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.

Sleep Respiratory Disorders and Clinical Profile in Patients with Type 2 Diabetes Mellitus

Introduction Sleep respiratory disorders (SRDs) are often found in patients with type 2 diabetes mellitus (T2DM). Objective The aim was to establish the prevalence of risk to develop an SRD using the Clinical Berlin Questionnaire (CBQ) and Epworth Sleepiness Scale (ESS) in patients with T2DM and verifying the correlation of anthropometric measurements and life quality (LQ) with ESS. Methods A descriptive and analytical study of a case series evaluating 208 patients with T2DM, submitted to clinical and biochemical evaluation and implementation of CBQ, ESS, and WHOQOL-bref to evaluate LQ. Results Mean age was 60.8 8.8 years, and 65.4% were women. Most diabetics were overweight (36.1%), and 29.8% were class I obese. One-third had positive risk signals for a SRD, with 87.0 and 34.1% having high risk in CBQ and sleep disorders in ESS, respectively. There was a significant difference in the general LQ between the low- and high-risk groups in the CBQ. Conclusion In this scenario, it is noteworthy that the active search for sleep disorders must start from simple methods, such as application of protocols. .

Antirretroviral zidovudina para uso no tratamento de leucemia/linfoma de células T associado ao HTLV-1 / Antiretroviral zidovudine for use in the treatment of HTLV-1 associated T cell leukemia / lymphoma

INTRODUÇÃO: O HTLV é um retrovírus descoberto em 1981 que possui as mesmas vias de transmissão do HIV e apresenta prevalência variada mundialmente. No Brasil estudos com gestantes e doadores em bancos de sangue refletem uma baixa prevalência do HTLV, segundo própria classificação do vírus em termos de prevalência, na população (entre 0,1-1%). Dos pacientes infectados pelo vírus, 90% permanecerão assintomáticos por toda vida. Em relação à leucemia/linfoma associada aos portadores de HTLV as taxas variam entre 1 a 5%. A medicação AZT encontra-se incorporada no SUS para uso terapêutico de Pessoas vivendo com HIV/Aids (PVHA), a indicação do uso desse medicamento para pacientes acometidos pela leucemia/linfoma associado ao HTLV não está contemplada no SUS. No entanto é constatada demanda de todas as partes do Brasil no que se refere à liberação do AZT para esse fim. Anteriormente não constavam trabalhos científicos que dessem embasamento para o uso do AZT no tratamento da leucemia/linfoma associado ao HTLV. Realizava-se a solicitação da liberação do AZT diretamente para o Ministério da Saúde e a liberação era realizada em formato de parecer individualizado. A leucemia/linfoma associada ao HTLV-1 é um evento raro e de prognóstico reservado, porém no momento atual trabalhos relacionados ao tema mostram que terapia antiviral com zidovudina e alfainterferona é eficaz na forma leucêmica da doença, com aumento significativo na sobrevida livre de progressão quando comparado ao uso da quimioterapia. A forma linfomatosa se beneficia do uso associado da quimioterapia com os antivirais. A demanda para utilização do AZT como tratamento para leucemia/linfoma associada ao HTLV- 1 é baixa, já que o acometimento da doença citada é um evento raro. EVIDÊNCIAS CIENTÍFICAS: Os trabalhos científicos selecionados para dar subsídio à solicitação da incorporação do medicamento AZT para tratamento de leucemia/linfoma associado ao HTLV-1 demonstraram aumento importante na sobrevida dos indivíduos tratados com antirretroviral exclusivamente ou associado à quimioterapia nos casos linfomatosos quando comparados ao tratamento apenas com quimioterapia, mostrando ser essa terapêutica eficaz para todas as formas de leucemias/linfomas associados ao HTLV-1. Em relação à segurança, os trabalhos avaliaram como sendo seguro o uso de AZT para a população em questão. Os estudos selecionados incluem série de casos, estudos retrospectivos e prospectivos. Abaixo segue tabela 1 com referências principais sobre o uso do AZT para tratamento de leucemia/linfoma associado ao HTLV-1. CONCLUSÃO: A solicitação da incorporação da zidovudina para uso no tratamento de leucemia/linfoma associado ao HTLV-1 tem como base trabalhos que demostram diferença no prognóstico dos pacientes que fizeram uso da zidovudina. Na prática clínica a utilização do AZT, nesses casos, encontra barreira burocrática na liberação da medicação pela incompatibilidade entre a indicação e o registro. Nos últimos anos os trabalhos relacionados ao tema surgiram e dão sustentação para a solicitação da incorporação em questão. Com o intuito de atualizar e sincronizar Ministério da Saúde e a prática clínica baseada em evidência, a Secretaria de Vigilância em Saúde (SVS/MS) solicitou a avaliação da incorporação do AZT para esta condição pela CONITEC. Mesmo sendo a leucemia/linfoma associada ao HTLV-1 um evento menos frequente na população, existem brasileiros em tratamento para essa patologia e que, para os quais, a liberação do AZT traz mudança nos seus prognósticos. DELIBERAÇÃO FINAL: Os membros da CONITEC presentes na reunião do plenário do dia 05/08/2015 deliberaram, por unanimidade, recomendar a incorporação do antirretroviral zidovudina para uso no tratamento de leucemia/linfoma de células T associado ao HTLV- 1 conforme Protocolo Clínico e Diretrizes Terapêuticas do Ministério da Saúde. Foi assinado o Registro de Deliberação nº 135/2015. DECISÃO: Portaria nº 50, de 29 de setembro de 2015 - Torna pública a decisão de incorporar no âmbito do Sistema Único de Saúde-SUS o antirretroviral zidovudina para uso no tratamento de leucemia/linfoma de células T associado ao HTLV-1, conforme Protocolo do Ministério da Saúde.

