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1.
Cardiovasc J Afr ; 30(2): 95-102, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30839048

RESUMO

HIV-infected populations receiving antiretroviral therapy (ART) have an increased risk of cardiovascular disease. The beneficial cardiovascular effects of rooibos are well described; however, it is unknown whether rooibos ameliorates harmful ART-induced cardiovascular side effects. We investigated the cardiometabolic effects of rooibos co-treatment in rats receiving ART (efavirenz, emtricitabine, tenofovir) for nine weeks. Rooibos treatment reduced total cholesterol levels; however, triglyceride, phospholipid and thiobarbituric acidreactive substance levels were unaffected by ART, rooibos or combination treatment. In isolated hearts exposed to ischaemia-reperfusion injury, ART resulted in increased infarct sizes compared to controls, which was not observed when co-treated with rooibos. Vascular studies showed reduced aortic relaxation with ART, and improved relaxation when co-treated with rooibos. In conclusion, we show that rooibos treatment reduced total cholesterol levels in control rats, and that rooibos co-treatment ameliorated the harmful ART-induced cardiovascular effects. These findings are novel and warrant further studies into underlying mechanisms and clinical relevance.


Assuntos
Fármacos Anti-HIV/toxicidade , Aspalathus , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/toxicidade , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Extratos Vegetais/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/fisiopatologia , Aspalathus/química , Biomarcadores/sangue , Cardiotoxicidade , Colesterol/sangue , Modelos Animais de Doenças , Regulação para Baixo , Preparação de Coração Isolado , Masculino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/induzido quimicamente , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/patologia , Extratos Vegetais/isolamento & purificação , Ratos Wistar , Vasodilatação/efeitos dos fármacos
3.
AIDS ; 32(12): 1633-1641, 2018 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-29746294

RESUMO

BACKGROUND: Antiretroviral drugs contained in single tablet Atripla have pharmacokinetic properties that could allow for longer than once-daily dosing. We hypothesized that simplifying Atripla once daily to 3-day per week would be feasible, able to maintain viral suppression and less toxic. METHODS: Virologically suppressed (≥2 years) HIV+ adults on Atripla once daily, CD4 greater than 350 cells/µl at inclusion, and no prior documented virological failure or evidence of resistance mutations to efavirenz, tenofovir, or emtricitabine were randomized to maintain their once-daily (OD) regimen or to reduce it to 3 days (Mondays, Wednesdays, and Fridays) a week (3W) (A-TRI-WEEK pilot trial). Primary end-point was the proportion of patients free of treatment failure (noncompleter = failure) at 24 weeks. CD4 and CD8 cells, ultrasensitive HIV-1 RNA, Pittsburg Sleep Quality Index (PSQI), bone mineral density, plasma efavirenz levels, and fasting blood and urine chemistries were measured at baseline and 24 weeks. The study is registered at ClinicalTrials.gov, NCT01778413. RESULTS: Sixty-one patients were randomized. All patients in both arms remained free of treatment failure (estimated difference 0%; 95% confidence interval -14.1 to 14.1). Ultrasensitive plasma HIV-1 RNA below detection threshold showed no difference between arms (70% in the 3W arm vs. 71% in the OD arm, P = 0.933) at 24 weeks. Total cholesterol and femur T-score significantly increased, whereas PSQI, plasma efavirenz, albumin/creatinine and beta-2-microglobulin in urine significantly decreased in the 3W arm relative to OD arm. CONCLUSION: The A-TRI-WEEK study represents a proof of concept for the feasibility of three-day per week Atripla maintenance that should be further confirmed in a larger, well powered clinical trial.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/administração & dosagem , Infecções por HIV/tratamento farmacológico , Quimioterapia de Manutenção/métodos , Comprimidos/administração & dosagem , Adulto , Fármacos Anti-HIV/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Comprimidos/efeitos adversos , Resultado do Tratamento
4.
Arch Soc Esp Oftalmol ; 93(6): 310-312, 2018 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28886932

RESUMO

CASE REPORT: A 35-year-old male patient with a large unilateral haemorrhagic conjunctival tumour lesion and another contralateral haemorrhagic conjunctival flat lesion associated with violaceous cutaneous macules on the extremities and angiomatous lesions in the upper gastrointestinal tract as initial clinical manifestation of HIV-related immunodeficiency. Cutaneous, gastric mucosal and conjunctival biopsy was consistent with Kaposi's sarcoma with complete remission after highly active antiretroviral therapy and systemic chemotherapy. CONCLUSION: HIV-related conjunctival Kaposi's sarcoma, even a large one, can have a good response to antiretroviral therapy and systemic chemotherapy without any additional topical eye treatment.


