The Prevalence and Risk Factors of Renal Insufficiency among Korean HIV-Infected Patients: The Korea HIV/AIDS Cohort Study

BACKGROUND: Renal disease is one of the leading causes of morbidity and mortality among people infected with human immunodeficiency virus (HIV). However, there are very few published studies about renal insufficiency in HIV-infected persons in Asia, especially in South Korea. MATERIALS AND METHODS: A cross-sectional study was performed to investigate the prevalence and risk factors of renal insufficiency, defined as <60 mL/min/1.73 m², in subjects in the Korea HIV/AIDS Cohort Study enrolled from 19 institutions between December 2006 and July 2013. Data at entry into the cohort were analyzed. RESULTS: Of 454 enrolled subjects, 24 (5.3%) showed renal insufficiency at entry into the cohort. The mean age of patients in the renal insufficiency group was 5.28 years and the majority were male subjects (91.7%). All the patients were receiving antiretroviral agents, mostly protease inhibitor-based regimens (76.4%), for an average of 19 months. In univariate analysis, older age (P = 0.002), diabetes mellitus (DM) (P = 0.0002), unknown route of transmission (P = 0.007), and taking indinavir (P = 0.0022) were associated with renal insufficiency. In multivariable analysis, older age [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.03–1.12, P = 0.002], DM [OR 3.03, 95% CI 1.17–7.82, P = 0.022], unknown route of transmission [OR 6.15, 95% CI 1.77–21.33, P = 0.004], and taking indinavir [OR 3.07, 95% CI 1.17–8.05, P = 0.023] were independent risk factors of renal insufficiency. CONCLUSION: The prevalence of renal insufficiency in HIV-infected subjects in this study was relatively low, similar to that in other countries. Aging, DM, and taking indinavir were significantly associated with decreased glomerular filtration rate. Furthermore, unknown route of transmission was an independent risk factor, which was interpreted as a reflection of patient compliance. Further studies on the incidence and risk factors of renal insufficiency during HIV infection using follow-up cohort data are necessary.

Tamizaje virtual de compuestosinhibidores de la SA P-2de Candida albicans / Virtual screening of inhibitory compounds SEP-2 Candida albicans

El incremento de la resistencia a antifúngicos en Candida spp. una levadurade carácter oportunista asociada a múltiples infecciones superficiales y sistémicas,plantea la necesidad de buscar diferentes estrategias para hallar nuevas opciones terapéuticas más selectivas y específicas. Una alternativa es el tamizaje basado en el acoplamiento virtual. En el presente trabajo, se analizaron 13418 compuestos con estructuras similares a compuestos reconocidos como inhibidores de la proteína SAP-2,seleccionada como diana antifúngica para el análisis virtual. Materiales y métodos: el estudio se realizó utilizando el programa SYBYL 8, al tiempo que se evaluó la afinidadde estas estructuras con los sitios activos de la enzima seleccionada mediante el programa FlexX integrado en SYBYL 8 y se realizó un consenso comparando los resultados con el programa Autodock Vina. Resultados: los resultados obtenidos mostraron una mayor afinidad por móleculas con estructura similar a los antirretrovirales,inhibidores de proteasas; amprenavir, saquinavir e indinavir. Conclusiones: los resultados obtenidos sugieren que estos lnhibidores de proteasas pueden ser propuestos como modelos para la búsqueda de nuevos antifúngicos que sean más selectivos contra Candida spp...

In vivo assessment of antiretroviral therapy-associated side effects

Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI) indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs.

Alopecia Areata Associated with Abacavir Therapy

Abacavir is a nucleoside reverse-transcriptase inhibitor that has been approved for use in combination with other retroviral agents in the treatment of HIV infection. Common adverse reactions include headache, fatigue, nausea, and rash. A fatal hypersensitivity reaction may occur in 5% of patients receiving abacavir; therefore, screening for HLA-B5701 should be performed before starting abacavir. Alopecia areata (AA) is infrequently reported in HIV-infected patients. Certain underlying conditions have been associated with AA, including a decreased CD4:CD8 ratio related to the progression of HIV infection, some opportunistic infections, and syphilis. Several antiretroviral drugs, such as zidovudine, indinavir, indinavir/ritonavir, lopinavir/ritonavir, and atazanavir/ritonavir have been implicated in the development of AA. At present, the occurrence of AA has not been associated with abacavir use. We cannot exclude that the use of abacavir and the development of AA could be coincidental. Nevertheless, patients given abacavir should be monitored for hair loss and the drug discontinued promptly if such signs appear.

