Efeitos da administração diária da associação estavudina/nelfinavir sobre os fetos e placentas da rata albina / Effects of daily administration of a stavudine/nelfinavir association on the fetuses and placentas of female albino rats

OBJETIVO: avaliar o efeito da administração da associação estavudina/nelfinavir durante toda a prenhez da rata, avaliando seu peso e dos conceptos, bem como o número de implantações, fetos, placentas, reabsorções e mortalidades materna e fetal. MÉTODOS: quarenta ratas albinas EPM-1 Wistar, prenhes, foram aleatoriamente divididas em quatro grupos: GCtrl (controle do veículo) e três experimentais, ExpI, ExpII e ExpIII, que receberam, respectivamente, 1/40, 3/120 e 9/360 mg/kg por dia de estavudina/nelfinavir por via oral. As drogas e o veículo (água destilada) foram administrados por gavagem em duas tomadas diárias (12/12 horas), desde o dia 0 até o 20º dia da prenhez. No último dia do experimento, todos os animais foram anestesiados e eutanasiados. Foram avaliados a evolução do peso materno no 7º, 14º e 20º dias, número de fetos, placentas, implantações, reabsorções, óbitos intrauterinos, malformações maiores e o peso dos fetos e das placentas. A análise estatística foi realizada por análise de variância (ANOVA), complementada pelo teste de Kruskal-Wallis (p<0,05). RESULTADOS: em relação ao peso corporal das ratas, houve ganho gradual e progressivo durante o decorrer da prenhez em todos os grupos, sendo este ganho mais evidente no período final; porém não foram constatadas diferenças estatisticamente significantes entre eles. O número de fetos, placentas, implantações, assim como os pesos fetais e placentários também não mostraram diferenças estatisticamente significantes entre os grupos analisados. Não foram observadas, também nos grupos experimentais, reabsorções e malformações fetais maiores externas, no entanto, observamos entre o 8º e o 14º dias de gestação um caso de morte materna em cada grupo experimental. CONCLUSÕES: a administração da associação estavudina/nelfinavir não mostrou efeitos deletérios sobre os conceptos.

PURPOSE: to evaluate the effect of administration of a stavudine/nelfinavir combination on the rat pregnancy by assessing maternal and concepts weights, as well as the number of implantations, fetuses, placentas, resorptions and maternal and fetal mortality. METHODS: forty adult pregnant Wistar rats of the EPM-1 strain were randomly divided into four groups: control (GCtrl - drug vehicle control, n=10), and three experimental groups, which were treated with an oral solution of stavudine/nelfinavir (ExpI - 1/40 mg/kg b.w., n=10; ExpII - 3/120 mg/kg b.w., n=10; ExpIII - 9/360 mg/kg b.w., n=10) from day 0 to the 20th day of pregnancy. Maternal body weights were determined at the start of the experiment and on the 7th, 14th and the 20th day thereafter. At term (20th day) the rats were anesthetized and, upon laparotomy and hysterotomy, the number of implantations, resorptions, living fetuses, placentae and intrauterine deaths were recorded. The collected fetuses and placentae were weighed and the concepts were examined under a stereomicroscope for possible external malformations. Statistical analysis was performed by analysis of variance (ANOVA) complemented by the Kruskal-Wallis test (p<0.05). RESULTS: there was a progressive and gradual increase in body weight during the course of pregnancy in all groups, which was more evident in the final period, but with no significant difference between groups. The mean number of fetuses, placentas, implantations, and fetal and placental weights showed no significant differences between groups. Also, no resorptions or external malformations were found in the experimental groups. However, between the 8th and 14th days of gestation, there was one case of maternal mortality in each experimental group. CONCLUSIONS: the administration of a stavudine/nelfinavir combination had no deleterious effects on the concepts.

Antiretroviral agents and acid-base balance at delivery of the neonate

Limited evidence is available regarding antiretroviral (ARV) safety for uninfected infants exposed to these drugs in utero. Our objective was to determine if ARV administered to pregnant women is associated with decreasing umbilical arterial pH and base excess in uninfected infants. A prospective study was conducted on 57 neonates divided into three groups: ZDV group, born to mothers taking zidovudine (N = 20), triple therapy (TT) group, born to mothers taking zidovudine + lamivudine + nelfinavir (N = 25), and control group (N = 12), born to uninfected mothers. Umbilical cord blood was used to determine umbilical artery gases. A test was performed to calculate the sample by comparing means by the unpaired one-tailed t-test, with a = 0.05 and ß = 20 percent, indicating the need for a sample of 18 newborn infants for the study groups to detect differences higher than 20 percent. The control and ARV groups were similar in gestational age, birth weight, and Apgar scores. Values of pH, pCO2, bicarbonate, and base excess in cord arterial blood obtained at delivery from the newborns exposed to TT were 7.23, 43.2 mmHg, 19.5 mEq/L, and -8.5 nmol/L, respectively, with no significant difference compared to the control and ZDV groups. We conclude that intrauterine exposure to ARV is not associated with a pathological decrease in umbilical arterial pH or base excess. While our data are reassuring, follow-up is still limited and needs to be continued into adulthood because of the possible potential for adverse effects of triple antiretroviral agents.

