Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
1.
J Anal Toxicol ; 47(1): e1-e5, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35921238

RESUMO

Toxicological data on overdose with human immunodeficiency virus inhibitors are scarce. We present a case report of two independent suicide attempts by self-administered overdose with the same antiretroviral medicine Genvoya® (emtricitabine/elvitegravir/tenofovir alafenamide/cobicistat). Both patients were admitted to the hospital and presented with a loss of consciousness, lactic acidosis, elevated hepatic transaminase levels and hemodynamic instability. While one patient survived with advanced supportive measures, the other passed away. Emtricitabine levels were measured in vivo in various consecutive serum samples and postmortem urine, peripheral and cardiac serum samples and confirmed excessive use in both cases. This is the first time that emtricitabine levels following overdose are reported. Although measured concentrations for emtricitabine were quite similar in these cases, metabolic acidosis was more pronounced in the fatal case. The difference in outcomes between the two could be due to a difference in physiological status, susceptibility to accumulation and adverse effects, and perhaps a varying interval between ingestion and the start of supportive measures.


Assuntos
Fármacos Anti-HIV , Overdose de Drogas , Infecções por HIV , Humanos , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Fármacos Anti-HIV/toxicidade , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV , Combinação de Medicamentos , Emtricitabina/toxicidade , Emtricitabina/uso terapêutico
2.
J Clin Neuromuscul Dis ; 24(2): 75-79, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36409337

RESUMO

ABSTRACT: Patients with HIV have a higher incidence of rhabdomyolysis compared with the HIV negative population because of medication-related myotoxicity and drug-drug interactions. Statins and antiretroviral therapy have been previously reported to cause myopathy in patients with HIV when used alone or in combination. In this study, we describe a case of biopsy-proven noninflammatory and nonautoimmune myopathy associated with the use of simvastatin and Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate) and review 3 previously reported similar cases. Our patient presented with acute proximal limb weakness and significantly elevated serum creatine kinase. Muscle biopsy revealed scattered degenerating and regenerating muscle fibers without evidence for an inflammatory process. She did not respond to empiric treatment with high-dose intravenous steroids and intravenous immunoglobulin. Her creatine kinase only began to downtrend after discontinuation of both simvastatin and Genvoya, and she returned to baseline function at 2-month follow-up. Our case highlights the importance of recognizing drug-drug interactions between HIV and statin medications in causing significant noninflammatory myopathy. In these patients, both categories of medications need to be discontinued for recovery.


Assuntos
Infecções por HIV , Doenças Musculares , Feminino , Humanos , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Sinvastatina/efeitos adversos , Doenças Musculares/induzido quimicamente , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Creatina Quinase
3.
Dtsch Med Wochenschr ; 147(20): 1330-1335, 2022 10.
Artigo em Alemão | MEDLINE | ID: mdl-36195091

RESUMO

ANAMNESIS: We saw a previously healthy 30-year-old Southeast-Asian sailor with progredient coughing and fever. EXAMINATION: We found an atypical pneumonia along with a positive HIV-test. We performed a bronchial lavage and further diagnostics for opportunistic infections. The lab work showed a viral load of 3340 000 copies/ml and a CD4-cell-count of 36/µl. DIAGNOSIS: HIV late presenter in CDC stadium C3 with Pneumocystis jirovecii and CMV pneumonia. THERAPY: We treated with Meropenem, Moxifloxacin, Cotrimoxazol, Ganciclovir and Genvoya. CLINICAL COURSE: Due to a cardio-pulmonal deterioration invasive ventilation was necessary. In the end the patient died of multi organ failure twelve days after admission despite intensive care, hemodialysis and prone positioning. CONCLUSION: This case demonstrates the difficulties in the pharmacotherapy and with drug interactions in a HIV late presenter with multi organ failure. Consultation and advice of the hospital pharmacy and the antibiotic stewardship team was vital for treating this patient. In the end cases like the portrayed should be treated in specialized clinics.


Assuntos
Síndrome de Imunodeficiência Adquirida , Infecções por HIV , Militares , Pneumonia por Pneumocystis , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/diagnóstico , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Ganciclovir/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Meropeném/uso terapêutico , Moxifloxacina/uso terapêutico , Pneumonia por Pneumocystis/tratamento farmacológico
4.
AIDS ; 36(15): 2225-2227, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36205353

RESUMO

We estimated list and net prices for tenofovir disoproxil fumarate (TDF) products Truvada, Complera, and Stribild, and their tenofovir alafenamide (TAF) versions Descovy, Odefsey, and Genvoya. Gilead offered discounts for Descovy that resulted into lower net prices compared to Truvada. This strategy encouraged patients switching from Truvada to Descovy before the availability of generic Truvada. Conversely, Gilead offered lower discounts for Odefsey and Genvoya, which resulted into higher net prices compared to Complera and Stribild.


