Analysis of the occurrence time and risk factors of anemia in AIDS patients caused by HAART regimen containing zidovudine / 中国药房

OBJECTIVE To investigate the occurrence time and risk factors of anemia in patients with acquired immune deficiency syndrome （AIDS） after taking highly active antiretroviral therapy （HAART） containing zidovudine. METHODS The clinical data of 2 150 AIDS patients who were followed up in the care clinic of Liuzhou People’s Hospital from January 1， 2010 to December 31， 2022 were collected. The occurrence time of anemia was analyzed retrospectively， and the risk factors of anemia were analyzed by univariate analysis and binary Logistic regression analysis. RESULTS A total of 854 AIDS patients receiving HAART containing zidovudine were collected， and 107 patients （12.53%） developed anemia. Most of them （63.55%） developed anemia within 3 months after treatment. Baseline hemoglobin [OR＝2.944， 95%CI （1.195， 7.501）， P＝0.019]， baseline CD4+ T lymphocyte count [OR＝2.472， 95%CI （1.117， 5.469）， P＝0.026] and baseline human immunodeficiency virus-ribonucleic acid （HIV-RNA） [OR＝4.299， 95%CI （1.905， 9.705）， P＜0.001] was associated with anemia. CONCLUSIONS The median time of anemia in AIDS patients receiving HAART containing zidovudine is the second month after initiation of treatment. Baseline hemoglobin≤110 g/L， baseline CD4+ T lymphocyte E-mail：1315775863@qq.com count≤100 /mm3， and baseline HIV-RNA≥100 000 copies/mL are independent risk factors for anemia in these patients.

Effects and mechanism of zidovudine on glucolipid metabolic balance in mice / 中国药科大学学报

@#To study the effects of nucleoside antiviral drug zidovudine (AZT) on the flexibility of global metabolism and liver glucolipid metabolic balance in mice, male ICR mice were given zidovudine intragastric administration for 12 weeks, and their water and food intake was recorded daily.Serum glucose (GLU) and triglyceride (TG) levels and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected after 12 weeks of administration.Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed.HE staining was used to observe the pathological changes of liver.The gene levels of glucose transporter (Glut2), carnitine palmitate transferase (Cpt1α), medium chain acyl-coa dehydrogenase (Mcad), phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6pase) were detected by RT-PCR.Western blot was used to detect the protein levels of insulin signaling Akt, P-Akt, Glut2, Mcad and Cpt1α in liver.The results showed that zidovudine significantly decreased lipid metabolism, impaired glucose tolerance, increased liver cell volume, significantly increased liver triglyceride (TG) and non-esterified fatty acid (NEFA) content, increased Glut2 gene expression, down-regulated fatty acid oxidative metabolism genes Cpt1α, Mcad and gluconeogenesis related genes after fasting, and down-regulated protein expression of Cpt1α.The results suggest that zidovudine can induce the disorder of glucose and lipid metabolism after fasting in a dose-dependent manner.

Preliminary study on the causes of anemia in newborns delivered by human immunodeficiency virus infected mothers / 中华传染病杂志

Objective:To investigate the causes of anemia in newborns delivered by human immunodeficiency virus (HIV) infected mothers.Methods:This was a retrospective study. Forty-two newborns delivered by HIV infected mothers during January 2010 and May 2019 in Beijing Ditan Hospital Affiliated to Capital Medical University were selected. According to the hemoglobin levels of newborns on the days of their birth, newborn cases were divided into two groups, anemia group and non-anemia group. The clinical data including gestational ages, birth weight, maternal anemia status during pregnancy, using of antiviral drugs during pregnancy, percentages of HIV RNA positivity in early pregnancy/pre-treatment and before delivery, maternal percentage of different CD4 + T lymphocyte counts in early pregnancy/pre-treatment and before delivery between two groups were compared. The efficacies of relative indicators for prediction of anemia in newborns were evaluated by the area under receiver operating characteristic curve (AUROC). Differences between groups were compared by chi-square test. Results:Among 42 cases of newborns, 14 cases were in anemia group and 28 cases in non-anemia group. There were no statistical differences in gestational ages, birth weight, maternal anemia status during pregnancy and positive percentage of HIV RNA before delivery between two groups ( χ2=2.211, 1.025, 1.362 and 3.783, respectively, P=0.283, 0.763, 0.181 and 0.092, respectively). In anemia group, 11 mothers took zidovudine during pregnancy, which was 12(42.86%) in non-anemia group. The difference was statistically significant ( χ2=4.359, P=0.037). Eight cases of mothers with HIV RNA positive in early pregnancy/pre-treatment in the anemia group, which was 11(39.29%) in the non-anemia group. The difference was statistically significant ( χ2=6.490, P=0.011). The number of CD4 + T lymphocyte count ≤500/μL was 13 in early pregnancy/pre-treatment in anemia group, which was 20(71.43%) in the non-anemia group. The difference was statistically significant ( χ2=16.396, P<0.01). The number of CD4 + T lymphocyte ≤0.28 was 13 in early pregnancy/pre-treatment in the anemia group, which was 19(67.86%) in the non-anemia group ( χ2=19.908, P<0.01). The number of CD4 + T lymphocyte count ≤500/μL was 14 before delivery, which was 15(53.37%) in the non-anemia group ( χ2=9.536, P=0.008). The number of CD4 + T lymphocyte ≤0.28 before delivery was 14 in anemia group, which was 15(53.37%) in the non-anemia group ( χ2=9.750, P=0.006). According to the receiver operating characteristic curve results, the AUROC, optimal cut-off value, sensitivity and specificity of CD4 + T lymphocyte count before delivery in predicting neonatal anemia were 0.708, 476.0/μL, 100.0% and 50.0%, respectively. The AUROC, optimal cut-off value, sensitivity and specificity of maternal CD4 + T lymphocyte percentage before delivery in predicting neonatal anemia were 0.719, 0.275, 100.0% and 53.6%, respectively. Conclusion:Low CD4 + T lymphocyte level in HIV-infected mothers before delivery, HIV positive in early pregnancy/pre-treatment and using of zidovudine during pregnancy may be associated with neonatal anemia.

