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2.
Medicine (Baltimore) ; 99(32): e21454, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769872

RESUMO

The impact of different antiviral regimen on prognosis of chronic hepatitis B (CHB) related hepatocellular carcinoma (HCC) remains to be explored.A total of 479 CHB-related HCC patients after curative liver resection were enrolled receiving tenofovir (TDF, TDF group) or lamivudine, telbivudine, and entecavir (non-TDF group). Both the overall survival and diseases-free survival were analyzed and compared.A total of 242 patients received TDF treatment and 237 patients received other antiviral regimen. Child-Pugh score, serum α-fetoprotein (AFP) level, total bilirubin level, status of hepatitis B e antigen (HBeAg), and cirrhosis were compared between groups. Kaplan-Meier analysis revealed that patients with TDF treatment had significantly longer overall survival than those of patients with other regimen (P = .015). Similarly, compared with patients with non-TDF treatment, disease-free survival time was longer (P = .042) in those with TDF treatment. Multivariate analysis showed that TDF treatment (P = .04), AFP level (P = .03) were significant independent factors associated with overall survival of CHB-related HCC patients. While TDF treatment (P = .04) and serum AFP level (P = .03) were independent factors associated with disease-free survival.Anti-virus treatment with TDF benefits for both overall survival and disease-free survival of CHB-related patients than other Nucleos(t)ide analogues.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/complicações , Hepatectomia , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/complicações , Tenofovir/uso terapêutico , Adulto , Carcinoma Hepatocelular/cirurgia , China , Estudos de Coortes , Feminino , Hepatite B Crônica/etiologia , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento
3.
BMC Infect Dis ; 20(1): 582, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762646

RESUMO

BACKGROUND: Limited data are available on the effect of antiretroviral treatment (ART) or Tenofovir disoproxil fumarate (TDF) on renal function in Ethiopians. We aimed to assess factors associated with renal function changes during the first year of ART with special focus on TDF. METHODS: HIV positive persons who were ≥ 18 years of age and eligible for ART initiation were recruited. Creatinine measurement to estimate glomerular filtration rate (eGFR) and spot urine analyses were performed at baseline and after 3, 6 and 12 months of ART. Univariate and multivariate linear regression and univariate logistic regression were used to determine factors associated with eGFR as continuous and categorical variable respectively. A linear mixed model was used to assess 12 month eGFR difference in TDF and non-TDF based regimen. RESULT: Of 340 ART-naïve HIV patients with baseline renal function tests, 82.3% (279/339) were initiated on a TDF based ART regimen. All patients were on non-nucleoside reverse transcriptase inhibitors (NNRTI) based ART regimen. The median (IQR) change in eGFR with 12 months of ART was 0.8 (- 11.1; 10.0) ml/min/1.73m2. About 41 and 26.9% of HIV patients had a drop of greater than 3 and 10 mL/min/1.73 m2 in eGFR at 12 month, respectively. However, none of the HIV patients declined to < 60 ml/min/1.73m2 within 12 months. Moreover, none of the HIV patients had persistent proteinuria or glycosuria. Older HIV patients especially age > 45 years and those with unsuppressed viral load at 6 month of ART had a significantly lower eGFR at 12 months of ART initiation. However, there was no difference in 12 month eGFR between HIV patients initiated on TDF based regimen and non-TDF based regimen. CONCLUSION: Renal function remained stable with no difference between HIV patients treated with TDF or non-TDF NNRTI based ART regimen over 12 months. However, older HIV patients and those with unsuppressed viral load deserve special focus on renal monitoring. Data on long-term safety of TDF (> 1 year) is still warranted in this population.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Rim/efeitos dos fármacos , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , Adolescente , Adulto , Creatinina/sangue , Etiópia/epidemiologia , Feminino , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Infecções por HIV/sangue , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteinúria , Fatores de Risco , Carga Viral , Adulto Jovem
4.
Medicine (Baltimore) ; 99(27): e21032, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629728