Assuntos
Síndrome de Imunodeficiência Adquirida/complicações , Fármacos Anti-HIV/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Doxorrubicina/uso terapêutico , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/uso terapêutico , Sarcoma de Kaposi/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Terapia Antirretroviral de Alta Atividade , Neoplasias da Túnica Conjuntiva/etiologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Indução de Remissão , Sarcoma de Kaposi/etiologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/etiologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/etiologia
5.
Ther Drug Monit ; 39(2): 91-92, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28230617

RESUMO

We describe a patient with acute renal failure and irreversible kidney damage after an overdose with the fixed dose combination of efavirenz/tenofovir disoproxil fumarate/emtricitabine (Atripla). The acute kidney injury was most probably caused by tenofovir. Efavirenz and emtricitabine seemed relatively safe in overdose. The pharmacokinetics in overdose of all 3 drugs and the effect of hemodialysis on the tenofovir clearance were studied by measuring the plasma concentrations and by the use of clinical pharmacokinetic software.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Benzoxazinas/efeitos adversos , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/efeitos adversos , Emtricitabina/efeitos adversos , Tenofovir/efeitos adversos , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/uso terapêutico , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/uso terapêutico , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Tenofovir/uso terapêutico
6.
Curr HIV Res ; 15(1): 56-65, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27993121

RESUMO

BACKGROUND: Highly active antiretroviral therapy (HAART) has been commonly used for HIV treatment. Its main drawbacks like drug resistance and side effects raised researcher's interest to find new approaches for its treatment. Trimethyl chitosan is one of the drug carriers which has been introduced recently. MATERIALS AND METHODS: the conjugated atripla-trimethyl chitosan was designed and characterized by zetasizer, AFM and FTIR techniques. The drug conjugation with trimethyl chitosan and cellular uptake of nano-conjugate were determined by spectrophotometry. XTT test was used to measure the cytotoxicity. Anti-retroviral efficiency was studied by ELISA test. RESULTS: Zetasizer Results proved that the average size of nano-conjugate particles agglomeration was 493.4±24.6 nm but the size of the majority of the particles was 177.2±7.8 nm with the intensity of 87.9%. AFM technique revealed that the sizes of nano-conjugate and trimethyl chitosan were 129 nm and 59.78 nm, respectively. Zeta potential was -1.35±0.04 mv for nano-conjugate and -7.69±0.3 mv for drug. Conjugation efficiency of atripla with trimethyl chitosan was 5.27%. Measured cellular uptake with spectrophotometry for nano-conjugate was about twice of the free drug in examined concentrations (P=0.007). Compared to atripla, the nano-conjugate showed a higher inhibitory effect on HIV replication (P=0.0001). CONCLUSION: The result showed that atripla-TMC conjugate does not have a significant cytotoxicity effect. Due to the higher inhibitory effect of nano-conjugate on viral replication, it can be used in lower concentration for antiviral treatment, which resulted in reduction of drug resistance and other side effects.


Assuntos
Fármacos Anti-HIV/farmacologia , Quitosana/metabolismo , Portadores de Fármacos/metabolismo , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/farmacologia , HIV/efeitos dos fármacos , Nanopartículas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Portadores de Fármacos/química , Ensaio de Imunoadsorção Enzimática , Células HEK293 , HIV/fisiologia , Proteína do Núcleo p24 do HIV/análise , Humanos , Microscopia de Força Atômica , Nanopartículas/química , Nanopartículas/ultraestrutura , Espectrofotometria , Espectroscopia de Infravermelho com Transformada de Fourier , Replicação Viral/efeitos dos fármacos
7.
AIDS Res Hum Retroviruses ; 32(12): 1198-1201, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27216134

RESUMO

We investigated whether a treatment switch from Atripla® (tenofovir, emtricitabine, and efavirenz) to DRV/r monotherapy may improve neuropsychological performance, health-related quality of life, and sleep function. Virologically suppressed subjects and asymptomatic on Atripla for ≥6 months were randomized 1:1 to continue Atripla or switch to boosted darunavir (DRV/r) 800/100 mg once daily for 48 weeks. Neurocognitive tests, the International HIV Dementia Scale (IHDS), Medical Outcomes Study HIV Health Survey (MOS-HIV), EQ-5D-3L, and the Hospital Anxiety and Depression Scale (HADS) were completed at baseline and at week 48. Sleep function was evaluated at week 48. Twenty-six patients on DRV/r and 31 on Atripla completed the 48-week study. No significant difference in the change in scores from week 0 to week 48 between the two arms was observed in neurocognitive outcomes, IHDS, health outcomes (EQ-5D-3L and QOL), and HADS score. By contrast, the HADS score and sleep quality were both significantly better in the DRV/r arm. In conclusion, switching to DRV/r monotherapy did not affect neurocognitive function or quality of life but improved anxiety, and sleep quality was significantly better than in continued Atripla.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Cognição/efeitos dos fármacos , Darunavir/uso terapêutico , Substituição de Medicamentos , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/uso terapêutico , Infecções por HIV/tratamento farmacológico , Ritonavir/uso terapêutico , Sono/efeitos dos fármacos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida
9.
BMC Pregnancy Childbirth ; 16: 35, 2016 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-26867536

