RESUMO
Some people living with HIV present painful sensory neuropathy (HIV-SN) that is pharmacoresistant, sex-associated, and a major source of morbidity. Since the specific mechanisms underlying HIV-SN are not well understood, the aim of our study was to characterize a novel model of painful HIV-SN by combining the HIV-1 gp120 protein and the antiretroviral stavudine (d4T) in mice and to investigate the pronociceptive role of the family 2 voltage-gated calcium channel (VGCC) α1 subunit (Cav2.X channels) in such a model. HIV-SN was induced in male and female C57BL/6 mice by administration of gp120 and/or d4T and detected by a battery of behavior tests and by immunohistochemistry. The role of Cav2.X channels was assessed by the treatment with selective blockers and agonists as well as by mRNA detection. Repeated administration with gp120 and/or d4T produced long-lasting touch-evoked painful-like behaviors (starting at 6 days, reaching a maximum on day 13, and lasting up to 28 days after treatment started), with a greater intensity in female mice treated with the combination of gp120 + d4T. Moreover, gp120 + d4T treatment reduced the intraepidermal nerve fibers and well-being of female mice, without altering other behaviors. Mechanistically, gp120 + d4T treatment induced Cav2.1, 2.2, and 2.3 transcriptional increases in the dorsal root ganglion and the Cav2.X agonist-induced nociception. Accordingly, intrathecal selective Cav2.2 blockade presented longer and better efficacy in reversing the hyperalgesia induced by gp120 + d4T treatment compared with Cav2.1 or Cav2.3, but also presented the worst safety (inducing side effects at effective doses). We conclude that the family 2 calcium channels (Cav2.X) exert a critical pronociceptive role in a novel mouse model of HIV-SN.
Assuntos
Dor Crônica , Infecções por HIV , Doenças do Sistema Nervoso Periférico , Masculino , Camundongos , Feminino , Animais , Estavudina/efeitos adversos , Camundongos Endogâmicos C57BL , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Canais de Cálcio Tipo N/metabolismo , Infecções por HIV/tratamento farmacológico , Dor Crônica/induzido quimicamenteRESUMO
OBJECTIVE: This study aims to estimate the prevalence of thyroid diseases and anti-TPO status. We searched for an association among presence of immune reconstitution and use of stavudine, didanosine and protease inhibitors with thyroid diseases. MATERIALS AND METHODS: A cross-sectional study was performed to analyze the records of 117 HIV-infected patients who had their CD4+ cell count, viral load, anti-TPO, TSH and free T4 levels collected on the same day. Immune reconstitution was considered in those whose T CD4+ count was below 200 cells/mm3, but these values increased above 200 cells/mm3 after the use of antiretrovirals. The odds ratio obtained by a 2x2 contingency table and a chi-square test were used to measure the association between categorical variables. RESULTS: The prevalence of thyroid disease was 34.18%; of these, 4.34% were positive for anti-TPO. There was an association of risk between stavudine use and subclinical hypothyroidism (OR = 4.19, 95% CI: 1.29 to 13.59, X2 = 6.37, p = 0.01). Immune reconstitution achieved protection associated with thyroid disease that was near statistical significance OR = 0.45, 95% CI: 0.19 to 1.04, X2 = 3.55, p = 0.059. CONCLUSION: The prevalence of thyroid disease in the sample studied was higher than what had been found in the literature, with a low positive anti-TPO frequency. The historical use of stavudine has an association of risk for the presence of subclinical hypothyroidism, and immune reconstitution has trends towards protection for the presence of thyroid diseases.
Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Autoanticorpos/isolamento & purificação , Hipotireoidismo/epidemiologia , Iodeto Peroxidase/imunologia , Inibidores da Transcriptase Reversa/uso terapêutico , Estavudina/uso terapêutico , Doenças da Glândula Tireoide/epidemiologia , Síndrome da Imunodeficiência Adquirida/sangue , Síndrome da Imunodeficiência Adquirida/complicações , Adulto , Antirretrovirais/uso terapêutico , Doenças Assintomáticas/epidemiologia , Doenças Assintomáticas/terapia , Contagem de Linfócito CD4 , Estudos Transversais , Didanosina/uso terapêutico , Feminino , Humanos , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/imunologia , Masculino , Prevalência , Inibidores da Transcriptase Reversa/efeitos adversos , Estavudina/efeitos adversos , Doenças da Glândula Tireoide/tratamento farmacológicoRESUMO
Objective This study aims to estimate the prevalence of thyroid diseases and anti-TPO status. We searched for an association among presence of immune reconstitution and use of stavudine, didanosine and protease inhibitors with thyroid diseases. Materials and methods A cross-sectional study was performed to analyze the records of 117 HIV-infected patients who had their CD4+ cell count, viral load, anti-TPO, TSH and free T4 levels collected on the same day. Immune reconstitution was considered in those whose T CD4+ count was below 200 cells/mm3, but these values increased above 200 cells/mm3 after the use of antiretrovirals. The odds ratio obtained by a 2x2 contingency table and a chi-square test were used to measure the association between categorical variables. Results The prevalence of thyroid disease was 34.18%; of these, 4.34% were positive for anti-TPO. There was an association of risk between stavudine use and subclinical hypothyroidism (OR = 4.19, 95% CI: 1.29 to 13.59, X2 = 6.37, p = 0.01). Immune reconstitution achieved protection associated with thyroid disease that was near statistical significance OR = 0.45, 95% CI: 0.19 to 1.04, X2 = 3.55, p = 0.059. Conclusion The prevalence of thyroid disease in the sample studied was higher than what had been found in the literature, with a low positive anti-TPO frequency. The historical use of stavudine has an association of risk for the presence of subclinical hypothyroidism, and immune reconstitution has trends towards protection for the presence of thyroid diseases. .
Assuntos
Adulto , Feminino , Humanos , Masculino , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Autoanticorpos/isolamento & purificação , Hipotireoidismo/epidemiologia , Iodeto Peroxidase/imunologia , Inibidores da Transcriptase Reversa/uso terapêutico , Estavudina/uso terapêutico , Doenças da Glândula Tireoide/epidemiologia , Síndrome da Imunodeficiência Adquirida/sangue , Síndrome da Imunodeficiência Adquirida/complicações , Antirretrovirais/uso terapêutico , Doenças Assintomáticas/epidemiologia , Doenças Assintomáticas/terapia , Estudos Transversais , Didanosina/uso terapêutico , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/imunologia , Prevalência , Inibidores da Transcriptase Reversa/efeitos adversos , Estavudina/efeitos adversos , Doenças da Glândula Tireoide/tratamento farmacológicoRESUMO
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 4.5 million 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.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Farmacovigilância , Estavudina/efeitos adversos , Zidovudina/efeitos adversos , Colômbia , HumanosRESUMO
The aim of this study was to determine the impact of antiretroviral therapy on the lipid profile of human immunodeficiency virus (HIV) patients before and after the initiation of highly active antiretroviral therapy (HAART). This was a cross-sectional analysis of patients receiving HAART at a reference center in Belo Horizonte, Brazil, on the basis of medical records from 2002 to 2006. Patients were included if they had at least one lipid test or a clinical or laboratory diagnosis of dyslipidemia/lipodystrophy. Among the 692 patients, 620 met the eligibility criteria. The majority were males (66.5%), middle age (average 39 years), had a low educational level (60.4%), and low income (51.0%). HAART duration ranged from 11 days to 4.6 years, with a mean of 28.6 months (SD = ± 470.19 days). The prevalence of dyslipidemia/lipodystrophy nearly tripled (11.3% pre- and 32.4% post-HAART). Dyslipidemia was associated with older age (P = 0.007), nucleoside reverse transcriptase inhibitor (NRTI) + protease inhibitor (PI) regimens (P = 0.04), NRTI + non-NRTI (NNRTI) regimens (P = 0.026), the use of stavudine (d4T) in any regimen (P = 0.002) or in NRTI-based regimens (P = 0.006), and longer exposure to HAART (P < 0.000). In addition, there was no correlation between dyslipidemia and gender (P = 0.084). Only 2.0% of the patients received treatment for dyslipidemia during the trial. These results show a need for continuous monitoring of patients under antiretroviral therapy, particularly those using NRTI-based regimens, especially when combined with d4T and PIs. Secondly, interventions should be developed to correct metabolic changes.
