciones , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Taiwán/epidemiología
4.
Int J Infect Dis ; 126: 39-47, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36384186

RESUMEN

OBJECTIVES: Real-world experience with coformulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) is sparse as a switch regimen among people living with HIV (PLWH) having achieved viral suppression after previous virologic failures with the emergence of K65N/R. METHODS: In this retrospective study, PLWH aged ≥20 years who had previous virologic failures with emergent K65N/R were included for switching to BIC/FTC/TAF after having achieved plasma HIV RNA load (PVL) <200 copies/ml for ≥3 months. PLWH were excluded if integrase inhibitor resistance-associated mutations were detected. The primary end point was losing virologic control (PVL >50 copies/ml) at week 48 using a modified US Food and Drug Administration snapshot algorithm. RESULTS: A total of 72 PLWH with K65N/R who switched to BIC/FTC/TAF were identified. A total of 42 (59.7%) had concurrent M184V/I, and 9 (12.5%) had ≥1 thymidine analog mutations. The median duration of viral suppression was 4.7 years (interquartile range 2.3-5.8), and 97.2% (n = 70) had PVL <50 copies/ml before switching. After a median observation of 98.6 weeks (interquartile range 77.9-120.3), 94.4% (n = 68) continued BIC/FTC/TAF. At week 48, the rate of losing virologic control was 2.8% (2/72). M184V/I was not associated with viral rebound. CONCLUSION: Despite the emergence of K65N/R +/- M184V/I after virologic failures, BIC/FTC/TAF could be an option for simplification after viral suppression.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Adulto , Humanos , Emtricitabina/uso terapéutico , Tenofovir/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Estudios Retrospectivos , Combinación de Medicamentos , Adenina/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Mutación , Fármacos Anti-VIH/uso terapéutico , Alanina/uso terapéutico , Carga Viral
5.
Open Forum Infect Dis ; 10(6): ofad307, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37383254

RESUMEN

Using 3-stage pooled-plasma hepatitis C virus (HCV) RNA testing performed quarterly among at-risk people with human immunodeficiency virus (PWH), we found that if testing had been performed every 6 or 12 months, 58.6%-91.7% of PWH who recently acquired HCV would be delayed for diagnosis and might contribute to onward HCV transmission with longer durations.

6.
J Microbiol Immunol Infect ; 55(1): 18-25, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32690395

RESUMEN

BACKGROUND: Single dose hepatitis A virus (HAV) vaccine had been proven its efficacy in immunocompetent but not immunocompromised hosts. We aim to investigate the effectiveness of one dose versus 2 doses HAV vaccine among people living with HIV (PLHIV). METHOD: We conducted a 1:1 single center retrospective case-control study for PLHIV in Northern Taiwan. Case patients were those who received single dose HAV vaccine and controls were those who completed standard 2 doses HAV vaccine. Nationwide campaign of single dose HAV vaccine had been practiced for high risk population including PLHIV and those who had newly diagnosed sexually transmitted diseases. RESULTS: During February 2016 and December 2017, 90 cases received single dose HAV vaccine provided while the other 90 age-matched controls received 2 doses vaccine were enrolled. We found more injection drug users (22.22% vs. 1.11%, p < 0.0001), more co-infection with viral hepatitis C (28.89% vs. 5.56%, p < 0.0001), and history of syphilis infection (56.67% VS 30%, p = 0.0003) in single dose group than 2 doses group. Seroconversion rate at one year was significantly higher in 2 doses group (97.78% vs 56.67%, p < 0.0001). Among single dose group, people with hepatitis B or C virus co-infection (HBV: p = 0.02, aOR: 0.03, 95% CI: 0.002-0.55; HCV: p = 0.002, aOR: 0.22, 95% CI: 0.08-0.58) were less likely to achieve seropositivity, while those who had higher CD4 count at baseline and one year, had better response to vaccine. CONCLUSION: Two doses HAV vaccine is necessary among PLHIV to achieve sustained seroresponse rather than single dose.