RESUMO

BACKGROUND: Universal multi drug antiretroviral treatment in pregnancy is a global priority in our bid to eliminate paediatric HIV infections although few studies have documented the impact of antiretroviral coverage on overall pregnancy outcomes. METHODS: We conducted a maternity audit at a large regional hospital in South Africa during July-December 2011 and January-June 2014 with an aim to determine an association between pregnancy outcomes and the ARV treatment guidelines implemented during those specific periods. During 2011, women received either Zidovudine/sd Nevirapine or Stavudine/Lamivudine/Nevirapine if CD4+ count was < 350 cells/ml. During 2014, all HIV positive pregnant women were eligible for a fixed dose combination (FDC) of triple ARVs (Tenofovir/Emtracitabine/Efavirenz). RESULTS: In 2011, 622 (35.9%) of 1732 HIV positive pregnant women received triple antiretrovirals (D4T/3TC/NVP) and in 2014, 2104 (94.8%) of 2219 HIV positive pregnant women received the fixed dose combination (TDF/FTC/EFV). We observed a reduction in the proportion of unregistered pregnancies, caesarean delivery rate, still birth rate, very low birth weight rate, and very premature delivery rate in 2014. In a bivariate analysis of all 9,847 deliveries, unregistered pregnancies (2.2%) and HIV infection (37.8%) remained significant risk factors for SB(OR 6.36 and 1.43 respectively), PTD(OR 4.23 and 1.26 respectively),LBW (OR 4.07 and 1.26 respectively) and SGA(OR 2.17 and 1.151 respectively). In a multivariable analysis of HIV positive women only, having received AZT/NVP or D4T/3TC/NVP or EFV/TDF/FTC as opposed to not receiving any ARV was significantly associated with reduced odds of a SB (OR 0.08, 0.21 and 0.18 respectively), PTD (OR 0.52, 0.68 and 0.56 respectively) and LBW(0.37, 0.61 and 0.52 respectively). CONCLUSION: An improvement in birth outcomes is likely associated with the increased coverage of triple antiretroviral treatment for pregnant women. And untreated HIV infected women and women who do not seek antenatal care should be considered most at risk for poor birth outcomes.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/transmissão , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Complicações Infecciosas na Gravidez , Resultado da Gravidez/epidemiologia , Adolescente , Adulto , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Recém-Nascido , Lamivudina/uso terapêutico , Nevirapina/uso terapêutico , Gravidez , Cuidado Pré-Natal/estatística & dados numéricos , África do Sul/epidemiologia , Estavudina/uso terapêutico , Adulto Jovem , Zidovudina/uso terapêutico
10.
J Acquir Immune Defic Syndr ; 72(3): 281-8, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-26885802

RESUMO

BACKGROUND: Elvitegravir (EVG), a HIV integrase inhibitor, is metabolized primarily by CYP3A, and secondarily by UGT1A1/3; Efavirenz (EFV), a HIV non-nucleoside reverse transcriptase inhibitor, is metabolized by Cytochrome P450 (CYP) 2B6 and induces CYP3A and uridine diphosphate glucuronosyltransferase (UGT) with residual effects post discontinuation because of long T1/2 (40-55 hours). This study evaluated the pharmacokinetics after switching from efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) to elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF). METHODS: Healthy subjects (n = 32 including n = 8 CYP2B6 poor metabolizers) received EVG/COBI/FTC/TDF (150/150/200/300 mg) on days 1-7, and after a washout, received EFV/FTC/TDF (600/200/300 mg) on days 15-28 and switched to EVG/COBI/FTC/TDF (150/150/200/300 mg) for 5 weeks (days 29-62). Pharmacokinetic assessments occurred on days 7, 28, 35, and 42; trough samples (Ctrough) were collected periodically until day 63. Safety was assessed throughout the study. RESULTS: Twenty-nine subjects completed with 3 adverse events leading to discontinuation; no grade ≥3 adverse events were reported. Post-EFV/FTC/TDF, mean EVG area under concentration (AUCtau) was 37% and 29% lower and mean Ctrough ∼3- and ∼5-fold above IC95, respectively, on days 35 and 42, and 7-8-fold above IC95 by 5 weeks. COBI AUCtau returned to normal by day 42. EVG glucuronide, GS-9200, AUCtau was higher (46% and 32% on days 35 and 42, respectively) postswitch. CYP2B6 poor metabolizers displayed higher EFV AUCtau and Cmax (125% and 91%, respectively) versus non-poor metabolizers, and lower EVG and COBI exposures. EFV Ctrough was >IC90 (10 ng/mL) in all subjects postswitch. FTC and tenofovir (TFV) exposures were unaffected. CONCLUSIONS: After EFV/FTC/TDF to EVG/COBI/FTC/TDF switch, EVG and/or EFV exposures were in an active range. These findings support further evaluation of switching regimens in HIV-1 patients.