Resultados de una intervencion de farmacovigilancia en pacientes con VIH/SIDA tratados con estavudina / Pharmacosurveillance regarding Colombian patients beingtreated with stavudine

Objetivos Dado que la estavudina se ha asociado a toxicidad acumulativa e irreversible, se pretendió reducir la aparición de resultados negativos asociados al uso de estavudina mediante la notificación del riesgo a diferentes responsables de la atención sanitaria de pacientes con VIH/SIDA en Colombia. Métodos A partir de la base de datos de dispensación de medicamentos de Audifarma S.A a unos 4,5 millones de personas, se identificaron todos los usuarios de estavudina, se notificó el riesgo a los prestadores del servicio de salud y se recomendó la sustitución por zidovudina o tenofovir. Resultados En 2010 se identificaron 1 410 pacientes en tratamiento antirretroviral, de los cuales 109 (7,5 %) recibían estavudina, distribuidos en 20 ciudades del país y atendidos por 19 instituciones diferentes. Tras la intervención se consiguió en 28 meses reducir su empleo en 94,6 %. El medicamento más empleado en la sustitución fue zidovudina. Discusión Se consiguió exitosamente reemplazar estavudina siguiendo las recomendaciones de la Organización Mundial de la Salud, con lo cual se puede evitar la aparición de lipodistrofia y neuropatía periférica asociada a su empleo.(AU)

Objectives Reducing the occurrence of negative stavudine use-associated outcomes by reporting such risk to doctors responsible for the care of HIV/AIDS patients in Colombia as stavudine has been associated with cumulative and irreversible toxicity. Methods All stavudine users were identified from Audifarma S.A. (drug suppliers) databases (covering about 4.5million people). The risk was then reported to health service providers and the substitution of stavudine for zidovudine or tenofovir was recommended. Results It was found that 1,410 patients registered in the afore mentioned databases were receiving antiretroviral therapy during 2010, of whom 109 (7.5 %) were receiving stavudine; these patients were living in 20 cities and being attended by 19 institutions. Stavudine use became reduced by 94.6 % during the 28 months following the intervention. Zidovudine was the most commonly used replacement drug. Discussion Stavudine was successfully replaced following World Health Organization recommendations aimed at preventing the occurrence of lipodystrophy and the peripheral neuropathy associated with its use.(AU)

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.