Etiologia da anemia em pessoas infectadas com HIV / Anemia etiology in HIV-infected people

O HIV é o causador da AIDS, doença que representa um dos grandes problemas de saúde pública em todo o mundo. Apesar de avanços na terapia antirretroviral no sentido de aumentar a expectativa de vida dos indivíduos infectados, as alterações hematológicas, como a anemia, acompanham o curso clínico da doença. Essa condição, normalmente multifatorial, pode estar presente em qualquer fase da doença e afeta diretamente o prognóstico e a qualidade de vida do indivíduo infectado. Este artigo apresenta informações do surgimento do processo anêmico com base nas principais causas encontradas na literatura.

The human immunodeficiency virus is the cause of the acquired immunodeficiency syndrome, a disease that represents one of the major public health problems worldwide. In spite of advances in antiretroviral therapy that increase patients' life expectancy, hematological changes, such as anemia, follow the clinical course of the disease. This commonly multifactorial condition can be found in any phase of the disease and directly affects the prognosis and quality of life of patients. This article presents information on the emergence of the anemic process based on the main causes found in the literature.

Factors associated to modification of first-line antiretroviral therapy due to adverse events in people living with HIV/AIDS

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.

Knowledge, attitude and practice of needle stick injury and post exposure prophylaxis in undergraduate medical students

Background: Needle stick injury are the most common reason behind occupational blood exposure and most important source of exposure to another person’s blood.Methods: A cross-sectional observational questionnaire-based study of 450 undergraduate medical students which includes 100 from each years, Second year: Part I (II/I: Third Semester), Second year: Part II (II/III: Fifth Semester), Third Year (III: Seventh Semester), Fourth year (IV: Ninth Semester) MBBS and 50 Interns. The participation was voluntary and written consent was taken prior to enrollment. The objectives of study were explained, and validated questionnaire was administered to the students and collected in a single visit after 30-40 minutes.Results: The average age was 21.91±2.03 years. About 406 students were aware of disease transmitted by NSI. 189 students felt that occurrence of NSI, first person to be contacted is Medicine Physician. 208 don’t know of existence of PEP. 164 felt PEP is to be given for 4 weeks. According to 138 students PEP guidelines were proposed by NACO while 101 students felt WHO. 261 students felt that most probable chance of getting NSI was in emergency ward. 363students felt that need for NSI PEP training before clinical exposure is very important. 345 felt the need for insurance of HCWs for diseases transmitted by NSI.Conclusions: Medical students are highly vulnerable to NSI and there is need to provide adequate preventive measures, frequent training for needle stick injury and postexposure prophylaxis to all healthcare workers.

Idiopathic intracranial hypertension associated with anaemia, secondary to antiretroviral drug in a human immunodeficiency virus positive patient

Papilledema in a patient with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome is an alarming finding. Any condition giving rise to raised intracranial tension (ICT) can cause papilledema, and in these patients, it could be secondary to opportunistic infections like meningitis to neoplasm. We report a case of a 28-year old female with HIV on antiretroviral therapy, who presented to us, with papilledema. Her fundus examination revealed superficial hemorrhages and Roth's spots along with papilledema. Patient was diagnosed with idiopathic intracranial hypertension (IIH), and all other possible systemic associations were ruled out. Her blood tests showed severe anemia. The papilledema and retinal changes resolved with treatment of anemia. This is a rare presentation of IIH in HIV positive patient due to anemia, secondary to zidovudine adverse effect.

