In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System.

Long-acting drug delivery systems are promising platforms to improve patient adherence to medication by delivering drugs over sustained periods and removing the need for patients to comply with oral regimens. This research paper provides a proof-of-concept for the development of a new optimized in situ forming injectable depot based on a tetrabenzylamine-tetraglycine-d-lysine-O-phospho-d-tyrosine peptoid-D-peptide formulation ((NPhe)4GGGGk(AZT)y(p)-OH). The chemical versatility of the peptoid-peptide motif allows low-molecular-weight drugs to be precisely and covalently conjugated. After subcutaneous injection, a hydrogel depot forms from the solubilized peptoid-peptide-drug formulation in response to phosphatase enzymes present within the skin space. This system is able to deliver clinically relevant concentrations of a model drug, the antiretroviral zidovudine (AZT), for 35 days in Sprague-Dawley rats. Oscillatory rheology demonstrated that hydrogel formation began within ∼30 s, an important characteristic of in situ systems for reducing initial drug bursts. Gel formation continued for up to ∼90 min. Small-angle neutron scattering data reveal narrow-radius fibers (∼0.78-1.8 nm) that closely fit formation via a flexible cylinder elliptical model. The inclusion of non-native peptoid monomers and D-variant amino acids confers protease resistance, enabling enhanced biostability to be demonstrated in vitro. Drug release proceeds via hydrolysis of an ester linkage under physiological conditions, releasing the drug in an unmodified form and further reducing the initial drug burst. Subcutaneous administration of (NPhe)4GGGGk(AZT)y(p)-OH to Sprague-Dawley rats resulted in zidovudine blood plasma concentrations within the 90% maximal inhibitory concentration (IC90) range (30-130 ng mL-1) for 35 days.

Systemic inflammation in pregnant women with HIV: relationship with HIV treatment regimen and preterm delivery.

OBJECTIVE: HIV treatment regimen during pregnancy was associated with preterm delivery (PTD) in the PROMISE 1077 BF trial. Systemic inflammation among pregnant women with HIV could help explain differences in PTD by treatment regimen. We assessed associations between inflammation, treatment regimen, and PTD. DESIGN/METHODS: A nested 1 : 1 case-control study ( N  = 362) was conducted within a multicountry randomized trial comparing three HIV regimens in pregnant women: zidovudine alone, or combination antiretroviral therapy (ART) with lopinavir/ritonavir and either zidovudine or tenofovir. Cases were women with PTD (<37 weeks of gestational age). The following inflammatory biomarkers were measured in plasma samples using immunoassays: soluble CD14 (sCD14) and sCD163, intestinal fatty acid-binding protein, interleukin (IL)-6, interferon γ, and tumor necrosis factor α. We fit regression models to assess associations between second trimester biomarkers (measured before ART initiation at 13-23 weeks of gestational age and 4 weeks later), treatment regimen, and PTD. We also assessed whether inflammation was a mediator in the relationship between ART regimen and PTD. RESULTS: Persistently high interleukin-6 was associated with increased PTD. Compared with zidovudine alone, the difference in biomarker concentration between week 0 and week 4 was significantly higher ( P  < 0.05) for both protease inhibitor-based regimens. However, the estimated proportion of the ART effect on increased PTD mediated by persistently high biomarker levels was 5% or less for all biomarkers. CONCLUSION: Persistently high IL-6 during pregnancy was associated with PTD. Although protease inhibitor-based ART was associated with increases in inflammation, factors other than inflammation likely explain the increased PTD in ART-based regimens compared with zidovudine alone.

Efficacy and safety of three antiretroviral therapy regimens for treatment-naive African adults living with HIV-2 (FIT-2): a pilot, phase 2, non-comparative, open-label, randomised controlled trial.