AZT on telomerase activity and cell proliferation in HS 839.T melanoma cells / AZT na atividade da telomerase e na proliferação de células de melanoma HS 839.T

PURPOSE: To evaluate telomerase activity and proliferation of HS839.T melanoma cells, subjected to the action of AZT. METHODS: Cells were grown in triplicate, AZT at different concentrations: 50, 100 and 200μM, was added and left for 24 and 48 hours, and its effects were compared with the control group. Telomerase activity was detected by PCR and cell proliferation was evaluated by MTT. RESULTS: After 24 hours, there was no inhibition of cell proliferation or telomerase activity when compared to the control group. After 48 hours, there was a momentary decrease, suggesting that the cell lines used in this study are sensitive to AZT, but quickly recover both the enzyme activity and cell proliferation. CONCLUSION: The action of AZT on the melanoma cells studied, at the concentrations and times tested, did not inhibit telomerase activity nor affect cell proliferation.

OBJETIVO: Avaliar a atividade da telomerase e da proliferação de células de melanoma HS839.T submetidas à ação do AZT. MÉTODOS: As células foram cultivadas, em triplicata, com diferentes concentrações de AZT: 50, 100 e 200µM, por 24h e 48h, seus efeitos comparados com o grupo controle. A atividade da telomerase foi detectada por PCR e a proliferação celular avaliada por MTT. RESULTADOS: No tempo de 24 horas, não houve inibição da proliferação celular e da atividade da telomerase em comparação com o grupo controle. No período de 48 horas, houve uma diminuição momentânea, sugerindo que as células das linhagens utilizadas neste estudo são sensíveis ao AZT, mas que recuperam a atividade enzimática e proliferativa. CONCLUSÃO: Nas células de melanoma HS839.T estudadas e nas concentrações e tempos propostos, a ação do AZT não inibiu a atividade da telomerase e não afetou a proliferação celular.

Reversed phase HPLC determination of zidovudine in rat plasma and its pharmacokinetics after a single intranasal dose administration

The development and validation of a simple and accurate method based on HPLC with ultraviolet detection for the quantification of zidovudine in rat plasma and its application to a pharmacokinetic study following a single intranasal dose zidovudine is described. Zidovudine was extracted from the plasma using a single-step deproteinization. Chromatographic separation of zidovudine from interfering components was achieved with a C-18 reverse phase column, a mobile phase consisting of a mixture of sodium acetate buffer (55mM) with pH adjusted to 7.0 and acetonitrile (91:9 v/v) and UV detection set at 265 nm. The method was linear from 100 to 10000 ng.mL"¹ (r² > 0.9995), and zidovudine had a mean recovery from plasma of 92.8 percent. The coefficient of variation of inter-day and intra-day quality control samples was less than 15 percent. After a single intranasal dose of zidovudine administered to rats, pharmacokinetic parameters (AUC0 24, Cmax, t , t1/2) were determined. The proposed method was found to be simple, specific, accurate, and precise and could be applied to the quantitative analysis of clinical pharmacokinetic studies of zidovudine in rats.

Mother-to-child transmission of HIV among women who chose not to exclusively breastfeed their infants in Pune, India.

BACKGROUND & OBJECTIVE: The percentage of HIV cases attributed to mother-to-child transmission (MTCT) has increased several fold in recent years. No reports are available on HIV MTCT rates among HIV-infected choosing not be exclusively breastfeed their infants in India. We examined HIV MTCT rates among 41 Indian women in a prospective cohort who chose predominantly not to exclusively breastfeed. METHODS: Of the 41 women, 27 (66%) received MTCT prophylaxis: 3 received short course zidovudine (AZT), 19 single-dose nevirapine (NVP), and 5 both AZT and NVP. Maternal HIV-I RNA levels (viral load) were measured at the time of delivery. Infants were tested for HIV-1 infection by PCR up to 11 times is first year of life and viral load was measured in PCR positive infants. RESULTS: All infants received single dose NVP. Thirty two (76%) infants were exclusively formula-fed, 10 (24%) were mixed fed. Four infants were diagnosed with HIV infection for an overall 12- month transmission probability of 8 per cent [95% confidence interval (CI) of 3.2 to 22.1%]. Restricting analysis to 31 women who exclusively formula-fed, only one (3.1%) transmission event occurred. The 41 HIV-infected women gave birth to 42 live-born infants. INTERPRETATION & CONCLUSION: Our data from a small cohort of HIV-infected women suggest that short-course AZT or single dose NVP are effective in reducing MTCT in an Indian setting. Larger studies are needed to assess HIV MTCT rates in India, but in this small study rates were comparable to that observed among women who chose not to exclusively breastfeed in other resource-limited settings.