Pharmacokinetic study of cholesteryl-phosphoryl zidovudine in rats / 国际药学研究杂志

Objective: To develop and validate methods for determination of cholesteryl-phosphoryl zidovudine(CPZ)and its metabolite zidovudine(AZT)in rat plasma and tissues,and use the methods to investigate the pharmacokinetics of CPZ in rats. Meth- ods: An HPLC-UV method was applied for the determination of CPZ in biological samples. The biological samples were precipitated with acetonitrile at first,and then CPZ was separated on a Diamonsil C 18 column(200 mm×4.6 mm I.D.,5 μm)with a gradient elution system comprising 90% methanol and 10% isopropanol(containing 2 mmol/L cetyl trimethylammonium bromide,2% acetic acid and 0.1% ammonium hydroxide). The eluent was monitored at 266 nm by UV detector. The determination of AZT in biological samples was performed by LC-MS/MS after it was extracted from the biological samples by liquid-liquid extraction with methyl tertbutyl ether. Chro- matographic separation was performed on a Poroshell 120 EC-C 18 column(50 mm×2.1 mm I.D.,2.7 μm). Using the mobile phase con- sisted of 35% methanol and 65% water containing 0.2% acetic acid,the column was eluted by an isocratic elution with the flow rate of 0.3 ml/min. Detection of AZT and the internal standard(IS)acetaminophen was achieved by ESI MS/MS in the positive ion mode using m/z 268.2→m/z 127.0 and m/z 152.1→m/z 110.0 transitions,respectively. Results: The linear ranges for the quantitative determina- tion of CPZ and AZT were 5-400 μg/ml and 2-500 ng/ml,respectively,when 50 μl plasma was analyzed. The lower limit for the quan- tification of CPZ and AZT was 5 μg/ml and 2 ng/ml,respectively. The inter-and intra-day precision values were below 15%,and the accuracy(relative error)was within ± 13.8% in all quality control samples. CPZ was quickly metabolized in rats,while AZT was oppo-site. The half-life of AZT was about 8 h. The distribution of CPZ and AZT was more in the liver,spleen and lungs of rats,and less in the heart and kidney. Conclusion: The methods completely meet the requirements for pharmacokinetic study of CPZ in rats. The phar- macokinetic results show that CPZ could release AZT targeting liver,spleen,and lungs in rats.

Zidovudine/Lamivudine vs. Abacavir/Lamivudine vs. Tenofovir/Emtricitabine in fixed-dose combinations as initial treatment for HIV patients: a systematic review and network meta-analysis / Zidovudina/Lamivudina vs Abacavir/Lamivudina vs Tenofovir/Emtricitabina en combinaciones de dosis fija como tratamiento inicial en pacientes con VIH: revisión sistemática y metanálisis en red

Abstract Introduction: Initial treatment of the HIV is based on the use of three drugs, two of which are nucleoside analog reverse-transcriptase inhibitors. There are three combinations of these drugs which have been approved by different guidelines, each with divergent results in terms of efficacy and safety. Objective: To compare the efficacy and safety of these three combinations. Methods: Systematic review and network meta-analysis of randomized clinical trials comparing fixed doses of Tenofovir Disoproxil Fumarate / Emtricitabine (TDF/FTC), Abacavir / Lamivudine (ABC/3TC) and Zidovudine / Lamivudine (ZDV/3TC). Results: Seven clinical trials met the eligibility criteria. The results suggested higher efficacy with TDF/FTC vs. ABC/3TC at 96 weeks and vs. ZDV/3TC at 48 weeks. However, there is clinical and statistical heterogeneity. Subgroup analysis were performed by third drug and by level of viral load prior to treatment, and found no differences in virological control. Network meta-analysis could only be carried out with TDF/FTC vs. ZDV/3TC, and the proportion of patients with virological response, with no differences at 48 weeks nor at 96 weeks. Direct comparisons showed an increased risk of bone marrow suppression of ZDV/3TC vs. TDF/FTC and of ABC/3TC hypersensitivity reactions vs. ZDV/3TC Conclusions: The results did not show differences in effectiveness among the interventions. However, due to the heterogeneity of the third drug and the follow-up time between the included studies, this result is not definitive. The results raise the need for further studies to help improve treatment recommendations in patients infected with HIV.

Resumen Introducción: El tratamiento inicial de la infección por VIH se basa en el uso de tres medicamentos, dos de ellos inhibidores de transcriptasa reversa análogos de nucleósido. Existen tres combinaciones de estos medicamentos aprobadas por diferentes guías, con resultados divergentes en cuanto a eficacia y seguridad. Objetivo: Comparar la eficacia y seguridad de las 3 combinaciones Métodos: Revisión sistemática y metanálisis en red de ensayos clínicos con asignación aleatoria comparando dosis fijas de Tenofovir Disoproxil Fumarato/Emtricitabina (TDF/FTC), Abacavir/Lamivudina (ABC/3TC) y Zidovudina/Lamivudina (ZDV/3TC). Resultados: Siete ensayos clínicos cumplieron los criterios de elegibilidad. Los resultados sugirieron mayor eficacia con TDF/FTC vs ABC/3TC a 96 semanas y vs. ZDV/3TC a 48 semanas. Sin embargo, existe heterogeneidad clínica y estadística. Se realizó análisis de subgrupos por tercer medicamento y por nivel de carga viral previa al tratamiento, sin encontrar diferencias en control virológico. Se pudo realizar metanálisis en red con TDF/FTC vs ZDV/3TC y proporción de pacientes con respuesta virológica, sin diferencias a las 48 semanas ni 96 semanas. Las comparaciones directas evidenciaron mayor riesgo de supresión de médula ósea de ZDV/3TC vs TDF/FTC y de reacciones de hipersensibilidad de ABC/3TC vs ZDV/3TC. Conclusión: Los resultados no demostraron diferencias en efectividad entre las intervenciones; sin embargo, debido a heterogeneidad en cuanto al tercer medicamento y el tiempo de seguimiento entre los estudios incluidos, dicho resultado no es definitivo. Los resultados plantean la necesidad de realizar nuevos estudios que ayuden a mejorar las recomendaciones de tratamiento en los pacientes infectados por el VIH.

