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1.
Mikrobiyol Bul ; 54(1): 95-109, 2020 Jan.
Artigo em Turco | MEDLINE | ID: mdl-32050881

RESUMO

Chronic hepatitis B (CHB) is an important public health problem in the world and Turkey. The aim of this study was to evaluate the histological, virological, serological and biochemical response rates in CHB patients receiving tenofovir or entecavir therapy. Control liver biopsies were performed on patients who received tenofovir or entecavir therapy for one year or longer. Histopathological grading was scored according to the modified Knodell system. Eighty-seven CHB patients were included in this study, 56 patients were receiving tenofovir and 31 patients were receiving entecavir therapy. Patients in two treatment groups were similar in terms of baseline parameters (p> 0.05). At the end of the treatment, there was a significant decrease in mean values of HBV DNA, alanine aminotransferase and necroinflammatory scores for both groups (p<0.001); however, no statistically significant change was observed in fibrosis scores (p> 0.05). Histological responses were obtained 66.1% from the tenofovir group and 54.8% from the entecavir group. Treatment with tenofovir and entecavir resulted with improvement in Ishak fibrosis scores in 12.5% and 12.9% of the patients, respectively. For 14.3% of the tenofovir-treated patients and for 22.6% of the entecavir-treated patients, the Ishak fibrosis scores worsened. Baseline intermediate/ advanced fibrosis stage (Ishak fibrosis score: 3-6) was found as independent determinant factor on histological response and improvement of fibrosis score (OR= 3.99, p= 0.01; OR= 31.67, p= 0.002; respectively) and treatment duration longer than five years is an independent determinant for improvement of necroinflammatory score (OR= 5.79, p= 0.02). There was no significant difference in the virological, serological, biochemical and, histological responses and improvement of necroinflammatory and fibrosis scores between tenofovir and entecavir groups (p> 0.05). Similar histological, virological, serological and biochemical responses were obtained in patients with CHB receving tenofovir and entecavir treatments. Further studies involving a large number of patients receiving long-term therapy should be done to understand the effects of antiviral treatments on healing of liver histology.


Assuntos
Antivirais , Guanina/análogos & derivados , Hepatite B Crônica , Tenofovir , Antivirais/uso terapêutico , Guanina/uso terapêutico , Vírus da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Humanos , Fígado/patologia , Estudos Retrospectivos , Tenofovir/uso terapêutico , Resultado do Tratamento , Turquia
2.
Artigo em Inglês | MEDLINE | ID: mdl-31967210

RESUMO

A 37-year-old male patient, Fitzpatrick skin phototype IV, a student living in Belem, Amazon region, in 2015 had a confirmed diagnosis of acquired immunodeficiency virus (HIV) infection, but did not initiate antiretroviral treatment at his own option. Three years after the diagnosis, erythematous maculae appeared on the dorsum of the nose with rapid progression to the entire face, with posterior diffuse infiltration and appearance of nodules on the chin and shoulder. In December 2018, the patient presented with exacerbation of the condition with an increase in infiltrated violaceous plaques and disseminated violaceous nodules. A histopathological biopsy of the skin was performed, confirming the diagnosis of angiomatoid proliferation suggestive of Kaposi's sarcoma (KS), with an important dissemination of this disease to the noble organs. In addition, it is important to note that he only started antiretroviral therapy (ART) after the exacerbation of Kaposi (December 2018). In such cases, chemotherapy associated with ART is crucial for the treatment and follow-up of the patient, since Kaposi's sarcoma develops relatively low in patients who do not have immunodeficiency.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/complicações , Sarcoma de Kaposi/etiologia , Neoplasias Cutâneas/etiologia , Adulto , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Humanos , Lamivudina/administração & dosagem , Masculino , Sarcoma de Kaposi/diagnóstico , Tenofovir/administração & dosagem
3.
Gastroenterology ; 158(1): 215-225.e6, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31574268