Assuntos
Fármacos Anti-HIV , Combinação Emtricitabina, Rilpivirina e Tenofovir , Infecções por HIV , Humanos , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Combinação Emtricitabina, Rilpivirina e Tenofovir/uso terapêutico , Infecções por HIV/tratamento farmacológico , Tenofovir/uso terapêutico , Fármacos Anti-HIV/uso terapêutico
5.
BMC Infect Dis ; 21(1): 595, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34157984

RESUMO

BACKGROUND: We aimed to assess the overall cardiovascular and metabolic effect of the switch to three different single tablet regimens (STRs) [tenofovir alafenamide/emtricitabine/rilpivirine (TAF/FTC/RPV), TAF/FTC/elvitegravir/cobi (TAF/FTC/EVG/cobi) and ABC/lamivudine/dolutegravir (ABC/3TC/DTG)] in a cohort of people living with HIV/AIDS (PLWH) under effective ART. METHODS: All PLWH aged above 18 years on antiretroviral treatment with an HIV-RNA < 50 cp/mL at the time of the switch to TAF/FTC/RPV, TAF/FTC/EVG/cobi and ABC/3TC/DTG were retrospectively included in the analysis. Framingham risk score modification after 12 months from the switch such as lipid profile and body weight modification were assessed. The change from baseline to 12 months in mean cardiovascular risk and body weight in each of the STR's group were assessed by means of Wilcoxon signed-rank test whereas a mixed regression model was used to assess variation in lipid levels. RESULTS: Five-hundred and sixty PLWH were switched to an STR regimen of whom 170 (30.4%) to TAF/FTC/EVG/cobi, 191 (34.1%) to TAF/FTC/RPV and 199 (35.5%) to ABC/3TC/DTG. No difference in the Framingham cardiovascular risk score was observed after 12 months from the switch in each of the STR's groups. No significant overtime variation in mean total cholesterol levels from baseline to 12 months was observed for PLWH switched to ABC/3TC/DTG [200 (SD 38) mg/dl vs 201 (SD 35) mg/dl; p = 0.610] whereas a significant increment was observed in PLWH switched to TAF/FTC/EVG/cobi [192 (SD 34) mg/dl vs 208 (SD 40) mg/dl; p < 0.0001] and TAF/FTC/RPV [187 (SD 34) mg/dl vs 195 (SD 35) mg/dl; p = 0.027]. In addition, a significant variation in the mean body weight from baseline to 12 months was observed in PLWH switched to TAF/FTC/EVG/cobi [72.2 (SD 13.5) kilograms vs 74.6 (SD 14.3) kilograms; p < 0.0001] and TAF/FTC/RPV [73.4 (SD 11.6) kilograms vs 75.6 (SD 11.8) kilograms; p < 0.0001] whereas no difference was observed in those switched to ABC/3TC/DTG [71.5 (SD 12.8) kilograms vs 72.1 (SD 12.6) kilograms; p = 0.478]. CONCLUSION: No difference in the cardiovascular risk after 1 year from the switch to these STRs were observed. PLWH switched to TAF/FTC/EVG/cobi and TAF/FTC/RPV showed an increase in total cholesterol levels and body weight 12 months after the switch.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Combinação Emtricitabina, Rilpivirina e Tenofovir/uso terapêutico , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Lamivudina/uso terapêutico , Oxazinas/uso terapêutico , Piperazinas/uso terapêutico , Piridonas/uso terapêutico , Adulto , Fármacos Anti-HIV/metabolismo , Peso Corporal/efeitos dos fármacos , Estudos de Coortes , Didesoxinucleosídeos/metabolismo , Combinação de Medicamentos , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/metabolismo , Combinação Emtricitabina, Rilpivirina e Tenofovir/metabolismo , Feminino , Fatores de Risco de Doenças Cardíacas , Compostos Heterocíclicos com 3 Anéis/metabolismo , Humanos , Itália/epidemiologia , Lamivudina/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Oxazinas/metabolismo , Piperazinas/metabolismo , Piridonas/metabolismo , Estudos Retrospectivos , Comprimidos/uso terapêutico
6.
Sex Transm Infect ; 97(5): 329-333, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33106437