Asunto(s)
Infecciones por VIH , Hepatitis A , Estudios de Casos y Controles , Hepatitis A/epidemiología , Hepatitis A/prevención & control , Vacunas contra la Hepatitis A , Humanos , Estudios Retrospectivos , Taiwán/epidemiología , Vacunación
7.
J Microbiol Immunol Infect ; 55(6 Pt 1): 1052-1059, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36028414

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) has circulated in Taiwan since late 2019. Healthcare facilities are vulnerable to COVID-19 outbreaks due to clusters of symptomatic patients and susceptible hosts. Prompt control of outbreaks is crucial. In May 2021, an index case of COVID-19 was detected at Far Eastern Memorial Hospital (FEMH) in New Taipei City, Taiwan, 3 days after hospital admission, spreading to 26 patients and staff. Herein we evaluate control of this COVID-1 outbreak. METHODS: To control the outbreak, the index case ward was closed, and large-scale COVID-19 testing (RT PCR) was performed for all inpatients, caregivers and healthcare workers (HCWs). All exposed persons were quarantined. Thorough investigation was conducted to analyze the transmission route. RESULTS: The outbreak comprised 12 patients, 12 caregivers, and 3 HCWs. Seven patients expired and the remaining cases recovered. Overall, 456 patients/caregivers and 169 HCWs were quarantined. Analysis showed that longer exposure time was the main cause of HCW infection; all three infected HCWs were primary-care nurses related to the index case. To diminish hidden cases, all hospitalized patients/caregivers received PCR examinations and all results were negative. Thereafter, all patients/caregivers routinely received PCR examination on admission. Hospital-wide PCR screening for HCW detected 4 positive HCWs unrelated to this outbreak, and a second-round of screening detected 2 more cases, with no additional cases during the following 6 months. CONCLUSION: Prompt infection control measures and large-scale PCR screening can control a COVID-19 outbreak within 2 weeks. Exposure time is the major risk factor for HCW infection.


Asunto(s)
COVID-19 , Brotes de Enfermedades , Control de Infecciones , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Prueba de COVID-19 , Brotes de Enfermedades/prevención & control , Personal de Salud , Taiwán/epidemiología , Centros de Atención Terciaria , Trazado de Contacto
8.
Int J Infect Dis ; 104: 718-724, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33515776

RESUMEN

OBJECTIVE: To determine serogroups, multilocus sequence typing (MLST) of Listeria monocytogenes isolates and analyze clinical characteristics of these clones focusing on non-perinatal cases. METHODS: From 2000 to 2015, we analyzed 123 human listeriosis cases at a medical center in northern Taiwan using PCR serogrouping, MLST, and clinical presentations. RESULTS: The annual incidence of listeriosis increased since 2005 with a peak in 2008 (0.2 per 1000 admission) and decreased thereafter. Of the 115 non-perinatal listeriosis cases, we found a male predominance (60%) with an average age of 63.9 years old (standard deviation: 15.3 years), and almost all patients had underlying conditions including malignancies (61.7%), steroid usage (39.1%), diabetes mellitus (31.3%), renal insufficiency (27.8%), and liver cirrhosis (17.4%). Clinical presentations included bacteremia (74.8%), neurolisteriosis (20.0%), and spontaneous bacterial peritonitis (5.2%). The most frequently identified serogroup-sequence types (ST) were IIB-ST87 (30.9%), followed by IIA-ST378 (16.3%) and IIA-ST155 (14.6%). The 30-day all-cause mortality of non-perinatal listeriosis was 25.2% and was associated with age (Hazard ratio: 1.04, 95% C.I. = 1.01-1.07, p = 0.021), steroid usage (Hazard ratio: 2.54, 95% C.I. = 1.06-6.11, p = 0.038) and respiratory distress at presentation (Hazard ratio: 2.59, 95% C.I. = 1.05-6.39, p = 0.038); while no association was found with serogroups (IIA, IIB, and IVB) or three major ST types by multivariable analysis. All 8 mothers of perinatal listeriosis patients survived and three neonates died (mortality, 37.5%), and IIB-ST87 was the major type (62.5%). CONCLUSION: Predominant strains in Taiwan could cause significant morbidity and mortality. Further disease monitoring and source surveillance are warranted despite a declining trend of human listeriosis in Taiwan.


