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1.
Medicine (Baltimore) ; 98(32): e16813, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393412

RESUMO

Dolutegravir (DTG) has shown effectiveness in combination with rilpivirine in with experience of antiretroviral therapy (ART) and with 3TC in naïve patients (GEMINI trial). The main objectives of this real-life study were to analyze the effectiveness and safety of 3TC plus DTG in virologically suppressed HIV-1 patients and to conduct a pharmacoeconomic analysis.We conducted an observational, retrospective and multicenter study of HIV+ patients pretreated for at least 6 months with ART that was then simplified to 3TC + DTG for any reason. We gathered data on viral loads (VLs) during exposure to the DT, calculating the rate with VL < 50 copies/mL at week 48, and on associated adverse effects.The 177 HIV+ patients were collected, 77.4% male, with average age of 48.5 years and mean count of 252.2cell/µL CD4+ nadir lymphocytes; 96.6% had VL < 50 copies/mL and 674 cells/µL CD4+ lymphocytes. Median time since HIV diagnosis was 15 years, and median ART duration was 13 years, and 34.5% of patients were on mono- or dual-therapy before the switch. At week 48, 82.4% of patients had VL < 50 cop/µL using an intention-to-treat (ITT) analysis, 89.6% according to mITT, and 96.7% according to Per-Protocol analysis. 3.3% patients had virological failure (VF). These effectiveness data and costs were compared with those for 2 reference triple therapies (DTG/ABC/3TC and EVG/cobi/FTC/TAF) in a cost minimization analysis, showing cost savings with administration of DTG+3TC (2741 &OV0556;/year vs DTG/ABC/3TC and 4164 &OV0556;/year vs EVG/cobi/FTC/TAF) and in a cost-effectiveness analysis, finding the DT to be the most cost-effective approach (ICER = -548 vs DTG/ABC/3TC and ICER = -4,627&OV0556; vs EVG/cobi/FTC/TAF)The combination of 3TC with DTG appears to be a safe and effective option for the simplification of ART in pretreated and virologically stable HIV-positive patients, being cost-effective and offering the same effectiveness as the triple therapy it replaces.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Lamivudina/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/economia , Contagem de Linfócito CD4 , Análise Custo-Benefício , Quimioterapia Combinada , Farmacoeconomia , Honorários Farmacêuticos/estatística & dados numéricos , Feminino , HIV-1 , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/economia , Humanos , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Lamivudina/economia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Viral
2.
Clin Drug Investig ; 39(9): 835-846, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31228017

RESUMO

BACKGROUND AND OBJECTIVE: Oral nucleoside/nucleotide analogues (NAs) have been advocated for chronic hepatitis B (CHB) treatment with good efficacy. However, less attention has been put on their adverse events. Therefore, a Bayesian network meta-analysis (NMA) was performed to evaluate the relative safety of five NAs (lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate) in CHB treatment among adults. METHODS: Eligible randomized clinical trials (RCTs) and prospective cohort studies were systematically and thoroughly searched until May 1, 2019. Poisson-prior-based Bayesian NMA was performed to synthesize both direct and indirect evidence with reporting hazard ratios (HRs) and 95% credible intervals (CrIs) for serious adverse events (SAEs) and hepatic/renal impairments. RESULTS: Thirty-three RCTs and 11 prospective cohort studies were identified. As to SAEs, no statistically significant difference was found of any comparison among five NAs. In terms of hepatotoxicity, lamivudine was safer than telbivudine (HR 0.45; 95% CrI 0.21, 0.85), and entecavir increased the risk by 102% (entecavir vs lamivudine: HR 2.02; 95% CrI 1.19, 3.27). CONCLUSIONS: The findings from this large NMA could influence clinical practice, and the methodological framework of this study could provide evidence-based support to analyze sparse safety data in the field.


Assuntos
Antivirais/efeitos adversos , Teorema de Bayes , Hepatite B Crônica/tratamento farmacológico , Meta-Análise em Rede , Adenina/efeitos adversos , Adenina/análogos & derivados , Adenina/uso terapêutico , Antivirais/uso terapêutico , Guanina/efeitos adversos , Guanina/análogos & derivados , Guanina/uso terapêutico , Humanos , Lamivudina/efeitos adversos , Lamivudina/uso terapêutico , Organofosfonatos/efeitos adversos , Organofosfonatos/uso terapêutico , Estudos Prospectivos , Telbivudina/efeitos adversos , Telbivudina/uso terapêutico , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico
3.
Medicine (Baltimore) ; 98(17): e15149, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31027057