RESUMO

BACKGROUND: Postexposure prophylaxis (PEP) is a recommended public health intervention after a sexual assault to prevent HIV infection. METHODS: We conducted a retrospective case-control study on how use of a single-tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (Stribild) affected adherence to PEP and attendance of a follow-up visit to the STI clinic compared with those who received a multitablet regimen (MTR). Data from sexual assault victims consulting for PEP were prospectively recorded between January 2011 and December 2017. Data were systematically collected on patient demographics, time of medical contact, source risk factors, type of exposure, attendance to follow-up visit, reported completion of PEP and adherence based on pharmacy records. RESULTS: A total of 422 patients received PEP following a sexual assault, of whom 52% had documented completion of a 28-day PEP regimen and 71% attended a follow-up clinic visit. Patients who received an elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF)-based STR had a similar likelihood of attending their first follow-up visit (OR: 0.97; 95% CI: 0.64 to 1.48, p=0.90) but were more likely to complete the PEP regimen (OR: 1.70; 95% CI: 1.16 to 2.50, p=0.007). After adjusting for confounders, those who were prescribed an STR regimen were more likely to complete the PEP regimen (OR: 1.66, 95% CI: 1.09 to 2.53, p=0.019) than those who were prescribed an MTR such as stavudine/lamivudine/lopinavir/ritonavir or zidovudine/lamivudine/indinavir/ritonavir. CONCLUSIONS: Sexual assault victims who were prescribed an STR based on EVG/COBI/FTC/TDF were more likely to complete PEP than those who were prescribed an MTR.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Vítimas de Crime/psicologia , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/administração & dosagem , Infecções por HIV/prevenção & controle , Adesão à Medicação/estatística & dados numéricos , Profilaxia Pós-Exposição/métodos , Delitos Sexuais/psicologia , Adulto , Bélgica/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
7.
Infect Dis (Lond) ; 52(4): 249-256, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31876437

RESUMO

Objectives: Cardiovascular disease has become one of the most common comorbidities among HIV-infected patients, but available data about the correlation between antiretroviral drugs and progression rate of atherosclerotic disease are still limited. We evaluated the progression rate of carotid atherosclerosis in patients starting an initial antiretroviral regimen including one integrase strand transfer inhibitor (INSTI).Methods: Observational, prospective study involving HIV-1-infected, antiretroviral therapy-naive, adult patients who started an antiretroviral regimen including tenofovir alafenamide/emtricitabine (TAF/FTC) plus raltegravir (RAL group), elvitegravir/cobicistat (EVG/c group), or dolutegravir (DTG group). Patients with known cardiovascular disease or diabetes mellitus were excluded from the study. The progression rate of atherosclerosis has been assessed by carotid Doppler ultrasonography at baseline and after 24 months.Results: Overall, 102 patients were enrolled into the study: 73 males, with mean age of 48.7 years: 32, 36 and 34 patients were included in the RAL, EVG/c and DTG groups, respectively. The baseline features of the enrolled patients were comparable across the three groups. At 24 months, the mean intima-media thickness (IMT) increase at the carotid bifurcation was 0.026 mm in the RAL group, 0.029 mm in EVG/c group and 0.032 mm in DTG group. The mean IMT increases after 24 months were comparable across the three groups and statistically not significant in all the evaluated anatomical sites.Conclusions: The initial antiretroviral therapy with TAF/FTC plus RAL, EVG/c or DTG for 24 months led to a comparable and not significant effect on the progression rate of carotid atherosclerosis.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Doenças das Artérias Carótidas/etiologia , Infecções por HIV/complicações , HIV-1/efeitos dos fármacos , Adenina/efeitos adversos , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Fármacos Anti-HIV/uso terapêutico , Espessura Intima-Media Carotídea , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/efeitos adversos , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Emtricitabina/efeitos adversos , Emtricitabina/uso terapêutico , Feminino , Seguimentos , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Estudos Prospectivos , Piridonas , Raltegravir Potássico/efeitos adversos , Raltegravir Potássico/uso terapêutico , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , Ultrassonografia Doppler
8.
BMC Nephrol ; 20(1): 69, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808332