RESUMO

BACKGROUND: Chronic hepatitis B is often complicated with different degrees of hepatic fibrosis, which affects the quality of life. Nucleoside analogs are recommended by almost all guidelines in the world for the treatment of chronic hepatitis B. At present, there is no specific and effective chemical and biological agents for hepatic fibrosis. In China, Chinese compound prescription combined with nucleoside analogs have been used to treat hepatic fibrosis of chronic hepatitis B patients in more and more cases, and good results have been achieved. Several Chinese compound prescriptions that have been made into proprietary Chinese medicine for the convenience of use. This article aims to systematically evaluate the efficacy and safety of Chinese medicine compounds assisting nucleoside analogs in the treatment of hepatic fibrosis in chronic hepatitis B patients. METHOD: The following databases will be searched from their inception to September 2019: PubMed, EMBASE, EBSCOhost, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), VIP Database, Wanfang Database. Languages are limited to Chinese and English. The study includes randomized controlled trials using Chinese compound prescription combined with entecavir and Chinese compound prescription combined with tenofovir disoproxil fumarate to treat hepatic fibrosis of chronic hepatitis B patients. The primary outcomes including effective rate and biochemical parameters (levels of hyaluronic acid, laminin, pre-type-III collagen and type IV collagen will be tested. Additional outcomes include liver function indexes (levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin) and levels of hepatitis B virus DNA. Stata14.0 software will be used for meta-analysis. RESULT: The efficacy and safety of Chinese compound prescriptions assisting nucleoside analogs for hepatic fibrosis of chronic hepatitis B patients will be assessed from the effective rate, biochemical parameters, liver function indexes, and levels of hepatitis B virus DNA. CONCLUSION: The conclusion of this study will be used to evaluate the efficacy and safety of Chinese compound prescriptions assisting nucleoside analogs in the treatment of hepatic fibrosis of chronic hepatitis B patients, as well as the adjuvant effectiveness of Chinese compound prescriptions in combined therapy. PROSPERO REGISTRATION NUMBER: CRD42020156859.


Assuntos
Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Nucleosídeos/análogos & derivados , Antivirais/uso terapêutico , China/epidemiologia , Vírus de DNA/efeitos dos fármacos , Bases de Dados Factuais , Quimioterapia Combinada/métodos , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/psicologia , Testes de Função Hepática/métodos , Masculino , Nucleosídeos/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Tenofovir/uso terapêutico
5.
PLoS One ; 15(7): e0235759, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32634168

RESUMO

BACKGROUND: Renal abnormalities in HIV infected children may be due to the HIV infection or treatment among other factors. Tenofovir disoproxil fumarate (TDF) is associated with proximal renal tubular dysfunction, proteinuria and decrease in glomerular function. Studies in developed countries have shown variable prevalence of proximal renal tubular dysfunction in children on TDF. There are no known studies in developing countries, including Zimbabwe, documenting the proximal tubular function in HIV infected children on TDF. The aim of this study was to assess renal and proximal renal tubular function in HIV infected children receiving TDF and determine factors associated with proximal tubular dysfunction. METHODS: A descriptive cross-sectional study was conducted in HIV infected patients below 18 years of age attending outpatient clinics at two tertiary hospitals in Harare, who received a TDF-containing antiretroviral regimen for at least six months. Dipstick protein and glucose, serum and urine phosphate and creatinine levels were measured. Fractional excretion of phosphate was calculated. Estimated glomerular filtration rate (eGFR) was calculated using the Schwartz formula. Tubular dysfunction was defined by at least two of the following characteristics: normoglycaemic glycosuria, hypophosphatemia and fractional excretion of phosphate > 18%. FINDINGS: One hundred and ninety-eight children below 18 years of age were recruited over a period of six months. The prevalence of tubular dysfunction was 0.5%. Normoglycaemic glycosuria occurred in 1 (0.5%), fractional excretion of phosphate >18% in 4 (2%), and hypophosphatemia in 22 [11.1%] patients. Severe stunting was associated with increased risk of hypophosphatemia (OR 9.31 CI (1.18, 80.68) p = 0.03). Reduction in estimated glomerular filtration rate (eGFR) < 90ml/min/1.73m2 and proteinuria was evident in 35.9% and 32.8% of children, respectively. Concurrent TDF and HIV-1 protease inhibitor-based regimen was the only independent factor associated with reduction in GFR (OR 4.43 CI (1.32; 4.89) p = 0.016). CONCLUSION: Tubular dysfunction was uncommon in Zimbabwean children on a TDF-based ART regimen. Hypophosphatemia, proteinuria and reduction in eGFR were common. Reassessing renal function using more sensitive biomarkers is needed to examine the long-term tolerance of TDF.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Síndrome de Fanconi/etiologia , Infecções por HIV/complicações , Inibidores da Transcriptase Reversa/uso terapêutico , Tenofovir/uso terapêutico , Adolescente , Fármacos Anti-HIV/efeitos adversos , Criança , Estudos Transversais , Síndrome de Fanconi/induzido quimicamente , Feminino , Taxa de Filtração Glomerular , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Proteinúria/etiologia , Inibidores da Transcriptase Reversa/efeitos adversos , Tenofovir/efeitos adversos , Centros de Atenção Terciária , Zimbábue
6.
Lancet ; 396(10246): 239-254, 2020 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711800