RESUMO

BACKGROUND & AIMS: There have been conflicting results from studies comparing the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection treated with tenofovir disoproxil fumarate (TDF) vs those treated with entecavir. We compared the effects of TDF vs entecavir on HCC risk in a large cohort of patients with chronic HBV infection in China. METHODS: We performed a retrospective study of consecutive adults with chronic HBV infection who initially received treatment with entecavir or TDF, for at least 6 months, from January 2008 through June 2018. Patients who had cancers or liver transplantation before or within the first 6 months of treatment were excluded. Propensity score weighting and 1:5 matching were used to balance the clinical characteristics between the 2 groups. Fine-Gray model was used to adjust for competing risk of death and liver transplantation. RESULTS: We analyzed data from 29,350 patients (mean age, 52.9 ± 13.2 years; 18,685 men [63.7%]); 1309 were first treated with TDF (4.5%) and 28,041 were first treated with entecavir (95.5%). TDF-treated patients were younger (mean age, 43.2 years vs 53.4 years) and a lower proportion had cirrhosis (38 patients [2.9%] vs 3822 patients treated with entecavir [13.6%]). At a median follow-up time of 3.6 years after treatment began (interquartile range, 1.7-5.0 years), 8 TDF-treated patients (0.6%) and 1386 entecavir-treated patients (4.9%) developed HCC. Patients' clinical characteristics were comparable after propensity score weighting. TDF treatment was associated with a lower risk of HCC than entecavir treatment after propensity score weighting (weighted subdistribution hazard ratio, 0.36; 95% confidence interval 0.16-0.80; P = .013) and 1:5 matching (weighted subdistribution hazard ratio, 0.39; 95% confidence interval 0.18-0.84; P = .016). CONCLUSIONS: In a retrospective analysis of 29,350 patients with chronic HBV infection in China, treatment with TDF was associated with a lower risk of HCC than treatment with entecavir, over a median follow-up time of 3.6 years.


Assuntos
Antivirais/administração & dosagem , Carcinoma Hepatocelular/prevenção & controle , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controle , Tenofovir/administração & dosagem , Adulto , Assistência ao Convalescente , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , China/epidemiologia , Progressão da Doença , Feminino , Guanina/administração & dosagem , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Incidência , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/virologia , Cirrose Hepática/epidemiologia , Cirrose Hepática/prevenção & controle , Cirrose Hepática/virologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
5.
Medicine (Baltimore) ; 98(50): e18351, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852136

RESUMO

Tenofovir disoproxil fumarate (TDF) is thought to cause varying degrees of hypophosphatemia in patients with chronic hepatitis B (CHB). Therefore, we investigated factors that cause hypophosphatemia in patients treated with TDF and methods to increase serum phosphorus concentrations in clinical practice.We completed a retrospective review of patients with CHB treated with TDF initially at Kosin University Gospel Hospital, Busan, Korea from January 2012 to January 2017. Subclinical hypophosphatemia and hypophosphatemia were defined as serum phosphorus below 3.0 mg/dL and 2.5 mg/dL, respectively.We screened 206 patients with CHB treated with TDF, among which 135 were excluded for the following reasons: baseline malignancy (59), limited data (50), co-administered other antivirals (14), hypophosphatemia at baseline (7), and other reasons (5). The final study population comprised 71 patients. Subclinical hypophosphatemia developed in 43 (60.5%) patients. Hypophosphatemia occurred in 18 patients (25.3%). Liver cirrhosis was the most significant predictor of hypophosphatemia (P = .038, OR = 3.440, CI = 1.082-10.937) Patients diagnosed with subclinical hypophosphatemia were encouraged to increase their intake of nuts and dairy products (25 patients) or reduce their alcohol intake (2), dose reduction of TDF (4) or placed under observation (4). Among patients with subclinical hypophosphatemia, serum phosphorus concentrations were elevated (>3.0 mg/dL) in 23 of 36 patients (63.8%). Increased nut and dairy intake increased phosphorus concentrations to more than 3.0 mg/dl in 16 of 25 patients (64.0%).Entecavir or tenofovir alafenamide fumarate (TAF) should be considered rather than TDF in patients with liver cirrhosis because of the risk of hypophosphatemia. Instead of stopping TDF treatment, encouraging increased intake of phosphorus-rich foods could increase serum phosphorus concentrations in clinical practice.


Assuntos
Antivirais/efeitos adversos , Hepatite B Crônica/tratamento farmacológico , Hipofosfatemia/induzido quimicamente , Tenofovir/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
6.
S Afr Med J ; 109(12): 919-926, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31865953