Construction and validation of conformity test model for zidovudine film-coated tablets by near infrared reflectance spectroscopy / 国际药学研究杂志

Objective To establish a conformity test model for inspecting aluminum-plastic package and removed aluminum-plastic package zidovudine film-coated tablets by near infrared reflectance(NIR) spectroscopy respectively. Methods The method of first derivative and vector normalization was employed respectively to pretreat the corresponding NIR spectra of aluminum-plastic package and removed aluminum-plastic package zidovudine film-coated tablets with the spectral ranges of 12000~4000 cm-1. The optimum modeling band were 9000-7500cm-1, 6900-5600 cm-1and 5000-4250 cm-1, respectively, and the smoothing point was set as 17 and CI limit was 7. The conformity test model was constructed on the basis of the above parameters and validated respectively. Results The authentic aluminum-plastic package and removed aluminum-plastic package zidovudine film-coated tablets were distinguished from inauthentic ones using the conformity test model validated by spectra collected by different inspectors and different near infrared instruments, realizing the model transfer accurately and effectively and improving the universality of NIR calibration model. Conclusion The conformity test model is accurate, simple, feasible, and suitable for the drug examination of zidovudine film-coated tablets.

Construction and validation of conformity test model for zidovudine film-coated tablets by near infrared reflectance spectroscopy / 国际药学研究杂志

Objective To establish a conformity test model for inspecting aluminum-plastic package and removed aluminum-plastic package zidovudine film-coated tablets by near infrared reflectance(NIR)spectroscopy respectively. Methods The method of first derivative and vector normalization was employed respectively to pretreat the corresponding NIR spectra of aluminum-plastic pack?age and removed aluminum-plastic package zidovudine film-coated tablets with the spectral ranges of 12000~4000 cm-1. The optimum modeling band were 9000-7500cm-1,6900-5600 cm-1and 5000-4250 cm-1,respectively,and the smoothing point was set as 17 and CI limit was 7. The conformity test model was constructed on the basis of the above parameters and validated respectively. Results The authentic aluminum-plastic package and removed aluminum-plastic package zidovudine film-coated tablets were distinguished from inauthentic ones using the conformity test model validated by spectra collected by different inspectors and different near infrared instruments,realizing the model transfer accurately and effectively and improving the universality of NIR calibration model. Conclu?sion The conformity test model is accurate,simple,feasible,and suitable for the drug examination of zidovudine film-coated tablets.

A novel approach in mucoadhesive drug delivery system to improve zidovudine intestinal permeability

ABSTRACT Zidovudine (AZT) mucoadhesive solid dispersions (SD) were prepared using a sodium starch glycolate (SSG) and hypromellose phthalate (HPMCP) mixtures as carrier to enhance the intestinal permeability and bioavailability of zidovudine. SDs were prepared using the co-precipitation method followed by solvent evaporation and characterized according to their physicochemical properties such as particle size, crystallinity, thermal behavior, and liquid uptake ability. In vitro drug dissolution, mucoadhesiveness and AZT intestinal permeability were also determined. Thermal behavior and X-ray diffraction patterns demonstrated the amorphous state of AZT in SD systems. The HPMCP polymer restricted the liquid uptake ability in the acid medium; however, this property significantly increased with higher pH values. SDs allowed drug dissolution to occur in a controlled manner. HPMCP decreased the dissolution rates in the acid medium. The mucoadhesiveness of SDs was demonstrated and the permeability of AZT carried in solid dispersions was significantly improved. The effect of the SD carrier polymers on blocking efflux pump can be an important approach to improve the bioavailability of AZT.

Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites

Zidovudine (AZT), the first drug approved by the US Food and Drug Administration for the treatment of human immunodeficiency virus (HIV) infection, is metabolized in the host cells to 5'-AZT triphosphate (AZT-TP) which inhibits HIV reverse transcriptase. As the pharmacokinetics of AZT and its phosphorylated metabolites in human peripheral blood mononuclear cells (hPBMCs) is limited, the aim of this study was to determine the pharmacokinetic parameters of AZT and its phosphorylated metabolites in hPBMCs from 12 healthy Chinese male subjects after a single oral dose of 600 mg of AZT. Blood samples were collected prior to drug administration, then at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8 and 10 h after drug administration. Mononuclear cells collected by Ficoll-Hypaque density gradient centrifugation were used for determination of AZT and metabolites [AZT monophosphate (AZT-MP), AZT diphosphate (AZT-DP) and AZT-TP] and the plasma was used to evaluate the pharmacokinetics of AZT. Plasma concentration of AZT peaked within 0.583 h and intracellular concentrations of AZT, AZT-MP, AZT-DP and AZT-TP peaked within 1.083, 1.500, 1.417 and 1.583 h, respectively. AZT in plasma was eliminated rapidly with t 1/2 of 2.022 h, and AZT-MP, AZT-DP and AZT-TP were eliminated with t 1/2 of 13.428, 8.285 and 4.240 h, respectively. The plasma concentration of the phosphorylated metabolites was not quantifiable.