Asunto(s)
Listeria monocytogenes/genética , Listeriosis/epidemiología , Listeriosis/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/diagnóstico , Bacteriemia/epidemiología , Bacteriemia/microbiología , Bacteriemia/mortalidad , Femenino , Humanos , Incidencia , Listeria monocytogenes/aislamiento & purificación , Listeriosis/diagnóstico , Listeriosis/mortalidad , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Tipificación de Secuencias Multilocus , Reacción en Cadena de la Polimerasa , Taiwán/epidemiología
9.
Infect Dis Ther ; 10(3): 1363-1377, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34057690

RESUMEN

INTRODUCTION: Screening for cryptococcal antigen (CrAg) is recommended for people living with HIV (PLWH) who present with low CD4 lymphocyte counts. Real-world experience is important to identify gaps between the guidelines and clinical practice. We investigated the trends of CrAg testing and prevalence of cryptococcal antigenemia among PLWH at the time of HIV diagnosis and the related mortality in Taiwan from 2009 to 2018. METHODS: Medical records of newly diagnosed PLWH seeking care at six medical centers around Taiwan between 2009 and 2018 were reviewed. The annual trends of PLWH who had CrAg testing and cryptococcal antigenemia were examined by Cochran-Armitage test. Among PLWH with CD4 < 200 cells/µl, timing of CrAg testing was analyzed for association with 12-month all-cause mortality in Kaplan-Meier plots and in a Cox proportional hazards model after adjustments. RESULTS: Among 5372 included PLWH, 1150 (21.4%) presented with baseline CD4 < 100 cells/µl, and this proportion had decreased during the study period [from 108 (29.3%) in 2009 to 93 (22.3%) in 2018 (P = 0.039)]. The overall prevalence of cryptococcal antigenemia was 7.8% among PLWH with CD4 < 100 cells/µl, which remained stable during the 10-year study period (P = 0.356) and was 2.6% among PLWH with CD4 100-199 cells/µl. The uptake of CrAg testing had increased from 65.7% in 2009 to 78.0% in 2018 (P = 0.002) among PLWH with CD4 < 100 cells/µl. Late CrAg testing, defined by 14 days or later after HIV diagnosis, was associated with increased risk of 12-month mortality compared to early CrAg testing (adjusted hazard ratio 2.028, 95% CI 1.109-3.708). CONCLUSIONS: Burden of cryptococcosis remained high among PLWH with low CD4 lymphocyte counts in Taiwan. Uptake of CrAg screening among late HIV presenters was still suboptimal and delayed. Late CrAg testing was associated with a higher mortality.

11.
J Microbiol Immunol Infect ; 53(6): 909-915, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32859532

RESUMEN

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA)-associated central nervous system infections are potentially devastating. Linezolid has good penetration into cerebrospinal fluid and brain tissue. In clinical practice, linezolid may be used to treat central nervous system infections caused by MRSA resulting from glycopeptide intolerance or treatment failure. However, the clinical experience of linezolid in treating MRSA related central nervous system infections is scarce. METHODS: From 2006 to 2016, patients aged ≥20 years who had central nervous system infections caused by MRSA treated with linezolid for more than 24 hours were retrospectively included from two medical centers. The demographic details, treatment response, side effects, and relapse of infection were reviewed. RESULTS: Sixty-six patients with proven CNS infection caused by MRSA were treated with linezolid. The mean age was 53.3 years. The diagnoses in this cohort consisted of brain abscesses (n = 19, 28.8%), spinal epidural abscess (n = 18, 27.3%), meningitis only (n = 12, 18.2%), meningitis with brain epidural abscess (n = 9, 13.6%), and spine device-related infection (n = 5, 7.6%). The main reasons to prescribe linezolid were glycopeptide treatment failure (51.5%) and glycopeptide allergy (48.5%). Ninety-one percent of patients were treated with linezolid for more than 14 days. The in-hospital mortality rate was 13.6%. The relapse rate after treatment was 16.7%. Drug-related adverse events (mainly cytopenia) were observed in 27.3% of patients, but none of the adverse events was fatal. CONCLUSIONS: In our retrospective study, linezolid demonstrated promising effect as a salvage therapy for central nervous system infection caused by MRSA, whether due to drug allergy or glycopeptide treatment failure.