RESUMO

BACKGROUND: World Health Organization guidelines recommend that HIV patients who do not achieve viral suppression on efavirenz-based first-line antiretroviral therapy (ART) should be changed to a protease inhibitor (PI)-based regimen. In South Africa (SA), ~200 000 people are on second-line treatment, but little is known about these patients. OBJECTIVES: To describe second-line black African patients in a large urban area. METHODS: A quantitative retrospective study of 825 second-line patients in central Johannesburg, SA (subdistrict F), was performed with data extracted from government databases. Demographic characteristics, treatment status and laboratory information were gathered, then analysed with CD4+ cell count, viral load (VL) and retention-in-care data as outcome variables. RESULTS: The average recorded time to VL measurement after the switch to a PI-based ART regimen was 20 months, and 83.1% (570/686) of patients with a recent VL achieved viral suppression while on second-line treatment. The most recent median CD4+ cell count for the cohort was 286 cells/µL (interquartile range 160 - 478), which represented a 177 cells/µL increase from the baseline count at the start of first-line ART. Slightly less than three-quarters (72.4%) of the population remained active in care in the study clinics from initiation on first-line ART. Demographic characteristics such as being <25 years of age, male sex and geographical transfer (started initial treatment in a different region) independently predicted low CD4+ cell counts and virological failure on second-line treatment. Patients with virological failure were most likely (odds ratio (OR) 3.13, 95% confidence interval (CI) 1.50 - 6.56) to be lost to follow-up after the switch, while patients from Hillbrow Community Health Centre (OR 0.27, 95% CI 0.16 - 0.44), South Rand Hospital (OR 0.24, 95% CI 0.12 - 0.47) and Jeppe Clinic (OR 0.38, 95% CI 0.16 - 0.88), three larger sites, were most likely to remain active in care. CONCLUSIONS: VL suppression was high in patients on second-line treatment, but one-fifth of patients were lost to follow-up. Younger age, male sex and transfer from other treatment sites predicted poor treatment outcomes, highlighting opportunities for prioritisation of adherence interventions.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Carga Viral , Adulto , Fatores Etários , Contagem de Linfócito CD4 , Bases de Dados Factuais , Quimioterapia Combinada , Feminino , Infecções por HIV/imunologia , Humanos , Lamivudina/uso terapêutico , Lopinavir/uso terapêutico , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Retratamento , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/uso terapêutico , Fatores Sexuais , Tenofovir/uso terapêutico , Falha de Tratamento , Organização Mundial da Saúde , Zidovudina/uso terapêutico
7.
Top Antivir Med ; 27(3): 123-127, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31634859

RESUMO

Antiretroviral therapy (ART) should be started as soon as possible after HIV diagnosis. Recommended starting ART regimens in patients with any baseline viral load include ictegravir plus tenofovir alafenamide (TAF)/emtricitabine (FTC), dolutegravir (DTG) plus abacavir/lamivudine, DTG plus TAF (or TDF)/FTC, or DTG plus 3TC. Initial laboratory evaluation includes CD4+ cell count, plasma HIV-1 RNA, and testing for HIV reverse transcriptase and protease resistance mutations. ART regimens do not need to be altered for virologic blips due to release of virus from chronically latently infected cells in patients otherwise exhibiting viral suppression. Patients with continuously undetectable viral load on ART pose virtually no risk of transmitting infection through sexual contact. This article is based on a case-based presentation by Michael S. Saag, MD, at the 2018 Clinical Conference at the National Ryan White Conference on HIV Care & Treatment in December 2018 and intended for clinicians who are new to HIV disease management.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Contagem de Linfócito CD4 , Didesoxinucleosídeos/uso terapêutico , Combinação de Medicamentos , Quimioterapia Combinada , Emtricitabina/uso terapêutico , Feminino , Infecções por HIV/transmissão , Transcriptase Reversa do HIV/efeitos dos fármacos , HIV-1/genética , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Inibidores de Integrase/uso terapêutico , Lamivudina/uso terapêutico , Estágios do Ciclo de Vida/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Mutação , RNA Viral/sangue , Tenofovir/uso terapêutico , Carga Viral
8.
Medicine (Baltimore) ; 98(42): e17590, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626130

RESUMO

To date, a small number of studies concerning the effects and safety of tenofovir disoproxil fumarate (TDF) in Chinese individuals were conducted. In this study, we aimed to assess the antiviral effects and nephrotoxicity of TDF in Chinese patients with chronic hepatitis B virus (HBV) infection.Patients with chronic HBV infection were prospectively recruited and TDF treatment was given for 96 weeks. HBV serologic markers, HBV DNA, creatinine and phosphorus were collected.Fifty-seven treatment-naïve and 48 treatment-experienced patients were recruited. Irrespective of the prior treatment history, more than 95% of patients achieved virological response during 96 weeks treatment with TDF. Estimated glomerular filtration rate (eGFR) significantly declined in the first year of treatment in patients with chronic hepatitis B or younger age (<65 years old) (both P < .05), while that was not achieved in patients with liver cirrhosis or older age (≥65 years old) (both P > .05). For patients who were treatment-naïve or treated previously with adefovir dipivoxil, eGFR declined at the 48th week; however, eGFR was partially recovered at the 96th week. Furthermore, multivariable analysis showed that basal eGFR <90 mL/min/1.73 m (P = .001; odds ratio: 4.821; 95% confidence interval: 1.904-12.206) is the only independent risk factor for eGFR <90 mL/min/1.73 m at the 96th week.TDF has potent antiviral effect in both treatment-naïve and treatment-experienced patients.