RESUMO

BACKGROUND: Tenofovir alafenamide shows high antiviral efficacy and improved renal and bone safety compared with tenofovir disoproxil fumarate when used for HIV treatment. Here, we report primary results from a blinded phase 3 study evaluating the efficacy and safety of pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir alafenamide versus emtricitabine and tenofovir disoproxil fumarate for HIV prevention. METHODS: This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in regions of Europe and North America, where there is a high incidence of HIV or prevalence of people living with HIV, or both. We enrolled adult cisgender men who have sex with men and transgender women who have sex with men, both with a high risk of acquiring HIV on the basis of their self-reported sexual behaviour in the past 12 weeks or their recent history (within 24 weeks of enrolment) of bacterial sexually transmitted infections. Participants with current or previous use of PrEP with emtricitabine and tenofovir disoproxil fumarate were not excluded. We used a computer-generated random allocation sequence to randomly assign (1:1) participants to receive either emtricitabine (200 mg) and tenofovir alafenamide (25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine (200 mg) and tenofovir disoproxil fumarate (300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). As such, all participants were given two tablets. The trial sponsor, investigators, participants, and the study staff who provided the study drugs, assessed the outcomes, and collected the data were masked to group assignment. The primary efficacy outcome was incident HIV infection, which was assessed when all participants had completed 48 weeks of follow-up and half of all participants had completed 96 weeks of follow-up. This full analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug and had at least one post-baseline HIV test. Non-inferiority of emtricitabine and tenofovir alafenamide to emtricitabine and tenofovir disoproxil fumarate was established if the upper bound of the 95·003% CI of the HIV incidence rate ratio (IRR) was less than the prespecified non-inferiority margin of 1·62. We prespecified six secondary bone mineral density and renal biomarker safety endpoints to evaluate using the safety analysis set. This analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug. This trial is registered with ClinicalTrials.gov, NCT02842086, and is no longer recruiting. FINDINGS: Between Sept 13, 2016, and June 30, 2017, 5387 (92%) of 5857 participants were randomly assigned and received emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693). At the time of the primary efficacy analysis (ie, when all participants had completed 48 weeks and 50% had completed 96 weeks) emtricitabine and tenofovir alafenamide was non-inferior to emtricitabine and tenofovir disoproxil fumarate for HIV prevention, as the upper limit of the 95% CI of the IRR, was less than the prespecified non-inferiority margin of 1·62 (IRR 0·47 [95% CI 0·19-1·15]). After 8756 person-years of follow-up, 22 participants were diagnosed with HIV, seven participants in the emtricitabine and tenofovir alafenamide group (0·16 infections per 100 person-years [95% CI 0·06-0·33]), and 15 participants in the emtricitabine and tenofovir disoproxil fumarate group (0·34 infections per 100 person-years [0·19-0·56]). Both regimens were well tolerated, with a low number of participants reporting adverse events that led to discontinuation of the study drug (36 [1%] of 2694 participants in the emtricitabine and tenofovir alafenamide group vs 49 [2%] of 2693 participants in the emtricitabine and tenofovir disoproxil fumarate group). Emtricitabine and tenofovir alafenamide was superior to emtricitabine and tenofovir disoproxil fumarate in all six prespecified bone mineral density and renal biomarker safety endpoints. INTERPRETATION: Daily emtricitabine and tenofovir alafenamide shows non-inferior efficacy to daily emtricitabine and tenofovir disoproxil fumarate for HIV prevention, and the number of adverse events for both regimens was low. Emtricitabine and tenofovir alafenamide had more favourable effects on bone mineral density and biomarkers of renal safety than emtricitabine and tenofovir disoproxil fumarate. FUNDING: Gilead Sciences.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Tenofovir/uso terapêutico , Adenina/efeitos adversos , Adenina/uso terapêutico , Adulto , Fármacos Anti-HIV/efeitos adversos , Método Duplo-Cego , Emtricitabina/efeitos adversos , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/efeitos adversos , Europa (Continente)/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , HIV-1/efeitos dos fármacos , Homossexualidade Masculina/etnologia , Humanos , Masculino , América do Norte/epidemiologia , Placebos/administração & dosagem , Profilaxia Pré-Exposição/métodos , Prevalência , Segurança , Minorias Sexuais e de Gênero , Tenofovir/efeitos adversos , Resultado do Tratamento
7.
JAMA Netw Open ; 3(6): e207445, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32492164