RESUMO

RATIONALE: With the existence of the human immunodeficiency virus (HIV) infection as a chronic disease, more often adverse effects of its treatment with the various antiretroviral therapies (ARTs) available have been recognized. Going further, Triumeq has been associated with a myriad of adverse effects, of which rhabdomyolysis is rarely reported in the literature. PATIENT CONCERNS: The patient presented with muscle tenderness over the lower limbs and dark brown-to-red colored urine. DIAGNOSIS: Given the presenting symptoms, as well as the laboratory testing, including elevated serum creatine kinase and liver enzymes, the diagnosis of rhabdomyolysis was made. INTERVENTIONS: Improvement was achieved rapidly after starting intravenous fluid therapy and with discontinuation of Triumeq. OUTCOMES: After discharge, repeated creatine kinase levels in the clinic have been normal and decision was made to initiate another ART and until now, no further episodes of rhabdomyolysis have developed. Regular outpatient follow-up has been ongoing for over 1 year and no complications have been identified. LESSONS: This case aims to recognize rhabdomyolysis as a rare, but possible adverse effect associated with the use of Triumeq for HIV-infected patients and therefore clinicians prescribing this combination should be aware of this potential side effect and counsel their patients accordingly.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Didesoxinucleosídeos/efeitos adversos , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Lamivudina/efeitos adversos , Rabdomiólise/etiologia , Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Combinação de Medicamentos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Rabdomiólise/diagnóstico , Rabdomiólise/terapia
4.
Int J STD AIDS ; 30(5): 467-471, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30999834

RESUMO

Raltegravir (RAL) is an HIV-1 integrase strand transfer inhibitor that is well established as a component of highly active antiretroviral therapy regimens for the treatment of adults living with human immunodeficiency virus (HIV), due to its high virological efficacy and good tolerability profile. To date, limited data are available on the use of RAL with abacavir/lamivudine (ABC/3TC). We investigated retrospectively 62 HIV-1 infected patients managed by three Italian Infectious Diseases Outpatient Departments, including 57 treatment-experienced patients and 5 treatment-naïve patients, treated with ABC/3TC plus RAL. In all five naïve patients (100%), virological suppression was achieved and maintained , while 55 experienced patients (96.5%) maintained viral suppression at the most recent review. In the treatment-experienced patients, we observed a significant decrease in triglyceride levels (p < 0.01), while liver transaminases, renal function and cholesterol levels remained substantially stable. In the 34 treatment-experienced patients who switched from a protease inhibitor (PI)-based regimen, we observed a significant improvement of total cholesterol (p=0.03) and triglyceride (p < 0.01) levels. No significant alterations were found on renal and liver function and serum lipid profile of treatment-naïve patients. Despite the small number of participants, results support the efficacy and safety of ABC/3TC plus RAL, either in treatment-naïve or treatment-experienced patients.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Lamivudina/uso terapêutico , Raltegravir Potássico/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Colesterol/sangue , Didesoxinucleosídeos/efeitos adversos , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , Inibidores de Integrase de HIV/efeitos adversos , Humanos , Testes de Função Renal , Lamivudina/efeitos adversos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Raltegravir Potássico/efeitos adversos , Resultado do Tratamento , Triglicerídeos/sangue
5.
Acta Gastroenterol Belg ; 82(1): 31-34, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30888751

RESUMO

AIMS: To compare the efficacy of treatment with lamivudine (LAM) plus adefovir (ADV) or entecavir (ETV) monotherapy in LAM treatment failure patients with HBeAg negative chronic hepatitis B (CHB) patients during 48 weeks of therapy. PATIENTS AND METHODS: Thirty patients with HBeAg negative CHB were enrolled in the study. The serum levels of HBV DNA, HBsAg/HBsAb, and ALT were assessed by enzyme-linked immunosorbent assay at 0, 12, 24, 36, and 48 weeks. RESULTS: The rate of undetectable HBV DNA in the LAM+ADV group was 100%, which was higher than the ETV group at 48 weeks (73.33%, χ2 = 4.615, P = 0.032). Multivariate analysis using the Cox proportional hazards model showed that therapy with LAM+ADV or baseline levels of HBV DNA <107 copies/ml were independent predictive factors for undetectable HBV DNA rates in all patients (RR: 2.488, P = 0.042; RR: 0.201, P = 0.035). CONCLUSIONS: During the 48 weeks of treatment in patients with HBeAg negative CHB, LAM plus ADV suppressed HBV replication more effectively than ETV monotherapy. In addition, no virologic breakthrough was detected in the LAM add-on ADV group. Additionally, therapy with LAM+ADV or baseline levels of HBV DNA <107copies/ml were independent predictive factors for undetectable HBV DNA rates in patients.


Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , DNA Viral/efeitos dos fármacos , Farmacorresistência Viral/efeitos dos fármacos , Guanina/análogos & derivados , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Organofosfonatos/uso terapêutico , Adenina/efeitos adversos , Adenina/uso terapêutico , DNA Viral/sangue , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Guanina/efeitos adversos , Guanina/uso terapêutico , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Humanos , Lamivudina/efeitos adversos , Organofosfonatos/efeitos adversos , Modelos de Riscos Proporcionais , Falha de Tratamento , Resultado do Tratamento
6.
Neuropathology ; 39(2): 162-167, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30847961

RESUMO

Oral nucleoside analogs (NAs) reduce hepatitis B virus (HBV) replication by inhibiting HBV DNA polymerase. However, NAs can also affect human mitochondrial DNA (mtDNA) polymerase, which can lead to mtDNA depletion (quantitative abnormality). Indeed, several mitochondrial myopathy cases have been reported in which a reduced mtDNA copy number was induced by oral NAs for hepatitis B. Herein, we report a case of toxic myopathy with multiple mtDNA deletions (qualitative abnormality) associated with long-term use of NAs for hepatitis B. A 68-year-old woman, who underwent long-term treatment with lamivudine and adefovir for chronic hepatitis B, developed proximal muscle weakness in the four extremities. Neurological examination showed mild proximal muscle weakness and atrophy in the four extremities. Upon admission to our hospital, her blood lactate/pyruvate ratio during an aerobic exercise test was elevated. Myogenic patterns were observed in lower limb muscles on electromyographic examination. Muscle magnetic resonance imaging revealed diffuse atrophy of proximal muscles in the four extremities with no signal changes. A biopsy from the biceps brachii muscle showed an abnormally large variation in fiber size, scattered muscle fibers with decreased cytochrome c oxidase activity, and ragged-red fibers. Analysis of mtDNA from skeletal muscle revealed no decrease in copy number but increased incidence of multiple deletions, including a deletion of 4977 base pairs (known as the common deletion) reflecting oxidative stress-induced mtDNA damage. This case study indicates that long-term oral antiviral therapy for hepatitis B can induce chronic oxidative damage to mtDNA resulting in qualitative mtDNA abnormalities and toxic myopathy.


Assuntos
Antivirais/efeitos adversos , Hepatite B Crônica/tratamento farmacológico , Miopatias Mitocondriais/induzido quimicamente , Miopatias Mitocondriais/patologia , Adenina/efeitos adversos , Adenina/análogos & derivados , Administração Oral , Idoso , DNA Mitocondrial , Feminino , Deleção de Genes , Hepatite B Crônica/complicações , Humanos , Lamivudina/efeitos adversos , Miopatias Mitocondriais/complicações , Miopatias Mitocondriais/genética , Músculo Esquelético/patologia , Organofosfonatos/efeitos adversos
7.
BMC Infect Dis ; 19(1): 59, 2019 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-30654739

RESUMO

BACKGROUND: Direct comparisons between lamivudine plus bPIs and lamivudine plus dolutegravir as maintenance strategies in virologically-suppressed HIV positive patients are lacking. METHODS: Time to treatment discontinuation (TD) and virological failure (VF) were compared in a cohort of HIV+ patients on a virologically-effective ART starting lamivudine with either darunavir/r, atazanavir/r or dolutegravir. Changes in laboratory parameters were also evaluated. RESULTS: Four-hundred-ninety-four patients were analyzed (170 switching to darunavir/r, 141 to atazanavir/r, 183 to dolutegravir): median age was 49 years, with 8 years since ART start. Groups differed for age, HIV-risk factor, time since HIV-diagnosis and on ART, previous therapy and reasons for switching. Estimated proportions free from TD at week 48 and 96 were 79.8 and 48.3% of patients with darunavir/r, 87.0 and 70.9% with atazanavir/r, and 88.2 and 82.6% with dolutegravir, respectively (p < 0.001). Calendar years, HIV-risk factor, higher baseline cholesterol and an InSTI-based previous regimen predicted TD, whereas lamivudine+dolutegravir therapy and previous tenofovir use were protective. VF was the cause of TD in 6/123 cases with darunavir/r, 4/97 with atazanavir/r and 3/21 with dolutegravir. Other main reasons for TD were: toxicity (43.1% with darunavir/r, 39.2% with atazanavir/r, 52.4% with dolutegravir), further simplification (36.6% with darunavir/r, 30.9% with atazanavir/r, 14.3% with dolutegravir). Incidence of VF did not differ among study groups (p = 0.747). No factor could predict VF. Lipid profile improved in the dolutegravir group, whereas renal function improved in the bPIs groups. CONCLUSIONS: In real practice, a switch to lamivudine+dolutegravir showed similar efficacy but longer durability than a switch to lamivudine+bPIs.