Assuntos
Vírus da Hepatite B/fisiologia , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Carga Viral , Adulto , Antivirais/uso terapêutico , China/epidemiologia , DNA Viral/análise , Feminino , Seguimentos , Antígenos E da Hepatite B/análise , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/virologia , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
9.
BMC Infect Dis ; 19(1): 834, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601174

RESUMO

BACKGROUND: Tenofovir alafenamide (TAF)-containing combinations were introduced in Switzerland after October 2016 and are recommended over tenofovir disoproxil fumarate (TDF) in patients with osteoporosis or impaired renal function. METHODS: We included all participants of the Swiss HIV Cohort Study on TDF-containing antiretroviral therapy with follow-up visits after January 2016. We determined the proportion of switches from TDF to TAF overall, and among patients with risk factors for TDF toxicity, including osteoporosis, impaired renal function or marked proteinuria. We used multivariable logistic regression to explore predictors of switching from TDF to TAF. RESULTS: We included 5'012 patients, of whom 652 (13.0%) had risk factors for TDF toxicity. A switch from TDF to TAF was undertaken in 2'796 (55.8%) individuals overall, and in 465 (71.3%) with risk factors. Predictors of switching to TAF were male sex (adjusted odds ratio 1.27, 95% confidence interval 1.07-1.50), age > 50 years (1.43, 1.23-1.66) and the presence of risk factors for TDF toxicity (2.21, 1.77-2.75). In contrast, patients with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based single-pill regimen (0.11, 0.09-0.13), those treated in non-tertiary care centers (0.56, 0.46-0.70), as well as those with CD4 cell counts below 500/µL (0.77, 0.66-0.90) and with chronic hepatitis C infection (0.66, 0.54-0.80) were most likely to stay on TDF. CONCLUSIONS: Over 50% of patients on TDF-containing therapy, including the majority of patients at risk for TDF toxicity, were switched to TAF within two years of its introduction in Switzerland. Individuals on NNRTI-based single-pill regimens were most likely to remain on TDF.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adenina/uso terapêutico , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Interações de Medicamentos , Feminino , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Suíça , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico
11.
Int J Clin Pharmacol Ther ; 57(12): 623-632, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31549623

RESUMO

OBJECTIVE: This study was conducted to evaluate the pharmacokinetics and bioequivalence of two emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) tablets: a newly developed generic formulation (test) and a branded formulation (reference) in healthy Chinese subjects under fasting and fed states. MATERIALS AND METHODS: A randomized, open-label, two-way crossover study was conducted in 64 healthy Chinese subjects. Subjects were randomized to receive a single oral dose of FTC 200 mg/TDF 300 mg of test or reference tablets according to an open crossover design under fasting and fed states. Plasma canagliflozin levels of FTC/TDF were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS), and the pharmacokinetic parameters of maximum concentration (Cmax) and area under the concentration-time curve (AUC0-t and AUC0-∞) were used to evaluate bioequivalence. RESULTS: The geometric mean ratio 90% confidence intervals for fasting Cmax, AUC0-t, and AUC0-∞ were 89.03 - 101.98%, 94.90 - 101.36%, and 94.94 - 101.56%, respectively, and fed Cmax, AUC0-t, and AUC0-∞ were 94.12 - 108.87%, 96.89 - 104.05%, and 96.69 - 104.28%, respectively. CONCLUSION: The two types of FTC/TDF tablets were bioequivalent under both fasting and fed condition, and both were generally well tolerated.


Assuntos
Emtricitabina/farmacocinética , Emtricitabina/uso terapêutico , Tenofovir/farmacocinética , Tenofovir/uso terapêutico , Área Sob a Curva , Cromatografia Líquida , Estudos Cross-Over , Voluntários Saudáveis , Humanos , Comprimidos , Espectrometria de Massas em Tandem , Equivalência Terapêutica
12.
World J Gastroenterol ; 25(33): 4985-4998, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31543688