RESUMO

BACKGROUND: Genvoya® (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) is a recent single regimen for the treatment of Human Immunodeficiency Virus (HIV). However, because of its complexity, it is difficult to predict drug interactions, especially when associated with HMG-CoA reductase inhibitors and/or in the setting of other comorbidities. We discuss the mechanisms of these potential drug interactions as the cause of rhabdomyolysis and acute kidney injury in the context of prior and current medication therapy with possible underlying liver and kidney dysfunction. CASE PRESENTATION: We describe the case of a 54-year-old man diagnosed with HIV who developed severe rhabdomyolysis-induced anuric acute kidney injury (AKI) requiring renal replacement therapy following introduction of Genvoya® concomitantly with simvastatin, in the context of recently diagnosed hepatitis C and hepatitis A. Haemodialysis was continued over 5 weeks followed by progressive clinical and biological improvements. Five months later, a new antiretroviral regimen was started and has been well tolerated. CONCLUSION: Simvastatin, as well as lovastatin, because of their CYP3A4 metabolism, and to a lesser extent atorvastatin, which is only partially metabolized by CYP3A4, are the HMG-CoA reductase inhibitors with the greatest risk of drug interactions and should not be used in patients under HIV-therapy. Patients receiving HMG-CoA reductase inhibitors should be monitored regularly for the occurrence of muscular adverse effects and drug interactions should be considered with each new prescription or change in clinical status. There are many online tools that enable clinicians to rapidly check for drug interactions. We recommend the one from the University of Liverpool for patients under HIV-therapy ( https://www.hiv-druginteractions.org/checker ), while for patients under hepatitis C-therapy, we advise to consult http://www.hep-druginteractions.org/ . This case illustrates the importance of multidisciplinary collaboration in the treatment of HIV-positive patients because of their complexity, associated comorbidities and the potential of multiple drug-drug interactions potentially exacerbated by underlying liver and/or kidney dysfunction.


Assuntos
Injúria Renal Aguda , Cobicistat , Dislipidemias/tratamento farmacológico , Emtricitabina , Infecções por HIV/tratamento farmacológico , Hepatite A/complicações , Hepatite C/complicações , Quinolonas , Rabdomiólise , Sinvastatina , Tenofovir/análogos & derivados , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/fisiopatologia , Injúria Renal Aguda/terapia , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Cobicistat/administração & dosagem , Cobicistat/efeitos adversos , Combinação de Medicamentos , Interações Medicamentosas , Dislipidemias/complicações , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila , Emtricitabina/administração & dosagem , Emtricitabina/efeitos adversos , Infecções por HIV/complicações , Hepatite A/diagnóstico , Hepatite A/fisiopatologia , Hepatite C/diagnóstico , Hepatite C/fisiopatologia , Humanos , Hipolipemiantes/administração & dosagem , Hipolipemiantes/efeitos adversos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Quinolonas/administração & dosagem , Quinolonas/efeitos adversos , Diálise Renal/métodos , Rabdomiólise/induzido quimicamente , Rabdomiólise/fisiopatologia , Rabdomiólise/terapia , Sinvastatina/administração & dosagem , Sinvastatina/efeitos adversos , Tenofovir/administração & dosagem , Tenofovir/efeitos adversos , Resultado do Tratamento
9.
Basic Clin Pharmacol Toxicol ; 124(4): 479-490, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30388308

RESUMO

Two elvitegravir/cobicistat-based therapies combined with emtricitabine/tenofovir disoproxil fumarate (EVG/c/FTC/TDF) or emtricitabine/tenofovir alafenamide fumarate (EVG/c/FTC/TAF) are currently available for HIV patients. This study evaluated the modifications in the lipid profile of patients who received these treatments in the last three years at our institution. A retrospective observational study in HIV-infected patients who received EVG/c/FTC/TDF or EVG/c/FTC/TAF from January 2015 to January 2018 at a reference hospital in northwestern Spain was carried out. Epidemiological, clinical and immunovirological data were recorded. A statistical analysis was performed using SPSS software. A total of 384 EVG/c-based therapies were initiated during the study period, 151 EVG/c/FTC/TDF and 233 EVG/c/FTC/TAF. A significantly negative influence in all the lipid profile parameters in experienced patients and total cholesterol (TC), and LDL-C in naïve patients were observed after 48 weeks of treatment with EVG/c/FTC/TAF, while these parameters remained stable in the EVG/c/FTC/TDF group. During follow-up, a greater proportion of patients had lipid levels above the normal range (63.1% TC, 56.2% LDL-C) and new lipid-modifying drugs were prescribed (11.9%) in the EVG/c/FTC/TAF group. The number of cardiovascular risk factors (OR 1.66 [95% CI 1.01-2.72]; P = 0.043) was recognised as an independent predictor of lipid-lowering prescription for patients treated with both EVG/c/FTC/TDF and EVG/c/FTC/TAF. For patients treated with EVG/c/FTC/TAF, the mean total cholesterol to HDL ratio in the first 48 weeks of the study treatment was associated with a higher likelihood of lipid-lowering prescription in multivariate analysis (OR 1.6 [95% CI 1.12-2.52]; P = 0.011). Significant changes in lipid profile have been observed in patients who have received EVG/c/FTC/TAF. It was necessary to prescribe almost twice the number of lipid-lowering drugs to patients who received EVG/c/FTC/TAF (11.9%) vs EVG/c/FTC/TDF (4.7%).