Assuntos
Fármacos Anti-HIV/farmacocinética , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/farmacocinética , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/farmacocinética , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , Combinação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/efeitos adversos , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/efeitos adversos , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
11.
Antivir Ther ; 21(4): 287-96, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26460504

RESUMO

BACKGROUND: Efavirenz (EFV) has been associated with reductions in vitamin D (25[OH]D) and tenofovir (TDF) with increased bone turnover, reductions in bone mineral density (BMD) and renal tubular dysfunction. We hypothesized that switching from fixed-dose TDF/emtricitabine (FTC)/EFV to darunavir/ritonavir monotherapy (DRV/r) might increase 25(OH)D and BMD, and improve renal tubular function. METHODS: Subjects with HIV RNA <50 copies/ml on TDF/FTC/EFV for ≥6 months were randomized 1:1 to ongoing TDF/FTC/EFV or DRV/r (800/100 mg once daily) for 48 weeks. The primary end point was change from baseline in 25(OH)D at week 48. Secondary end points included changes in BMD, bone turnover markers and renal tubular function. RESULTS: A total of 64 subjects (86% male, 66% white, mean [sd] CD4(+) T-cell count 537.3 [191.5]/mm(3)) were analysed. After adjustment for baseline 25(OH)D and demographics, at week 48 DRV/r monotherapy was associated with a +3.6 (95% CI 0.6, 6.6) ng/ml increase in 25(OH)D compared to TDF/FTC/EFV (P=0.02). DRV/r monotherapy was associated with an increase in BMD (+2.9% versus -0.003% at the neck of femur and +2.6% versus +0.008% at the lumbar spine for DRV/r versus TDF/FTC/EFV; P<0.05 for all) and reductions in bone biomarkers compared with those remaining on TDF/FTC/EFV. No significant difference in renal tubular function was observed. Reasons for discontinuation in the DRV/r arm included side effects (n=4) and viral load rebound (n=3), all of which resolved with DRV/r discontinuation or regimen intensification. CONCLUSIONS: Switching from TDF/FTC/EFV to DRV/r in patients with suppressed HIV RNA resulted in significant improvements in 25(OH)D and bone biomarkers, and a 2-3% increase in BMD.


Assuntos
Fármacos Anti-HIV/farmacologia , Osso e Ossos/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Rim/efeitos dos fármacos , Vitamina D/sangue , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Calcifediol/sangue , Darunavir/efeitos adversos , Darunavir/uso terapêutico , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/efeitos adversos , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/farmacologia , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ritonavir/efeitos adversos , Ritonavir/uso terapêutico
12.
J Anal Toxicol ; 40(1): 49-57, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26487641

RESUMO

Liquid chromatography (LC) and mass spectral behavior and analytical performance characteristics of efavirenz (EFV), emtricitabine (EMT) and tenofovir (TFV), i.e., individual components of Atripla(®), were probed. This was followed by estimation of their analytical performance characteristics employing LC and a parallel direct infusion sample introduction procedure. Performance characteristics using both types of sample introduction procedures were compared. Using liquid chromatography-mass spectrometry (LC-MS), linearities, i.e., correlation coefficients of the calibration curves of EFV, EMT and TFV, ranged between 0.9300 and 0.9990 in the full scan, selected ion monitoring and mass spectrometry/mass spectrometry (MS-MS) modes. The limits of detection (LODs) ranged between 0.5 and 11.6 µg/L. The lower limits of quantification (LLOQs) and the upper limits of quantification (ULOQs) were in the ranges of 0.9-23.2 and 1.6-38.7 µg/L, respectively. The LODs ranged between 0.8 and 114.7 µg/L. The LLOQs and the ULOQs were in the ranges of 1.6-29.4 and 2.7-49.0 µg/L, respectively. In the case of EMT, sodiated molecular ion at m/z 270 was used to adduce analytical performance characteristics from which lower detection limits were obtained compared with those in the literature where [M+H](+) at m/z 248 was used.


