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Objective To investigate the effect of Elvitegravir,Cobicistat,Emtricitabine and Tenofovir Alafenamide single tablet alone versus tenofovir(TDF)+lamivudine(3TC)+efavirenz(EFV)scheme in the treatment of patients with acquired immunodeficiency syndrome(AIDS).Methods A total of 100 patients with AIDS who visited the hospital from January 2022 to October 2022 were selected and divided into two groups by random number table method,50 cases in each group.Group A was treated with Elvitegravir,Cobi-cistat,Emtricitabine and Tenofovir Alafenamide single tablet monotherapy and Group B was treated with TDF+3TC+EFV scheme.The human immunodeficiency virus(HIV)load,body immunity(CD4+,CD8+,CD4+CD38+cell ratio,CD8+CD38+cell ratio),lipid metabolism indexes[total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)],glucose metabolism indexes[fasting blood glucose(FPG),glycated hemoglobin(HbA1c)],glycoprotein 130(gp130),interleukin-35(IL-35)and its receptor IL-12Rβ2 levels were observed before and after treatment in the two groups,and the drug safety in the two groups was counted.Results After 3 months of treatment,HIV load,CD8+count,CD4+CD38+cell ratio,and CD8+CD38+cell ratio in both groups were lower than those before treatment,and CD4+count was higher than that before treatment(P<0.05),but the difference was not statistically significant when compared between A and B groups(P>0.05).After 3 months of treat-ment,the levels of IL-12Rβ2,gp130,IL-35,TC,TG,and LDL-C in both groups were higher than those before treatment,and HDL-C level was lower than that before treatment,and the change in group B was greater than that in group A(P<0.05).FPG and HbAlc levels were higher in group B after 1 month and 3 months of treatment,and were higher than those in group A(P<0.05).Drug safety analysis showed that the incidence rates of adverse reactions were 12.00%(6/50)in group A and 26.00%(13/50)in group B,and there was no statistically significant difference between the two groups(P>0.05).The incidence rates of liver and kidney injury in group A was 10.00%(5/50),and that in group B was 12.00%(6/50),and there was no statistically significant difference between two groups(P>0.05).Conclusion Elvitegravir,Cobicistat,Emtricitabine and Tenofovir Alafenamide single tablet monotherapy and the TDF+3TC+EFV scheme could significantly re-duce the HIV load of AIDS patients and improve their immune level,but the former has less effect on pa-tients'glycolipid metabolism and inflammatory factors,and the monotherapy scheme is superior based on the comprehensive consideration of safety and efficacy.
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Objective To develop an ultra-performance liquid chromatography-mass spectrometry(UPLC-MS/MS)method for the simultaneous quantification of dolutegravir,raltegravir,efavirenz,lamivudine and tenofovir in human plasma and to apply it to the therapeutic monitoring.Methods Dolutegravir-D5,raltegravir-D4,efavirenz-D5,lamivudine-13 C-15 N2 and tenofovir-D7 were used as internal standard,respectively.All samples were extracted using the protein precipitation method with acetonitrile and then diluted for analysis.Chromatographic separation was performed on Shim-pack XR-ODS Ⅲ(2.0 mmx50 mm,1.6 μm)column.Mobile phases A and B consisted of 0.1%formic acid in water and acetonitrile respectively.A programmed mobile phase gradient was used at a flow rate of 0.3 mL·min-1 and column temperature of 40 ℃.The tandem mass spectrometer was equipped with an electrospray ionization(ESI)source operating in multiple reaction monitoring(MRM)modes.After methodological validation,it can be used for therapeutic drug monitoring in HIV patients.Results There was good linearity in the validated concentration ranges of 62.5-3 000 ng·mL-1 for dolutegravir,10-500 ng·mL-1 for raltegravir,125-6 000 ng·mL-1for efavirenz,10-500 ng·mL-1 for lamivudine and 10-500 ng·mL-1 for tenofovir with the linear correlation coeffificients of determination(R2)of all higher than 0.998.The accuracy of both intra-day and inter-day studies ranged from 94.0%-109.3%,and the relative standard deviations were less than 7%.The IS-normalized matrix factor and extraction recoveries of all analytes were 95.7%-106.0%and 98.7%-104.5%at all concentrations.All analytes were stable in plasma at a certain storage environment.The trough blood concentrations of dolutegravir,efavirenz,lamivudine and tenofovir were 107.7-2 366.0,740.0-3 410.0,38.5-1 229.3,31.6-224.4ng·mL-1 in HIV patients,respectively.Conclusion The method is highly aceurate,easy to perform,low-cost,and suitable for therapeutic drug monitoring of dolutegravir,raltegravir,efavirenz,lamivudine and tenofovir in HIV patients.