Assuntos
Soropositividade para HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Carga Viral/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Sulfato de Atazanavir/uso terapêutico , Estudos de Coortes , Darunavir/uso terapêutico , Quimioterapia Combinada , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Soropositividade para HIV/virologia , HIV-1/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ritonavir/uso terapêutico , Tenofovir/uso terapêutico , Resultado do Tratamento
9.
Int J Med Sci ; 16(1): 17-22, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30662324

RESUMO

Introduction: Most chronic hepatitis B (CHB) patients in China are primitively treated with a combination of lamivudine (LAM) and adefovir dipivoxil (ADV). Although antiviral resistance can be avoided with this combination therapy, using it can have harmful side effects related to ADV, specifically kidney and bone injury. This study was designed to compare viral suppression and kidney safety when switching LAM and ADV combination therapy de novo to entecavir (ETV) monotherapy in patients with CHB and compensated hepatic cirrhosis. Materials and methods: In total, 360 CHB and compensated liver cirrhosis patients who received treatment of LAM and ADV combination therapy for more than 1 year were included in this study. One hundred and eighty patients continued combination therapy to serve as a control group and the other 180 patients were switched to ETV monotherapy to serve as the experimental group. The total course of therapy was 3 years. Laboratory studies were done every 3 months to measure liver and kidney function. Studies included glomerular filtration rate (eGFR), HBV-DNA, urine ß2-microglobulin (ß2-M) and retinol binding protein (RBP). Results: In the experimental group, an HBV-DNA level below 20 IU/ml was found in 77.65%, 85.88%, and 94.77% in years 1, 2, and 3, respectively. In the control group, HBV-DNA levels were below 20 IU/ml in 69.66%, 75.42%, and 85.80% in years 1, 2, and 3, respectively. Low HBV-DNA levels in the experimental group were significantly less common than in the control group on the second and third year; P values were 0.009 and 0.006 for years 2 and 3, respectively. The cumulative genetic mutation rate was 3.49% in the experimental group and 8.88% in the control group (P=0.044). Decreases in eGFR more than 30% from baseline were found in 0%, 0.56%, and 1.74% of patients in the experimental group and 4.49%, 9.14% and 14.79% in patients in the control group in the first, second, and third year, respectively. Serum creatinine more than 50 µmol/L above baseline was found in 0%, 0% and 1.74% of patients in the experimental group and 1.12%, 4.00% and 5.32% of patients in the control group in years 1, 2, and 3, respectively. The urine ß2-M and RBP levels were abnormal more often in the experimental group than in the control group. Conclusion: Switching to ETV monotherapy can decrease HBV-DNA levels, reduce the genetic mutation rate, and prevent renal damage caused by LAM and ADV combination therapy in patients with CHB and compensated liver cirrhosis. Patients receiving LAM and ADV combination therapy de novo should be switched to ETV monotherapy immediately.


Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , Guanina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Rim/fisiopatologia , Lamivudina/efeitos adversos , Cirrose Hepática/tratamento farmacológico , Organofosfonatos/efeitos adversos , Adenina/efeitos adversos , Adenina/uso terapêutico , Adulto , China , Creatinina/metabolismo , DNA Viral , Farmacorresistência Viral , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Guanina/uso terapêutico , Vírus da Hepatite B/genética , Hepatite B Crônica/genética , Humanos , Lamivudina/uso terapêutico , Cirrose Hepática/genética , Masculino , Pessoa de Meia-Idade , Mutação/efeitos dos fármacos , Organofosfonatos/uso terapêutico , Proteínas de Ligação ao Retinol/metabolismo , Adulto Jovem
10.
Medicine (Baltimore) ; 98(1): e13818, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30608393