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/administração & dosagem , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/administração & dosagem , Infecções por HIV/tratamento farmacológico , Lipídeos/sangue , Adenina/administração & dosagem , Adenina/efeitos adversos , Adulto , Alanina , Fármacos Anti-HIV/efeitos adversos , Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Seguimentos , Humanos , Hipolipemiantes/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Espanha , Tenofovir/análogos & derivados , Adulto Jovem
10.
Antivir Ther ; 23(7): 629-632, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30281025

RESUMO

BACKGROUND: Increased insulin resistance (IR), associated with specific antiretroviral drugs or drug classes, is an established risk factor for type 2 diabetes in HIV patients, ultimately increasing morbidity and mortality. To date, data on the risk of IR in tenofovir alafenamide (TAF)-based protocols are unavailable. METHODS: This prospective randomized, open-label study evaluated the effects of IR on 30 healthy volunteers receiving fixed-dose combinations (FDCs) of emtricitabine/tenofovir alafenamide (F/TAF), elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or rilpivirine/emtricitabine/tenofovir alafenamide (R/F/TAF). IR was measured before and after 14-day treatments using the hyperinsulinemic-euglycaemic clamp technique (HEGC). Changes in IR in each group were evaluated using the mean glucose disposal rate, normalized with body weight (MBW [mg glucose/(min×kg)]). RESULTS: A total of 30 subjects underwent randomization: one subject in the F/TAF arm withdrew consent after randomization and one in the R/F/TAF arm had to be excluded because of technical failure during HEGC, resulting in 28 subjects in the per-protocol population (F/TAF, n=9 subjects; E/C/F/TAF, n=10 subjects; R/F/TAF n=9 subjects). No significant differences were detected on the baseline characteristics. IR did not differ among the groups before treatment. None of the studied antiretroviral combinations resulted in a significant change in IR after 14 days compared with baseline values, as measured by MBW (F/TAF, 11.42 ±3.04 mean [±sd] versus 11.43 ±3.23, P=0.49; E/C/F/TAF, 10.04 ±2.49 versus 10.95 ±4.26, P=0.30; R/F/TAF, 11.03 ±1.96 versus 13.01 ±4.11, P=0.13). CONCLUSIONS: Short-term treatment for F/TAF, E/C/F/TAF or R/F/TAF did not increase IR in healthy male volunteers.


Assuntos
Fármacos Anti-HIV/farmacocinética , Glicemia/metabolismo , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/farmacocinética , Resistência à Insulina/fisiologia , Rilpivirina/farmacocinética , Adenina/análogos & derivados , Adulto , Fármacos Anti-HIV/sangue , Peso Corporal , Combinação de Medicamentos , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/sangue , Emtricitabina , Técnica Clamp de Glucose , Voluntários Saudáveis , Humanos , Masculino , Estudos Prospectivos , Rilpivirina/sangue , Tenofovir
11.
BMC Infect Dis ; 18(1): 310, 2018 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-29980192

RESUMO

BACKGROUND: Tenofovir alafenamide (TAF) is associated with less renal and bone toxicity compared with tenofovir disoproxil (TDF). TAF's recent FDA approval has spurred HIV providers to consider switching antiretroviral therapy (ART) regimens containing TDF to TAF to minimize long term risks. Patient views on the process of such medication switches have not been explored. METHODS: Patients taking elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) following the Food and Drug Administration's (FDA) approval of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) received medication education from an HIV pharmacist prior to switching to the tenofovir alafenamide (TAF) formulation. Patients were asked to complete a cross-sectional survey assessing satisfaction with the switch process and knowledge about the new medication 4 to 8 weeks post-switch. RESULTS: Sixty five patients completed the switch and 57 (88%) completed a follow-up survey. Most (86%) reported understanding why the switch was made, while 91% correctly identified that TAF is associated with reduced renal toxicity, and 73% correctly identified that TAF is associated with reduced bone toxicity. No statistically significant difference was found in satisfaction with or understanding of why the medication switch was made when assessed by sex, age, race, or education, but there was a trend toward significance in the distribution of answers based on education level with those with a high school diploma, General Educational Development (GED) or less being more likely to be satisfied with the medication switch (p = 0.074). CONCLUSIONS: Education from an ambulatory clinic-based HIV pharmacist resulted in high rates of patient satisfaction and understanding of the switch from TDF to TAF-containing ART.