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.

Effects of antiretroviral agents during pregnancy on liver enzymes and amylase in HIV-exposed, uninfected newborn infants

This study assessed the effect of antiretroviral drugs administered to pregnant women on amylase and liver enzymes of the neonate. A prospective study was conducted on 52 neonates divided into three groups: infants born to HIV-infected mothers taking zidovudine (ZDV group, n = 18), infants born to mothers taking zidovudine + lamivudine + nelfinavir (TT group, n = 22) and infants born to normal women (control group, n = 12). Umbilical cord blood from the newborn infant was used to determine liver transaminases and amylase. Data were analyzed statistically by nonparametric tests, with the level of significance set at p<0.05. The median levels for TT group newborns were 33.3 U/L for oxaloacetic transaminase, 21.5 U/L for pyruvic transaminase, 1.9 mg/dL for total bilirubin, 153 mg/dL for alkaline phosphatase, and 9.6 U/L for amylase. These results did not differ from those obtained for Control newborns or newborns exposed to ZDV alone. No association was observed between the use of antiretroviral drugs during pregnancy and adverse effects on neonatal amylase and hepatic parameters at birth.

Alertes sanitaires: quelques elements de pharmacovigilance

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HIV-infected child with recurrent parotitis: a case report

Human immunodeficiency virus [HIV] infection in children causes a broad spectrum of diseases and varied clinical courses. Parotitis is one of the manifestations of paediatric HIV infection, occurs in 4-47% of children. We present a 4-year old boy with recurrent bilateral parotitis. He had been admitted twice with the diagnosis of iron deficiency anaemia and chronic hepatitis. During the last admission for recurrent parotitis, based on clinical and paraclinical findings, he was suspected to have HIV infection that was finally confirmed with laboratory tests. Despite low prevalence of HIV-infection among children, physicians should consider HIV infection in any pediatric patient who presents with unexplained signs and symptoms such as chronic or recurrent parotitis

Efeitos do uso crônico do nelfinavir sobre a prenhez da rata albina: ensaio biológico / Effects of chronic nelfinavir treatment on rat pregnancy: biological assay

OBJETIVO: avaliar o efeito do uso crônico do nelfinavir sobre o peso de ratas albinas prenhes e seus conceptos, bem como o número de implantações, fetos, placentas, reabsorções e mortalidade materna e fetal. MÉTODOS: 50 ratas albinas EPM-1 Wistar, prenhes, foram aleatoriamente divididas em cinco grupos: 2 controles, Contr1 (controle do estresse) e Contr2 (controle do veículo), e três experimentais, Exp40, Exp120 e Exp360, que receberam, respectivamente, 40, 120 e 360 mg/kg por dia de nelfinavir por via oral. A droga e o veículo (água destilada) foram administrados por gavagem em duas tomadas diárias (12/12 horas), desde o primeiro dia até o dia 20 da prenhez. No último dia do experimento, todos os animais foram anestesiados e sacrificados. Foram avaliados a evolução do peso, número de implantações, reabsorções, fetos, placentas, óbitos intra-uterinos, o peso dos fetos e das placentas e malformações maiores. A análise estatística foi realizada pela análise de variância (ANOVA) completada pelo teste de Kruskal-Wallis. RESULTADOS: em relação ao ganho de peso das ratas, houve ganho normal em todos os grupos, não sendo constatadas diferenças significantes entre eles. ANOVA mostrou ausência de diferenças significativas entre os grupos quanto aos parâmetros estudados. As médias do número de fetos foram: controles = 9,7±0,50; grupos tratados com nelfinavir = 9,7±0,81. Para as médias de números de placentas e implantações, controles = 9,7±0,50; grupos tratados com nelfinavir = 9,7±0,78. Quanto às médias de pesos fetais, controles = 4,04±0,50; grupos tratados com nelfinavir = 3,91±0,33 g. Finalmente, para as médias de pesos de placentas, controles = 0,64±0,02; grupos tratados com nelfinavir = 0,67±0,02 g. Além disto, não foram observadas reabsorções, mortalidade das matrizes, óbitos e malformações fetais. CONCLUSÕES: o nelfinavir, em todas as doses administradas, não influiu no ganho de peso das ratas prenhes e não mostrou efeitos deletérios sobre...