Desenvolvimento de nanopartículas de poli (n-butil-cianoacrilato) com zidovudina revestidas por ácido hialurônico para veiculação em gel de uso transdérmico / Development nanoparticles poly (n -butyl cyanoacrylate) zidovudine coated with hyaluronic acid to serve transdermal gel using

A zidovudina (AZT) ainda é o fármaco mais empregado no tratamento da AIDS, isoladamente ou em associação a outros antirretrovirais, porém é um fármaco administrado em altas doses e que apresenta efeitos adversos que comprometem a adesão do paciente ao tratamento. Assim, um novo sistema de liberação de zidovudina composto por nanopartículas de poli (n-butil-cianoacrilato) (PBCA) revestidas por ácido hialurônico (AH) foi desenvolvido e caracterizado com o objetivo de prolongar a liberação do fármaco e diminuir sua toxicidade. As nanopartículas têm sido amplamente estudadas como veículo para fármacos por permanecer na circulação por um tempo maior e, portanto, liberar o fármaco de forma prolongada. Para polimerização e, portanto, obtenção das nanopartículas, n-butil-cianoacrilato e Dextran® foram adicionados a HCl 0,1 M (pH 2,5), sob agitação a 800 rpm, por 1 h. O AZT foi adicionado e o processo foi neutralizado com adição de NaOH 0,1M após mais 3 h de agitação. Após filtração as partículas foram revestidas pela adição de uma dispersão aquosa de ácido hialurônico (AH) a baixa rotação. O diâmetro hidrodinâmico médio das nanopartículas não revestidas foi de 152,3 nm, com um índice de polidispersividade médio igual a 0,055. O potencial zeta médio dessas partículas foi -0,678 mV. O diâmetro hidrodinâmico médio das nanopartículas revestidas com AH obtido foi de 196,9 nm, com um índice de polidispersividade médio igual a 0,440. O potencial zeta médio dessas partículas foi de -25,6 mV. Os valores resultantes dessas análises são indicativos da estabilidade das nanopartículas obtidas e da boa reatividade dos monômeros dos cianoacrilatos. Ainda, pelos resultados é possível confirmar a ocorrência do revestimento. Assim, a eficiência do processo de revestimento das nanopartículas pode ser comprovada por meio dos resultados das análises de calorimetria exploratória diferencial (DSC) e pelos resultados das análises de espectroscopia de absorção na região do infravermelho. Para quantificar o fármaco associado às nanopartículas, um método empregando espectrofotometria derivada (ED1) no UV aplicando a técnica do ponto de anulação foi desenvolvido e validado. Tal método possibilitou a eliminação da interferência dos excipientes, o que permitiu a quantificação do AZT na suspensão de nanopartículas com precisão e exatidão adequadas. A porcentagem de fármaco associado às nanoestruturas obtidas pelo método foi de 64%, considerado satisfatório. As nanopartículas foram incorporadas a uma formulação base de gel de Carbopol® 940 que, apresentou estabilidade após ser submetida a diferentes condições de armazenamento, com incidência de luz e variação da temperatura

Zidovudine (AZT) is still the most widely used drug in the treatment of AIDS, alone or in combination with other antiretroviral drugs, however it is indicated in high doses and has adverse effects that compromise patient compliance to treatment. Thus, a new zidovudine delivery system made of poly (n-butyl-cyanoacrylate) nanoparticles coated with hyaluronic acid (HA) was developed and characterized in order to extend the drug release and reduce its toxicity. The nanoparticles have been widely studied as drug carriers once they remain in circulation for a longer period and, consequently, release the drug gradually. For the polymerization, and, therefore synthesis of nanoparticles, n-butyl-cyanoacrylate and Dextran® were added to 0.1 M HCl (pH 2.5) and stirred at 800 rpm for 1 hour. AZT was added and the reaction was neutralized by the addition of 0.1 M NaOH after 3 more hours of agitation. After filtration the particles were coated by addition of an aqueous dispersion of hyaluronic acid (HA) at low revs. The mean hydrodynamic diameter of non-coated nanoparticles was 152.3 nm with an average polydispersity index of 0.055. The average zeta potential of these particles was -0.678 mV. The average hydrodynamic diameter of the coated nanoparticles was 196.9 nm, presenting an average polydispersity index of 0.440. The average zeta potential of these particles was -25.6 mV. The resulting values of these tests are indicative not only of the stability of the obtained nanoparticles but also the good reactivity of the monomers of cyanoacrylates. Moreover, the results can confirm the occurrence of coating. Thus, the efficiency of the coating process of the nanoparticles can be demonstrated by the results of the analysis of differential scanning calorimetry (DSC) and the results of the absorption spectroscopy in the infrared region. In order to quantify the drug associated with the nanoparticles, a method employing derivative spectrophotometry (ED1) UV applying the zero-crossing technique was developed and validated. This method allowed the elimination of interference of excipientes, allowing the quantification of AZT nanoparticles in suspension with adequate accuracy and precision. The percentage of the drug associated with the obtained nanostructures by the method was 64%. The nanoparticles were incorporated into a Carbopol® 940 gel formulation, which was stable after being subjected to different storage conditions, with incidence of light and temperature variation