Assuntos
Adenina/análogos & derivados , Infecções por HIV/tratamento farmacológico , Satisfação do Paciente , Farmacêuticos , Tenofovir/uso terapêutico , Adenina/uso terapêutico , Adulto , Alanina , Fármacos Anti-HIV/uso terapêutico , Estudos Transversais , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade
13.
J Pharm Biomed Anal ; 156: 163-169, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29709783

RESUMO

A liquid chromatography with triple quadrupole mass spectrometry method was developed and validated for the determination of tenofovir and tenofovir alafenamide concentrations in human plasma and cerebrospinal fluid. Tenofovir and tenofovir alafenamide were extracted from matrix by solid phase extraction. The dried extraction eluents were dissolved in water for LC-MS/MS analysis. Separation was achieved with a Phenomenex Synergi 4 µm Polar-RP 80A column (50 × 2 mm) with a gradient elution of 0.1% formic acid in water and acetonitrile. The total run time was 5 min. Detection of analytes was achieved using electrospray ionization (positive mode) and triple quadrupole selected reaction monitoring. Standard curve concentrations ranged from 0.5 to 500 ng/mL for the plasma assay and 0.1-50 ng/mL for the cerebrospinal fluid assay. The intra- and inter-day accuracy and precision were less than 12% in low, medium, and high quality control samples for both matrices. The validated methods were applied to the analysis of plasma and cerebrospinal fluid samples of a patient undergoing tenofovir therapy which involved the switch from Stribild® (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) to Genvoya® (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg).


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/análise , Infecções por HIV/tratamento farmacológico , Tenofovir/análise , Adenina/análise , Adenina/uso terapêutico , Alanina , Cromatografia Líquida de Alta Pressão , Cobicistat/análise , Cobicistat/uso terapêutico , Combinação de Medicamentos , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/análise , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Emtricitabina/análise , Emtricitabina/uso terapêutico , Infecções por HIV/sangue , Infecções por HIV/líquido cefalorraquidiano , Humanos , Quinolonas/análise , Quinolonas/uso terapêutico , Reprodutibilidade dos Testes , Extração em Fase Sólida , Espectrometria de Massas em Tandem , Tenofovir/análogos & derivados , Tenofovir/uso terapêutico
14.
Clin Infect Dis ; 67(10): 1588-1594, 2018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-29672676

RESUMO

Background: There is an urgent need for safe and effective antiretroviral therapy (ART) for human immunodeficiency virus type 2 (HIV-2) infection. We undertook the first clinical trial of a single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (E/C/F/TDF) to assess its effectiveness in HIV-2-infected individuals in Senegal, West Africa. Methods: HIV-2-infected, ART-naive adults with World Health Organization stage 3-4 disease or CD4 count <750 cells/µL were eligible for this 48-week, open-label trial. We analyzed HIV-2 viral loads (VL), CD4 counts, clinical and adverse events, mortality, and loss to follow-up. Results: We enrolled 30 subjects who initiated E/C/F/TDF. Twenty-nine subjects completed 48 weeks of follow-up. The majority were female (80%). There were no deaths, no new AIDS-associated clinical events, and 1 loss to follow-up. The median baseline CD4 count was 408 (range, 34-747) cells/µL, which increased by a median 161 (range, 27-547) cells/µL at week 48. Twenty-five subjects had baseline HIV-2 VL of <50 copies/mL of plasma. In those with detectable HIV-2 VL, the median was 41 (range, 10-6135) copies/mL. Using a modified intent-to-treat analysis (US Food and Drug Administration Snapshot method), 28 of 30 (93.3%; 95% confidence interval, 77.9%-99.2%) had viral suppression at 48 weeks. The 1 subject with virologic failure had multidrug-resistant HIV-2 (reverse transcriptase mutation: K65R; integrase mutations: G140S and Q148R) detected at week 48. There were 8 grade 3-4 adverse events; none were deemed study related. Adherence and acceptability were good. Conclusions: Our data suggest that E/C/F/TDF, a once-daily, single-tablet-regimen, is safe, effective, and well tolerated. Our findings support the use of integrase inhibitor-based regimens for HIV-2 treatment. Clinical Trials Registration: NCT02180438.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adulto , África Ocidental , Idoso , Feminino , HIV-1/efeitos dos fármacos , Recursos em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Comprimidos , Adulto Jovem
15.
J Int Assoc Provid AIDS Care ; 17: 2325957417752260, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29385867