PURPOSE: to evaluate the chronic effects of nelfinavir on body weight gain of pregnant albino rats and their concepts, as well as on the number of implantations, reabsorptions, fetuses, placentae, and maternal and fetal mortality. METHODS: fifty pregnant EPM-1 Wistar albino rats were randomly divided into five groups: two controls, Contr1 (control of stress) and Contr2 (drug vehicle control), and 3 experimental groups, Exp40, Exp120, Exp360, which received 40, 120 or 360 mg/kg per day of oral solution of nelfinavir, respectively. The drug and the vehicle (distilled water) were administered twice a day (12/12 h) by gavage from the first up to the 20th day of pregnancy. After sacrifice under deep anesthesia, the following parameters were evaluated: number of implantations and reabsorptions, the weight of fetuses and placentae, and the number of intrauterine deaths as well as inspection for major malformations. Data were evaluated by ANOVA followed by the Kruskal-Wallis multiple comparison test. RESULTS: body weight gain during pregnancy was normal for all the groups, and no significant differences were detected between them. ANOVA did not reveal any significant effect of nelfinavir on the studied parameters. The means of number of fetuses were: control = 9.7±0.50; nelfinavir-treated groups = 9.7±0.81. Regarding the means of number of placentae and implantations, controls = 9.7±0.50; nelfinavir-treated groups = 9.6±0.78. The mean fetal weights were as follows: controls = 4.04±0.50; nelfinavir-treated groups = 3.91±0.33 g. Finally, control placental weights averaged 0.64±0.02; nelfinavir-treated groups = 0.67±0.02 g. CONCLUSION: nelfinavir was well tolerated at all the administered doses; no damage was produced on the fetuses.

HIV-1 genotypes related to failure of nelfinavir as the first protease inhibitor treatment

Combined antiretroviral therapy results in sustained viral suppression and a decrease in mortality and morbidity due to HIV infection. Intrinsic strength, durability and absence of cross-resistance are key factors in the selection of antiretrovirals. Failure with nelfinavir has been associated with two protease gene mutations, D30N and L90M. The D30N mutation does not result in cross-resistance with other protease inhibitors, and it decreases viral fitness. In order to check for this mutation after failure with nelfinavir, the 246 HIV-1 genotyping test was performed on virus samples from 55 patients with failure of nelfinavir as the first protease inhibitor. Most (84 percent) of the viral strains were of subtype B. Nucleosides associated with mutations (NAM) were observed in 80 percent of the tests; no INS69, complex 151, K65R and L74V mutations, which give multi-resistance to nucleoside analogue reverse transcriptase inhibitors to tenofovir and DDI, respectively, were observed. In the tests for protease gene mutations, the D30N mutation was found in 57 percent, L90M in 18 percent and the wild-type virus in 25 percent. These data are similar to published reports, showing that alternative therapies used after failure with nelfinavir may be more successful, as the D30N mutation does not cause cross-resistance to other protease inhibitors.

Effect of antiretroviral drugs on maternal CD4 lymphocyte counts, HIV-1 RNA levels, and anthropometric parameters of their neonates

OBJETIVOS: Estudar o efeito das drogas anti-retrovirais sobre a quantificação dos linfócitos TCD4 e RNA do HIV-1 de gestantes portadoras do HIV-1 e parâmetros antropométricos de seus neonatos. MÉTODOS: Estudo prospectivo avaliando 57 gestantes e seus neonatos em três grupos: Grupo AZT, gestantes portadoras do HIV utilizando zidovudina (n=20); Grupo TT, mães utilizando zidovudina+lamivudina+nelfinavir (n=25), e Grupo Controle, mulheres saudáveis (n=12). A quantificação dos linfócitos TCD4 e RNA do HIV-1 de gestantes portadoras do HIV foi analisada em dois períodos durante a gestação. O prognóstico perinatal levou em consideração as taxas de pré-termos, restrição de crescimento intra-útero, mortalidade perinatal e transmissão vertical do HIV-1. Os dados foram analisados utilizando-se testes não paramétricos de qui-quadrado, Mann-Whitney, Friedman, Kruskal-Wallys e Wilcoxon para amostras pareadas, considerando-se significativos valores associados a p<0,05. RESULTADOS: Observou-se homogeneidade entre os dados demográficos e antropométricos de realce. A carga viral, inicialmente elevada (14.370 cópias/ml), reduziu-se significativamente no grupo com tratamento tríplice , chegando a 40 cópias/ml. Quanto à contagem de linfócitos CD4, observou-se recuperação significativa nas pacientes do grupo TT, no final da gestação, sendo esse valor significativamente diferente em comparação ao grupo AZT (p = 0,0052). Não se observou diferença entre os grupos quanto à duração da gestação, aos índices de Apgar, e à classificação antropométrica neonatal. Não houve nenhum caso de transmissão vertical do HIV-1. CONCLUSÕES: Os resultados obtidos na presente casuística demonstram eficiência e sugerem segurança no uso de anti-retrovirais na gestação sobre parâmetros antropométricos dos neonatos.