RESUMO

Importance: With the goal of ending the HIV epidemic in the United States, access to HIV pre-exposure prophylaxis (PrEP) is essential to help curb new HIV infections. There has been differential uptake of PrEP by region, with the South lagging behind other regions. Discriminatory benefit design (benefit design that prevents or delays people with complex or expensive conditions from obtaining appropriate treatment) through prior authorization requirements could be a systemic barrier that contributes to the decreased PrEP uptake in the South. Objectives: To investigate whether there are regional disparities in prior authorization requirements for combined tenofovir disoproxil fumarate and emtricitabine for qualified health plans (QHPs) and to assess whether any QHP characteristics explain the disparities. Design, Setting, and Participants: This design was a cross-sectional study of QHPs offered in the 2019 Affordable Care Act Marketplace. The QHPs studied included all Affordable Care Act-compliant individual and small-group market plans in the United States. Exposures: The primary exposure was the 4 census regions (Northeast, West, Midwest, and South). Additional covariates included other plan characteristics. Main Outcomes and Measures: Prior authorization requirement for combined tenofovir disoproxil fumarate and emtricitabine at the QHP level. Results: In total, 16 853 QHPs were analyzed (18.2% in the Northeast, 19.5% in the West, 25.0% in the Midwest, and 37.3% in the South). Overall, 18.9% of QHPs required prior authorization for combined tenofovir disoproxil fumarate and emtricitabine. This percentage varied by region, with 2.3%, 6.2%, 13.3%, and 37.3% of plans requiring prior authorization in the Northeast, West, Midwest, and South, respectively. Compared with QHPs in the Northeast, QHPs in the South were 15.89 (95% CI, 12.57-20.09) times as likely to require prior authorization, whereas the Midwest and West were 5.69 (95% CI, 4.45-7.27) and 2.65 (95% CI, 2.02-3.47) times as likely, respectively. Other plan characteristics did not account for the regional variation. Conclusions and Relevance: Compared with QHPs in the Northeast, QHPs in the South were almost 16 times as likely to require prior authorization for PrEP, and the reasons for these disparities are unknown. The prior authorization requirement is a possible barrier to PrEP access in the South, which is the region of the United States with the most annual new HIV diagnoses. There is limited regulation of QHPs' prior authorization requirements. Federal- or state-level health policy laws may be necessary to remove this system-level barrier to ending the HIV epidemic in the United States.


Assuntos
Infecções por HIV , Acesso aos Serviços de Saúde , Profilaxia Pré-Exposição , Autorização Prévia , Fármacos Anti-HIV/uso terapêutico , Estudos Transversais , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/economia , Infecções por HIV/prevenção & controle , Acesso aos Serviços de Saúde/economia , Acesso aos Serviços de Saúde/estatística & dados numéricos , Humanos , Patient Protection and Affordable Care Act , Profilaxia Pré-Exposição/economia , Profilaxia Pré-Exposição/estatística & dados numéricos , Tenofovir/uso terapêutico , Estados Unidos/epidemiologia
8.
Aliment Pharmacol Ther ; 52(3): 500-512, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32583915