BACKGROUND: Due to the low number of individuals with HIV-2, no randomised trials of HIV-2 treatment have ever been done. We hypothesised that a non-comparative study describing the outcomes of several antiretroviral therapy (ART) regimens in parallel groups would improve understanding of how differences between HIV-1 and HIV-2 might lead to different therapeutic approaches. METHODS: This pilot, phase 2, non-comparative, open-label, randomised controlled trial was done in Burkina Faso, Côte d'Ivoire, Senegal, and Togo. Adults with HIV-2 who were ART naive with CD4 counts of 200 cells per µL or greater were randomly assigned 1:1:1 to one of three treatment groups. A computer-generated sequentially numbered block randomisation list stratified by country was used for online allocation to the next available treatment group. In all groups, tenofovir disoproxil fumarate (henceforth tenofovir) was dosed at 245 mg once daily with either emtricitabine at 200 mg once daily or lamivudine at 300 mg once daily. The triple nucleoside reverse transcriptase inhibitor (NRTI) group received zidovudine at 250 mg twice daily. The ritonavir-boosted lopinavir group received lopinavir at 400 mg twice daily boosted with ritonavir at 100 mg twice daily. The raltegravir group received raltegravir at 400 mg twice daily. The primary outcome was the rate of treatment success at week 96, defined as an absence of serious morbidity event during follow-up, plasma HIV-2 RNA less than 50 copies per mL at week 96, and a substantial increase in CD4 cells between baseline and week 96. This trial is registered at ClinicalTrials.gov, NCT02150993, and is closed to new participants. FINDINGS: Between Jan 26, 2016, and June 29, 2017, 210 participants were randomly assigned to treatment groups. Five participants died during the 96 weeks of follow-up (triple NRTI group, n=2; ritonavir-boosted lopinavir group, n=2; and raltegravir group, n=1), eight had a serious morbidity event (triple NRTI group, n=4; ritonavir-boosted lopinavir group, n=3; and raltegravir group, n=1), 17 had plasma HIV-2 RNA of 50 copies per mL or greater at least once (triple NRTI group, n=11; ritonavir-boosted lopinavir group, n=4; and raltegravir group, n=2), 32 (all in the triple NRTI group) switched to another ART regimen, and 18 permanently discontinued ART (triple NRTI group, n=5; ritonavir-boosted lopinavir group, n=7; and raltegravir group, n=6). The Data Safety Monitoring Board recommended premature termination of the triple NRTI regimen for safety reasons. The overall treatment success rate was 57% (95% CI 47-66) in the ritonavir-boosted lopinavir group and 59% (49-68) in the raltegravir group. INTERPRETATION: The raltegravir and ritonavir-boosted lopinavir regimens were efficient and safe in adults with HIV-2. Both regimens could be compared in future phase 3 trials. The results of this pilot study suggest a trend towards better virological and immunological efficacy in the raltegravir-based regimen. FUNDING: ANRS MIE.

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. .

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.

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)

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.

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...

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.

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

Evaluación de la quimioprofilaxis con zidovudine a la mujer embarazada VIH(+) y su hijo / Evaluation of Zidovudine treatment of HIV (+) pregnant woman and his child

En 1994 se publicaron los resultados del protocolo ACTG 076 sobre quimioprofilaxis (QP) con Zidovudine (AZT) para reducir 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. Material y métodos. Se analizaron en forma retrospectiva los datos de 304 binomios madre-hijo captados en la Policlínica materno infantil del CHPR desde junio de 1990 al 31 de diciembre de 1998. Se definió QP incompleta, cuando faltaron una o dos fases del tratamiento. Los niños fueron clasificados como serorrevertidos (S), infectados (I) o perinatalmente expuestos (E), según criterios del C.D.C. Resultados. Hasta el 31/12/1994, se estudiaron 116 binomios madre -hijo y el porcentaje de transmisión vertical fue de 28,4 por ciento

Estudio fase II de un tratamiento antirretroviral altamente activo a dosis reducidas en pacientes con formas avanzadas de la infección por el virus de la inmunodeficiencia humana tipo 1 / A phase II trial of reduced doses of a highly active antiretroviral treatment in patients with advanced stages of the type 1human immunodeficiency virus infection

Antecedentes: en un grupo de más de 125 pacientes infectados por el HIV hemos demostrado que el uso de 300 mg/día de zidovudina (AZT) produce resultados similares a los descritos con dosis mayores y se asocia con una reducción considerable de los efectos adversos del fármaco y de los costos. Objetivo: evaluar la eficacia de un tratamiento antirretroviral altamente activo (TARAA) a dosis reducidad en pacientes con formas avanzadas de la infección por el HIV-1. Material y métodos: entre enero de 1996 y septiembre de 1998 se trataron de manera prospectiva 24 pacientes con formas avanzadas de la infección por el HIV-1. Con un tratamiento antirretroviral altamente activo (TARRA) a dosis reducidas: 100 mg c/8 h de zidovudina, 150 mg c/12 h de lamivudina y 400 mg c/8 h de indinavir, por periodos de 7 a 28 meses. Doce pacientes habían recibido tratamientos antirretrovirales previos; se incluyeron 19 hombres y 5 mujeres con una media de edad de 57 años. Resultados: en todos los pacientes hubo mejoría en los marcadores sucedáneos de la enfermedad: en el 100 por ciento hubo incremento en las células CD4 (las medianas antes y después del tratamiento fueron de 105 de 246/ml, respectivamente, p< 0.001) y en 91 por ciento de los casos hubo disminución de la carga viral (las medianas antes y depués del tratamiento fueron de 35 x 103 y menos de 400 copias de ARN viral/ml, respectivamente). En 68 por ciento de los casos la carga viral se volvió indetectable y la antigenemia p24 desapareció en 95 por ciento de los casos en que era positiva. Las dosis reducidas de esta TARR fueron útiles para lograr la mejoría de los marcadores sucedáneos de la enfermedad por periodos hasta de 28 meses. Conclusiones: se requieren estudios adicionales para definir si este esquema puede ser otra modalidad en el tratamiento de los pacientes infectados por el HIV