Assuntos
Dislipidemias/epidemiologia , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Lipodistrofia/epidemiologia , Inibidores da Transcriptase Reversa/efeitos adversos , Estavudina/efeitos adversos , Adolescente , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Brasil/epidemiologia , Estudos Transversais , Quimioterapia Combinada/efeitos adversos , Dislipidemias/induzido quimicamente , Feminino , Humanos , Lipodistrofia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Resultado do Tratamento , Adulto JovemRESUMO
The aim of this study was to determine the impact of antiretroviral therapy on the lipid profile of human immunodeficiency virus (HIV) patients before and after the initiation of highly active antiretroviral therapy (HAART). This was a cross-sectional analysis of patients receiving HAART at a reference center in Belo Horizonte, Brazil, on the basis of medical records from 2002 to 2006. Patients were included if they had at least one lipid test or a clinical or laboratory diagnosis of dyslipidemia/lipodystrophy. Among the 692 patients, 620 met the eligibility criteria. The majority were males (66.5 percent), middle age (average 39 years), had a low educational level (60.4 percent), and low income (51.0 percent). HAART duration ranged from 11 days to 4.6 years, with a mean of 28.6 months (SD = ± 470.19 days). The prevalence of dyslipidemia/lipodystrophy nearly tripled (11.3 percent pre- and 32.4 percent post-HAART). Dyslipidemia was associated with older age (P = 0.007), nucleoside reverse transcriptase inhibitor (NRTI) + protease inhibitor (PI) regimens (P = 0.04), NRTI + non-NRTI (NNRTI) regimens (P = 0.026), the use of stavudine (d4T) in any regimen (P = 0.002) or in NRTI-based regimens (P = 0.006), and longer exposure to HAART (P < 0.000). In addition, there was no correlation between dyslipidemia and gender (P = 0.084). Only 2.0 percent of the patients received treatment for dyslipidemia during the trial. These results show a need for continuous monitoring of patients under antiretroviral therapy, particularly those using NRTI-based regimens, especially when combined with d4T and PIs. Secondly, interventions should be developed to correct metabolic changes.
Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Dislipidemias/epidemiologia , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Lipodistrofia/epidemiologia , Inibidores da Transcriptase Reversa/efeitos adversos , Estavudina/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Brasil/epidemiologia , Estudos Transversais , Quimioterapia Combinada/efeitos adversos , Dislipidemias/induzido quimicamente , Lipodistrofia/induzido quimicamente , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of the study was to evaluate the predictive value of clinical and molecular risk factors, including peripheral blood mononuclear cell (PBMC) mitochondrial DNA (mtDNA) and mitochondrial RNA (mtRNA), for the development of lactic acidosis (LA) and symptomatic hyperlactataemia (SHL). METHODS: In a substudy of a large multicentre, randomized trial of three antiretroviral regimens, all containing didanosine (ddI) and stavudine (d4T), in antiretroviralnaïve, HIV-1-infected patients, patients with LA/SHL ('cases') were compared with those without LA/SHL in a univariate analysis, with significant parameters analysed in a multivariate model. In a molecular substudy, PBMC mtDNA and mtRNA from cases and matched controls at baseline and time of event were examined. RESULTS: In 911 subjects followed for a median of 192 weeks, 24 cases were identified (14 SHL and 10 LA). In univariate analysis, cases were more likely to be female (P=0.05) and to have a high body mass index (BMI) (P=0.02). In multivariate analyses, only BMI remained an independent predictor of the development of LA/SHL (P=0.03). Between cases and controls there was no significant difference in mtDNA copy number at baseline (389 vs. 411 copies/cell, respectively; P=0.60) or at time of event (329 vs. 474 copies/cell, respectively; P=0.21), in the change in mtDNA copy number from baseline to event (-65 vs. +113 copies/cell, respectively; P=0.12), in mtRNA expression at baseline or time of event, or in the change in mtRNA expression from baseline to event. CONCLUSION: The development of LA/SHL was associated with increased BMI, but PBMC mtDNA and mtRNA did not predict LA/SHL. This demonstrates the ineffectiveness of routine measurement of PBMC mtDNA in patients on ddI and d4T as a means of predicting development of LA/SHL.