RESUMO

BACKGROUND: Hepatitis B virus (HBV) DNA polymerase mutations usually occur to long term use of nucleos(t)ide analogues (NAs), but they can occur spontaneously in treatment-naïve chronic hepatitis B (CHB) patients. The naturally occurring HBV DNA polymerase mutations might complicate antiviral therapy with NAs, leading to the generation of drug-resistant viral mutants and disease progression. The most common substitutions are known to be YMDD-motif mutations, but their prevalence and the influence on antiviral therapy is unclear. AIM: To investigate prevalence of the naturally occurring rtM204I mutations in treatment-naïve CHB genotype C2 patients and their influence on antiviral therapy. METHODS: A total of 410 treatment-naïve CHB patients infected with HBV genotype C2 strains were enrolled in this retrospective study. Among the 410 patients, 232 were treated with NAs for at least 12 mo. Significant fibrosis was defined as fibrosis-4 index > 3.25 or aspartate aminotransferase to platelet ratio index > 1.5. Complete viral response (CVR) during NAs was defined as undetectable serum HBV DNA (< 24 IU/mL). The rtM204I variants were analyzed by a newly developed locked nucleotide probe (LNA probe) based real-time PCR (LNA-RT-PCR) method. RESULTS: The LNA-RT-PCR could discriminate rtM204I mutant-type (17 patients, 4.2%) from rtM204 wild-type (386 patients, 95.8%) in 403 of 410 patients (98.3% sensitivity). Multivariate analysis showed that naturally occurring rtM204I variants were more frequently detected in patients with significant fibrosis [odd-ratio (OR) 3.397, 95% confidence-interval (CI) 1.119-10.319, P = 0.031]. Of 232 patients receiving NAs, multivariate analysis revealed that achievement of CVR was reversely associated with naturally occurring rtM204I variants prior to NAs treatment (OR 0.014, 95%CI 0.002-0.096, P < 0.001). Almost patients receiving tenofovir achieved CVR at 12 mo of tenofovir, irrespective of pre-existence of naturally occurring rtM204I mutations (CVR rates: patients with rtM204I, 100%; patients without rtM204I, 96.6%), whereas, pre-existence of naturally-occurring rtM204I-mutations prior to NAs significantly affects CVR rates in patients receiving entecavir (at 12 mo: Patients with rtM204I, 16.7%; patients without rtM204I, 95.6%, P < 0.001). CONCLUSION: The newly developed LNA-RT-PCR method could detect naturally occurring rtM204I mutations with high-sensitivity. Theses mutations were more frequent in patients with liver fibrosis. Tenofovir is a more suitable treatment than entecavir for CHB patients carrying the naturally occurring rtM204I mutations.


Assuntos
Produtos do Gene pol/genética , Guanina/análogos & derivados , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Adulto , Análise Mutacional de DNA/métodos , Sondas de DNA/genética , DNA Viral/isolamento & purificação , Farmacorresistência Viral/genética , Estudos de Viabilidade , Feminino , Guanina/farmacologia , Guanina/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Oligonucleotídeos/genética , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Tenofovir/farmacologia
13.
J. bone miner res ; 34(9): 1574-1584, Sept. 2019. tab, ilus
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IIERPROD, Sec. Est. Saúde SP | ID: biblio-1016986

RESUMO

Bone mineral density (BMD) loss is a known complication of human immunodeficiency virus (HIV) infection and its treatment, particularly with tenofovir disoproxil fumarate (TDF)-containing antiretroviral regimens. Although renal proximal tubular dysfunction and phosphaturia is common with TDF, it is unknown whether BMD loss results from inadequate mineralization. We evaluated change in BMD by dual-energy X-ray absorptiometry (DXA) and bone histomorphometry by tetracycline double-labeled transiliac crest biopsies in young men living with HIV before (n = 20) and 12 months after (n = 16) initiating TDF/lamivudine/efavirenz. We examined relationships between calciotropic hormones, urinary phosphate excretion, pro-inflammatory and pro-resorptive cytokines, and bone remodeling-related proteins with changes in BMD and histomorphometry. Mean age was 29.6 ± 5.5 years, with mean CD4 + T cell count of 473 ± 196 cells/mm3 . At baseline, decreased bone formation rate and increased mineralization lag time were identified in 16 (80%) and 12 (60%) patients, respectively. After 12 months, we detected a 2% to 3% decrease in lumbar spine and hip BMD by DXA. By histomorphometry, we observed no change in bone volume/total volume (BV/TV) and trabecular parameters, but rather, increases in cortical thickness, osteoid volume, and osteoblast and osteoclast surfaces. We did not observe significant worsening of renal phosphate excretion or mineralization parameters. Increases in PTH correlated with decreased BMD but not histomorphometric parameters. Overall, these data suggest abnormalities in bone formation and mineralization occur with HIV infection and are evident at early stages. With TDF-containing antiretroviral therapy (ART), there is an increase in bone remodeling, reflected by increased osteoblast and osteoclast surfaces, but a persistence in mineralization defect, resulting in increased osteoid volume