RP-HPLC assay of contents of nevirapine zidovudine and lamivudine tablets and related substances / 中国药学杂志

OBJECTIVE: To develop a method for determination of the contents and related substances in nevirapine zidovudine and lamivudine tablets. METHODS: The samples were separated on a Welch Ultimate AQ-C18 (4.6 mm × 250 mm, 5 μm) column by gradient elution using acetonitrile-methanol-0.025 mol·L-1 ammonium acetate solution (pH 4.0) as the mobile phase at a flow rate of 1.0 mL·min-1. The detection wavelength was set at 277 nm, and the column temperature was 30°C. RESULTS: Nevirapine, lamivudine, and zidovudine had good liner relationship in the range of 10.3 - 310.9, 7.9 - 237.1, and 14.9 - 449.6 μg·mL-1, respectively. The correlation coefficients were all more than 0.9998. The average recoveries were 100.6% (RSD 0.4%), 100.0%(RSD 0.7%), and 100.2% (RSD 0.6%), respectively. Complete separation was achieved for the related substances (lamivudine acid, lamivudine related compound B, uracil, cytosine, thymine, nevirapine related compound A, and nevirapine related compound B). Cytosine, uracil, and thymine had good liner relationship in the range of 76.8 - 1152, 76.8 - 1152, and 744-14880 ng·mL-1, respectively. The correlation coefficients were all more than 0.9991. The average recoveries were 101.5% (RSD 4.8%), 102.8% (RSD 4.2%), and 101.2% (RSD 1.2%), respectively. CONCLUSION: The method is rapid, simple, and accurate with good reproducibility. It can be used for the quality control of nevirapine zidovudine and lamivudine tablets.

Evaluación de la respuesta y seguridada diferentes esquemas de tratamiento antirretroviral en Colombia / Response assessment and safety of different schemes of Anti-HIV Agents in Colombia / Avaliação da resposta e segurança a diferentes esquemas de tratamento antirretroviral em Colombia

Introducción: establecer variables asociadas a falla terapéutica, adherencia al tratamiento, cambio de esquema y efectos indeseables asociados al tratamiento de VIH/SIDA.Métodos: estudio de corte transversal realizado en población de pacientes condiagnóstico de VIH/SIDA en tratamiento antirretroviral de 19 ciudades colombianas afiliados al Sistema General de Seguridad Social en Salud. Se evaluaron variables socio-demográficas, esquemas terapéuticos, tiempo desde inicio de la terapia y cambio de esquema, reporte de falta de adherencia, falla terapéutica y efectos indeseables. Se hicieron análisis bivariados y multivariados. Resultados: se hallaron 510 pacientes; el tratamiento antirretroviral sufriómodificaciones al primer esquema en 56,4% de casos. Se reportó: falta de adherencia en 38,8%, falla terapéutica en 26,5% de pacientes; las reacciones adversas más frecuentes fueron: dislipidemia (14,9%), intolerancia gástrica (9,2%) y anemia (7,1%). El régimen de tratamiento Lamivudina/Zidovudina + Efavirenz se asoció con menor riesgo de cambio de esquema (p<0,001), de falla terapéutica (p<0,001) y de intolerancia (p<0,001). El fracaso terapéutico se asoció con antecedentes de neumocistosis, tomar 7 píldoras al día, repartidas en 3 a 4 dosis diarias, en tratamiento para diferentes comorbilidades, con falta de adherencia y efectos indeseables asociados a los antirretrovirales. Conclusiones: la identificación de los esquemas de tratamiento asociados con peortolerabilidad por su riesgo de afectar la adherencia al manejo del VIH, con mástabletas diarias y consumidos varias veces al día, permite orientar la selección de medicamentos que garanticen mayor adherencia y tolerabilidad.