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ABSTRACT Objective To compare viral suppression in treatment-naïve adults starting antiretroviral therapy with dolutegravir (50mg)- and efavirenz (600mg)-based regimens. Methods We analyzed secondary data from Brazilian health information systems of people living with human immunodeficiency virus who started antiretroviral therapy between 2015 and 2017 in Minas Gerais, Brazil. The outcome was viral suppression, defined as the achievement of the first viral load <50 copies/mL within 12 months after initiating antiretroviral therapy. This outcome was also compared with viral load <1,000 copies/mL and analyzed in two scenarios: intention-to-treat versus per-protocol. Time to viral suppression and adjusted odds ratio accompanied by 95% confidence intervals were estimated. Results Of the 2,599 participants enrolled, 77.5% were men, and the median age was 34 years. In the intention-to-treat analysis, viral suppression was 58.1% for efavirenz and 76.7% for dolutegravir. People living with HIV on dolutegravir-based regimen were more likely to achieve viral suppression (aOR: 2.44; 95%CI: 2.01-2.95) and had a shorter median time to viral suppression (p<0.0001). Antiretroviral therapy initiation within <120 days, baseline CD4⁺T-cells ≥200 cells/mm3, and viral load <100,000 copies/mL had higher odds of viral suppression. According to the per-protocol analysis, viral suppression ≥90% was observed by considering viral load <1,000 copies/mL. Conclusion Our study demonstrated that viral suppression improved after introducing dolutegravir, although the proportion of patients with viral load <50 copies/mL was lower than expected. Improved access to routine viral load examinations and continuous surveillance of the effectiveness of antiretroviral therapy should be considered.
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A randomized, open, fasting, single dose, two sequence, two cycle and double cross administration trial design was adopted. Took the test or reference efavirenz tablets of 200 mg orally in a single time. The plasma concentration of efavirenz in healthy subjects was determined by LC-MS/MS. WinNonLin8.1 software was used to calculate the main pharmacokinetic parameters of efavirenz and to evaluate the bioequivalence. The main pharmacokinetic parameters within 72 h: tmax were 2.574 ± 0.871 and 2.808 ± 0.912 h; Cmax were 1 586.732 ± 424.538 and 1 549.518 ± 366.086 ng·mL-1; AUC0-72 h were 28 464.672 ± 5 682.518 and 27 828.826 ± 5 082.487 h·ng·mL-1; t1/2 were 63.524 ± 26.037 and 58.748 ± 20.950 h; λz were 0.013 ± 0.006 and 0.013 ± 0.005 h-1. The main bioequivalence indicators were as follows: The 90% confidence interval of Cmax was 95.62%-107.15%, and the geometric mean ratio was 101.22%; The 90% confidence interval of AUC0-72 h was 100.43%-104.38%, and the geometric mean ratio was 102.38%. The results showed that the main pharmacokinetic parameters of the test drug and the reference drug were similar, and the two preparations had bioequivalence. This human bioequivalence clinical study was approved by the drug clinical trials ethics committee of the Second Hospital of Anhui Medical University (ethics approval No.: YW2021-110).
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Abstract Efavirenz is one of the most commonly used drugs in HIV therapy. However the low water solubility tends to result in low bioavailability. Drug nanocrystals, should enhance the dissolution and consequently bioavailability. The aim of the present study was to obtain EFV nanocrystals prepared by an antisolvent technique and to further observe possible effect, on the resulting material, due to altering crystallization parameters. A solution containing EFV and a suitable solvent was added to an aqueous solution of particle stabilizers, under high shear agitation. Experimental conditions such as solvent/antisolvent ratio; drug load; solvent supersaturation; change of stabilizer; addition of milling step and solvents of different polarities were evaluated. Suspensions were characterized by particle size and zeta potential. After freeze- dried and the resulting powder was characterized by PXRD, infrared spectroscopy and SEM. Also dissolution profiles were obtained. Many alterations were not effective for enhancing EFV dissolution; some changes did not even produced nanosuspensions while other generated a different solid phase from the polymorph of raw material. Nevertheless reducing EFV load produced enhancement on dissolution profile. The most important modification was adding a milling step after precipitation. The resulting suspension was more uniform and the powder presented grater enhancement of dissolution efficacy.