Comparison of the effectiveness of initial combined antiretroviral therapy with nelfinavir or efavirenz at a university-based outpatient service in Brazil

Since there are some concerns about the effectiveness of highly active antiretroviral therapy in developing countries, we compared the initial combination antiretroviral therapy with zidovudine and lamivudine plus either nelfinavir or efavirenz at a university-based outpatient service in Brazil. This was a retrospective comparative cohort study carried out in a tertiary level hospital. A total of 194 patients receiving either nelfinavir or efavirenz were identified through our electronic database search, but only 126 patients met the inclusion criteria. Patients were included if they were older than 18 years old, naive for antiretroviral therapy, and had at least 1 follow-up visit after starting the antiretroviral regimen. Fifty-one of the included patients were receiving a nelfinavir-based regimen and 75 an efavirenz-based regimen as outpatients. Antiretroviral therapy was prescribed to all patients according to current guidelines. By intention-to-treat (missing/switch = failure), after a 12-month period, 65 percent of the patients in the efavirenz group reached a viral load <400 copies/mL compared to 41 percent of the patients in the nelfinavir group (P = 0.01). The mean CD4 cell count increase after a 12-month period was also greater in the efavirenz group (195 x 10(6) cells/L) than in the nelfinavir group (119 x 10(6) cells/L; P = 0.002). The efavirenz-based regimen was superior compared to the nelfinavir-based regimen. The low response rate in the nelfinavir group might be partially explained by the difficulty of using a regimen requiring a higher patient compliance (12 vs 3 pills a day) in a developing country.

Implementação oportuna de intervenções para reduzir a transmissão vertical do HIV: uma experiência brasileira bem-sucedida / Timely implementation of interventions to reduce vertical HIV transmission: a successful experience in Brazil

OBJETIVO: Descrever o impacto da implementação oportuna de novas condutas recomendadas por consensos clínicos nacionais dirigidos à prevenção da transmissão vertical de HIV na maternidade de um hospital universitário público no Brasil. MÉTODO: Realizou-se um estudo retrospectivo de coorte dos partos de mulheres infectadas pelo HIV atendidos na instituição de 1990 a 2000. As condutas adotadas nesse período foram: 1) até 1994, amamentação contra-indicada, sem uso de drogas anti-retrovirais; 2) de 1995 a 1996, uso de zidovudina (AZT) pela gestante e pelo recém-nascido; 3) de 1997 a 1998, uso de AZT conforme protocolo ACTG 076; e 4) de 1999 a 2000, terapia anti-retroviral múltipla e cesárea eletiva. Em todos os períodos, a distribuição das drogas foi gratuita. Foram calculadas as taxas de transmissão nas quatro fases e as razões de risco de transmissão congênita para as fases e para cada intervenção profilática (amamentação, tipo de terapia anti-retroviral, tipo de parto). RESULTADOS: Foram estudadas 197 gestações. Houve redução na transmissão vertical da primeira para a quarta fase, de 32,3 para 25,7, 2,2 e 2,9 por cento. A maior queda, observada na terceira fase, ocorreu após a introdução do esquema completo do ACTG 076. O uso de terapia anti-retroviral combinada aumentou de 0 por cento na primeira fase para 46,4 por cento na quarta fase. Não houve nenhum caso de transmissão vertical nas gestantes tratadas com múltiplas drogas. O risco de transmissão vertical foi 5 vezes maior com amamentação do que sem amamentação (razão de risco = 5,06), 5 vezes maior sem terapia anti-retroviral contra uso do esquema ACTG completo (razão de risco = 5,29) e 4 vezes maior para parto com fórcipe contra cesárea eletiva (razão de risco = 4,13). CONCLUSÃO: A adoção oportuna de intervenções atualizadas, recomendadas por consenso nacional de especialistas, com provisão gratuita de drogas, mostrou-se eficiente para reduzir a transmissão congênita do HIV.