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones del Sistema Nervioso Central/tratamiento farmacológico , Linezolid/uso terapéutico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Terapia Recuperativa , Infecciones Estafilocócicas/tratamiento farmacológico , Absceso Encefálico/tratamiento farmacológico , Absceso Encefálico/microbiología , Infecciones del Sistema Nervioso Central/microbiología , Absceso Epidural/tratamiento farmacológico , Absceso Epidural/microbiología , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Meningitis Bacterianas/tratamiento farmacológico , Meningitis Bacterianas/microbiología , Persona de Mediana Edad , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/microbiología , Estudios Retrospectivos , Taiwán
12.
PLoS Negl Trop Dis ; 14(6): e0008400, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32530918

RESUMEN

Recent outbreaks of enterically transmitted infections, including acute hepatitis A and shigellosis, have raised the concerns of increasing Entamoeba histolytica infection (EHI) among people living with HIV (PLWH) in Taiwan. This study investigated the prevalence of EHI, its temporal trends, and associated factors among newly diagnosed PLWH in Taiwan. Medical records of newly diagnosed PLWH at six medical centers in Taiwan between 2009 and 2018 were reviewed. The annual prevalence of invasive amoebiasis and seroprevalence of E. histolytica were determined and examined by the Cochran-Armitage test. The clinical characteristics associated with invasive amoebiasis and seropositivity for E. histolytica were analyzed in multivariable regression models. Among 5362 patients seeking HIV care at six medical centers in Taiwan during the 10-year study period, 119 (2.2%) had invasive amoebiasis at the time or within six months of their HIV diagnosis. Among 3499 who had indirect hemagglutination antibody (IHA) determined, 284 (8.1%) had positive IHA (≥1:32) and 205 (5.9%) had high-titre IHA (≥1:128). The prevalence of invasive amoebiasis increased from 1.3% in 2012 to 3.3% in 2018 (p = 0.024). Invasive amoebiasis was independently associated with a greater age, men who have sex with men, rapid plasma reagin titre ≥1:4, and concurrent shigellosis and giardiasis. Increasing prevalence of invasive amoebiasis among newly diagnosed PLWH in Taiwan calls for strategies to prevent ongoing transmission in this population. Routine screening of EHI for early diagnosis and treatment is recommended, especially among men who have sex with men and those who present with other sexually or enterically transmitted infections.


Asunto(s)
Entamoeba histolytica , Entamebiasis/epidemiología , Entamebiasis/transmisión , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Adulto , Factores de Edad , Anticuerpos Antiprotozoarios/sangre , Estudios Transversales , Entamebiasis/diagnóstico , Femenino , Homosexualidad Masculina , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Seroepidemiológicos , Minorías Sexuales y de Género , Taiwán/epidemiología , Adulto Joven
14.
Clin Lung Cancer ; 20(3): e274-e283, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30930121

RESUMEN

BACKGROUND: As the first-line treatment, afatinib is commonly used in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, dose adjustments are frequently required. The optimal dose of afatinib for brain metastasis has seldom been investigated. PATIENTS AND METHODS: From May 2014 to March 2017, treatment-naive patients with advanced EGFR-mutated NSCLC and brain metastases at diagnosis who received afatinib therapy were retrospectively enrolled. Clinical data was reviewed and analyzed, including age, gender, performance status, smoking history, EGFR mutation status, initial doses of afatinib, average daily doses of afatinib, and best intracranial treatment responses. RESULTS: A total of 74 patients were included for analysis. The overall intracranial objective response rate (IORR) and intracranial disease control rate (IDCR) were 81.1% and 95.9%, respectively. For patients treated with afatinib alone (N = 45), no significant difference between an initial daily dose of 30 mg (N = 15) and 40 mg (N = 30) (30 mg vs. 40 mg, IORR: 86.7% vs. 80.0%; P = .581 and IDCR: 93.3% vs. 93.3%; P = 1.000, respectively). The IORRs were 75.0%, 91.7%, 80.0%, and 85.7% (P = .707), and the IDCRs were 93.8%, 100.0%, 90.0%, and 85.7% (P = .638) in patients with an average daily dose of 40 mg (N = 16), < 40 mg and > 30 mg (N = 12), 30 mg (N = 10), and < 30 mg and > 20 mg (N = 7), respectively. No significant differences in intracranial treatment responses between groups treated with afatinib alone or afatinib plus local treatments. CONCLUSION: Dose reduction may not affect intracranial treatment responses to afatinib therapy, either alone or combined with local treatments, in patients with advanced EGFR-mutated NSCLC and brain metastases.