Optimization of human immunodeficiency virus type one replication assay using single cycle replicable virions

HIV virions with replication capacity are needed for HIV researches, like investigating for new anti HIV agents. Here HIV-1 replication assay was optimized with HIV-1 single cycle replicable [SCR] virions to improve biological safety condition. pSPAX2, pmzNL4-3 and pMD2G plasmids were co-transfected to the HEK293T by using polyfect reagent to produce the SCR HIV-1 virions. Virions were quantified using capture ELISA P24. Different MOI of SCR virions were used for infecting of Target cells [HEK] and the load of the supernatant P24 was monitored days after infection. Single cycle replication assay [SCRA] was developed using kinetic studies data. The P24 load of the infected cells supernatant has linear relation to the beginning infectious MOI. 24 hours post infection with HIV-1 SCR virions the viral particle production was detectable. The highest load of P24 in infected cells supernatant was detected 48 hours after infection. Using this developed method, the 50 and 95 percent inhibitory concentration of [IC[95] and IC[50]] Indinavir and Nevirapine were calculated as 25nM and 50nM. In this study, using SCR HIV-1 virions the SCRA was developed. SCR HIV-1 virions are replicable only for one cycle and this improves the safety of developed assays. The accuracy of assay was examined by quantifying the anti HIV-1 potential of two commercial anti-AIDS drugs and the calculated activity for test agents was equal to previously known amounts

Causas de cambio de tratamiento en un grupo de pacientes VIH/SIDA cubanos / Causes of change in treatment in a group of HIV/AIDS Cuban patients

La infección por virus de inmunodeficiencia humana (VIH) es uno de los mayores problemas de salud actuales, se estima que más de 40 millones de personas están infectadas en el mundo. Se realizó un estudio descriptivo de corte transversal en 40 pacientes VIH/SIDA pertenecientes al servicio de Medicina del IPK con el propósito de caracterizar las causas del cambio de tratamiento antirretroviral y los tipos de reacciones adversas presentadas con este tratamiento en un grupo de pacientes VIH/SIDA..Los pacientes recibieron diferentes esquemas de antirretrovirales entre los que predominaron los siguientes: 3TC, d4T e Indinavir (57,5 por ciento), seguido de 3TC, AZT e Indinavir (22,5 por ciento). Las causas más frecuentes de cambio de tratamiento fueron las reacciones adversas y la mala adherencia al tratamiento. Entre las personas que están recibiendo terapia contra el VIH, existe una tendencia cada vez más frecuente de abandonar o cambiar la terapia. Las causas de estos cambios y del abandono de las terapias suelen estar relacionadas con los efectos secundarios, la fatiga del tratamiento, la fase de la infección por VIH en que se encuentra el paciente, y factores relativos a su estilo de vida. Las causas más frecuentes de cambio de tratamiento fueron las reacciones adversas, seguidas de la mala adherencia al tratamiento antirretroviral. Las reacciones adversas más frecuentes en el grupo de estudio fueron los vómitos y los trastornos digestivos respectivamente

The HIV virus infection is one of the major current problems of health estimating that more than 40 millions of persons are infected at world level. A cross-sectional and descriptive study was conducted in 40 HIV/AIDS patients from the Tropical Medicine Institute service to characterize the causes of the change in antiretroviruses treatment and the types of adverse reactions related to this treatment in a group of HIV/AIDS patients. Patients received different antiretroviruses schemes with predominance of 3TC, d4T and Indinarir (57,5 percent), followed by 3TC, AZT and Indinavir (22,5 percent). The more frequent causes of change of this treatment were the adverse reactions and a poor adherence to it. Among the persons with therapy HIV there is a more and more frequent trend to give up or to change of therapy. The causes of these changes and the leaving the therapy are related to side effects, treatment fatigue, and the HIV infection phase in patient and relative factors related to the lifestyle. The more frequent causes of the change of treatment were the adverse reactions followed by a poor adherence to antiretroviruses treatment. The more frequent adverse reactions were vomiting and digestive disorders, respectively