RESUMO

BACKGROUND: Limited data exist regarding tenofovir disoproxil fumarate (TDF) safety and effectiveness in chronic hepatitis B virus-infected (CHB) patients with renal impairment (RI). AIMS: To compare real-world data on renal safety and effectiveness of TDF vs entecavir (ETV) in CHB patients with moderate-to-severe RI. METHODS: Retrospective, non-interventional, cohort study analysing medical records for TDF/ETV-treated CHB patients (54 European centres). Included patients experienced moderate-to-severe RI (creatinine clearance 20-60 mL/min [Cockcroft-Gault]) either before TDF/ETV initiation ('before' subgroup [baseline = treatment initiation]) or after TDF/ETV initiation ('after' subgroup [baseline = first RI occurrence]). The primary objective was TDF safety, particularly renal-related adverse events of special interest (AESI). TDF and ETV safety and effectiveness were compared and multivariate analyses were performed using inverse probability treatment weighting. RESULTS: 'Before' subgroup included 107 TDF- and 91 ETV-treated patients; 'after' subgroup included 212 TDF- and 77 ETV-treated patients. Mean baseline creatinine clearance was higher for TDF- vs ETV-treated patients (both subgroups). Median follow-up was 3.1 years (both treatments). AESI were more frequent with TDF vs ETV ('before': 18.7% vs 8.8%; 'after': 9.9% vs 3.9%); however, differences were not significant by multivariate analysis. Only TDF-treated patients experienced renal tubular dysfunction (6.5% 'before'; 1.9% 'after') as well as renal adverse events leading to treatment discontinuation (8.4% 'before'; 7.1% 'after'). Effectiveness was similar between treatments. CONCLUSIONS: Overall safety was similar for TDF vs ETV (both subgroups). Given that renal tubular dysfunction occurred with TDF and not with ETV, renal safety concerns may be greater with TDF in CHB patients with RI.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Insuficiência Renal/tratamento farmacológico , Tenofovir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Feminino , Guanina/efeitos adversos , Guanina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tenofovir/efeitos adversos , Resultado do Tratamento , Adulto Jovem
11.
Pharmacol Ther ; 214: 107618, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32592716

RESUMO

Safe and efficient drugs to combat the current COVID-19 pandemic are urgently needed. In this context, we have analyzed the anti-coronavirus potential of the natural product glycyrrhizic acid (GLR), a drug used to treat liver diseases (including viral hepatitis) and specific cutaneous inflammation (such as atopic dermatitis) in some countries. The properties of GLR and its primary active metabolite glycyrrhetinic acid are presented and discussed. GLR has shown activities against different viruses, including SARS-associated Human and animal coronaviruses. GLR is a non-hemolytic saponin and a potent immuno-active anti-inflammatory agent which displays both cytoplasmic and membrane effects. At the membrane level, GLR induces cholesterol-dependent disorganization of lipid rafts which are important for the entry of coronavirus into cells. At the intracellular and circulating levels, GLR can trap the high mobility group box 1 protein and thus blocks the alarmin functions of HMGB1. We used molecular docking to characterize further and discuss both the cholesterol- and HMG box-binding functions of GLR. The membrane and cytoplasmic effects of GLR, coupled with its long-established medical use as a relatively safe drug, make GLR a good candidate to be tested against the SARS-CoV-2 coronavirus, alone and in combination with other drugs. The rational supporting combinations with (hydroxy)chloroquine and tenofovir (two drugs active against SARS-CoV-2) is also discussed. Based on this analysis, we conclude that GLR should be further considered and rapidly evaluated for the treatment of patients with COVID-19.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Ácido Glicirrízico/farmacologia , Ácido Glicirrízico/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Alarminas/efeitos dos fármacos , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Quimioterapia Combinada , Humanos , Hidroxicloroquina/uso terapêutico , Microdomínios da Membrana/efeitos dos fármacos , Simulação de Acoplamento Molecular , Pandemias , Pneumonia Viral/epidemiologia , Tenofovir/uso terapêutico
12.
Int J Infect Dis ; 97: 365-370, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32553717