Assuntos
Benzoxazinas/sangue , Cromatografia Líquida de Alta Pressão , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/administração & dosagem , Emtricitabina/sangue , Espectrometria de Massas em Tandem , Tenofovir/sangue , Calibragem , Humanos , Limite de Detecção
13.
AIDS Care ; 28(3): 401-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26489045

RESUMO

This 96-week, randomized, open-label study was designed to assess the efficacy and safety of two single-tablet regimens in treatment naïve HIV-1-infected adults: rilpivirine (RPV) + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and efavirenz (EFV) + FTC/TDF. Assessments included patient-reported Medication Adherence Self-Report Inventory, SF-12v2 Quality of Life assessment, HIV Treatment Satisfaction Questionnaire, and HIV Symptom Index Questionnaire through Week 48. Additional evaluations included study drug discontinuations due to treatment-emergent adverse events (TEAEs). A total of 786 participants (n=394 RPV/FTC/TDF, n=392 EFV/FTC/TDF) were included. Fewer RPV/FTC/TDF-treated than EFV/FTC/TDF-treated participants discontinued study drug due to TEAEs (2.5% vs. 8.7%), with 41% (14/34) TEAE-related discontinuations in the EFV/FTC/TDF group occurring within the first four weeks of treatment. Treatment adherence and satisfaction remained high through Week 48 and quality of life improved from baseline in both groups. There were no significant between-group differences in virologic success (HIV-1 RNA <50 copies/mL) regardless of adherence (<95% or ≥95%). Significant between-group differences favouring RPV/FTC/TDF were observed for the HIV SIQ symptoms of difficulty falling or staying asleep (p = .022) and diarrhea or loose bowel movements (p = .002). In conclusion, 48-week treatment with RPV/FTC/TDF or EFV/FTC/TDF was associated with high adherence, high treatment satisfaction, and improved quality of life. TEAE-related discontinuations and patient-reported symptoms indicate that RPV/FTC/TDF may be somewhat better tolerated than EFV/FTC/TDF.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/uso terapêutico , Combinação Emtricitabina, Rilpivirina e Tenofovir/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Avaliação de Resultados da Assistência ao Paciente , Adulto , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/efeitos adversos , Combinação Emtricitabina, Rilpivirina e Tenofovir/efeitos adversos , Feminino , Infecções por HIV/psicologia , HIV-1/genética , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Qualidade de Vida , RNA Viral/sangue , Autorrelato , Comprimidos , Resultado do Tratamento , Carga Viral
14.
Antiviral Res ; 123: 163-71, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26427554

RESUMO

Although an effective combination of antiretroviral therapy (cART) controls HIV-1 viraemia in infected patients, viral latency established soon after infection hinders HIV-1 eradication. It has been shown that bryostatin-1 (BRY) inhibits HIV-infection in vitro and reactivates the latent virus through the protein kinase C-NF-κB pathway. We determined the in vitro potential effect of BRY in combination with currently used antiretroviral drugs. BRY alone or in combination with maraviroc (MVC)/Atripla (ATP) was tested for its capacity to reactivate latent virus and inhibit new infections. JLTRG-R5 cells and two latent HIV-1-infected cell lines, J89GFP and THP89GFP, were used as latency models. To quantify HIV infection, the reporter cell line TZM-bl was used. We found that BRY reactivates HIV-1 even in combination with MVC or ATP. Antiretroviral combinations with BRY do not interfere with BRY activity (i.e., the reactivation of latently infected cells) or with the antiviral activity of antiretroviral drugs. In addition, BRY-mediated down-modulation of surface CD4 and CXCR4 was not affected when it was used in combination with other antiretrovirals, and no hyperactivation or high-proliferation effects were observed in primary T cells. Moreover, the BRY treatment was able to reactivate HIV-1 in CD4+ T cells from HIV-1-infected patients under cART. Thus, we propose the use of BRY to purge the viral reservoir and recommend its combination with current antiretroviral treatments.