RESUMO

Nucleos(t)ide analogs are used for preventing liver cirrhosis in chronic hepatitis B patients, but the risk factors of hepatocellular carcinoma (HCC) in these patients remain unclear. We designed this retrospective cohort study, the aim is to determine the risk factors for HCC development and its image presentation under nucleos(t)ide analogs treatment.In this study, patients were treated with lamivudine (LAM), entecavir 0.5 mg (ETV), or telbivudine (LdT), and followed-up for at least 2 years to detect HCC and its presentation. Assessment of the risk factors for HCC included age, sex, HBeAg, viral load, liver cirrhosis, current and previous medications, and liver function tests.Totally, 396 patients were recruited, and 18 patients developed HCC. The mean time from the treatment to HCC development was 28.5 ±â€Š16.7 months. The clinical characteristics in HCC and no-HCC groups showed significant differences among age (52.8 ±â€Š6.1 vs 47.1 ±â€Š12.6 years, P <.01), baseline alanine transaminase (ALT) levels (161.4 ±â€Š177.3 vs 361.7 ±â€Š496.3, P <.01), and baseline liver cirrhosis (72.2% vs 29.9%, P <.01). In patients aged ≥45 years, the hazard ratio of HCC was 10.2 and liver cirrhosis was 4.1. Majority of HCCs developed in the right liver (14/18), were single numbered (13/18), had tumor size about 1.9 ±â€Š0.7 cm, were classified as T1 (14/18, TNM staging), and the atypical image occupied 88% of the HCC cases.The patients aged ≧45 years on long-term nucleos(t)ide analog therapy, and with baseline liver cirrhosis were at a high risk of HCC. Regular alpha-fetoprotein (AFP) assessment and image study of these patients are the gold standards for early HCC detection in patients with high percentage atypical HCC appearances.


Assuntos
Antivirais/efeitos adversos , Carcinoma Hepatocelular/induzido quimicamente , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/induzido quimicamente , Nucleosídeos/efeitos adversos , Adulto , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/virologia , Detecção Precoce de Câncer/métodos , Feminino , Seguimentos , Guanina/efeitos adversos , Guanina/análogos & derivados , Hepatite B Crônica/complicações , Humanos , Lamivudina/efeitos adversos , Cirrose Hepática/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Telbivudina/efeitos adversos , alfa-Fetoproteínas/análise
11.
Int J STD AIDS ; 30(5): 447-452, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30630396

RESUMO

Hyperparathyroidism has been described in people living with HIV undergoing tenofovir disoproxil fumarate (TDF)-containing antiretroviral therapy (ART), but differences in calcium levels have never been investigated in detail. We aimed to compare the prevalence of hypocalcemia between patients with and without TDF-containing ART. The patients and methods were a retrospective cohort study in HIV-infected adult patients receiving dolutegravir and either abacavir (ABC)/lamivudine (3TC) or TDF/emtricitabine in a single center in Munich, Germany. Of 172 patients, 126 (73.3%) were male and the median age was 48.5 years (interquartile range 42-54). Average calcium levels were 2.24 (2.21-2.29) mmol/l and 2.21 (2.16-2.26) mmol/l (P < 0.001) with a prevalence of at least one episode of total calcium <2.12 mmol/l of 16.2 and 34.4% in the groups treated with ABC/3TC and TDF/emtricitabine, respectively (P = 0.006). TDF use was independently associated with the occurrence of albumin-corrected calcium levels of <2.12 mmol/l (odds ratio: 6.7 [1.3-35.6]; P = 0.025). Hypocalcemia seems to occur more often in TDF-treated patients. Further research into hypocalcemia with TDF and potential cardiovascular effects may be of benefit based on these findings.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Didesoxinucleosídeos/efeitos adversos , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Hipocalcemia/induzido quimicamente , Lamivudina/efeitos adversos , Tenofovir/efeitos adversos , Adulto , Fármacos Anti-HIV/uso terapêutico , Cálcio/sangue , Estudos de Coortes , Didesoxinucleosídeos/uso terapêutico , Combinação de Medicamentos , Feminino , Infecções por HIV/virologia , Inibidores de Integrase de HIV/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Hipocalcemia/diagnóstico , Hipocalcemia/epidemiologia , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Tenofovir/uso terapêutico , Resultado do Tratamento
12.
J Bras Nefrol ; 41(1): 48-54, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30010693