Renal manifestations in HIV-infected Jamaican children / Manifestaciones renales en niños jamaicanos infectados por el VIH

BACKGROUND: Documentation regarding the renal complications of paediatric HIV infection from developing countries is scarce. In the era prior to highly active antiretroviral therapy (HAART), HIV-infected children in Jamaica who developed HIV-associated nephropathy (HIVAN) progressed to end stage renal disease (ESRD) and death within a few months of diagnosis. With increased public access to antiretroviral therapy since 2002 and subsequent survival, renal complications are increasingly recognized among the surviving cohort of infected children. METHODS: A cohort of 196 HIV-infected children was followed in four multicentre ambulatory clinics from September 1, 2002 to August 31, 2005 as part of the Kingston Paediatric and Perinatal HIV/AIDS Programme, Jamaica. We describe the clinical presentations and natural history of those patients who developed renal complications. RESULTS: Urinary tract infections were the most common diagnosis, occurring in 16.8% of patients, with a high recurrence rate and the most common organism was Escherichia coli. Four of seven patients who started indinavir developed complications of nephrolithiasis and tubulointerstitial nephropathy. Six patients (3%) fulfilled the criteria for HIVAN, five of whom were male. Median age at diagnosis was five years; all presented with advanced HIV disease, nephrotic syndrome or nephrotic range proteinuria and three with chronic renal failure. Patients received standard medical management and were initiated on angiotensin-converting enzyme (ACE) inhibitors and HAART. While the mortality ratio was 50%, only one death was associated with HIVAN and the median survival time was 3.1 years. CONCLUSIONS: HIV-infected children present with a variety of renal complications. With improved survival since the introduction of HAART, the incidence of HIVAN is expected to increase among this maturing paediatric cohort. Early detection and treatment will optimize the outcomes for these children.

ANTECEDENTES: La documentación en relación con las complicaciones renales de la infección pediátrica por VIH en países en vías de desarrollo, es escasa. En la era de la terapia antiretroviral pre-altamente activa (TARAA), los niños infectados por VIH en Jamaica que desarrollaron nefropatía asociada con VIH evolucionaron hacia la enfermedad renal en fase terminal (ERFT) y la muerte dentro de pocos meses de hecho el diagnóstico. Con el aumento del acceso público a la terapia antiretroviral a partir de 2002 y la subsiguiente supervivencia, cada vez más las complicaciones renales se observan entre la cohorte sobreviviente de niños infectados. MÉTODOS: A una cohorte de 196 niños infectados con VIH, se le practicó un seguimiento en cuatro clínicas ambulatorios multicentros, desde septiembre 1 de 2002 hasta agosto 31 de 2005, como parte del Programa VIH/SIDA Prenatal y Pediátrico de Kingston, Jamaica. El trabajo describe las presentaciones clínicas y la historia natural de los pacientes que desarrollaron complicaciones renales. RESULTADOS: Las infecciones de las vías urinarias fueron el diagnóstico más común en 16.8% de los pacientes, acompañadas de una alta tasa de recurrencia, y el organismo más común fue el Escherichia coli. Cuatro de siete pacientes que comenzaron tratamiento con indinair, desarrollaron complicaciones de nefrolitiasis y nefropatía tubulointersticial. Seis pacientes (3%), cinco de ellos varones, satisfacían los criterios de NAVIH. La edad promedio al momento del diagnóstico fue de cinco años. Todos representaron con la enfermedad de VIH avanzada, síndrome nefrótico o proteniuria de rango nefrótico, y tres con fallo renal crónico. Los pacientes recibieron tratamiento médico estándar y se iniciaron en el uso de inhibidores de enzimas convertidoras de angiotensina (IECAs) y el TARAA. Si bien la proporción de la mortalidad fue 50%, sólo una muerte estuvo asociada con NAVIH y el tiempo medio de supervivencia fue 3.1 años. CONCLUSIONES: Los niños infectados con VIH se presentaron con una variedad de complicaciones renales. Con el mejoramiento de la supervivencia a partir de la introducción del TARAA, se espera que la incidencia de NAVIH aumente entre la cohorte pediátrica en maduración. La detección precoz y el tratamiento temprano optimizarán los resultados obtenidos con estos niños.