Asunto(s)
Afatinib/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Encéfalo/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Afatinib/provisión & distribución , Encéfalo/efectos de los fármacos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/secundario , Cálculo de Dosificación de Drogas , Receptores ErbB/genética , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación/genética , Resultado del Tratamiento
15.
J Int AIDS Soc ; 22(8): e25383, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31423752

RESUMEN

INTRODUCTION: An age-specific evaluation and management algorithm for reduced bone mineral density (BMD) is suggested for HIV-positive patients without major risk factors. Whether combination of BMD and the Fracture Risk Assessment Tool (FRAX) may detect more individuals for therapeutic interventions remains unclear. We aimed to determine the prevalence of middle-aged or older HIV-positive males fitting the criteria of therapeutic interventions with different approaches. METHODS: From July 2016 to February 2018, HIV-positive male patients aged ≥45 years receiving suppressive antiretroviral therapy were recruited in a cross-sectional study, at two designated hospitals for HIV care in northern Taiwan. Patients with malignancy, AIDS, pre-existing bone disease or immobilization were excluded. Information on clinical and demographic characteristics, FRAX questionnaire, activity questionnaire, BMD and serum 25(OH)D was obtained. FRAX scores combined with BMD (FRAX/BMD) and without BMD (FRAX) were calculated. The data were analysed on the basis of major risk factors for fragility fracture and age stratification, FRAX score and BMD results respectively. RESULTS: We enrolled 330 patients with a mean age of 51.6 years and CD4 610 cells/µL, in whom 98.1% (n = 324) underwent BMD assessment of one site or more. By FRAX, 6.7% (n = 22) reached treatment thresholds (10-year risk of major osteoporotic fracture ≥20% and/or hip fracture ≥3%). The prevalence of osteopenia (-2.5

Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Fracturas Óseas/etiología , Seropositividad para VIH/complicaciones , Adulto , Algoritmos , Densidad Ósea , Estudios Transversales , Seropositividad para VIH/tratamiento farmacológico , Seropositividad para VIH/epidemiología , Fracturas de Cadera/etiología , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/etiología , Fracturas Osteoporóticas/etiología , Prevalencia , Factores de Riesgo , Encuestas y Cuestionarios , Taiwán/epidemiología
16.
J Microbiol Immunol Infect ; 52(5): 700-709, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29555411

RESUMEN

BACKGROUND/PURPOSE: Acute HIV infection is characterized by a high concentration of HIV RNA in the plasma and rapid depletion of the CD4 cell count. This multicenter, retrospective observational study aimed to characterize the manifestations of acuteHIV infection in Taiwan. METHODS: Between 1 January 2012 and 31 December 2016, all patients aged 20 years or greater who presented with acute HIV infection were included. Demographic and clinical characteristics of the patients at diagnosis were collected. Baseline laboratory assessment included hemogram, CD4 count, plasma HIV RNA load (PVL), serologic markers of syphilis and hepatitis A, B, and C viruses, and serum biochemistry. RESULTS: The proportion of acute HIV infection was 6.9% among the patients with newly diagnosed HIV infection during the study period. The most common presenting symptoms of acute HIV infection were fever, fatigue, and myalgia. The median PVL at diagnosis was 5.9 log10 copies/ml, and median CD4 count was 307 cells/mm3. A total of 68 patients (27%) had baseline CD4 count less than 200 cells/mm3. Multiple logistic regression analysis, showed that the baseline CD4 count (OR, 4.02; p = 0.013) and aspartate aminotransaminase levels (OR, 3.49; p = 0.002) were associated with high PVL (>5 log10 copies/ml); and high baseline PVL (OR, 2.64; p = 0.002) was associated with symptomatic acute HIV infection. CONCLUSIONS: Manifestations of acute HIV infection are nonspecific and of wide spectrum ranging from fever to severe illness. A higher proportion of patients with initial CD4 counts of 200 cells/mm3 or less during acute HIV infection warrants early, timely diagnosis and treatment to prevent rapid disease progression.