RESUMO

AIM: To determine the prevalence of chronic kidney disease (CKD) and the epidemiological, clinical, and laboratory factors associated with CKD in Mexican HIV-infected patients. METHODS: Cross-sectional study. We included 274 patients with HIV/AIDS. CKD was defined by the estimated glomerular filtration rate (eGFR < 60 mL/min/1.73 m2 assessed by CKD-EPI) and albuminuria criteria from KDIGO guidelines. Clinical, epidemiological, and laboratory characteristics were compared between patients with and without CKD. The factors associated with CKD were assessed by logistic regression analysis. RESULTS: The mean age was 41±11 years, and 72.3% of the patients were men. The global prevalence of CKD was 11.7% (n = 32); 7.2% (n = 20) were defined by eGFR criterion; 7.6% (n = 21), by the albuminuria criterion; and 3.2% (n = 9), by both CKD criteria. The most frequently observed stages of CKD were KDIGO G3A1 stage with 4.7% (n = 13), KDIGO G1A2 stage with 3.6% (n = 10) and KDIGO G3A2 stage with 1.7% (n = 5). The factors associated with CKD were use of abacavir/lamivudine (OR 3.2; 95% CI 1.1-8.9; p = 0.03), a CD4 lymphocyte count < 400 cells/µL (OR 2.6; 95% 1.03-6.4, p = 0.04), age (OR 1.1; 95% CI 1.04-1.2, p = 0.001) and albuminuria (OR 19.98; 95% CI: 5.5-72.2; p < 0.001). CONCLUSIONS: CKD was a frequent complication in HIV-infected patients. These findings confirm the importance of screening and the early detection of CKD, as well as the importance of identifying and treating traditional and non-traditional risk factors associated with CKD.


Assuntos
Infecções por HIV/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Adulto , Fatores Etários , Albuminúria , Fármacos Anti-HIV/efeitos adversos , Contagem de Linfócito CD4 , Estudos Transversais , Complicações do Diabetes , Didesoxinucleosídeos/efeitos adversos , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/complicações , Lamivudina/efeitos adversos , Modelos Logísticos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco
13.
Eur J Clin Microbiol Infect Dis ; 38(3): 423-426, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30443683
14.
Lancet ; 393(10167): 143-155, 2019 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-30420123

RESUMO

BACKGROUND: Effective two-drug regimens could decrease long-term drug exposure and toxicity with HIV-1 antiretroviral therapy (ART). We therefore aimed to evaluate the efficacy and safety of a two-drug regimen compared with a three-drug regimen for the treatment of HIV-1 infection in ART-naive adults. METHODS: We conducted two identically designed, multicentre, double-blind, randomised, non-inferiority, phase 3 trials: GEMINI-1 and GEMINI-2. Both studies were done at 192 centres in 21 countries. We included participants (≥18 years) with HIV-1 infection and a screening HIV-1 RNA of 500 000 copies per mL or less, and who were naive to ART. We randomly assigned participants (1:1) to receive a once-daily two-drug regimen of dolutegravir (50 mg) plus lamivudine (300 mg) or a once-daily three-drug regimen of dolutegravir (50 mg) plus tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Both drug regimens were administered orally. We masked participants and investigators to treatment assignment: dolutegravir was administered as single-entity tablets (similar to its commercial formulation, except with a different film colour), and lamivudine tablets and tenofovir disoproxil fumarate and emtricitabine tablets were over-encapsulated to visually match each other. Primary endpoint was the proportion of participants with HIV-1 RNA of less than 50 copies per mL at week 48 in the intention-to-treat-exposed population, using the Snapshot algorithm and a non-inferiority margin of -10%. Safety analyses were done on the safety population. GEMINI-1 and GEMINI-2 are registered with ClinicalTrials.gov, numbers NCT02831673 and NCT02831764, respectively. FINDINGS: Between July 18, 2016, and March 31, 2017, 1441 participants across both studies were randomly assigned to receive either the two-drug regimen (n=719) or three-drug regimen (n=722). At week 48 in the GEMINI-1 intention-to-treat-exposed population, 320 (90%) of 356 participants receiving the two-drug regimen and 332 (93%) of 358 receiving the three-drug regimen achieved plasma HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference -2·6%, 95% CI -6·7 to 1·5); in GEMINI-2, 335 (93%) of 360 in the two-drug regimen and 337 (94%) of 359 in the three-drug regimen achieved HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference -0·7%, 95% CI -4·3 to 2·9), showing non-inferiority at a -10% margin in both studies (pooled analysis: 655 [91%] of 716 in the two-drug regimen vs 669 [93%] of 717 in the three-drug regimen; adjusted treatment difference -1·7%, 95% CI -4·4 to 1·1). Numerically, more drug-related adverse events occurred with the three-drug regimen than with the two-drug regimen (169 [24%] of 717 vs 126 [18%] of 716); few participants discontinued because of adverse events (16 [2%] in the three-drug regimen and 15 [2%] in the two-drug regimen). Two deaths were reported in the two-drug regimen group of GEMINI-2, but neither was considered to be related to the study medication. INTERPRETATION: The non-inferior efficacy and similar tolerability profile of dolutegravir plus lamivudine to a guideline-recommended three-drug regimen at 48 weeks in ART-naive adults supports its use as initial therapy for patients with HIV-1 infection. FUNDING: ViiV Healthcare.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Adulto , Fármacos Anti-HIV/efeitos adversos , Antirretrovirais/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Emtricitabina/efeitos adversos , Emtricitabina/uso terapêutico , Feminino , Infecções por HIV/virologia , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Lamivudina/efeitos adversos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , Carga Viral/efeitos dos fármacos
15.
Ann Dermatol Venereol ; 145(12): 773-776, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30301570