Indinavir-associated toxicity mimicking urinary tuberculosis in a patient with AIDS

This case reported to a patient with AIDS who presented persistent sterile leukocyturia and hematuria, lower back pain, bladder suffering symptoms, and renal papillary necrosis which were thought to be secondary to urinary tuberculosis but were demonstrated to be indinavir-associated side effects. The intention of this report is to remind medical professionals involved in the care of HIV+ patients of this possible association in order to avoid unnecessary investigation and to stress the need of careful periodical assessment of renal function and urinalysis in patients treated with indinavir.

Clinical manifestations for diabetes mellitus in HIV-infected Koreans on highly active antiretroviral therapy / 대한내과학회지

BACKGROUND/AIMS: The introduction of highly active antiretroviral therapy (HAART) has significantly modified the course of HIV infection. However, the HAART regimens, and especially those including protease inhibitors (PIs), have been shown to cause diabetes mellitus. We evaluated the incidence and clinical manifestations of HIV-infected Koreans who received HAART and the risk factors for diabetes mellitus in those patients. METHODS: We conducted a retrospective cohort study and a case-control study to evaluate the clinical manifestations, the incidence and the risk factors for diabetes mellitus in 215 HIV-infected patients who were on HAART at Yonsei University College of Medicine from 1991 to 2006. RESULTS: 215 patients were analyzed and the total duration of follow up was 1079 person-years. The incidences of diabetes mellitus and impaired fasting glucose were 1.39 case/100person-years and 6.02 case/100person-years. Most of the cases were non-obese type II diabetes and these patients showed insulin resistance and impaired beta cell function. On the risk factor analysis, the factors contributing to the development of diabetes were age, a decrease of the viral load and indinavir use. CONCLUSIONS: In our study, the incidence of diabetes among Korean HIV-positive patients on HAART was 1.39case/100person-years. Age, a decrease of the viral load and indinavir use were the risk factors for development of diabetes mellitus.

Improved synthesis and pharmacological evaluation of racemic 11 -demethylcalanolide A / 药学学报

An improved and practical synthesis of racemic 11-demethylcalanolide A [(+/-)-1] was developed. This improved process involved Pechmann reaction on phloroglucinol with ethyl butyrylacetate to give 5,7,-dihydroxy4-n-propylcoumarin (3). Poly phosphoric acid (PPA) catalyzed acylation of compound (3) with crotonic acid, then intramolecular cyclization was achieved simultaneously in one step to afford the key intermediate chromanone (4). A microwave assisted synthetic method preparing chromene (6) using chromenynation of chromanone (4) with 1, 1-diethoxy-methyl-2-butene was conducted. Luche reduction of chromene (6) using NaBH4 with CeCl3 x 7H2O preferably gave (+/-)-1. The overall yield of this four step synthesis of (+/-)-1 was around 32% increasing one fold more than that of the previous method. An in vitro investigation showed that (+/-)-1 exhibited inhibitory activities against both wild-type and drug-resistant HIV-1 in HIV-1 RT and cell culture assay, and significant synergistic effects in combination with AZT, T-20, and indinavir. Its LD50 of acute toxicity in mice by intragastric administration and by intraperitoneal injection were 735.65 mg kg(-1) and 525.10 mg x kg(-1), respectively. The Cmax and AUC(0-infinity) were 0.54 microg x mL(-1) and 1.08 (microg x mL(-1) x h, respectively. The dynamics study of the inhibition of mice sera on HIV-1 RT showed that mice treated with 100 mg x kg(-1 (+/-)-1 once intraperitoneally were similar to that of 5 mg x kg(-1) of known clinical effective anti-HIV-1 drug neverapine. The results suggested that further investigation of the anti-HIV candidate (+/-)-1 was warranted.