Introduction: estimate variables associated with treatment failure, treatment adherence, schema change and adverse reactions associated with the treatment of HIV/AIDS.Methods: cross-sectional study conducted in a population of patients with HIV/ AIDS antiretroviral treatment in 19 cities of Colombia affiliates at Social Security System in Health. We assessed socio-demographic variables, treatment regimens, and time from start of therapy and schema change, report non-adherence, treatment failure and adverse reactions. Were used bivariate and multivariate analysis.Results: we found 510 patients, antiretroviral therapy was modified to the first scheme in 56.4% of cases, nonadherence in 38.8%, treatment failure in 26.5% of patients, and the most common adverse reactions were: dyslipidemia (14.9%), gastric intolerance (9.2%) and anaemia (7.1%). The treatment regimen Lamivudine / Zidovudine + Efavirenz was associated with lower risk of schema change (p <0.001), treatment failure (p <0.001) and intolerance (p <0.001). Treatment failure was associated with a history of pneumocystosis, taking 7 pills a day, divided into 3-4 daily doses, in treatment for different comorbidities, lack of adherence and adverse effects associated with antiretrovirals.Conclusions: the identification of treatment regimens associated with poorer tolerability for their risk of affecting adherence to HIV management, with more tablets daily and consumed several times a day can guide the selection of drugs to ensure greater adherence and tolerability.

Introdução: estabelecer variavéis associadas à falha terapêutica, aderência ao tratamento, mudança de esquema e efeitos indesejaveis associados ao tratamento de VIH/SIDA.Métodos: estudo de corte transversal realizado em grupos de pacientes com diagnóstico de VIH/SIDA em tratamento antirretroviral de 19 cidades colombianas filiados ao Sistema Geral de Segurança Social em Saúde. Avaliaram-se variavéis socio-demográficas, esquemas terapêuticos, tempo desde o inicio da terapia e mudança de esquema, anotação sobre falta de aderência, falha terapêutica e efeitos indesejaveis. Foram feitas análises bivariados y multivariados.Resultados: acharam-se 510 pacientes, e o tratamento antirretroviral sofreu modificações ao primeiro esquema em 56,4% dos casos, se reportou: falta de aderência em 38,8%, falha terapêutica em 26,5% dos pacientes; as reações adversas mais frequentes foram: dislipidemia (14,9%), intolerência gástrica (9,2%) e anemia (7,1%). O regime de tratamento Lamivudina/Zidovudina + Efavirenz se associou com menor risco de mudança de esquema (p<0,001), de falha terapêutica (p<0,001) e de intolerância (p<0,001). O fracasso terapêutico se associou com antecedentes de neumocistosis, tomar 7 comprimidos por dia, distribuido em 3 a 4 doses diárias, em tratamento para diferentes comorbilidades, com falta de aderência e efeitos indesejados associados aos antirretroviraies.Conclusões: a identificação dos esquemas de tratamento associados com pior tolerância pelo risco de afetar a aderência ao tratamento do VIH, com mais comprimidos diários e consumidos várias vezes ao dia, permite orientar a seleção de medicamentos que garantam maior aderência e tolerabilidade.

Administração de medicamentos para crianças nascidas expostas ao vírus da imunodeficiência humana / Administration of medications for children born exposed to human immune deficiency virus

OBJETIVO: Avaliar a capacidade de mães com HIV/Aids de administrar a zidovudina e a profilaxia com sulfametoxazol-trimetoprima aos filhos nascidos expostos ao HIV. MÉTODOS: Estudo transversal e quantitativo, realizado em hospital de referência no atendimento a casos de HIV/Aids em Fortaleza (CE), Brasil. Utilizou-se a Escala de Avaliação da Capacidade para Cuidar de Crianças Expostas ao HIV, que foi respondida por 60 mães. RESULTADOS: O nível de capacidade de administrar a zidovudina variou de moderado a alto, sem diferenças significantes em relação às variáveis maternas (p>0,05). Em relação à administração do sulfametoxazol-trimetoprima, o nível de capacidade variou entre baixo, moderado e alto. A variável materna "paridade" apresentou relação com o nível de cuidado alto (p=0,051). CONCLUSÃO: O nível de capacidade das mães para administrar o AZT xarope (Fator I) variou de moderado a alto e para administrar e SMZ-TMP (Fator IV), o nível de capacidade de administração distribuiu-se sem diferença entre baixo, moderado e alto.

OBJECTIVE: To evaluate HIV-positive mothers' ability to administer zidovudine and trimethoprim-sulfamethoxazole (SMZ/TMP) prophylaxis for HIV-exposed infants. METHODS: This cross-sectional and quantitative study was carried out at a reference hospital for HIV/AIDS patients in Fortaleza (CE), Brazil. A total of 60 mothers responded to the ability assessment scale for the care of HIV-exposed children. RESULTS: The level of ability to administer zidovudine varied from moderate to high. Maternal variables did not show significant differences (p>0.05). TMP/SMZ administration varied from low, moderate, and high. The variable "parity" was related to a high level of care (p=0.051). CONCLUSION: The level of ability of mothers to administer AZT syrup (factor I) varied from moderate to high; with SMZ-TMP administration (factor IV), no difference among low, moderate, and high was seen.