OBJECTIVE: To describe the impact, at the public maternity facility of a university hospital in Brazil, of the rapid implementation of new guidelines recommended by national consensus panels concerning the prevention of vertical HIV transmission. METHOD: We performed a retrospective study of deliveries by HIV-infected women at the public maternity facility of a university hospital in the city of Campinas, São Paulo, Brazil, from 1990 through 2000. The guidelines utilized at the facility during this period were: (1) from 1990 through 1994, contraindication to breast-feeding and no use of antiretroviral drugs; (2) 1995 and 1996, use of zidovudine (AZT) by the pregnant woman and the newborn; (3) 1997 and 1998, use of AZT according to the ACTG 076 protocol; and (4) 1999 and 2000, multiple antiretroviral agents and elective cesarean delivery. All the antiretroviral drugs were provided for free by Brazil's public health care system. The vertical transmission rate was calculated for each of the four stages, and the risk ratio for congenital transmission was calculated for each stage and for each prophylactic intervention separately (breast-feeding, type of antiretroviral drug, type of delivery). RESULTS: We studied 197 deliveries at the public maternity facility over that 1990-2000 period. Over the four stages, the rate of vertical transmission decreased: it was 32.3 percent in the first stage, 25.7 percent in the second, 2.2 percent in the third, and 2.9 percent in the fourth. The most pronounced decrease, observed from the second to the third stage, occurred after introduction of the full ACTG 076 regimen. The use of combined antiretroviral agents increased from 0 percent in the first stage to 46.4 percent in the fourth stage. There were no cases of vertical transmission in pregnant women treated with multiple drugs. The risk of vertical HIV transmission was 5 times as great with breast-feeding vs. no breast-feeding (risk ratio = 5.06), 5 times...

Evaluation of the bioequivalence of zidovudine 100 mg capsules in healthy Thai male volunteers.

OBJECTIVE: The bioequivalence study of two oral formulations of zidovudine were evaluated; Antivir (Government Pharmaceutical Organization (GPO), Thailand) as the test formulation and Retrovir (Glaxo-SmithKline, USA), as the reference formulation. MATERIAL AND METHOD: The two products were orally administered as a single dose of 100 mg zidovudine three capsules according to a randomized two-way crossover design to 28 healthy fasted Thai male volunteers. The washout period between treatments was 1 week. After drug administration, serial blood samples were collected at a specific time interval from 0-10 hours. The plasma zidovudine concentrations were determined via HPLC technique. Individual plasma zidovudine concentration-time profile was analyzed for relevant pharmacokinetic parameters; the comparative bioavailability of the two products was determined by the analysis of variance (ANOVA) for two way crossover design, using logarithmic transformed data. RESULTS: The results found that the mean peak (X+/- SD) plasma concentration (Cmax) of Antivir was 3.34 +/- 0.15 ng/mL and of Retrovir was 3.32 +/- 0.21 ng/mL. The 90% confidence interval (CI) for the difference of mean Cmax was 90.76-120.81%. The time to peak plasma concentration (Tmax) of Antivir was 0.49 +/- 0.16 hours and for Retrovir was 0.62 +/- 0.35 hours with a difference time to peak of 20.96%. The half life (t1/2) of Antivir was 1.16 +/- 0.28 hours and t1/2 of Retrovir was 1.05 +/- 0.25 hours. The mean area under the curve (AUC0-->t) of Antivir was 3.34 +/- 0.12 ng.hr/mL and of Retrovir was 3.35 +/- 0.15 ng.hr/mL. The 90%CI for the difference ofmean AUC0-->t was 91.83-103.99%. The mean AUC0-->infinity of Antivir was 3.37 +/- 0.12 nghr/mL and for and Retrovir was 3.38 +/- 0.14 ng.hr/mL. The 90%CI for the difference of mean AUC0-->infinity was 91.22-104.69%. CONCLUSION: The present study revealed that the 90%CI for the difference of Cmax AUC0-->t and AUC0-->infinity means were in the criteria ofacceptance, which should be within 80-125%. Thus, the present study demonstrated the bioequivalence of the test drug (Antivir) and the reference drug (Retrovir).

Efficacy and safety of zidovudine and zalcitabine combined with a combination of herbs in the treatment of HIV-infected Thai patients.