Assuntos
HIV , Antirretrovirais , Tenofovir/uso terapêutico
14.
BMC Infect Dis ; 19(1): 721, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31416439

RESUMO

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a promising and effective tool to prevent human immunodeficiency virus (HIV) transmission; however, context-specific data to guide optimal implementation are currently lacking in China. This study aims to systematically collect comprehensive, empirical data to determine effective ways to implement PrEP among at-risk men who have sex with men (MSM) in China. METHODS: The CROPrEP project, a real-world study of PrEP use, will recruit 1000 high-risk HIV-negative MSM participants from four cities in China, who will be able to choose between daily or event-driven dosing regimens, according to their preference. Participants will be followed up at months 1, 3, 6, 9, and 12 for PrEP provision, clinical evaluation, laboratory testing (e.g., emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) concentrations, and HIV/sexually transmitted infections), alongside detailed, self-administered online questionnaires regarding sexual behaviors, adherence, and attitudes. Online weekly notes will be used to record pill use and sexual practice. Various measurements will be triangulated to assess adherence, including: self-reported adherence, pill count, and drug concentration. A propensity score matching model will be fitted to examine the effectiveness of PrEP use in HIV seroconversion compared with non-PrEP users selected from a local expanding cohort study of HIV-1-negative MSM at participating research centers. Analyses using a generalized estimating equation model will focus on elucidation of the cascade of PrEP implementation, effectiveness, safety, and possible effects of PrEP use on sexual behaviors. This study will provide a comprehensive assessment of real-world PrEP use among Chinese MSM, to develop guidelines and strategies for PrEP implementation in China. DISCUSSION: The CROPrEP project is the first study of the TDF/FTC combination as PrEP in China, which will provide primary data on PrEP implementation, including: the cascade of PrEP use, "real-world" effectiveness, adherence, and safety. The findings from this study have potential to be vital for promoting the integration of PrEP within the portfolio of HIV prevention interventions and developing guidance on PrEP implementation in China. TRIAL REGISTRATION: ChiCTR-IIN-17013762 (Chinese Clinical Trial Registry). Date of registration: 8 December 2017.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Profilaxia Pré-Exposição/métodos , Adulto , China , Estudos de Coortes , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Estudos Multicêntricos como Assunto , Sexo Seguro , Autorrelato , Comportamento Sexual/estatística & dados numéricos , Minorias Sexuais e de Gênero , Inquéritos e Questionários , Tenofovir/uso terapêutico
15.
Medicine (Baltimore) ; 98(34): e16943, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441888

RESUMO

BACKGROUND: Chronic hepatitis b (CHB) is a serious problem worldwide. Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) both are first-line drugs for CHB, but there is debate about which is more appropriate in nucleos(t)ide analogue-naive CHB. OBJECTIVE: To systematically evaluate the effectiveness and safety of tenofovir and ETV in nucleos(t)ide analogue-naive CHB. METHODS: The Web of Science, PubMed, The Cochrane Library, EMBASE, Clinical Trials, and China National Knowledge Infrastructure databases will be electronically searched to collect randomized controlled trials regarding the comparison between tenofovir and ETV in nucleos(t)ide analogue-naive CHB since the date of database inception to July 2019. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. RevMan 5.3 software will be used for the meta-analysis. RESULT: We will provide practical and targeted results assessing the effectiveness and safety of TDF and ETV for nucleos(t)ide analogue-naive CHB patients, try to compare the advantages of TDF and ETV. CONCLUSION: The stronger evidence about the effectiveness and safety of TDF and ETV for nucleos(t)ide analogue-naive CHB patients will be provided for clinicians. PROTOCOL REGISTRATION NUMBER: PROSPERO CRD42019134194.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Guanina/uso terapêutico , Humanos , Metanálise como Assunto , Revisão Sistemática como Assunto
16.
Int J Pharm ; 570: 118643, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31446023

RESUMO

Although vaginal films were initially developed for a fast release of the drug, with the adequate formulation they can also be useful for sustained release. The latest strategies for the prevention of the sexual transmission of HIV have moved towards sustained-release dosage forms, so films may be an effective strategy that could also improve the patient's comfort. A hydrophilic polymer (hydroxypropylmethyl cellulose) and an amphiphilic polymer (zein) have been evaluated for the development of Tenofovir sustained-release vaginal films. The modification of the film's properties by the inclusion of polar (glycerol and polyethylene glycol 400 (PEG)) and amphiphilic (tributyl citrate and oleic acid) plasticisers was also evaluated. The films' physicochemical and mechanical properties were determined. The in vitro release of Tenofovir from the films and their bioadhesive capacity and behaviour in simulated vaginal fluid were also assessed. The combination of hydroxypropylmethyl cellulose and zein in films (ratio 1:5), with the inclusion of PEG (40% w/w) proved not only to have excellent mechanical properties, but was also able to release TFV in a sustained manner for 120 h and remain attached to biological tissues throughout this time. This film could be an interesting option for the prevention of sexual transmission of HIV.