RESUMO

BACKGROUND: Patients with drug-resistant HIV often require complex antiretroviral regimens. However, combining fixed-dose combination tablets such as tenofovir-disoproxil-fumarate, emtricitabine, and cobicistat-boosted elvitegravir (TDF/FTC/EVG/cobi) with darunavir (DRV) can provide a simple, once-daily (QD), 2-tablet regimen for patients with drug-resistant HIV. Primary objective was to determine the percentage of patients with HIV-1 RNA <40 copies/mL at 48 weeks. METHODS: We performed a retrospective chart review of patients initiated on TDF/FTC/EVG/cobi plus DRV. RESULTS: Among the 21 included patients, prior resistance showed a median of 2 nucleoside reverse transcriptase inhibitor mutations, 1 nonnucleoside reverse transcriptase mutation, and 1 protease inhibitor mutation. At week 48, 14 (67%) patients achieved HIV-1 RNA <40 copies/mL, 1 patient experienced viral rebound, and 6 (29%) had missing data or discontinued therapy. No patient discontinued for adverse events. CONCLUSION: According to this observational study, QD TDF/FTC/EVG/cobi plus DRV is considered safe, well tolerated, and generally effective in suppressing HIV drug-resistant virus.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Darunavir/administração & dosagem , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/administração & dosagem , Infecções por HIV/tratamento farmacológico , Adulto , Fármacos Anti-HIV/uso terapêutico , Darunavir/uso terapêutico , Esquema de Medicação , Farmacorresistência Viral , Quimioterapia Combinada , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Feminino , HIV-1 , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Cult Health Sex ; 20(11): 1185-1198, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29360420

RESUMO

Limited data suggest that some gay and other men who have sex with men are using antiretroviral medications informally, without a prescription, for HIV prevention. This qualitative study examined this phenomenon among gay and other men who have sex with men in South Florida. Participants initiated informal antiretroviral medication use as a means of protecting each other and because of the confidence in knowledge of antiretroviral medications shared by their friends and sex partners. The most commonly used medications included Truvada and Stribild. Motivations for use included condom avoidance, risk reduction, and fear of recent HIV exposure. Participants described positive and negative sentiments related to informal use, including concerns about informal antiretroviral medications offering sufficient protection against HIV, and limited knowledge about pre-exposure prophylaxis (PrEP). Because the antiretroviral medications used for PrEP have the potential to prevent HIV infection, future research must consider the informal antiretroviral medication use and related concerns, including adherence, diversion and viral resistance.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Profilaxia Pré-Exposição/métodos , Automedicação , Minorias Sexuais e de Gênero , Adolescente , Adulto , Preservativos , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Florida , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Pesquisa Qualitativa , Comportamento de Redução do Risco , Adulto Jovem
17.
J Pharm Pract ; 31(2): 216-221, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28558493

RESUMO

INTRODUCTION: This review evaluates the efficacy and safety of Genvoya® (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide [EVG/c/TAF/FTC]), a single-tablet regimen used for the management of HIV-1 infection. Phase II and III randomized clinical trials evaluate the efficacy and safety of EVG/c/TAF/FTC and tenofovir disoproxil fumerate (TDF)-containing arms; renal impairment, bone mineral density, metabolic effects, and other adverse events are topics explored within this review. METHODS: A MEDLINE with full text and PubMed literature search was conducted for the past 5 years, up to April 2016. RESULTS: Virologic suppression was similar between the EVG/c/TAF/FTC and TDF-containing groups (<50 copies/mL) at week 48. The bone mineral density in the hip and spine showed a significant reduction in the TDF-containing groups. The glomerular filtration rate increased in patients in the EVG/c/TAF/FTC arm and there were significant differences in total proteinuria, albuminuria, and tubular proteinuria in patients switching to EVG/c/TAF/FTC. The most common adverse events were diarrhea, nausea, and headache. DISCUSSION: The coformulated Genvoya regimen is well tolerated and effective in treatment-naive and virologically suppressed patients. Data seem to suggest it may also be effective and safe in patients with mild to moderate renal impairment. The lower-dosed single-tablet regimen has significantly reduced bone and renal side effects.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Cobicistat/uso terapêutico , Gerenciamento Clínico , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Quinolonas/uso terapêutico , Tenofovir/análogos & derivados , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacologia , Ensaios Clínicos Fase III como Assunto/métodos , Cobicistat/efeitos adversos , Cobicistat/farmacologia , Diarreia/induzido quimicamente , Combinação de Medicamentos , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila , Emtricitabina/efeitos adversos , Emtricitabina/farmacologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Cefaleia/induzido quimicamente , Humanos , Náusea/induzido quimicamente , Quinolonas/efeitos adversos , Quinolonas/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Tenofovir/efeitos adversos , Tenofovir/farmacologia , Tenofovir/uso terapêutico , Resultado do Tratamento
18.
J Int Assoc Provid AIDS Care ; 16(6): 535-539, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28895486