A randomized double blind placebo controlled trial to determine the efficacy and safety of combined-herbs (SH) given with zidovudine (ZDV) and zalcitabine (ddC) for the treatment of HIV infection in Thai adults was conducted in 3 hospitals in northern Thailand during 2002 to 2003. The eligible subjects were HIV-infected Thai adults who had never received anti-retrovirals, had a Karnofski Performance Score (KPS) of > or = 70, and had no opportunistic infections. The subjects were randomized to receive either a combination of ZDV 200 mg three times per day, ddC 0.75 mg three times per day, and SH 2.5 g three times per day or a combination of ZDV 200 mg three times per day, ddC 0.75 mg three times per day, and placebo 2.5 g three times per day for 24 weeks. The main outcome measures were HIV-RNA, CD4 cells, and blood chemistry profiles prior to the treatment and then every 4 weeks for 24 weeks. The baseline characteristics of 60 evaluable subjects, 40 in the SH group and 20 in the placebo group, were not significantly different. HIV RNA at week 4 and thereafter was significantly decreased from the baseline value in both groups (p<0.001). However, the decline in HIV RNA in the SH group was significantly more than that in the placebo group. The CD4 cells in the SH group at week 12 and thereafter were significantly increased from the baseline value. Serious adverse events in the two groups were not observed. It is concluded that an addition of SH herbs to two nucleoside reverse transcriptase inhibitors has greater antiviral activity than antiretrovirals only. The SH herbs may be an alternative for the third anti-retroviral agent in the triple drug regimen for the treatment of HIV infected patients in countries with limited resources.

HIV seroprevalence, uptake of interventions to reduce mother-to-child transmission and birth outcomes in greater Kingston, Jamaica

BACKGROUND: The seroprevalence of HIV among pregnant women in the Caribbean is 2-3 and increasing. The Kingston Paediatric and Perinatal HIV Programme is developing and implementing a unified programme to eliminate mother-to-child transmission (MTCT) of HIV in Kingston, Jamaica. METHODS: Pregnant women presenting to Kingston Metropolitan Antenatal Clinics, Victoria Jubilee Hospital, Spanish Town Hospital and the University Hospital of the West Indies had HIV serology performed by ELISA, or by the new Determine Rapid Test after receiving group counselling. HIV-positive women were referred to High Risk Antenatal Clinics. Antiretroviral prophylaxis with zidovudine (AZT), or nevirapine was given. Care was administered using a standard protocol by a multi-disciplinary team of public and academic healthcare personnel. RESULTS: In year one, 19,414 women delivered Among 14,054 women who started antenatal care for this period, 5,558 (40) received group counselling and 7,383 (53) received HIV-testing. During the fourth quarter of follow-up, these comparative rates were 66 (2049/3 118) and 72 (2260/3118) respectively. HIV seroprevalence overall was 2.1 (152/7 383). One hundred and seven HIV+ women at varying gestational ages were identified in the programme, 72 had so far received AZT and nine nevirapine (76). 0f 84 deliveries, birth outcomes were 75 live births (89), six neonatal deaths and four maternal deaths (all from HIV/AIDS). Major challenges include repeat pregnancies of 36 despite prior knowledge of HIV seropositivity and poor partner notification with only 30 (32) having a HIV-test. Although rates of HIV testing in pregnant women in Greater Kingston are increasing, rates of testing overall remain sub-optimal. On the labour ward, there was sub-optimal identification of the HIV+ pregnant woman and administration of AZT chemoprophylaxis, along with issues of patient confidentiality and stigma. CONCLUSION: This programme needs strengthening in order to reduce maternal-fetal transmission of HIV in Greater Kingston, Jamaica [quot]pMTCT-PLUS, or comprehensive family-centred care, is the next step[quot]

The efficacy of combined zidovudine and lamivudine compared with that of combined zidovudine, lamivudine and nelfinavir in asymptomatic and early symptomatic HIV-infected children.