RESUMO

OBJECTIVES: The aim was to fully characterize the plasma and urine washout pharmacokinetics of tenofovir (TFV) in adults following 6 weeks of controlled levels of tenofovir disoproxil fumarate (TDF) adherence, in order to inform the utility of clinic-based adherence testing. DESIGN: This was a three-arm, randomized, open-label study in adult volunteers. Participants were randomized to receive TDF 300 mg/emtricitabine (FTC) 200 mg as (1) 7 doses/week (perfect adherence), (2) 4 doses/week (moderate adherence), or (3) 2 doses/week (low adherence). Plasma and urine samples were collected regularly during the 6-week dosing phase and for 4 weeks following drug cessation. RESULTS: Twenty-eight adults were included in this analysis. Median (range) age was 33 (20-49) years. No differences in TFV pharmacokinetic parameters during the washout were observed across the study arms. Small differences in TFV plasma concentrations occurred across arms between 4 and 10 h post-dose. The cumulative amount of TFV excreted in urine was not different at 24 h post-dose, but at 148 h it was 24.8 mg, 21.0 mg, and 17.2 mg for the perfect, moderate, and low adherence arms, respectively (p = 0.043). CONCLUSIONS: Among adults with different TDF adherence patterns, relative differences in plasma concentrations and cumulative urine extraction of TFV were minor following cessation. TFV measurement in plasma or urine is more indicative of last drug ingestion, rather than prior dose patterns.


Assuntos
Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Tenofovir/farmacocinética , Adulto , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/urina , Emtricitabina/administração & dosagem , Emtricitabina/sangue , Emtricitabina/farmacocinética , Feminino , Infecções por HIV/sangue , Infecções por HIV/urina , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Plasma/química , Tenofovir/sangue , Tenofovir/uso terapêutico , Tenofovir/urina , Adulto Jovem
13.
Lancet HIV ; 7(8): e554-e564, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32473657

RESUMO

BACKGROUND: Information about incidence, clinical characteristics, and outcomes of HIV-infected individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is scarce. We characterised individuals with COVID-19 among a cohort of HIV-infected adults in Madrid. METHODS: In this observational prospective study, we included all consecutive HIV-infected individuals (aged ≥18 years) who had suspected or confirmed COVID-19 as of April 30, 2020, at the Hospital Universitario Ramón y Cajal (Madrid, Spain). We compared the characteristics of HIV-infected individuals with COVID-19 with a sample of HIV-infected individuals assessed before the COVID-19 pandemic, and described the outcomes of individuals with COVID-19. FINDINGS: 51 HIV-infected individuals were diagnosed with COVID-19 (incidence 1·8%, 95% CI 1·3-2·3). Mean age of patients was 53·3 years (SD 9·5); eight (16%) were women, and 43 (84%) men. 35 (69%) cases of co-infection had laboratory confirmed COVID-19, and 28 (55%) required hospital admission. Age and CD4 cell counts in 51 patients diagnosed with COVID-19 were similar to those in 1288 HIV-infected individuals without; however, 32 (63%) with COVID-19 had at least one comorbidity (mostly hypertension and diabetes) compared with 495 (38%) without COVID-19 (p=0·00059). 37 (73%) patients had received tenofovir before COVID-19 diagnosis compared with 487 (38%) of those without COVID-19 (p=0·0036); 11 (22%) in the COVID-19 group had previous protease inhibitor use (mostly darunavir) compared with 175 (14%; p=0·578). Clinical, analytical, and radiological presentation of COVID-19 in HIV-infected individuals was similar to that described in the general population. Six (12%) individuals were critically ill, two of whom had CD4 counts of less than 200 cells per µL, and two (4%) died. SARS-CoV-2 RT-PCR remained positive after a median of 40 days from symptoms onset in six (32%) individuals, four of whom had severe disease or low nadir CD4 cell counts. INTERPRETATION: HIV-infected individuals should not be considered to be protected from SARS-CoV-2 infection or to have lower risk of severe disease. Generally, they should receive the same treatment approach applied to the general population. FUNDING: None.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por HIV/complicações , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Fármacos Anti-HIV/uso terapêutico , Índice de Massa Corporal , Contagem de Linfócito CD4 , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pandemias , Pneumonia Viral/tratamento farmacológico , Estudos Prospectivos , Espanha/epidemiologia , Tenofovir/uso terapêutico , Adulto Jovem
14.
HIV Med ; 21(8): 536-540, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32544304

RESUMO

The unprecedented global scale of COVID-19 globally has triggered a race to discover interventions to reduce associated morbidity and mortality and rapid release of research findings prior to any degree of critical review. As with previous novel infection outbreaks, antiretrovirals are just one drug class that has been held up as a potential strategy for prophylaxis and treatment with scant evidence and risk of harm. Here we summarize the evidence for antiretrovirals to treat COVID-19 and, as a drug that has also been studied in HIV, hydroxychloroquine, and flag some of the pitfalls of using therapies that have not been evaluated robustly.