Determination of indinavir in human plasma and its use in pharmacokinetic study

We report the development and validation of a new sensitive, accurate and precise HPLC method with ultraviolet detection for the determination of indinavir sulfate (IND) in human plasma and its application to a bioequivalence study of a new generic formulation. The extraction of IND from plasma samples was achieved by using liquid-liquid extraction with a mean recovery of 73.9 percent. The lower limit of quantification was 0.05 µg/mL. Bioequivalence between the products was determined by calculating 90 percent confidence intervals (CI) for the ratio of Cmax, AUC0-t and AUC0-inf values for the test and reference products, within the 0.80-1.25 interval proposed by ANVISA and FDA. Therefore the medications are bioequivalent and inter-exchangeable.

Foi desenvolvido e validado um novo método, sensível, exato e preciso por Cromatografia a Líquido de Alta Eficiência com detecção em UV para a determinação do sulfato de indinavir (IND) em plasma humano. O fármaco foi extraído do plasma através de extração líquido-líquido obtendo recuperação média de 73.9 por cento, com limite inferior de quantificação de 0.05 µg/mL. O método foi aplicado em estudo de farmacocinética para verificar a bioequivalência entre um novo medicamento genérico e seu produto de referência. A bioequivalência entre os produtos foi determinada calculando-se um intervalo de confiança (IC) de 90 por cento para a razão das médias do produto teste e referência compreendidas entre o intervalo de 0.80-1.25 proposto pela ANVISA e O FDA. Os produtos estudados são bioequivalentes e, portanto, intercambiáveis.

Desarrollo y Estabilidad de Sulfato de Indinavil en una formulación Oral Pediátrica / Development and stability of indinavir sulfate in a pediatric oral formulation

Se estudió estabilidad del sulfato de indinavir en un liquido oral extemporáneo almacenado a 4ºC, 25ºC y 37º C. Una solución concentrada fue preparada de cápsulas disponibles en el comercio del sulfato del indinavir, y después diluida con un vehiculo adecuado, para obtener una concentración final de 20 mg/mL. El liquido fue dividido en tres envases de vidrio color caramelo de 30 ML y almacenado a 4ºC, 25ºC y 37ºC. El contenido de sulfato del indinavir de cada uno de los tres envases fue ensayado por cromatografía líquida de alta performance (HPLC). Cada muestra fue ensayada por triplicado a tiempo O y a los 1, 7, 14, 30, 45, 60 días. Las muestras, además fueron observadas visualmente y fue medido el pH. La concentración de sulfato del indinavir excedió el 95% de la concentración inicial a 4ºC por 45 días, a 25ºC por 30 días y a 37ºC por 7 días. El sulfato de indinavir, 20 mg/mL en un liquido oral extemporáneo, fue estable a 4ºC, 45 días; a 25ºC, 30 días y 7 días a 37ºC.

Cápsulas de sulfato de indinavir: desenvolvimento farmacotécnico-industrial, desenvolvimento do método de dissolução e avaliação / Indinavir sulfate capsules: pharmaceutics-technical-industrial and dissolution method development and evaluation

O sulfato de indinavir é um inibidor da protease no ciclo do vírus da imunodeficiência humana (HIV). O objetivo deste trabalho foi o desenvolvimento da formulação, desenvolvimento e avaliação da metodologia para dissolução, estudo micromerítico, transposição de escala industrial, estudo de estabilidade e estudo comparativo para cápsulas de sulfato de indinavir 500 mg (equivalente a 400 mg de indinavir). Para o desenvolvimento farmacotécnico, realizou-se uma planificação qualitativa de diluentes. As metodologias analíticas para peso médio, desintegração, umidade e uniformidade de peso, seguiram The United States Pharmacopeia 28, enquanto que a metodologia utilizada para dissolução foi desenvolvida e avaliada atendendo à Resolução RE nº 899, de 29 de maio de 2003, da Agência Nacional de Vigilância Sanitária (ANVISA). Os resultados demonstraram que a formulação selecionada correspondeu às especificações de controle físico-químico, além de apresentar viabilidade econômica. Os resultados obtidos com o desenvolvimento e avaliação do método para dissolução mostram que o método atende aos requisitos de Boas Práticas de Fabricação e Controle, pois apresentam a reprodutibilidade, a precisão, a robustez e finalmente a confiabilidade requerida para um método analítico. As cápsulas desenvolvidas de sulfato de indinavir, quando comparadas com o medicamento de referência, são equivalentes entre si, frente a diferentes parâmetros avaliados.