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Eficacia/clasificación , VIH/patogenicidad , Cristalización/instrumentación , Disolución/métodos , Tamaño de la Partícula , Solubilidad , Preparaciones Farmacéuticas/administración & dosificación , Excipientes/farmacología , Disolución/clasificación , Nanopartículas/administración & dosificación , MétodosRESUMEN
A baixa solubilidade aquosa dos insumos farmacêuticos ativos (IFA) é um grande desafio no desenvolvimento de formulações farmacêuticas, pois pode resultar em biodisponibilidade insuficiente e variável. Diversas estratégias de modificação do estado sólido dos compostos ativos, têm sido propostas para incrementar a solubilidade de fármacos pouco solúveis em água. Dentre as estratégias abordadas a ispersão sólida (DS) é uma das formas mais promissoras de aumentar a solubilidade, dissolução e a biodisponibilidade de IFAs com baixa solubilidade aquosa. O efavirenz (EFV) é um inibidor não nucleosídeo da transcriptase reversa (NNRTI) e um dos componentes da terapia antirretroviral de alta atividade (HAART), sendo parte da primeira linha de tratamento de infecções do vírus HIV tipo 1. O antirretroviral está classificado como pertencente à classe II do SCB, e exibe baixa solubilidade aquosa (solubilidade menor que 10 µg/mL) e alta permeabilidade com absorção dependente da taxa de dissolução, resultando em biodisponibilidade oral baixa e variável. A administração de fármacos pouco solúveis na forma de DS é um método atraente para aumentar a biodisponibilidade in vivo. Neste estudo, um método de triagem rápida por evaporação de solvente foi empregado para preparar DS de EFV, variando-se proporções em misturas compostas pelos carreadores, polivinilpirrolidona K-28/32 (PVP K-28/32), copovidona (CoPVP), hidroxipropilmetilcelulose ftalato (HPMCP-50, HPMCP-55 e HPMCP-55s), poloxâmero 188 (P188) e poloxâmero 407 (P407). A solubilidade das DS foi avaliada por meio do método do equilíbrio (shake-flask), onde selecionou-se os polímeros P188 e P407 que conduziram a uma elevada capacidade de saturação em meio aquoso, superior a 1.000 vezes ao fármaco puro. As propriedades físico-químicas e do estado sólido das amostras foram avaliadas por meio de calorimetria exploratória diferencial (DSC); termogravimetria (TG); espectroscopia do infravermelho com transformada de Fourier (FTIR), difratometria de raios X pelo método do pó (DRXP) e ensaios de dissolução com emprego do aparato IV USP. Os resultados de DRXP demonstraram que os carreadores P188 e P407 foram capazes de estabilizar o EFV na forma amorfa nas DS, fato esse evidenciado pela ausência de picos característicos do antirretroviral
he low aqueous solubility of the active pharmaceutical ingredient (API) is a major challenge in the development of pharmaceutical formulations as it may result in insufficient and variable bioavailability. Several strategies for modifying the solid-state of the active compounds have been proposed to increase solubility of drugs that are poorly soluble in water. Among the strategies approaches, solid dispersion (SD) is one of the most promising ways to increase solubility, dissolution and bioavailability of APIs with low aqueous solubility. Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and one of the components of highly active antiretroviral therapy (HAART), being part of the first line of treatment of type 1 HIV virus infections. The antiretroviral is classified as belonging to BCS class II, and exhibits low aqueous solubility (solubility less than 10 µg / mL) and high permeability with dissolution ratedependent absorption, resulting in low and variable oral bioavailability. Drug delivery of poorly aqueous soluble drugs in form SD is an appealing method to increase in vivo bioavailability. In this study, a fast screening method of solvent evaporation method was used to prepare EFV SD, varying the proportions in mixtures composed by the carriers polyvinylpyrrolidone K-28/32 (PVP K-28/32), copovidone (CoPVP), hydroxypropylmethylcellulose phthalate (HPMCP-50, HPMCP-55 e HPMCP-55s), poloxamer 188 (P188) e poloxamer 407 (P407). The solubility of the samples was evaluated by the method of equilibrium (shake-flask), wherein the polymers P188 and P407 were selected due to the capacity to promote high saturation in aqueous medium, 1,000 times superior to the pure drug. The physicochemical and solid-state properties of the samples were evaluated by differential scanning calorimetry (DSC); thermogravimetry (TG); Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD) and dissolution assays using the IV USP apparatus. The results of XRPD demonstrated that the carriers P188 and P407 were able to stabilize the EFV in amorphous form in the SD, a fact evidenced by the absence of characteristic peaks of the antiretroviral
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Preparaciones Farmacéuticas/administración & dosificación , Insumos Farmacéuticos , Disolución , Análisis Espectral/instrumentación , Rastreo Diferencial de Calorimetría/métodos , ADN Polimerasa Dirigida por ARN/efectos adversos , Espectroscopía Infrarroja por Transformada de Fourier , Poloxámero/análogos & derivados , Terapia Antirretroviral Altamente Activa/instrumentación , Derivados de la Hipromelosa/metabolismo , Análisis de FourierRESUMEN
ABSTRACT Antiretroviral therapy (ART) has modified the outcome of patients with HIV infection, providing virological control and reducing mortality. However, there are several reasons as to why patients may discontinue their antiretroviral therapy, with adverse events being one of the main reasons reported in the literature. This is a case-control nested in a cohort of people living with HIV/AIDS, conducted to identify the incidence of ART modification due to adverse events and the associated factors, in two referral services in Recife, Brazil, between 2011 and 2014. Of the modifications occurred in the first year of ART, 25.7% were driven by adverse events. The median time elapsed between initiating ART and the first modification due to adverse events was 70.5 days (95% CI: 26-161 days). The main adverse events were dermatological, neuropsychiatric and gastrointestinal. Dermatological events were the earliest to appear after initiating ART. Efavirenz was the most prescribed and most modified drug during the study period. The group of participants who used zidovudine, lamivudine, and efavirenz had a 2-fold greater chance (adjusted OR: 2.16 95% CI: 1.28-3.65) of switching ART due to adverse events when compared to the group that used tenofovir with lamivudine and efavirenz.