In this 6-month prospective study, we compared the efficacy of two treatment regimens: double-drug therapy with zidovudine (ZDV) and lamivudine (3TC) and triple-drug therapy with ZDV plus 3TC plus nelfinavir (NFV), in the treatment of asymptomatic and early symptomatic HIV-infected children. Twenty-five children were enrolled in this study and were divided into 2 groups: group A, consisting of 13 children who were given ZDV+3TC; group B, consisting of 12 children who were given ZDV+3TC+NFV. Serial determinations of weight, CD4-cell count, HIV RNA or plasma viral load (VL) and complete blood counts (CBC), liver function tests (LFT), blood urea nitrogen (BUN) tests, creatinine and serum amylase tests were performed at study entry and at 1, 3 and 6 months. The side-effects of drugs were recorded. Over the 6-month period, the median weight increase in group B (24%) was higher than in group A (2%). The median CD4-cell count increase from baseline in group B (94.5%) was better than in group A (9.4%). The reduction of VL below baseline in group B (1.2 log10; 20.8%) was also better than in group A (0.72 log10; 13.8%). However, these differences were not statistically significant (p>0.05). Both combination regimens could not completely suppress HIV RNA below detectable limits (<400 copies/ml). Both groups tolerated the regimens well; no side-effects or toxicities occurred. The efficacy levels of triple-drug therapy (ZDV+3TC+NFV) and double-drug therapy (ZDV+3TC) were not different. There were no side-effects and no deaths during the 6-month study period.

A randomized, open-label, comparative trial of BID and TID dosing of saquinavir enhanced oral formulation as part of a triple therapy for advanced AIDS patients.

OBJECTIVE: To compare the efficacy and safety of 1,400 mg BID and 1,200 mg TID of saquinavir soft gel given with zidovudine and lamivudine in antiretroviral-naïve, advanced AIDS patients. METHOD: A randomized, open-label study conducted at a university hospital. RESULTS: Forty cases were enrolled in the study, 20 cases in each group. The mean CD4 cell count was 29 cells/mm3. The mean log10 HIV-1 RNA was 5.27 copies/mL. Using an on-treatment analysis, the reduction in plasma log10HIV-1 RNA of BID and TID groups was not statistically significant at -2.44 vs -2.60 copies/mL (-0.16, 95% CI -0.63 to 0.30; p= 0.48). The mean increase in CD4 cell counts was not statistically significant at +144 and +159 cells/mm3 (11, 95% CI -75 to 97; p=0.79). CONCLUSION: The preliminary data suggests that in antiretroviral-naïve, advanced AIDS patients, 1,400 mg BID of saquinavir soft gel given with two nucleoside analogues might be as effective as the standard 1,200 mg TID.

Intrapartum and neonatal zidovudine treatment in reduction of perinatal HIV-1 transmission in Bangkok.

OBJECTIVE: To evaluate the efficacy of zidovudine (ZDV) administered during labor and to the infants in the first 6 weeks of life in reduction of perinatal HIV-1 transmission. DESIGN: Open label clinical trial. SITE: King Chulalongkorn Memorial Hospital, Bangkok, Thailand. MATERIAL AND METHOD: One hundred asymptomatic, antiretroviral naive HIV-1 infected pregnant women who had either late or no prenatal care were recruited from the obstetric service of King Chulalongkorn Memorial Hospital, Bangkok, Thailand. They were given ZDV 300 mg orally every 3 hours during the intrapartum period until delivery. ZDV syrup 2 mg/kg orally every 6 hours were given to the infants immediately after birth for 6 weeks. Breast feeding was not allowed. Infant's blood for HIV-1 PCR test was obtained at age 1 day, and 1, 3 and 6 months. HIV-antibody test was determined at age 18 months. Infants with at least one positive HIV-1 PCR test performed at or after 1 month of age or positive HIV-antibody test at age 18 months were classified as HIV-1 infected infants. RESULTS: There were 100 healthy infants delivered without complication. Fourteen infants were excluded due to; 13 lost to follow-up and 1 drug intolerance. Of the remaining 86 infants who were followed-up, 27 infants (31.4%) did not receive intrapartum ZDV treatment and 9 infants were HIV-1 infected. The perinatal transmission rate was 10.5 per cent, (95% CI 3.9, 17.1). CONCLUSION: The result of this study suggests that intrapartum oral ZDV treatment in asymptomatic HIV-1 infected mothers together with ZDV treatment in the neonates for 6 weeks can reduce the rate of perinatal HIV-1 transmission. This regimen may be an alternative treatment for prevention of HIV-1 infection in infants born to HIV-1 seropositive mothers who have had either late or no prenatal care.

Short course zidovudine maternal treatment in HIV-1 vertical transmission: randomized controlled multicenter trial.