Assuntos
Adesivos/química , Fármacos Anti-HIV/química , Infecções por HIV/prevenção & controle , Derivados da Hipromelose/química , Polímeros/química , Vagina/efeitos dos fármacos , Zeína/química , Adesivos/administração & dosagem , Administração Intravaginal , Animais , Fármacos Anti-HIV/administração & dosagem , Linhagem Celular , Química Farmacêutica/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Feminino , Glicerol/química , Humanos , Polietilenoglicóis/química , Doenças Sexualmente Transmissíveis/prevenção & controle , Células THP-1 , Tenofovir/administração & dosagem , Tenofovir/química
17.
Int J Pharm ; 570: 118597, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31401297

RESUMO

Efavirenz (EFZ) and tenofovir disoproxil fumarate (TDF) can be used simultaneously in the treatment of human immunodeficiency virus type1 infection. In this work the impact of TDF, a hydrophilic drug, on the solubility and dissolution rate of EFZ, a poorly water-soluble drug, was evaluated. EFZ/TDF binary mixtures in different molar ratios were prepared. Differential scanning calorimetry (DSC) results indicate the formation of a eutectic mixture, the molar ratio of 65/35 being the eutectic point. It was observed an increase in the EFZ solubility in water and acidic conditions (0.1 N HCl and biorelevant medium), in the presence of TDF. On the other hand, there was a decreasing on EFZ solubility in phosphate buffer pH 6.8, probably influenced by the lower solubility of TDF in this medium. The high solubility of TDF in water and acidic medium may have contributed to improve the solubility of EFZ, as well as the formation of a eutectic mixture, supported by X-ray powder diffraction (XRPD) and Fourier Transform infrared spectroscopy (FTIR) analyses. However, TDF solubility and dissolution rate was not significantly influenced by the presence of EFZ.


Assuntos
Benzoxazinas/química , Solubilidade/efeitos dos fármacos , Tenofovir/química , Varredura Diferencial de Calorimetria/métodos , Pós/química , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X/métodos
18.
J Microbiol Immunol Infect ; 52(5): 710-719, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31427111

RESUMO

BACKGROUND: The regimen containing tenofovir disoproxil fumarate (TDF)+lamivudine or emtricitabine + efavirenz remains the recommended first-line antiretroviral therapy (ART) by the WHO. Limited studies, however, have been conducted on the incidence of renal impairment among Chinese patients with long-term exposure to TDF-containing ART regimens. METHODS: We retrospectively analyzed 269 eligible patients who had no comorbidities and received TDF-containing ART from July 2014 to April 2015. TDF-related renal impairment was defined as a decrease of eGFR by >25% from baseline or eGFR <90 ml/min/1.73 m2. Decreased renal function was defined as a decrease of eGFR by > 10 mL/min/1.73 m2 from baseline. RESULTS: 97.0% of study patients were male (median age 29, eGFR 124.0 ml/min/1.73 m2). After 168-week of ART, renal impairment occurred in 7 patients (2.7%). The incidence of decreased renal function was significantly higher at Week 168 compared with that observed at Week 12 (24.8% vs 3.7%, p < 0.001). In generalized estimating equation analysis, patients receiving ART for 144-week (aOR4.1, 95%CI 2.0-8.4) and 168-week (aOR8.4, 95%CI 4.2-16.4) were more likely to develop decreased renal function compared with those receiving ART for 12-week, so were the patients with a weight <58 kg (aOR2.3, 95%CI 1.2-4.3) and 58-66 kg (aOR2.0, 95%CI 1.0-3.8) compared to those with a weight ≥67 kg. At 168-week, 41.0% of 100 patients examined had elevated urine ß2-microglobulin levels, which were negatively correlated with eGFR (r = -0.22, p = 0.02). CONCLUSIONS: TDF-related renal impairment remained rare in HIV-positive Chinese patients with a median age of 29 years who had no comorbidities. A lower weight and duration of ART were associated with decreased renal function.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Insuficiência Renal/induzido quimicamente , Tenofovir/efeitos adversos , Adulto , Grupo com Ancestrais do Continente Asiático , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Infecções por HIV/complicações , Hepatite B Crônica/etiologia , Humanos , Rim/efeitos dos fármacos , Túbulos Renais Proximais/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Proteinúria , Insuficiência Renal/etiologia , Estudos Retrospectivos , Adulto Jovem
19.
Medicine (Baltimore) ; 98(33): e16778, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415381