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Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Fármacos Anti-VIH/efectos adversos , Factores de Tiempo , Brasil , Zidovudina/efectos adversos , Modelos Logísticos , Factores de Riesgo , Síndrome de Inmunodeficiencia Adquirida/mortalidad , Ritonavir/efectos adversos , Lamivudine/efectos adversos , Terapia Antirretroviral Altamente Activa/efectos adversos , Benzoxazinas/efectos adversos , Combinación de Medicamentos , Estimación de Kaplan-Meier , Lopinavir/efectos adversos , Tenofovir/efectos adversosRESUMEN
Objective: To investigate the influence of ABCB1 polymorphisms on the plasma level of efavirenz in Thai adult cases infected with HIV-1. Methods: A single nucleotide polymorphism of ABCB1 3435C>T (rs1045642) in the gene encoding ABCB1 was genotyped using real-time PCR-based alleles in 149 HIV-infected Thai adults receiving efavirenz treatment. Plasma concentrations of efavirenz were measured by high-performance liquid chromatography 12 hr after administration. The relationship between plasma efavirenz concentrations and ABCB1 3435C>T polymorphisms was analyzed. Results: Logistic regression analysis showed no significant predictors of high plasma efavirenz concentration in relation to age, gender, body weight, CD4 count and plasma HIV-1 RNA, blood biochemical parameters, antiretroviral duration or ABCB1 3435C>T polymorphisms, except for height (OR=0.902, 95% CI: 0.835-0.973) (PT was 0.446. The frequency of the heterozygous mutant ABCB1 3435C/ T was 53.02% (n=79), ABCB1 3435T/T homozygous mutant was 18.12% (n=27) and the wild type ABCB1 3435C/C genotype was 28.86% (n=43). The overall median plasma concentration of efavirenz in 149 HIV-infected Thai cases was 2.41 mg/L [IQR: (1.46-4.12) mg/L]. The plasma concentration of efavirenz was higher in cases with ABCB1 3435T/T homozygous mutant [2.73 mg/L, IQR: (2.02-4.19) mg/L] and ABCB1 3435C/T heterozygous mutant [2.29 mg/L, IQR: (1.41-4.28) mg/L] genotypes compared to the wild type ABCB1 3435C/C homozygous [2.1 mg/L, IQR: (1.37-3.53) mg/L]. However, there was no statistically significant difference in the efavirenz concentration between the different genotypes (P>0.05). Conclusions: There is no statistical significance for a tendency toward higher plasma efavirenz concentration in the ABCB1 3435T/T and ABCB1 3435C/T genotypes. No parameters of physiological characteristics in this study except for height were found to be predictors of high plasma efavirenz concentration in Thai HIV-1 infected cases.