Infección por VIH y embarazo / VIH infection and pregnancy

El objetivo de este trabajo fue estudiar las características clínicas del embarazo con infección por virus de inmunodeficiencia humana (VIH) y la transmisión vertical. Se analizaron embarazadas con esta infección, controladas en la Fundación Arriarán, cuya gestación y parto fueron atendidos en la Maternidad del Hospital San Borja Arriarán. Durante la gestación se hizo pesquisa de otras infecciones. La zidovudina (AZT) fue usada según protocolo ACTG 076 en 6 mujeres. En el parto se prefirió la cesárea electiva. Se impidió la lactancia. Se hizo seguimiento de los niños. Diecisiete mujeres tuvieron 19 partos. Presentaron infección genitourinaria 4 pacientes (21,1 por ciento); infecciones no ginecológicas 5 (26,3 por ciento); patología del embarazo 4 (21,1 por ciento); rotura prematura de membranas de término 1 (5,3 por ciento); parto prematuro 3 (15,8 por ciento). El parto fue por cesárea en 15 casos (78,9 por ciento). La transmisión vertical fue 26,3 por ciento (5/19), 33,3 por ciento (5/15) en la cesárea y 16,7 por ciento con tratamiento de AZT. Un niño presentó muerte fetal y trece (68,4 por ciento) están sanos. Ocho mujeres están asintomáticas, tres sintomáticas, cuatro abandonaron controles y dos fallecieron. Es conveniente que la embarazada con infección por VIH use AZT y sea controlada por especialistas para disminuir los factores de riesgo en la transmisión vertical. La cesárea facilita la administración de AZT durante el parto. La lactancia materna debe suprimiese

Didesoxicitidina y zidovudina secuenciales en infección avanzada por virus VIH-1: estudio fase II / Efficacy of sequential dideoxycytidine and zidovudine in stage IV HIV-1 infection: phase II study

Se estudiaron prospectivamente 17 pacientes infectados por VIH-1 tratados con ddC (0.375 mg tid durante 30 días), alternado con AZT (100 mg tid durante 30 días), por periodos de 8 a 32 semanas, medida de 17. Trece pacientes recibieron este tratamiento después de otros antirretrovirales, y cuatro lo recibieron desde el diagnóstico. Antes y después de AZT/ddC, la medida de células CD4 cambió de 184 a 164/uL (p NS), y la media de peso de 60 a 61 kg (p NS). Los parámetros hematológicos mejoraron en pacientes expuestos previamente a AZT. En uno de los cuatro casos desapareció la antigenemia P24 y en tres de nueve disminuyeron los niveles de beta-2-microglobulina sérica. En uno hubo neuropatía periférica sensorial reversible como efecto colateral de ddC y en ocho cedieron efectos adversos de AZT como intolerancia gástrica, cefalea y fiebre. La administración combinada secuencial de AZT/ddC fue bien tolerada y se disminuyó la toxicidad de AZT.

Terapeútica actual del compromiso neurológico primario por VIH / Current therapeutics of primary neurological: involvement by HIV

En la infección por el virus de la inmunodeficiencia humana (VIH), la afección del sistema nervioso central (SNC) es muy común. El compromiso neurológico observado con mayor frecuencia es el complejo cognoscitivo motor, también llamado demencia asociada al SIDA. Este es provocado directamente por la infección del VIH y la respuesta secundaria del sistema inmune, específicamente del sistema monocito-macrofágico. Revisamos la patogénesis y presentamos las posibilidades terapéuticas actuales en el manejo de esta compleja enfermedad, dividiéndola en terapia antirretroviral, control de la inflamación asociada a la infección y fármacos protectores del SNC. El pilar fundamental del tratamiento son las drogas antirretrovirales. Dentro de éstas, la zidovudina (AZT) ha demostrado hasta ahora la mayor efectividad. Actualmente se emplean terapias combinadas, utilizando inhibidores de la transcriptasa reversa e inhibidores de proteasas. Dentro de estas asociaciones, la terapia triasociada es la de elección, ya que permite cambiar la condición de la enfermedad, desde un problema mortal, al de una situación crónica controlable. Se revisa la terapéutica enfocada a frenar la reacción inflamatoria nociva, producida por macrófagos y microglia infectados y las drogas utilizadas en la protección del sistema nervioso central

Cytomegalovirus retinitis in AIDS patients: a clinical review

Cytomegalovirus (CMV) retinitis is an ocular condition previously seen in organ transplant recipients, patient on chemotherapy for malignancy, and in infants with congenital infections. As it present in immunocompromised, the AIDS patient has integrated this group of patients that can present with CMV retinitis. Moreover, it is the leading cause of opportunistic ocular infection in the AIDS patient, and the second most common ocular manifestation. As new drugs and modes of administration are studied that can effectively halt this progressively blinding condition, the awareness and recognition of CMV retinitis on AIDS patients has become increasingly important. This author will review the epidemiology, clinical presentation, and differential diagnosis of this condition. The current treatments being used and complications will also be discussed