RESUMO

BACKGROUND: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are antiretroviral drugs often used in the first-line treatment regimen of HIV1 infection worldwide. We report a case of successive gynecomastia and Stevens-Johnson syndrome (SJS) respectively induced by efavirenz and nevirapine in a single patient. CASE REPORT: A 16-year-old boy, HIV1-infected since birth, was started on antiretroviral treatment (ART) in August 2015 and was taking a regimen comprising abacavir, lamivudine and efavirenz. In April 2016, when his weight reached 35kg, abacavir was replaced with tenofovir. Bilateral breast enlargement, previously hidden by the patient, was diagnosed two years after the start of ART. History-taking, physical examination and laboratory tests ruled out known causes of gynecomastia, and efavirenz was thus considered the most likely cause. This drug was then withdrawn and replaced with nevirapine in July 2017. Thirty-three days after the patient started nevirapine treatment, a skin rash appeared. Physical examination revealed erythematous macules and flaccid bullae with estimated skin detachment of 10%. There were also conjunctival, buccal and genital lesions. A diagnosis was made of SJS induced by nevirapine. Three months after withdrawal of efavirenz, breast size decreased by 3cm on the left breast and 2cm on the right breast; two months after the SJS, cutaneous sequelae alone persisted, such as diffuse hyperchromic macules. DISCUSSION: Recognition of gynecomastia as a side-effect of efavirenz is important to allow the condition to be treated while it is still potentially reversible. Moreover, when efavirenz is replaced, a protease inhibitor should be preferred to nevirapine.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Ginecomastia/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Nevirapina/efeitos adversos , Inibidores da Transcriptase Reversa/efeitos adversos , Síndrome de Stevens-Johnson/etiologia , Adolescente , Benzoxazinas/administração & dosagem , Benzoxazinas/efeitos adversos , Benzoxazinas/uso terapêutico , Didesoxinucleosídeos/administração & dosagem , Didesoxinucleosídeos/efeitos adversos , Didesoxinucleosídeos/uso terapêutico , Substituição de Medicamentos , Infecções por HIV/complicações , Humanos , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Lamivudina/uso terapêutico , Masculino , Mucosite/induzido quimicamente , Nevirapina/administração & dosagem , Nevirapina/uso terapêutico
16.
J Correct Health Care ; 24(4): 371-381, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30189786

RESUMO

This study evaluated the effectiveness of formulary substitution from products or regimens containing name brand emtricitabine to alternative regimens containing generic lamivudine among virologically suppressed HIV-infected patients in a correctional managed health care system. Results of this retrospective cohort study showed that 94.9% of patients switched from emtricitabine to lamivudine ( n = 447) and 93.0% of emtricitabine control patients ( n = 449) had an undetectable viral load at last available test over a 2-year period. The two groups also showed similar values for CD4 counts, compliance, discontinuation, and M184V mutation; however, a slightly greater proportion of lamivudine patients experienced respiratory symptoms. Nonetheless, this study demonstrates that switching virologically suppressed HIV-infected patients from name brand emtricitabine-containing regimens to generic lamivudine-based regimens may reduce costs without compromising safety or effectiveness in correctional managed health care systems with directly observed therapy.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Medicamentos Genéricos/uso terapêutico , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Adulto , Medicamentos Genéricos/efeitos adversos , Medicamentos Genéricos/economia , Emtricitabina/efeitos adversos , Emtricitabina/economia , Feminino , Humanos , Lamivudina/efeitos adversos , Lamivudina/economia , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Cooperação do Paciente , Estudos Retrospectivos , Carga Viral
17.
Virol J ; 15(1): 139, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30201035