In vitro pharmacodynamic evaluation of anti-HIV cholesteryl-phosphoryl zidovudine self-assemblies / 国际药学研究杂志

Objective To evaluate the anti-HIV activity of the self-assemblies of cholesteryl-phosphoryl zidovudine (CPZ) and provide evidence for the promising new anti-HIV drug. Methods CPZ self-assemblies were prepared. The MT4 cells infected by HIV-1 were the model to evaluate the anti-HIV activity of CPZ self-assemblies, which based on the generation of combined ceHs, was compared to that of the parent drug-zidovudine (AZT). The cytotoxicity of CPZ self-assemblies as evaluated by the MTT method. Phagocytosis of macrophage to CPZ self-assemblies was evaluated in RAW264. 7 ceHs. Results The anti-HIV activity of CPZ self-assemblies was much higher than that of AZT, with the half effective concentration (EC50) 1/10 to 1/50 that of AZT. The selectivity index (SI) was high, indicating that the self-assemblies were safe. Conclusion CPZ self-assemblies have high anti-HIV activity and is apromisinganti-HIV drug.

Prevalence and Risk Factors of Low Bone Mineral Density in Korean HIV-Infected Patients: Impact of Abacavir and Zidovudine

Low bone mineral density (BMD) is common in HIV-infected patients. We aimed to describe the prevalence of low BMD and risk factors in Korean HIV-infected patients and to assess the effects of antiretroviral therapy (ART) on BMD. We retrospectively evaluated 224 HIV infected-patients. The prevalence of osteopenia and osteoporosis were 41.5% and 12.9%. These were much higher in 53 patients aged 50 yr and older (52.8% and 34.0%). Older age, lower body mass index, and ART > 3 months were independent risk factors for low BMD. Osteoporosis was more prevalent in patients on the abacavir-based regimen for or = 1 yr; however, it was more prevalent in patients on the zidovudine-based regimen for > or = 1 yr than < 1 yr (P = 0.017). Osteoporosis in patients on the abacavir-based regimen was more common in the spine than in the femur (P = 0.01). Given such a high prevalence of low BMD, close monitoring of BMD for HIV-infected patients on ART is required. The different prevalence of osteoporosis over time and affected areas between two regimens suggest they may play roles in different mechanisms in bone loss.

Evaluation of preventive measures for mother-to-child transmission of HIV in Aracaju, State of Sergipe, Brazil / Avaliação das ações de prevenção da transmissão materno-infantil do HIV em Aracaju, Estado de Sergipe, Brasil

INTRODUCTION: The main route of human immunodeficiency virus (HIV) infection in children is from mother to child. The preventive measures established for the Aids Clinical Trial Group protocol 076 (ACTG 076) significantly reduces HIV vertical transmission rates. This study aims to evaluate the implementation of the ACTG 076 protocol in the maternity units of State of Sergipe, Brazilian northeast. METHODS: This is a descriptive, retrospective study with a quantitative approach, with HIV positive women and children exposed, attending a Maternity reference for high-risk pregnancies. Data were obtained from patient records registered in the years 1994 to 2010. RESULTS: Amongst the 110 pregnant women and exposed newborns, the ACTG 076 protocol was fully utilized in only 31.8% of the participants. During the prenatal period, zidovudine (ZDV) was taken by 79.1% of the pregnant women. Only 49.1% of HIV seropositive patients used ZDV during delivery. Two (1.8%) children were considered infected and 50 (45.5%) do not have a conclusive diagnosis to date. CONCLUSIONS: There were significant deficiencies in the prevention of mother-to-child transmission of HIV, including lack of compliance with the three phases of the ACTG 076 protocol; inadequacies in prenatal care; inappropriate mode of delivery and lack of adequate follow up of exposed children.

INTRODUÇÃO: A principal forma de infecção do vírus da imunodeficiência humana (HIV) em crianças é pela transmissão materno-infantil. As ações profiláticas estabelecidas pelo protocolo Aids Clinical Trial Group 076 (ACTG 076), reduziram significativamente as taxas de transmissão vertical do HIV. Este estudo objetivou avaliar a aplicação do protocolo ACTG 076 na maternidade de referência no Estado de Sergipe, nordeste brasileiro. MÉTODOS: Trata-se de um estudo descritivo, retrospectivo com abordagem quantitativa, com mulheres HIV soropositivas e crianças expostas atendidas em uma maternidade para gestações de alto risco. Os dados foram obtidos dos registros de pacientes registrados nos anos de 1994 a 2010. RESULTADOS: Entre as 110 gestantes e recém-nascidos expostos, o uso completo do protocolo ACTG 076 foi utilizado em apenas 31,8% dos participantes. No pré-natal, a zidovudina (ZDV) foi utilizada em 79,1% das gestantes. O uso da ZDV durante o trabalho de parto ocorreu em 49,1% das gestantes HIV reagentes. Duas (1,8%) crianças foram consideradas infectadas e 50 (45,5%) ainda não têm diagnóstico definido. CONCLUSÕES: Foram detectadas falhas significativas na prevenção da transmissão materno-infantil, dentre as quais, a falta do cumprimento das três fases do protocolo ACTG 076: carências no pré-natal, tipo de parto inadequado e perdas de seguimento para acompanhamento da criança exposta.