Assuntos
Antirretrovirais/metabolismo , Briostatinas/metabolismo , Interações Medicamentosas , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Latência Viral/efeitos dos fármacos , Adulto , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/virologia , Células Cultivadas , Cicloexanos/metabolismo , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/metabolismo , Humanos , Masculino , Maraviroc , Pessoa de Meia-Idade , Triazóis/metabolismo
15.
J Med Econ ; 18(10): 763-76, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25934146

RESUMO

OBJECTIVE: Data from the SINGLE trial demonstrated that 88% of treatment-naïve HIV-1 patients treated with dolutegravir and abacavir/lamivudine (DTG + ABC/3TC) achieved viral suppression at 48 weeks compared with 81% of patients treated with efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC). It is unclear how this difference in short-term efficacy impacts long-term cost-effectiveness of these regimens. This study sought to evaluate long-term cost-effectiveness of DTG + ABC/3TC vs EFV/TDF/FTC from a US payer perspective. METHODS: This study is an individual discrete-event simulation which tracked the disease status and treatment pathway of HIV-1 patients. The model simulated treatment over a lifetime horizon by tracking change in patients' CD4 count, clinical events occurrence (opportunistic infections, cancer, and cardiovascular events), treatment switch, and death. The model included up to four lines of treatment. Baseline patient characteristics, efficacy, and safety of DTG + ABC/3TC and EFV/TDF/FTC were informed by data from the SINGLE trial. The efficacy of subsequent treatment lines, clinical event risks, mortality, cost, and utility inputs were based on literature and expert opinion. Outcomes were lifetime discounted medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). RESULTS: Compared with EFV/TDF/FTC, DTG + ABC/3TC increased lifetime costs by $19,153 and per person survival by 0.12 QALYs, resulting in an ICER of $158,890/QALY. ICERs comparing DTG + ABC/3TC to EFV/TDF/FTC remained above the traditional, US willingness-to-pay threshold of $50,000/QALY gained in all scenarios, and above $100,000 or $150,000/QALY gained in most scenarios. LIMITATIONS: Due to data limitations, the treatment patterns, CD4 count during viral rebound and treatment switch, viral rebound after trial end, and long-term adverse event-related treatment discontinuation were based on assumptions, presented to and approved by clinical experts. CONCLUSIONS: Compared with EFV/TDF/FTC, DTG + ABC/3TC resulted in higher cost and only slightly increased QALYs over a lifetime, with an ICER that exceeded the standard cost-effectiveness threshold. This indicates that the incremental benefit in effectiveness associated with DTG + ABC/3TC may not be worth the incremental increase in costs.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Didesoxinucleosídeos/economia , Didesoxinucleosídeos/uso terapêutico , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/economia , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/economia , HIV-1/efeitos dos fármacos , Lamivudina/economia , Lamivudina/uso terapêutico , Infecções Oportunistas Relacionadas com a AIDS/etiologia , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/economia , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Simulação por Computador , Análise Custo-Benefício , Didesoxinucleosídeos/efeitos adversos , Combinação de Medicamentos , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/efeitos adversos , Infecções por HIV/complicações , Humanos , Estimativa de Kaplan-Meier , Lamivudina/efeitos adversos , Anos de Vida Ajustados por Qualidade de Vida , Estados Unidos
16.
Infection ; 42(4): 757-62, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24902520

RESUMO

ATRIPLA is licensed for use only in HIV-positive persons whose viral loads <50 for ≥ 3 months. We investigated the use of ATRIPLA as first-line antiretroviral therapy (ART) in EuroSIDA using a web-based survey performed in Autumn 2012. 96/112 clinics (85.7 %) completed the survey. Recommendations when initiating first-line ART was TRUVADA plus efavirenz in 36 (37.5 %), ATRIPLA in 35 (36.5 %), a different first-line regimen in 12 clinics (12.5 %), and no recommendation in 7 clinics (7.3 %). ATRIPLA was commonest in Northern (15/21 clinics; 71.4 %), and least common in Eastern Europe (2/31 clinics; 6.5 %; p < 0.0001). Over one-third of the participating clinics in this survey were using ATRIPLA as first-line antiretroviral therapy, despite EMA recommendations.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Desoxicitidina/análogos & derivados , Uso de Medicamentos , Infecções por HIV/tratamento farmacológico , Organofosfonatos/uso terapêutico , Oxazinas/uso terapêutico , Adenina/uso terapêutico , Adulto , Estudos de Coortes , Coleta de Dados , Desoxicitidina/uso terapêutico , Combinação de Medicamentos , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila , Europa (Continente) , Feminino , Humanos , Masculino , Estudos Prospectivos
17.
HIV Clin Trials ; 15(1): 1-13, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24518210