Assuntos
Antirretrovirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos , Pneumonia Viral/tratamento farmacológico , Pesquisa/normas , Infecções por Coronavirus/prevenção & controle , Combinação de Medicamentos , Reposicionamento de Medicamentos/normas , Reposicionamento de Medicamentos/tendências , Humanos , Hidroxicloroquina/uso terapêutico , Lopinavir/uso terapêutico , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pesquisa/tendências , Ritonavir/uso terapêutico , Tenofovir/uso terapêutico , Fatores de Tempo
15.
Infection ; 48(5): 681-686, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32394344

RESUMO

INTRODUCTION: Data on people living with human immunodeficiency virus (PLWH) in the current SARS-CoV-2 pandemic are still scarce. This case series of 33 PLWH patients with COVID-19 reveals symptoms and outcome in this special population. METHODS: Retrospective analysis of anonymized data including age, gender, HIV-associated parameters, symptoms, and outcome. RESULTS: Three out of 32 patients with documented outcomes died (9%). 91% of the patients recovered and 76% have been classified as mild cases. All patients were on antiretroviral treatment, of them 22 on tenofovir-containing regimen and 4 on the protease inhibitor darunavir. CONCLUSIONS: This preliminary case series does not support excess morbidity and mortality among symptomatic COVID-19 PLWH and with viral suppression on ART. SARS-CoV-2 infections may occur during boosted darunavir-based and/or on tenofovir-containing ART.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Darunavir/uso terapêutico , Infecções por HIV/virologia , HIV/patogenicidade , Pneumonia Viral/virologia , Tenofovir/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Coinfecção , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Feminino , HIV/efeitos dos fármacos , HIV/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Infecções por HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Carga Viral/efeitos dos fármacos
16.
Am J Gastroenterol ; 115(8): 1217-1225, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32355123

RESUMO

INTRODUCTION: Chronic hepatitis B (CHB) remains a major worldwide public health concern. Besifovir dipivoxil maleate (BSV) is a new promising treatment for CHB. However, long-term efficacy and safety have not yet been evaluated. Therefore, the goal of the study is to determine the antiviral efficacy and safety of BSV treatment over a 144-week duration (BSV-BSV) in comparison with those of a sequential treatment with tenofovir disoproxil fumarate (TDF) followed by a 96-week duration BSV administration (TDF-BSV). METHODS: After 48 weeks of a double-blind comparison between BSV and TDF treatments, patients continued the open-label BSV study. We evaluated antiviral efficacy and drug safety up to 144 weeks for BSV-BSV and TDF-BSV groups. The primary endpoint was a virological response (hepatitis B virus DNA < 69 IU/mL). RESULTS: Among the 197 patients enrolled, 170 and 158 patients entered the second-year and third-year open-label phase extensional study, respectively, whereas 153 patients completed the 144-week follow-up. The virological response rate over the 144-week period was 87.7% and 92.1% in BSV-BSV and TDF-BSV groups, respectively (P = 0.36). The rates of ALT normalization and HBeAg seroconversion were similar between the groups. No drug-resistant mutations to BSV were noted. Bone mineral density and renal function were well preserved in the BSV-BSV group and were significantly improved after switching therapy in TDF-BSV patients. DISCUSSION: This extensional study of a phase 3 trial (NCT01937806) suggests that BSV treatment is efficacious and safe for long-term use in treatment-naïve and TDF-experienced patients with CHB.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/uso terapêutico , Adulto , Antivirais/administração & dosagem , Densidade Óssea , Método Duplo-Cego , Esquema de Medicação , Feminino , Guanina/administração & dosagem , Guanina/uso terapêutico , Vírus da Hepatite B , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Organofosfonatos/administração & dosagem , República da Coreia , Tenofovir/administração & dosagem , Tenofovir/uso terapêutico , Resultado do Tratamento , Carga Viral
17.
J Gastroenterol Hepatol ; 35(10): 1684-1693, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32343431