Efeito diabetogênico das drogas anti-retrovirais em ratas Wistar prenhes / Diabetogenic effect of antiretroviral drugs on pregnant Wistar rats

OBJETIVO: estudar a ação diabetogênica de drogas anti-retrovirais em ratas prenhes e o prognóstico perinatal das crias. MÉTODOS: estudo com ratas fêmeas prenhes adultas da raça Wistar, pesando entre 200-230 g. Foram testadas a azidotimidina (AZT), lamivudina (3TC) e nelfinavir (NFV), cujas dosagens foram padronizadas em 10 vezes a dose utilizada em gestantes, proporcionalmente ao peso dos animais. Foram avaliados sete grupos, incluindo o controle, contendo 10 ratas por grupo. O início do experimento foi o dia zero da prenhez e as cesarianas realizadas no 21º dia, após decapitação, sendo os fetos contados e pesados. Procedeu-se a dosagens de glicemia, insulina, glucagon e lactato no 21º dia. Avaliou-se também o peso do tecido adiposo retroperitoneal. Os dados foram analisados utilizando-se o teste t de Student para a análise estatística. RESULTADOS: os grupos tratados com 3TC, AZT + 3TC e AZT + 3TC + NFV demonstraram alterações com a redução das médias de ganho de peso materno diário, do peso da gordura retroperitoneal e peso das crias (grupo controle: 6,2 g; grupos contendo 3TC: 4,1 a 5,6 g), bem como dos valores de lactato (grupo controle: 5,8 mmol/mL; grupos contendo 3TC: 3,2 a 3,7 mmol/mL), quando comparados ao controle. Todos os grupos tratados com drogas anti-retrovirais apresentaram redução significativa do número de fetos por ninhada (grupo controle: 14,7; grupos medicamentos: 11,1 a 12,7) e dos valores séricos de insulinemia (grupo controle: 6,2 µUI/mL; grupos medicamentos: 2,1 a 2,7 µUI/mL) e elevação da glucagonemia (grupo controle: 88,2 pg/mL; grupos medicamentos: 99,7 a 120,7 pg/mL). Não houve diferenças estatisticamente significantes entre o grupo controle e tratados nos valores de glicemia. CONCLUSÕES: o uso de anti-retrovirais em ratas prenhes causa interferência no metabolismo glicídico dos animais durante o período de prenhez, provocando significativa redução do número das crias. Observou-se que o uso do 3TC resultou em menor ganho de peso materno e das crias, redução de insulina e lactato e elevação do glucagon.

Impairment of IRS-2 signaling in rat insulinoma INS-1 cells by nelfinavir / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate whether HIV-1 protease inhibitor nelfinavir alters the insulin stimulated phosphorylation of insulin signaling parameters in rat insulinoma INS-1 cells.</p><p><b>METHODS</b>INS-1 cells were incubated with nelfinavir for 48 h and stimulated with 100 nmol/L insulin for 2 min. Immunoprecipitation and Western blot analysis of the insulin stimulated insulin receptor substrate (IRS)-1,-2 and Akt-Thr(308) phosphorylation were performed on cell lysates. Cytotoxic effects of nelfinavir were measured by cell count with trypan blue and MTT reduction test.</p><p><b>RESULT</b>Nelfinavir decreased insulin stimulated phosphorylation of IRS-2 and Akt-Thr(308) in a dose-dependent manner; for 10 micromol/L of nelfinavir, the decrease was 52% and 55%, respectively.</p><p><b>CONCLUSION</b>Treatment with nelfinavir might impair IRS-2-mediated signaling in pancreatic beta cells.</p>