RESUMO

OBJECTIVES: Statins are lipid-lowering drugs that exhibit anti-Inflammatory and immune-modulatory properties, leading to a reduction of serum levels of C-reactive protein (CRP) in the general population. DESIGN: To assess the anti-inflammatory effects of statins in HIV-infected patients, because very limited data are available today. METHODS: Longitudinal, observational study of HIV-infected adult patients naive to antiretroviral therapy who started tenofovir/emtricitabine/efavirenz and were followed-up for 48 weeks. Patients with baseline normal cholesterol level and taking only antiretroviral drugs (group A) were compared to those with baseline hypercholesterolemia who received rosuvastatin (10 mg daily) in association with antiretroviral treatment (group B). The primary observation was change in serum markers of inflammation (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], interleukin-8 [IL-8]) and tumor necrosis factor-α [TNF- α]) in both groups, whereas secondary observations include variations in CD4 lymphocyte count, HIV viral load, and occurrence of adverse events. RESULTS: Eighty-six patients were enrolled into the study: 46 in group A and 40 in group B. After 48 weeks, patients treated with antiretroviral therapy plus rosuvastatin had significantly greater decreases in serum concentrations of all Inflammatory markers than those taking antiretroviral therapy only. Changes in mean levels of hsCRP and TNF-α were -35.1% and -22.4% in group B and -8.2% and 5.4% in group A, respectively (P < .001, for both parameters). No significant differences in immunovirological parameters and safety profile were reported across the compared groups. CONCLUSIONS: Our findings suggest that tenofovir/emtricitabine/efavirenz plus rosuvastatin has a greater antiInflammatory effect than antiretroviral drugs only.


Assuntos
Adenina/análogos & derivados , Antirretrovirais/uso terapêutico , Proteína C-Reativa/análise , Desoxicitidina/análogos & derivados , Fluorbenzenos/administração & dosagem , Infecções por HIV/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inflamação/tratamento farmacológico , Organofosfonatos/administração & dosagem , Oxazinas/administração & dosagem , Pirimidinas/administração & dosagem , Sulfonamidas/administração & dosagem , Adenina/administração & dosagem , Adulto , Biomarcadores/sangue , Colesterol/sangue , Desoxicitidina/administração & dosagem , Combinação de Medicamentos , Quimioterapia Combinada , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila , Feminino , Infecções por HIV/sangue , Humanos , Inflamação/sangue , Interleucina-6/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Rosuvastatina Cálcica , Fator de Necrose Tumoral alfa/sangue
18.
J Acquir Immune Defic Syndr ; 64(3): 279-83, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-24278992

RESUMO

We performed a randomized controlled trial in 30 HIV-infected participants to either continue tenofovir/emtricitabine/efavirenz (Continuation Group) or switch to tenofovir/emtricitabine/raltegravir (Switch Group) for 24 weeks. There were no significant differences in the changes in flow-mediated dilation, 25(OH) vitamin D, or parathyroid hormone levels. Total cholesterol, high sensitivity C-reactive protein, serum alkaline phosphatase, sCD14 levels, and renal function significantly declined in the Switch Group compared with the Continuation Group; however, sCD163 levels significantly increased in the Switch Group. These findings suggest that raltegravir is not inherently more beneficial to endothelial function compared with efavirenz but may impact renal function and monocyte activation.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Osso e Ossos/metabolismo , Proteína C-Reativa/metabolismo , Desoxicitidina/análogos & derivados , Endotélio Vascular/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Organofosfonatos/uso terapêutico , Oxazinas/uso terapêutico , Pirrolidinonas/uso terapêutico , Insuficiência Renal/induzido quimicamente , Adenina/sangue , Adenina/uso terapêutico , Adulto , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Colesterol/sangue , Desoxicitidina/sangue , Desoxicitidina/uso terapêutico , Combinação de Medicamentos , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila , Feminino , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Humanos , Indiana/epidemiologia , Inflamação , Masculino , Organofosfonatos/sangue , Oxazinas/sangue , Raltegravir Potássico , Insuficiência Renal/sangue , Resultado do Tratamento , Carga Viral
19.
Bull Soc Pathol Exot ; 106(4): 239-43, 2013 Oct.
Artigo em Francês | MEDLINE | ID: mdl-24136661

RESUMO

The objective of this study was to evaluate the effectiveness and the clinical tolerance of a combination containing TDF/FTC/EFV in the treatment of HIV infection. This was a retrospective and descriptive study which included 196 adults infected by HIV-1 and treated by a combination containing TDF/FTC/EFV during 29 months in the daily hospital of Bobo Dioulasso. The median duration of follow-up was 7 months IQR [5-14 month]. The median age was 37 years IQR [31-45].With the initiation of treatment ARV, the median of the index of body mass was of 19 IQR [17-22]. The median of the lymphocytes TCD4 was 201/µl IQR [74-298/µl]. During the follow-up, we reported 25 deaths (12.8%). HIV-1 RNA plasma viral load was undetectable in 91.9% of the patients (124/135) at six months of treatment. The majority of the adverse effects of the treatment were of a neurosensory nature (40.5%). The TDF/FTC/EFV combination showed a good effectiveness in the treatment of the infection with HIV-1 in the first intention just as a good clinical tolerance.