RESUMO

BACKGROUND AND AIM: Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have been shown to reduce incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This systematic review aims to evaluate the magnitude, change over time, and prediction of residual HCC risks in CHB patients treated with ETV/TDF therapy. METHODS: Available literature was systematically reviewed through searches of PubMed and EMBASE databases from January 1, 2006 to September 1, 2019, to identify cohort studies that reported HCC incidence in CHB patients during ETV/TDF therapy. Studies were screened by title and abstract and then evaluated for eligibility in terms of full text. RESULTS: We identified 141 studies for full-text review, and 34 were eligible for analysis. From 19 studies with data separated by cirrhosis status, the 5-year cumulative incidence of HCC was 0.5-6.9% in patients without cirrhosis, 4.5-21.6% in compensated cirrhosis, and 36.3-46.5% in decompensated cirrhosis. All four studies that addressed temporal changes in HCC risks consistently found the incidence rate decreased over time in patients with cirrhosis, although the findings were inconsistent in patients without cirrhosis. Six predictive scores were developed and validated to predict incident HCC during ETV/TDF therapy in CHB patients. Common scoring variables included age, sex, cirrhosis (fibrosis grade), and hepatic function. Conflicting results were reported in seven individual studies and two meta-analyses that compared ETV versus TDF. CONCLUSIONS: The residual risk of HCC remains during ETV/TDF treatment in CHB patients with cirrhosis but declines over time. Risk stratification is attainable by validated predictive scores.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/prevenção & controle , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controle , Tenofovir/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Comorbidade , Feminino , Previsões , Guanina/uso terapêutico , Hepatite B Crônica/complicações , Hepatite B Crônica/epidemiologia , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Risco
18.
PLoS One ; 15(4): e0232104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32324800

RESUMO

BACKGROUND: While the scale-up of HIV services has improved national health management information systems (HMIS), there remain challenges in using routine data to guide the introduction of optimized antiretroviral (ARV) drugs. METHODS: Building on the recent enhancements to the HMIS in Kenya and coinciding with the introduction of a new ARV regimen, tenofovir+lamivudine+dolutegravir (TLD), we developed and implemented an enhanced data system (EDS) to improve availability of safety and efficacy data among people living with HIV (PLHIV) in Kenya. Using data from one health facility, we showcase how the EDS can be used to monitor ARV transition and identify missed opportunities to transition eligible patients to optimized regimes. RESULTS: The EDS was designed to create a comprehensive PLHIV database by triangulating patient-level data from the EMR, the pharmacy ARV dispensing tool (ADT) and HIV viral load (VL) databases. On a monthly basis, the database is de-identified and uploaded into a national data warehouse, with interactive dashboards. Using the EDS, we determined that of the 5,500 PLHIV ≥15 years on first-line ART at one facility, 4,233 (77%) had transitioned to optimized ARVs. Of the 1,267 still on legacy regimens, 459 (36%) were determined to be eligible and prioritized to switch. CONCLUSIONS: This project illustrates how enhancements to the national HMIS can facilitate the use of routine patient-level data to monitor the transition to new ARVs and inform the national HIV response.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Sistemas de Dados , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/farmacologia , Sistemas de Gerenciamento de Base de Dados , Monitoramento de Medicamentos , Infecções por HIV/virologia , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Quênia , Lamivudina/uso terapêutico , Tenofovir/uso terapêutico , Resultado do Tratamento , Carga Viral/métodos
19.
Artigo em Inglês | MEDLINE | ID: mdl-32340799

RESUMO

Women at childbearing age and pregnant ladies living in the areas of high or intermediate prevalence of hepatitis B virus (HBV) remain at risk of getting the infection and passing the infections to their offspring via mother-to-child transmission (MTCT) of HBV. HBV infection may affect the mothers by active hepatitis, very occasionally liver cirrhosis and rarely fulminant hepatitis and liver failure. The virus may be transmitted to the babies despite immunoprophylaxis in the setting of very high maternal viral load. Tenofovir disoproxil fumarate (TDF) has been shown to be efficacious to reduce MTCT of HBV, which contributes to the elimination of chronic HBV infection by 2030, the goal set by World Health Organization.


Assuntos
Antivirais/uso terapêutico , Gastroenterologistas/psicologia , Hepatite B/tratamento farmacológico , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Telbivudina/uso terapêutico , Tenofovir/uso terapêutico , Adulto , Criança , DNA Viral , Feminino , Hepatite B/transmissão , Antígenos E da Hepatite B/sangue , Antígenos E da Hepatite B/uso terapêutico , Vírus da Hepatite B , Humanos , Lactente , Inflamação/tratamento farmacológico , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/virologia
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