Indinavir sulfate is a protease inhibitor in the cycle of the human immunodeficiency virus (HIV). The purpose of this study was the development of formulation, and its evaluation methodology for dissolution, rheological study, scale transposition, stability study and comparative study for indinavir sulfate 500 mg capsules (equivalent to 400 mg of indinavir). A qualitative design of diluents has been performed for the pharmaceutics development. The analytical methodologies for medium weight, disintegration, humidity and uniformity of weight followed The United States Pharmacopeia 28, while the methodology used for dissolution was developed and evaluated in accordance with Resolution RE nº 899, as of May 29, 2003, issued by the Agência Nacional de Vigilância Sanitária [National Agency for Sanitary Surveillance] (ANVISA). The results have evidenced that the selected formulation corresponds to the specifications of physical-chemical control, besides showing its economic feasibility. The results obtained from the development and evaluation of dissolution method have evidenced that the method complies with the requirements of Good Manufacturing and Control Practices, since it shows the reproducibility, the precision, the robustness and finally the reliability required for an analytical method. The developed indinavir sulfate capsules, when compared with the reference drug, are equivalent, in the light of different evaluated parameters.

High prevalence of indinavir-associated renal complications in Thai HIV-infected patients.

BACKGROUND: Indinavir (IDV) is the protease inhibitor (PI) used most often in resource-limited countries. The present study aimed to determine the prevalence of IDV-associated renal complications as well as their clinical characteristics. MATERIAL AND METHOD: The authors reviewed all patients participating in cohorts of indinavir-containing regimens at the HIV-NAT research center during the period of indinavir treatment. Patients who had pre-existing renal diseases were excluded. Renal toxicities included presence of urologic symptoms, nephrolithiasis, abnormal urine sediments, crystalluria and loss of renal function. Radiological studies of KUB system were reviewed as well. RESULTS: Two-hundred and four patients treated with IDV were included. Median (IQR) follow up period was 216 (150-312) weeks. One hundred and eighty patients were treated with ritonavir-boosted regimens at some point, and 24 patients were treated only with unboosted regimens. Leukocyturia (51.9%) was the most common finding of IDV-associated renal complications. Thirty-five percent of patients had urologic symptoms such as flank pain or dysuria. Almost half of the patients had significant loss of renal function that was associated with prolonged use of IDV The most common radiological finding was nephrolithiasis. Less common, but of greater clinical importance, are nephrocalcinosis or renal atrophy. CONCLUSION: A high prevalence of IRC was found in Thai HIV-infected patients. As long as no other cost-effective boosted PI regimens are available, strategies to prevent irreversible loss of renal function are warranted.

Urinary NO3 excretion and renal failure in indinavir-treated patients

Treatment with indinavir (IDV), a protease inhibitor, is frequently associated with renal abnormalities. We determined the incidence of renal failure (creatinine clearance <80 mL min-1 1.73 (m²)-1) in HIV patients treated with highly active antiretroviral therapy, including IDV, and investigated the possible mechanisms and risk factors of IDV nephrotoxicity. Thirty-six patients receiving IDV were followed for 3 years. All were assessed for age, body weight, duration of infection, duration of IDV treatment, sulfur-derivative use, total cholesterol, triglycerides, magnesium, sodium, potassium, creatinine, and urinalysis. We also determined renal function in terms of creatinine clearance, urine osmolality and fractional excretion of sodium, potassium, and water. Urinary nitrate (NO3) excretion was measured in 18 IDV-treated patients and compared with that of 8 patients treated with efavirenz, a drug without renal side effects. Sterile leukocyturia occurred in 80.5 percent of the IDV-treated patients. Creatinine clearance <80 mL min-1 1.73 (m²)-1 was observed in 22 patients (61 percent) and was associated with low body weight and the use of sulfur-derivatives. These patients also had lower osmolality, lower urine volume and a higher fractional excretion of water compared to the normal renal function group. Urinary NO3 excretion was significantly lower in IDV-treated patients (809 ± 181 æM NO3-/mg creatinine) than in efavirenz-treated patients (2247 ± 648 æM NO3-/mg creatinine, P < 0.01). The lower NO3 excretion suggests that IDV decreases nitric oxide production.