Assuntos
Adenina/análogos & derivados , Antirretrovirais/uso terapêutico , Desoxicitidina/análogos & derivados , Infecções por HIV/tratamento farmacológico , Organofosfonatos/uso terapêutico , Oxazinas/uso terapêutico , Adenina/uso terapêutico , Adulto , Burkina Faso , Desoxicitidina/uso terapêutico , Combinação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila , Feminino , Infecções por HIV/epidemiologia , HIV-1 , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
20.
J Acquir Immune Defic Syndr ; 63(1): 77-85, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23412015

RESUMO

BACKGROUND: STARTMRK, a phase III noninferiority trial of raltegravir-based versus efavirenz-based therapy in treatment-naive patients, remained blinded until its conclusion at 5 years. We now report the final study results. METHODS: Previously untreated patients without baseline resistance to efavirenz, tenofovir, or emtricitabine were eligible for a randomized study of tenofovir/emtricitabine plus either raltegravir or efavirenz. Yearly analyses were planned, with primary and secondary end points stipulated at weeks 48 and 96, respectively. The primary efficacy outcome was the percentage of patients with viral RNA (vRNA) levels <50 copies per milliliter counting noncompleters as failures (NC=F). Changes from baseline CD4 count were computed using an observed-failure approach to missing data. No formal hypotheses were formulated for testing at week 240. RESULTS: Overall, 71 of 281 raltegravir recipients (25%) and 98 of 282 efavirenz recipients (35%) discontinued the study; discontinuations due to adverse events occurred in 14 (5%) and 28 (10%) patients in the respective groups. In the primary NC=F efficacy analysis at week 240, 198 of 279 (71.0%) raltegravir recipients and 171 of 279 (61.3%) efavirenz recipients had vRNA levels <50 copies per milliliter, yielding a treatment difference {Δ [95% confidence interval (CI)] = 9.5 (1.7 to 17.3)}. Generally comparable between-treatment differences were seen in both the protocol-stipulated sensitivity analyses and the prespecified subgroup analyses. The mean (95% CI) increments in baseline CD4 counts at week 240 were 374 and 312 cells per cubic millimeter in the raltegravir and efavirenz groups, respectively [Δ(95% CI) = 62 (22 to 102)]. Overall, significantly fewer raltegravir than efavirenz recipients experienced neuropsychiatric side effects (39.1% vs 64.2%, P < 0.001) or drug-related clinical adverse events (52.0% vs 80.1%, P < 0.001). CONCLUSIONS: In this exploratory analysis of combination therapy with tenofovir/emtricitabine in treatment-naive patients at week 240, vRNA suppression rates and increases in baseline CD4 counts were significantly higher in raltegravir than efavirenz recipients. Over the entire study, fewer patients experienced neuropsychiatric and drug-related adverse events in the raltegravir group than in the efavirenz group. Based on better virologic and immunologic outcomes after 240 weeks, raltegravir/tenofovir/emtricitabine seemed to have superior efficacy compared with efavirenz/tenofovir/emtricitabine.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV , Benzoxazinas , Desoxicitidina/análogos & derivados , Infecções por HIV/tratamento farmacológico , Organofosfonatos , Pirrolidinonas , Inibidores da Transcriptase Reversa , Adenina/administração & dosagem , Adenina/efeitos adversos , Adenina/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/administração & dosagem , Benzoxazinas/efeitos adversos , Benzoxazinas/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Método Duplo-Cego , Combinação de Medicamentos , Quimioterapia Combinada , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila , Emtricitabina , Feminino , Infecções por HIV/virologia , HIV-1 , Humanos , Masculino , Organofosfonatos/administração & dosagem , Organofosfonatos/efeitos adversos , Organofosfonatos/uso terapêutico , Oxazinas , Pirrolidinonas/administração & dosagem , Pirrolidinonas/efeitos adversos , Pirrolidinonas/uso terapêutico , Raltegravir Potássico , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Tenofovir , Resultado do Tratamento
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