RESUMO

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been widely recommended as a first-line antiviral agent to treat chronic hepatitis B (CHB). Qingzhong and Viread, formulations of TDF commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd and GlaxoSmithKline, respectively, have both been approved by the State Food and Drug Administration, China. This study analyzed the efficacy and safety of these 2 TDF agents in Chinese patients with CHB. METHODS: In this multicenter, randomized, double-blind, double-dummy, noninferiority phase 3 clinical trial (ClinicalTrials.gov identifier: NCT02287857), 330 Chinese patients with CHB [hepatitis B envelope antigen-positive (HBeAg) (+): 232] were randomly assigned to receive Qingzhong (group A: 161 patients) or Viread (group B: 169 patients) 300 mg once daily for 48 weeks. Subsequently, all patients were administered Qingzhong 300 mg once daily from week 49 to week 240. The primary end point was the degree of decline of plasma hepatitis B virus (HBV) DNA levels at week 48 and the secondary endpoints were viral suppression, normalization of alanine aminotransferase (ALT) levels, hepatitis B surface antigen (HBsAg)/HBeAg loss or seroconversion, and virological breakthrough. RESULTS: Among patients with CHB who were HBeAg (+), the mean HBV DNA titer decreased similarly between the groups at week 48. The percentages of patients who achieved undetectable HBV DNA were similar between the groups (85.11% and 82.35% in groups A and B, respectively) and similar losses of HBeAg and HBeAg seroconversion rates were achieved. Moreover, for patients with CHB who were HBeAg (-), reductions in HBV DNA were similar. Among all patients with CHB, the rates of normalization of ALT and the loss of HBsAg were similar. The overall incidence of adverse events was comparable between the groups. CONCLUSION: In conclusion, the 48-week administration of Qingzhong showed noninferior efficacy and safety profiles compared to Viread in Chinese patients with CHB.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/administração & dosagem , China , Método Duplo-Cego , Esquema de Medicação , Composição de Medicamentos , Feminino , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Tenofovir/administração & dosagem , Resultado do Tratamento , Adulto Jovem
20.
Przegl Epidemiol ; 73(2): 249-255, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31385682

RESUMO

INTRODUCTION: Chronic kidney disease is a significant cause of morbidity and mortality among patients infected with human immunodeficiency virus (HIV). Tenofovir disoproxil fumarate (TDF) is widely used as the part of combination antiretroviral therapy (cART) and may cause renal function impairment. AIM: The primary objective of this analysis was to determine the rate of reversibility of kidney dysfunction and factors correlated with eGFR improvement in patients treated with TDF. MATERIALS AND METHODS: All patients who discontinued TDF between 2003 and 2015 were screened and included in the study if the reason for withdrawal was nephrotoxicity. Kidney function (eGFR, proteinuria, haematuria) was assessed on treatment and one year after discontinuation. Factors associated with not achieving eGFR recovery one year after discontinuing TDF were assessed. RESULTS: A total of 69 patients out of 1625 screened discontinued TDF due to nephrotoxicity and were included in the analysis. At the end of the study period eGFR (CKD-EPI) improved in 52 (75,4%) patients. The eGFR difference was 11,7 ml/min/1,73m2 (95% CI: 6,0 ­ 14,5). Two factors were associated with kidney function improvement: the length of TDF treatment and baseline eGFR. Better recovery was observed in patients treated with shorter (difference: 15,6 ml/min/1,73m2, 95% CI: 5,99 ­ 23,0) and in those with impaired renal function at baseline (difference: 21 ml/min/1,73m2, 95% CI: 11,0 ­ 27,99). CONCLUSIONS: In majority of patients who discontinue TDF therapy, kidney function improves during oneyear period. The drug withdrawal in case of eGFR deterioration should not be postponed.


Assuntos
Nefropatias/induzido quimicamente , Tenofovir/efeitos adversos , Adulto , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Antirretrovirais/toxicidade , Feminino , Taxa de Filtração Glomerular , Infecções por HIV/tratamento farmacológico , Hematúria , Humanos , Masculino , Pessoa de Meia-Idade , Proteinúria , Estudos Retrospectivos , Tenofovir/uso terapêutico , Tenofovir/toxicidade
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