RESUMO

BACKGROUND: Currently, there is no consensus on the efficacy and safety of lamivudine (LAM) plus tenofovir disoproxil fumarate (TDF) combination therapy versus lamivudine monotherapy in HBV/HIV coinfected patients. METHODS: A comprehensive literature search was performed in English and Chinese databases. Both relevant dichotomous and continuous variables were extracted, and the combined outcomes were expressed as a risk ratio (RR) or a standard mean difference (SMD). RESULTS: Eleven eligible studies were included in our analysis. For HBV-relevant outcomes, the proportion of patients with undetectable HBV, the rates of serum alanine aminotransferase (ALT) normalization and hepatitis B e antigen (HBeAg) loss were higher in the combination therapy group than the monotherapy group (RR = 1.42, 95% CI: 1.14-1.76, P = 0.002; RR = 1.36, 95% CI: 1.17-1.58, P < 0.0001; RR = 2.74, 95% CI: 1.20-6.22, P = 0.02). In addition, the rate of HIV RNA-negative conversion was higher in the combination therapy group than the monotherapy group (RR = 1.26, 95% CI: 1.11-1.42, P = 0.0003). CONCLUSION: LAM plus TDF combination therapy was more efficacious than LAM monotherapy in HBV/HIV coinfected patients. As time passes, this difference becomes more pronounced.


Assuntos
Antivirais/administração & dosagem , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepatite B/tratamento farmacológico , Lamivudina/administração & dosagem , Tenofovir/administração & dosagem , Alanina Transaminase/sangue , Antivirais/efeitos adversos , Quimioterapia Combinada , Infecções por HIV/complicações , Hepatite B/complicações , Antígenos E da Hepatite B/sangue , Humanos , Lamivudina/efeitos adversos , RNA Viral/sangue , Tenofovir/efeitos adversos , Resultado do Tratamento
18.
Clin Pharmacol Ther ; 104(5): 785-787, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30084119

RESUMO

The article by Adkison et al. described sorbitol effects on lamivudine exposures. The results indicate a plausible mechanism for lower lamivudine exposures in pediatric patients receiving the solution formulation with concomitant medications containing sorbitol. In this commentary, we discuss lower lamivudine exposures in pediatric patients receiving the solution formulation, the impact of sorbitol on lamivudine exposures, and the US Food and Drug Administration's (FDA's) decision to increase the dose of the lamivudine solution for all pediatric patients.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Lamivudina/administração & dosagem , Lamivudina/farmacocinética , Sorbitol/administração & dosagem , Edulcorantes/administração & dosagem , Administração Oral , Fatores Etários , Fármacos Anti-HIV/efeitos adversos , Disponibilidade Biológica , Criança , Pré-Escolar , Cálculos da Dosagem de Medicamento , Humanos , Lamivudina/efeitos adversos , Soluções Farmacêuticas , Medição de Risco , Sorbitol/efeitos adversos , Edulcorantes/efeitos adversos , Estados Unidos , United States Food and Drug Administration
20.
BMC Pharmacol Toxicol ; 19(1): 28, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29871665

RESUMO

BACKGROUND: Human Immunodeficiency Virus (HIV) is one of the main causes of morbidity and mortality; because of this it continues to be a major global public health concern. It has believed to kill more than 34 million lives so far. Sub Saharan Africa constitutes about 70% of people living with HIV among the 37 million on the globe. This region, accounted for more than two third of the global new HIV infections and about 15 million (40%) were receiving antiretroviral therapy (ART) at the end of 2014 throught the world. ART has fundamentally changed the treatment of HIV and transformed this infection from a disease of high mortality to chronic and medically managed disease. The issues of drug induced toxicities & complexity of current highly active antiretroviral therapy (HAART) regimens has remained of great concern. The aim of this study was to determine factors leading to antiretroviral regimen changes among HIV/AIDS Patients in the study area. METHODS: A facility based retrospective cross-sectional study was conducted from April 28, 2017 to May 30, 2017 in the ART clinics of east and west Wollega zone health institutions using a pre-tested data collecting form and chart review. The sample included the 243 patients whose medication had been switched. RESULTS: Majority 145 (59.67%) of the patients had been on ART for > 10 years duration. More than half 126(51.9%) of the patients had received tuberculosis (TB) treatment and almost three out of five patients (57.2%) had received isoniazid & cotrimoxazole prophylaxis. The most common reason for regimen change was peripheral neuropathy 146(60.1%) and the most common medication for this reason was stavudine, lamivudine and neverapine based 108(44.44%). CONCLUSIONS: The number of patients who changed ARV drug in our resource constrained setting present a challenge to the restricted treatment choices that we currently own. Less toxic and better-tolerated HIV treatment options should be available and used more frequently.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Substituição de Medicamentos/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas , Estudos Transversais , Etiópia , Humanos , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Nevirapina/administração & dosagem , Nevirapina/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Estudos Retrospectivos , Estavudina/administração & dosagem , Estavudina/efeitos adversos
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