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Objective: To investigate the influence of ABCB1 polymorphisms on the plasma level of efavirenz in Thai adult cases infected with HIV-1. Methods: A single nucleotide polymorphism of ABCB1 3435C>T (rs1045642) in the gene encoding ABCB1 was genotyped using real-time PCR-based alleles in 149 HIV-infected Thai adults receiving efavirenz treatment. Plasma concentrations of efavirenz were measured by high-performance liquid chromatography 12 hr after administration. The relationship between plasma efavirenz concentrations and ABCB1 3435C>T polymorphisms was analyzed. Results: Logistic regression analysis showed no significant predictors of high plasma efavirenz concentration in relation to age, gender, body weight, CD4 count and plasma HIV-1 RNA, blood biochemical parameters, antiretroviral duration or ABCB1 3435C>T polymorphisms, except for height (OR=0.902, 95% CI: 0.835-0.973) (PT was 0.446. The frequency of the heterozygous mutant ABCB1 3435C/ T was 53.02% (n=79), ABCB1 3435T/T homozygous mutant was 18.12% (n=27) and the wild type ABCB1 3435C/C genotype was 28.86% (n=43). The overall median plasma concentration of efavirenz in 149 HIV-infected Thai cases was 2.41 mg/L [IQR: (1.46-4.12) mg/L]. The plasma concentration of efavirenz was higher in cases with ABCB1 3435T/T homozygous mutant [2.73 mg/L, IQR: (2.02-4.19) mg/L] and ABCB1 3435C/T heterozygous mutant [2.29 mg/L, IQR: (1.41-4.28) mg/L] genotypes compared to the wild type ABCB1 3435C/C homozygous [2.1 mg/L, IQR: (1.37-3.53) mg/L]. However, there was no statistically significant difference in the efavirenz concentration between the different genotypes (P>0.05). Conclusions: There is no statistical significance for a tendency toward higher plasma efavirenz concentration in the ABCB1 3435T/T and ABCB1 3435C/T genotypes. No parameters of physiological characteristics in this study except for height were found to be predictors of high plasma efavirenz concentration in Thai HIV-1 infected cases.
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Efavirenz, a non-nucleotide reverse transcriptase inhibitor is an important drug for treating patients with Human Immunodeficiency Virus infections. It belongs to BCS class II have low solubility and poor intrinsic dissolution rate. It is highly basic (pKa 10.2) which makes it suitable candidate for floating dosage form for continuous delivery in stomach.The study was aimed to improve the solubility by solid dispersion technique.Saturation solubility study and drug content were evaluated for solid dispersion preparation. Saturation solubility shows 8 fold increases in 0.1 N HCL compared to plain drug and drug content was found to be between 95%-102%. Further effervescent floating gastroretentive drug delivery system was prepared by 32 full factorial design with independent variables i.e., concentration of HPMC K100 as matrix forming agent and citric acid as gas generating agent. Lag time, floating time, percent drug release were studied as responses. The optimized batch exhibited floating lag time of 40 sec and the in vitro release studies showed 89.5% drug release in 9 h and tablet remained floating for greater than 8 h. The study thus demonstrated that solubility is increased by solid dispersion technique and floating delivery systems may increase solubility and bioavailability of Efavirenz.
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En el presente trabajo se seleccionaron pacientes adultos HIV en tratamiento antirretroviral que contenían efavirenz de más de tres años de duración que hubieron tenido efectos adversos del sistema nervioso central iniciales, comprobando la desaparición completa de los mismos en el 94% de los pacientes evaluados al cabo de 36 meses de tratamiento. Se empleó como método el análisis observacional retrospectivo, utilizando una encuesta de valoración de frecuencia temporal de efectos adversos del sistema nervioso central. Se tuvieron en cuenta los siguientes: mareos: depresión; trastornos del sueño; pesadillas e ideación suicida. De los efectos adversos del sistema nervioso central investigados, los más frecuente fue pesadillas 100% y mareos 81%. Esta frecuencia decreciente hasta su desaparición, fortalece la hipótesis del "fenómeno de tolerancia" similar al observado con ciertas indolaminas, debido a que efavirenz presenta una similitud estructural con estas e interacciona con algunos receptores de la superfamilia de receptores de 5 hidroxitriptamina (5HT). Además las diferencias interindividuales de efectos adversos del SNC podrían estar dadas por las diferencias alélicas en citocromo p 450 que determinan niveles plasmáticos de metabólitos hidroxilados neurotóxicos
In the present study, adult HIV patients were selected on antiretroviral treatment that contained efavirenz for more than three years that had adverse effects on the initial central nervous system, proving their complete disappearance in 94% of the patients evaluated after 36 months of treatment. A retrospective observational analysis was used as a method, using a survey of temporal frequency assessment of adverse effects of the central nervous system. The following were taken into account: dizziness; anxiety; depression; sleep disorders; nightmares and suicidal ideation. Of the adverse effects of the central nervous system investigated, the most frequent was nightmares 100% and dizziness 81%. This decreasing frequency until its disappearance, strengthens the hypothesis of the "tolerance phenomenon" similar to that observed with certain indolamines, because efavirenz has a structural similarity with these and interacts with some receptors of the superfamily of 5-hydroxytryptamine (5HT) receptors. In addition, the interindividual differences of CNS adverse effects could be due to allelic differences in cytochrome p 450 that determine plasma levels of neurotoxic hydroxylated metabolites.