A multicenter randomized, double blind, placebo-controlled clinical trial was conducted to evaluate the effectiveness of a short course of oral zidovudine (ZDV) treatment in HIV-1 infected pregnant women, starting at 38 weeks of gestation plus ZDV infusion during labor until delivery, to reduce HIV-1 vertical transmission in non-breast fed infants. One hundred and eighty two asymptomatic antiretroviral naïve HIV-1 infected pregnant women were enrolled. Each patient was randomly allocated into either the ZDV or placebo group. The ZDV group received 250 mg ZDV orally twice a day initiated at 38 weeks' gestation until the onset of labor. During the intrapartum period, ZDV infusion at the rate of 2 mg/kg was administered within the first hour and then continuously infused at the rate of 1 mg/kg/h until delivery. The placebo group received an identical capsule during pregnancy and normal saline infusion during labor until delivery. HIV-1 transmission was documented by nested polymerase chain reaction in infants at birth and at 1, 3 and, 6 months of age. The estimated HIV-1 vertical transmission rate was 14.9 per cent (95% CI = 11.1 to 18.7) and 16.3 per cent (95% CI = 12.3 to 20.9) in ZDV and placebo group, respectively (p > 0.05). The short course ZDV in antiretroviral naïve pregnant women initiated at 38 weeks' gestation plus intrapartum ZDV infusion without treatment in the infants was not effective to prevent HIV-1 vertical transmission.

Evaluación de la quimioprofilaxis con zidovudine a la mujer embarazada VIH+ y su hijo / Evaluation of chemoprophylaxis with zidovudine in HIV+ women and their children

En 1994 se publicaron los resultados del protocolo ACTG076 sobre quimioprofilaxis(QP)con Zidovudine(AZT)para la transmisión vertical del VIH,el grupo de madres que recibió QP con AZT tuvo un porcentaje de transmisión de 8,4 por ciento,comparado con el 24,2 por ciento de los que recibían placebo.El objetivo del presente trabajo fue evaluar la QP con AZT y los resultados obtenidos.Conclusiones.A partir de 1995 el número de binomios madre-hijo que recibieron QP con AZT ha ido en aumento progresivo,conn un impacto favorable al disminuir el número de niños infectados.La campaña de prevención de la transmisión vertical del VHI en Uruguay demostró resultados importantes.Una adecuada relación costo-beneficio y la disminución del número de niños infectados,debe ser la meta para el 100 por ciento de los binomios madre-hijo

Alcances y limitaciones de los inhibidores no nucleósidos de la transcriptasa inversa del HIV: una revisión / Scopes and limitations of nonnucleoside inhibitors of the reversed transcriptase of HIV: revission

Los inhibidores no nucleósidos de la transcriptasa inversa (INTI) son drogas potentes para el tratamiento de la infección por el virus de la inmunodeficiencia humana (HIV). Los compuestos aprobados por la FDA hasta la fecha son Nevirapina (NVP), Delavirdina (DLV) y Efavirenz (EFV). Múltiples estudios demostraron la eficacia de estas drogas para reducir la carga viral (CV) y aumentar el recuento de linfocito CD4+(RCD4), pero ninguno demostró todavía beneficio clínico. Las principales ventajas de su uso son la simple posología y buena tolerancia. Los efectos adversos más importante son el rash, de características e intensidad variables y las alteraciones neurológicas producidas por EFV. Algunas limitaciones que presentan son la interacción farmacológicas con las rifamicinas (que limitan las opciones para las pacientes coinfectados con Mycobacterium Tuberculosis) y el rápido desarrollo de resistencia por parte del HIV a todas las drogas del grupo. La indicación del tratamiento antirretroviral a un paciente infectado con el virus de la inmunodeficiencias humana (HIV) es un momento único y complejo para el paciente y para el médico. El primero pone su esperanza en el tratamiento, mientras que el médico, debe evaluar muchos aspectos además de la efectividad potencial del esquema a indicar. En la práctica médica diaria, el paciente juega un rol fundamental en la elección del esquema farmacológico pues introduce un elemento no siempre considerado por el médico: es él quien tendrá que tomar los fármacos, quien se beneficiará de los resultados biológicos pero también quien deberá afrontar los efectos adversos (EA). Teniendo en cuenta lo anteriormente dicho, los INNTI debieran ser consideradas como tratamiento de primera linea para los pacientes infectados con HIV