Asunto(s)
Infecciones por VIH/sangre , Infecciones por VIH/diagnóstico , Infecciones por VIH/fisiopatología , Adulto , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Fatiga , Femenino , Fiebre , Infecciones por VIH/complicaciones , Humanos , Mononucleosis Infecciosa , Modelos Logísticos , Masculino , Meningitis Aséptica/etiología , Mialgia , ARN Viral/sangre , Análisis de Regresión , Estudios Retrospectivos , Sífilis , Taiwán , Carga Viral , Adulto Joven
19.
Eur J Cancer ; 103: 32-40, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30199768

RESUMEN

INTRODUCTION: Afatinib is commonly used as the first-line treatment for EGFR-mutated lung adenocarcinoma. However, dose adjustments are frequently required. This study aimed to investigate the treatment effectiveness of afatinib administered at different doses to patients with EGFR-mutated lung adenocarcinoma. METHODS: Treatment-naïve patients with advanced EGFR-mutated lung adenocarcinoma who received afatinib therapy between May 2014 and September 2016 were enrolled retrospectively. Collected clinical data included age, sex, smoking history, performance status, disease stages, EGFR mutation status, initial doses of afatinib, dose adjustments, treatment responses, progression-free survival and treatment-associated adverse events. The average daily dose was calculated by dividing the summation of all doses of prescribed tablets during the treatment period by the total days of afatinib use. The patients were classified into five treatment groups based on average daily doses: 40 mg, <40 and >30 mg, 30 mg, <30 and ≥ 20 mg and <20 mg. RESULTS: A total of 254 patients were included. No significant differences were found among these five treatment groups with respect to response rates (69.3%, 68.3%, 70.5%, 77.8% and 66.7%, respectively, p = 0.920) and disease control rates (97.4%, 95.2%, 97.7%, 100% and 100%, respectively, p = 0.749). However, the treatment group with an average daily dose of <20 mg had a significant shorter progression-free survival as compared with the other groups (16.8, 12.4, 13.9, 17.0 and 5.3 months, respectively, p = 0.049). CONCLUSIONS: Dose reduction may not affect the treatment effectiveness until the average daily dose is below 20 mg. Further prospective studies of afatinib therapy at different daily doses are warranted.


Asunto(s)
Adenocarcinoma del Pulmón/tratamiento farmacológico , Afatinib/uso terapéutico , Antineoplásicos/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Adenocarcinoma del Pulmón/patología , Afatinib/farmacología , Antineoplásicos/farmacología , Receptores ErbB , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/farmacología
20.
Infect Drug Resist ; 11: 849-859, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29892199

RESUMEN

BACKGROUND: Increasing trends of resistance-associated mutations (RAMs) to non-nucleoside reverse-transcriptase inhibitors (nNRTIs) have raised concerns about the effectiveness of the regimens in the national HIV treatment programs in resource-limited countries. We aimed to retrospectively investigate the incidence and patterns of emergent RAMs of HIV-1 in HIV-positive adults experiencing virological failure to first-line nNRTI-containing combination antiretroviral therapy (cART) in Taiwan. PATIENTS AND METHODS: Between June 2012 and March 2016, 1138 antiretroviral-naïve HIV-positive adults without baseline RAMs who initiated nNRTI-containing regimens were included for analysis. Virological failure was defined as plasma viral load (PVL) ≥200 copies/mL after 6 months of cART or confirmed PVL ≥200 copies/mL after achieving PVL <50 copies/mL. Population sequencing was retrospectively performed to detect baseline and emergent RAMs. RAMs were interpreted using the International AIDS Society-USA 2016 mutations list. RESULTS: Seventy-one patients (6.2%) developed virological failure, which occurred in 14.8% (43/291), 3.9% (26/675), and 1.2% (2/172) of patients receiving 2 nucleoside reverse-transcriptase inhibitors (NRTIs) plus nevirapine, efavirenz, and rilpivirine, respectively. Among those, 53 (74.6%) had emergent RAMs identified, which included 43 (81.1%), 53 (100.0%), and 1 (1.9%) with RAMs to NRTIs, nNRTIs, and protease inhibitors, respectively; and 43 (81.1%) had multi-drug resistance. The most common emergent RAMs to NRTIs were M184V/I (42.3%) and K65R (28.2%), and those to nNRTIs were Y181C (42.3%), K103N (15.5%), G190A/E/Q (12.7%), V179D/E (12.7%), and V108I (9.9%). CONCLUSION: While the rates of virological failure varied with the nNRTI used, the rate of emergent RAMs of HIV-1 to NRTIs and nNRTIs among the antiretroviral-naïve patients who failed nNRTI-containing cART remained low.

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