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Humanos , Adulto , Persona de Mediana Edad , Sistema Nervioso Central/efectos de los fármacos , Estudios Retrospectivos , VIH/efectos de los fármacos , Terapia Antirretroviral Altamente Activa/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/terapia , Tiempo de Tratamiento , Combinación Efavirenz, Emtricitabina y Fumarato de Tenofovir Disoproxil/efectos adversosRESUMEN
Efavirenz is a widely prescribed anti-retroviral drug that belongs to BCS class II and exhibit low and variable oral bioavailability due to its poor aqueous solubility and it requires enhancement in solubility and dissolution rate for increasing its oral bioavailability. The aim of this study was to increase the solubility of Efavirenz (EFA) by complexing it with Hydroxypropyl-β-cyclodextrin (HPβCD). Solid binary systems were prepared by co-grinding and microwave irradiation methods. The interaction of EFA with HPβCD was evaluated by Phase solubility studies, in vitro dissolution studies and different analytical techniques including Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). The apparent stability constant revealed EFA with HPβCD produces 1:1 M stoichiometric complex. The host guest interactions studied by FTIR and DSC confirmed true inclusion of EFA with HPβCD at 1:2 M. The Dissolution rates of EFA- HPβCD binary systems were faster when compared to physical mixture and pure drug. Overall the rank order of improvement in dissolution properties of Efavirenz with ratios is 1:2M > 1:1M and methods MW > CG > PM > Pure drug. One-way ANOVA suggest the DP60 and DE60 values were significantly higher (P<0.05) in solid binary systems prepared by microwave irradiation method when compared to co-grinding and its corresponding physical mixtures and pure drug.
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OBJECTIVE: To investigate the influence of HBV and HCV co-infection on the plasma concentrations, efficacy and hepatotoxicity of efavirenz in HIV/AIDS patients. METHODS: The peripheral blood HIV RNA viral loads, CD4+ T-cells, liver function and plasma efavirenz concentrations of 494 cases of HIV monoinfected, HIV/HBV and HIV/HCV co-infected patients were determined by PCR, flow cytometry, automatic biochemical analysis and HPLC and statically compared. RESULTS: The median (IQR) efavirenz concentrations at week 48 of HIV-monoinfected patients, HBV- and HCV-coinfected patients were 3.781 mg•L-1(3.012-4.980 mg•L-1), 3.057 mg•L-1(2.040-5.144 mg•L-1), 2.557 mg•L-1(2.212-4.334 mg•L-1), respectively (P<0.05), while the proportions of patients achieving partial and complete virus inhibition were 78.59%, 76.36%, and 100.00%, respectively. The mean±SD CD4 cell counts steadily increased over time from (290±118), (273±120), and (282±134)cells•mm-3 at baseline to (442±184), (457±221), and (391±151) cells•mm-3 at week 48, respectively(P<0.05). The indexes of liver functions were all basically within normal limits. CONCLUSION: The immune reconstruction of most patients is smooth and they also have favorable prognosis. Co-infection with HBV or HCV will not cause accumulation of efavirenz or hepatic damage. Efavirenz is safe and effective for treatment-naive HIV/AIDS patients with HBV and HCV co-infection.
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Backgrounds: This randomised controlled, open-label, non-inferiority trial was conducted in antiretroviral-na飗e HIV-1-infected patients to assess the efficacy and safety of 48-week dual therapy of LPV/r plus 3TC (DT group) compared with Chinese first-line triple-therapy regimen (TT group). Methods: 198 were randomised to DT (n = 100) or TT (n = 98). Results: Ninety-two DT patients (92%) and 88 TT patients (89.8%) achieved HIV-1 RNA <50 copies/ml at week 48 (P = 0.629). Moreover, the safety profile was similar between two groups, and no secondary HIV resistance was observed. Conclusion: The results suggest that dual therapy of LPV/r plus 3TC is non-inferior to the first-line triple-therapy regimen in China.
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Efavirenz is the first line non-nucleoside reverse transcriptase inhibitor suggested by World Health Organization for newly diagnosed patients started on antiretroviral therapy. Dermatologic manifestations are the usual side effects associated with this drug. Authors hereby, present a case report of efavirenz induced drug hypersensitivity reported at a tertiary care hospital at Allahabad, Uttar Pradesh. The patient developed rashes and vomiting within a week of start of TLE regimen. Re-challenge test revealed confirmation of the adverse drug reaction by efavirenz. Change of the regimen was done for the patient following hospitalization for the event. This case report explains that strict pharmacovigilance is essential in the initial days of start of antiretroviral therapy. Further trials to improve the safety profile of the patients on ART are the need of the hour.