Quality of antiretroviral drugs, stavudine and indinavir capsules available in the Tanzanian market

Background: The number of antiretroviral drugs (ARVs) available to HIV/AIDS patients in Tanzania is increasing due to a number of intervention programs such as PEPFAR and the Clinton Foundation. These ARVs are imported from a number of countries. However; currently there are no reports on the quality of these medicines imported into Tanzania.The sale of substandard and counterfeit drugs has been well documented particularly in developing countries. The marketing of counterfeit and substandard antiretroviral drugs has also been widely reported in Africa. It is therefore important to closely monitor the quality of ARVs marketed in Tanzania to ensure that substandard or fake products are uncovered before great harm is done to public health.Objective: To assess the quality of ARVs marketed in Tanzania.Methodology: A total of five samples of two generic drugs (stavudine and indinavir) from different manufacturers were randomly collected from various retail pharmacies.Assessment of package inserts and labels was carried out using the Tanzania Food and Drugs Authority (TFDA) specifications. The capsules were analyzed for the content of the active components using validated in-house methodsResults: All samples of Indinavir and Stavudine investigated conformed to the packaging and labeling specifications. However; all Indinavir samples were found to contain excess amount of active ingredient (112.6- 118) compared to the official limit of 95 - 105. One sample of stavudine capsules failed the dissolution test; releasing only 56instead of the specified 80of the active ingredient. Conclusion: The results of this study emphasize the need for careful monitoring of the quality of drugs to ensure their safety and efficacy

Monitoreo terapéutico de indinavir en niños con infección HIV / Therapeutic monitoring of indinavir in children with HIV infection

El objetivo de este trabajo es realizar una evaluación de los resultados del monitoreo terapéutico (MT) de las concentraciones plasmáticas (Cp) de Indinavir, realizados durante la práctica clínica, en pacientes pediátricos que reciben TARV en esquemas que contienen Indinavir más Ritonavir. Métodos: fueron incluidos 13 pacientes en seguimiento ambulatorio en el Hospital de Pediatría Juan P. Garrahan, a los que se le realizaron dos determinaciones de Cp de Indinavir. Un valle y un pico (una hora posterior a la dosis). La dosis estimada que reciben los pacientes de 250 mg/m2/ 12 Hs. Resultados: ocho de los trece pacientes presentaron niveles subterapéuticos, de los cuales dos tuvieron niveles no detectables (mediana: o,73 ug/ml). El rango terapéutico propuesto por el Indinavir está entre 0,150 y 10 ug/mL. aunque estos valores fueron difinidos para la población adulta. Uno de los pacientes presentó niveles superiores a dicho rango (14,6 ug/ml). Conclusión: trabajos previos sugieren un régimen de 400 mg/m2 Indinavir más 125 mg/m2 Ritonavir cada 12 horas. Debido a que datos previos de pacientes de nuestro hospital habían mostrado que pautas similares podían resultar en niveles plasmáticos elevados asociados a manifestaciones tóxicas, la pauta inicial utilizada fue de 250 mg/m2 Indinavir más 100 mg/m2 Ritonavir cada doce horas. El MT de Indinavir mostró sin embargo que la administración de esta pauta resultó en niveles subterapéuticos. Aun cuando el Indinavir se asocia al Ritonavir la alta variabilidad observada en los niveles plasmáticos de Indinavir sugieren la necesidad de monitorizarlo.