RESUMO

We report the first identified case of suspected iatrogenic adrenal insufficiency after an interlaminar injection of triamcinolone acetonide while on concomitant Stribild (elvitegravir 150 mg/cobicistat 150 mg/tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg [EVG/c/TDF/FTC]). A 49-year-old female with HIV on EVG/c/TDF/FTC therapy presented to our endocrinology clinic to be evaluated for suspected Cushing syndrome. Prior to presentation, the patient had been given 2 interlaminar spinal injections of triamcinolone. Thereafter, she developed a swollen face, had unexplained weight gain, and fatigue. Cosyntropin stimulation test was positive for adrenal insufficiency. By applying the Naranjo Nomogram for Causality and the Drug Interaction Probability Scale to this drug-drug interaction, we calculated a score of 6 ( probable) and 5 ( probable), respectively. Symptoms resolved without further intervention. The EVG/c/TDF/FTC contains cobicistat, a strong cytochrome P450 3A4 (CYP3A4) inhibitor, which can potentiate drug interactions involving metabolizing of medications via this pathway. Clinicians are reminded to be vigilant while assessing the potential pharmacokinetic drug interactions not mentioned by the manufacturer.


Assuntos
Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Insuficiência Adrenal/induzido quimicamente , Fármacos Anti-HIV/efeitos adversos , Inibidores do Citocromo P-450 CYP3A/efeitos adversos , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/efeitos adversos , Glucocorticoides/efeitos adversos , Dor Lombar/tratamento farmacológico , Triancinolona/efeitos adversos , Interações Medicamentosas , Feminino , Humanos , Doença Iatrogênica , Injeções Espinhais , Pessoa de Meia-Idade
19.
J Acquir Immune Defic Syndr ; 75(5): 535-539, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28696345

RESUMO

STRUCTURE: The study evaluated elvitegravir/cobicistat/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) ("Quad pill") for postexposure prophylaxis (PEP). BACKGROUND: HIV-exposed individuals may benefit from PEP, but completion rates have been suboptimal because of regimen complexity and side effects. Newer antiretroviral combinations coformulated as single daily pills may optimize PEP adherence. SETTING: One hundred HIV-uninfected individuals who presented to a Boston community health center after an acute HIV sexual exposure were enrolled and initiated PEP with the daily, single-pill combination Quad pill for a 28-day course. METHODS: Side effects and medication completion rates from study participants were compared with historical controls who had used PEP regimens consisting of TDF/FTC daily and raltegravir twice daily, or earlier regimens of twice daily zidovudine (AZT)/lamivudine (3TC) and a protease inhibitor, using χ tests for independence. RESULTS: Of the 100 participants who initiated the Quad pill for PEP after a high-risk sexual exposure, 71% completed the 28-day Quad pill regimen, which was significantly greater than historical controls who used TDF/FTC and raltegravir (57%, P < 0.05) or AZT/3TC plus a protease inhibitor (39%, P < 0.001). The most common side effects reported by Quad pill users were as follows: abdominal discomfort or pain, gas or bloating (42%), diarrhea (38%), fatigue (28%), nausea or vomiting (28%), headache (14%), or dizziness or lightheadedness (6%). Most symptoms were mild, limited, and did not result in medication discontinuation. No participants became HIV infected. CONCLUSIONS: Fixed-dose combination of elvitegravir/cobicistat/TDF/FTC was safe and well tolerated for PEP, with higher regimen completion rates than more frequently dosed PEP regimens.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/administração & dosagem , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Infecções por HIV/tratamento farmacológico , Profilaxia Pós-Exposição/métodos , Adulto , Fármacos Anti-HIV/efeitos adversos , Boston , Contagem de Linfócito CD4 , Esquema de Medicação , Quimioterapia Combinada , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/efeitos adversos , Feminino , Infecções por HIV/prevenção & controle , Humanos , Masculino , Adesão à Medicação , Estudos Prospectivos , Resultado do Tratamento , Carga Viral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...