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Resumen ANTECEDENTES La infección por el virus de inmunodeficiencia humana (VIH) incrementa la prevalencia de prolongación del intervalo QT corregido (QTc), lo que es un factor independiente de eventos de enfermedad cardiovascular en esta población. En la bibliografía mundial se asocia este cambio con la administración de los antirretrovirales inhibidores de proteasa y efavirenz. Sin embargo, no se conocen datos de estos cambios en la población mexicana. MATERIAL Y MÉTODO Estudio prospectivo observacional en el que se seleccionaron expedientes de marzo de 2015 a mayo de 2016 de la consulta externa del Instituto Nacional de Enfermedades Respiratorias (INER); se dividieron en dos grupos: sin tratamiento, por reciente diagnóstico, y con tratamiento antirretroviral. Se registraron datos clínicos, tratamiento farmacológico, electrocardiograma y química sanguínea. RESULTADOS No se encontraron diferencias entre ambos grupos respecto a edad ni electrólitos séricos. Tampoco se encontró relación entre la prolongación del QTc con efavirenz o los inhibidores de proteasa. Raltegravir disminuyó la duración del QTc (p = 0.001) mientras que la coinfección por molusco contagioso se asoció con prolongación del QTc (p = 0.02). CONCLUSIÓN En nuestro estudio no logramos demostrar en población mexicana relación de la prolongación del QTc con los antirretrovirales de primera ni segunda línea. Se requieren más estudios para determinar la importancia clínica del efecto de raltegravir y molusco contagioso en el QTc.
Abstract BACKGROUND Human immunodeficiency virus (HIV) infection increases the prevalence of QTc prolongation (QTc), which is an independent factor of cardiovascular disease events in this population. In the world literature this change is associated with the use of the protease inhibitors and efavirenz antiretrovirals. However, no data are available on these changes in the Mexican population. MATERIAL AND METHOD A prospective observational study was done selecting records from March 2015 to May 2016 of the external consultation of the National Institute of Respiratory Diseases (INER), Mexico City; they were divided into two groups, those without treatment, because recent diagnosis, and with antiretroviral treatment. We recorded clinical data, pharmacological treatment, electrocardiogram and blood chemistry. RESULTS We found no differences between the two groups regarding age or serum electrolytes. We found no association between QTc prolongation and efavirenz or protease inhibitors. Raltegravir decreased QTc duration (p = 0.001) while molluscum contagiosum coinfection was associated with QTc prolongation (p = 0.02). CONCLUSION In our study, we failed to demonstrate in Mexican population association of QTc prolongation with first- and second-line antiretrovirals. More studies are needed to determine the clinical significance of the effect of raltegravir and molluscum contagiosum on QTc.
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ABSTRACT This study aimed to identify the 516 G>T polymorphism of the CYP2B6 gene and evaluate its influence on central nervous system (CNS) side effect development in HIV-positive individuals undergoing Efavirenz (EFV) treatment in a population from southern Brazil. Additionally, we performed a survey on the clinical and epidemiological characteristics of our sample. In addition to medical records evaluation, whole blood of 89 individuals was analyzed for viral load, T lymphocyte count (CD4+ and CD8+), and the polymorphism. Considering the side effects of the CNS reported by individuals but without considering the genetic variables, no statistically significant association was noted between the adverse effects and the antiretroviral treatment (including or not EFV). In addition, no statistically significant difference was noted for the influence of genotype on the viral load or the number of T lymphocytes (CD4+ and CD8+) among individuals undergoing EFV treatment. This is the first study that investigated the impact of the 516 G>T polymorphism of the CYP2B6 gene among HIV-positive individuals from southern Brazil. Its clinical significance indicates the need for prospective studies in this population.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Polimorfismo Genético/genética , Infecciones por VIH/genética , Infecciones por VIH/tratamiento farmacológico , Sistema Nervioso Central/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Benzoxazinas/efectos adversos , Citocromo P-450 CYP2B6/genética , Estudios Prospectivos , Relación CD4-CD8 , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Carga Viral , Benzoxazinas/uso terapéutico , GenotipoRESUMEN
OBJECTIVE:To study the interaction between bovine serum albumin(BSA)with lamivudine,efavirenz,tenofovir and its mechanism. METHODS:Fluorescence spectroscopy was used to determine the interaction between BSA with different con-centrations of lamivudine,efavirenz,tenofovir under different temperatures. The fluorescence intensity of them were determined re-spectively;quenching constant(KSV),apparent quenching constant(Kq),binding constant(KA),binding site(n),thermodynamic enthalpy change(ΔH),free energy diversification(ΔG)and entropy change(ΔS)were calculated according to Stern-Volmer equa-tion and so on. Molecular docking model of 3 drugs with BSA was established by using Sybyl 6.7 Flex X model. RESULTS:Kq for the interaction between 3 drugs with BSA were all higher than 2.0×1010 L/(mol·s),and were decreased with the increase of temper-ature;all n were close to 1,and thermodynamic functions ΔG<0,ΔS<0,ΔH<0. Molecular docking model showed that 3 drugs were mainly bound with BSA at Sudlow Ⅰ subdomain site. CONCLUSIONS:There are the interaction between 3 drugs with BSA;fluorescence quenching mainly manifests as static quenching;binding reaction belongs to spontaneous molecular action pro-cess;binding force mainly includes hydrogen bond and Van der Waals'force. The result of fluorescence experiment is consistent with those of molecular docking,and they complement each other.