Ação crônica do indinavir durante a prenhez da rata albina(rattus norvegicus albinus, Rodentia, Mammalia): aspectos microscópicos e bioquímicos / Effects of indinavir on albino rat pregnancy: microscopical and biochemical aspects

Introdução: o uso de anti-retrovirais, dentre eles o indinavir, por mulheres em idade reprodutiva, incluindo grávidas, tornou-se necessário para prevenir a transmissão vertical do HIV. Objetivo: avaliar a ação crônica do indinavir durante toda prenhez da rata albina através de estudo histopatológico dos fígados e rins maternos e fetais e avaliação materna de provas de funções hepática e renal. Métodos: utilizamos 40 ratas albinas da colônia EPM - 1 Wistar, prenhes com aproximadamente 200g. A partir do dia zero da prenhez os animais foram divididos em 4 grupos, numericamente iguais: grupo controle (Contr), sem qualquer manuseio; grupos Exper1, Exper2 e Exper3 que receberam respectivamente as doses de 9,27, 81mg/kg/dia de indinavir, diluídas em 1 ml de água destilada (veículo utilizado), todas por gavagem, durante toda a prenhez. No 20° dia foram, anestesiadas, realizada uma incisão externo-púbica, expostos coração, fígado e rins maternos, colhidos sangue do coração para as dosagens de alanina aminotransferase - AL T, aspartato aminotransferase - AST, creatinina e uréia. A seguir, retirados fragmentos de fígados e rins maternos e fetais, para estudo histopatológico através de microscopia óptica. A análise estatística foi realizada pelo teste de Kruskal-Wallis e pelo teste de comparações múltiplas de Dunn. Resultados: microscopia óptica dos fígados maternos de Exper3 apresentaram hepatócitos com citoplasma eosinófilo, núcleos pequenos e vasodilatação. Rins maternos de Exper2 apresentaram alguns túbulos contorcidos com áreas eosinófilas e núcleos hipercromáticos além de vasodilatação. No grupo Exper3 foram semelhantes, porém mais intensas. Órgãos fetais sem alterações. A AL T mostrou no teste de comparações múltiplas que o grupo Exper2 apresentou valores de AL T significantemente maiores do que os outros grupos (p < 0,001). Creatinina valores menores nos grupos Exper2 e Exper3 do que no Exper1 (p = 0,012). Uréía o grupo Exper3 apresentou valores significantemente menores do que os outros grupos (p = 0,003). As alterações nas dosagens são muito leves e não expressam significância biológica. Conclusão: o indinavir foi bem tolerado nas doses terapêuticas e nas doses mais elevadas discretas alterações morfológicas ocorreram nas matrizes, porém sem expressão funcional que levasse a efeitos deletérios sobre o binônio materno-fetal.

Fármacos antirretrovirales (2º parte) / Antiretroviral medicine (Part Two)

En esta segunda parte se presentan los fármacos antirretrovirales incluidos en el grupo de los inhibidores NO Nucleósidos de la Transcriptasa Inversa y los inhibidores de Proteasa

Nefrolitíase associada ao uso de indinavir: relato de caso / Nephrolithiasis triggered by indinavir use: case report

O sulfato de indinavir, em associação com inibidofores d transcripfase reversa, promove, de forma efetiva, aumento da contagem de células CD4+ e redução da carga viral (ARN-VIH) em pacientes com sindrome de imunodeficiência adquirida. Esse inibidor da protease provoca nefrolitiase em até 34,4% dos pacientes. Em decorrência do uso ainda freqüente deste antiretroviral, seus efeitos adversos devem ser prontamente reconhecidos e prevenidos, quando possível. Este trabalho descreve a associação de litíase urinária com manifestações clínicas exuberantes com o uso de indinavir.

A case of nephrolithiasis related to the use of indinavir sulfate is described. This drug, in association with reverse transcriptase inhibitors, effectively promotes a rise in the CD4+ T cell count and a decrease in the levels of HIV RNA in AIDS patients. This protease inhibitor elicits the development of nephrolithiasis in up to 34.4% of patients. Since indinavir sulfate is a frequently prescribed drug, its side effects should be well known and avoided whencver possibie.