Ação crônica do nelfinavir sobre os fígados e rins maternos e fetais durante toda a prenhez da rata albina (rattus norvegicus albinus, Rodentia, mammalia): aspectos morfológicos e funcionais / Chromic effects of nelfinavir on the albino rat pregnancy (Rattus norvegicus albinus - Rodentia mammalia): morphology and biochemistry aspects

Objetivos - Mais de 20 milhões de pessoas morreram de AIDS nos últimos 25 anos no mundo. No Brasil, a redução do número de mortes entre as mulheres ocorre em uma velocidade duas vezes mais lenta que para os homens, onde o diagnóstico é mais precoce. A gravidez representa oportunidade para o diagnóstico evitando-se a transmissão vertical. O nelfinavir é um importante inibidor de protease, lançado em 1997, indicado em esquemas para gestantes aidéticas com menos de 28 semanas e com imunodepressão mais acentuada. O nosso objetivo foi estudar a ação crônica do nelfinavir durante toda a prenhez da rata albina não infectada através do estudo histopatológico dos fígados e rins maternos e fetais e da avaliação materna de provas de função hepática e renal, glicemia e possíveis repercussões sobre o sangue periférico. Métodos - Utilizamos 50 ratas albinas da colônia EPM-1 Wistar, prenhes com aproximadamente 200mg. A partir do dia zero da prenhez, os animais foram divididos aleatoriamente em 5 grupos, numericamente iguais: grupo controle C1, sem qualquer manuseio; grupo controle C2 que recebeu 6 mL de água destilada/dia, enquanto os grupos E1, E2 e E3, receberam, respectivamente, 40, 120, 360 mg/kg/dia de nelfinavir, divididos em duas doses diárias iguais com intervalo de 12 horas, durante toda a prenhez. No 20° dia, anestesiadas, foi realizada incisão xifo-púbica, onde foram expostos coração, fígados e rins maternos, colhidos sangue do coração para dosagens de alanina aminotransferase-ALT, aspartato de aminotransferase-AST, creatinina, uréia, glicose e hemograma (eritrócitos, hemoglobina, hematócrito e leucócitos). A seguir, foram retirados fígados e rins maternos e fetais, que foram encaminhados para microscopia de luz para estudo histopatológico. O estudo estatístico foi realizado pelo Teste de Kruskal-Wallis e pelo Teste de Comparações Múltiplas de Dunn. Resultados - Nos fígados das ratas prenhes do grupo E3 houve sinais moderados de toxicidade da droga. No grupo E2, sinais discretos e normais em E1. Os rins maternos, fígados e rins fetais apresentaram-se normais. As dosagens de AST e ALT não expressaram lesão hepática isoladas provas de função renal demonstraram ausência de nefrotoxicidade. Quanto à glicose, o grupo E3 apresentou valores significantemente maiores que os que receberam a menor dose e os controles...

Estimating the length of the first antiretroviral therapy regiment durability in Säo Paulo, Brazil

Brazil was the first country to provide unrestricted, cost-free access to antiretroviral (ARV) medicine for AIDS treatment. However, there is little data about the benefits of such a policy for these patients. We evaluated the duration of benefit obtained with the introduction of ARVs, defined as the durability of the first ARV regiment. We reviewed the medical charts of patients attended from 1996-2000, at the outpatient clinics of the Federal University of Säo Paulo, Brazil. A total of 120 drug-naive HIV-1 infected patients were eligible to participate in the study. About half of the individuals (53 percent) presented with disease symptoms; 59 percent of them had CD4 count below 200 cells/mm³. Mean estimated duration of the benefit of therapy was 14.1 months. The most used regimen in this cohort was Zidovudine/3TC/Indinavir (26 percent), followed by Zidovudine/DDI (17 percent), and Zidovudine/3TC/Nelfinavir (13 percent). The most frequent cause of interruption of therapy was gastrointestinal intolerance. Use of treatment regimens with three drugs was more effective than with two drugs, but only for patients with CD4<200 cells/mm³ or CV>100,000 copies RNA/mL. However, the use of triple therapy was associated with a significantly higher probability of reaching maximum viral suppression, during a longer period (p<0.05).The patients enrolled in the study benefitted from therapy for a limited time, after the introduction of double or triple antiretroviral therapy. The incidence of adverse events was significantly associated with loss of the benefits provided by the initial therapeutic regimen.

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.

Viracept (Nelfinavir): potência e baixa indução de resistência / Viracept (Nelfinavir): power and low resistance induction

Apresenta um estudo sobre o Nelfinavir como um inibidor altamente sletivo de enzima protease de HIV. Traz a farmacologia clínica e virologia, os testes clínicos, e a experiência pós-comercialização