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An accurate and precise UPLC method was developed for the simultaneous estimation of efavirenz and lamivudine in pharmaceutical dosage forms. The chromatographic analysis was performed on Acquity UPLC BEH Shield RP18 (50 × 3 mm, 1.7 μm) column with mobile phase consisting of 10% acetonitrile in methanol and 10 mM phosphate buffer (pH 4.0) in the gradient mode, at a flow rate of 0.4 mL/min, and eluents monitored at 254 nm. The calibration curves of peak area versus concentration, which was linear from 10-60 μg/mL for efavirenz and 5.0-30 μg/mL for lamivudine, had regression coefficient (r2) greater than 0.999. The method had the requisite accuracy, precision, and robustness for simultaneous determination of efavirenz and lamivudine in tablets. The proposed method is simple, economical, accurate, and precise and could be successfully employed in routine quality control for the simultaneous analysis of efavirenz and lamivudine in pharmaceutical formulations.
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O efavirenz (EFZ) é considerado um dos fármacos anti- HIV mais utilizados, porém, como a grande maioria dos antirretrovirais, é classificado como fármaco de classe II, segundo o Sistema de Classificação Biofarmacêutica (SCB), por apresentar baixa solubilidade e alta permeabilidade. É bem conhecido que a solubilidade aquosa de um fármaco constitui requisito prévio à absorção e, assim, se faz uma das mais importantes barreiras à eficácia do medicamento. Desta forma, o aumento, através de tecnologias farmacêuticas, da dissolução aquosa e, conseqüentemente, da biodisponibilidade de fármacos pouco solúveis em água é considerado como um dos mais desafiantes aspectos no desenvolvimento moderno de fármacos. Este trabalho tem como objetivo realizar um levantamento da literatura cientifica e discussão sobre as principais técnicas aplicadas no melhoramento da dissolução do EFZ, dentre elas: dispersões sólidas, complexos de inclusão, sistemas multicomponentes e sistemas particulados nos últimos 10 anos (2004 ? 2014). Após levantamento bibliográfico, verificou-se maior número de publicações empregando a técnica de dispersões sólidas, provavelmente, porque a mesma é considerada uma técnica simples e de baixo custo. Desta forma, ficou claro que há grande interesse, por parte dos pesquisadores, de desenvolver métodos eficientes e econômicos que visam o melhoramento da dissolução aquosa deste fármaco e que o desenvolvimento de dispersões sólidas é, sem dúvida, uma solução interessante.(AU)
Efavirenz (EFZ) is considered one of the most used anti-HIV drugs. However, like the others anti-retroviral drugs, it is classified as a class II drug, according to the Biopharmaceutics Classification System (BCS), due to its low solubility and high permeability. It is well-known that the aqueous solubility of a drug is the prerequisite for its absorption and becomes one of the major barriers to the effectiveness of it. Thus, the improvement of the aqueous dissolution and, therefore, the bioavailability of drugs that are poorly soluble in water, is pursued by the pharmaceutical technology, once they are challenging aspects in the modern drug development. This paper aims, besides discussing, to perform a systematic review of the scientific literature regarding the main techniques applied in improving the dissolution of EFZ, including: solid dispersions, inclusion complexes, systems and multicomponent particulate systems; in the last 10 years (2004-2014). A greater number of publications using the technique of solid dispersions (SD) were found, probably because it is considered a simple and inexpensive technique. Therefore it is clear that there is great interest from researchers to develop efficient and economical methods aimed at improving the aqueous dissolution of EFZ and that the development of SD is, with no doubt, an interesting solution.(AU)