Assuntos
Acidose Láctica/etiologia , Índice de Massa Corporal , DNA Mitocondrial/metabolismo , Infecções por HIV/complicações , HIV-1 , Leucócitos Mononucleares/metabolismo , RNA/metabolismo , Acidose Láctica/induzido quimicamente , Acidose Láctica/epidemiologia , Acidose Láctica/genética , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Australásia/epidemiologia , DNA Mitocondrial/efeitos dos fármacos , DNA Viral/efeitos dos fármacos , DNA Viral/metabolismo , Didanosina/administração & dosagem , Didanosina/efeitos adversos , Europa (Continente)/epidemiologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/genética , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Análise Multivariada , América do Norte/epidemiologia , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , RNA/efeitos dos fármacos , RNA Mitocondrial , RNA Viral/efeitos dos fármacos , RNA Viral/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fatores Sexuais , América do Sul/epidemiologia , Estavudina/administração & dosagem , Estavudina/efeitos adversosRESUMO
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.
Assuntos
Animais , Ratos , Antirretrovirais , Estavudina/efeitos adversos , Feto , Nelfinavir/efeitos adversos , PrenhezRESUMO
INTRODUCTION: The objective of this study was to evaluate the frequency of thyroid function alterations and its associated factors in a group of patients from a university hospital in Colombia. METHODS: From June 2007 through June 2008, 636 HIV patients were followed in order to assess the relation of thyroid function with the use of HAART. RESULTS: The overall prevalence of hypothyroidism (TSH > 4.6 µUI/mL) was 15.5% (100/636). The association of hypothyroidism in the independent analysis showed significant relation only for the use of nevirapine (RR 1.6; CI 95% 1.1- 2.34) and stavudine (RR 1.5; CI 95%, 1 - 2.3). CONCLUSIONS: The prevalence of hypothyroidism was surprisingly high among the studied population.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Hipotireoidismo/induzido quimicamente , Nevirapina/efeitos adversos , Estavudina/efeitos adversos , Adolescente , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade , Estudos de Coortes , Colômbia , Estudos Transversais , Feminino , Hospitais Universitários , Humanos , Hipotireoidismo/diagnóstico , Masculino , Pessoa de Meia-Idade , Tireotropina/sangue , Carga Viral , Adulto JovemRESUMO
Objetivos: Evaluar la frecuencia de alteración tiroidea y los factores asociados en los pacientes con VIH/SIDA de un hospital universitario en Colombia. Pacientes y Métodos: Estudio tipo corte transversal de pacientes con VIH/SIDA durante el periodo de 2007 a 2008. Se registró niveles hormonales, inmunológicos, carga viral y tratamiento anti-retroviral. Resultados: En 636 pacientes la prevalencia de hipotiroidismo (TSH > 4,6 μUI/mL) fue de 15,5 por ciento (100/636). El análisis independiente demostró relación significativa para el uso de nevirapina (RR 1,6; IC 95 por ciento 1,1 - 2,3) y estavudina (RR 1,5; IC 95 por cientoo 1 - 2,3). Conclusiones: La prevalencia de hipotiroidismo fue alta y se relacionó con el uso de nevirapina.
Introduction: The objective of this study was to evaluate the frequency of thyroid function alterations and its associated factors in a group of patients from a university hospital in Colombia. Methods: From June 2007 through June 2008, 636 HIV patients were followed in order to assess the relation of thyroid function with the use of HAART. Results: The overall prevalence of hypothyroidism (TSH > 4.6 μUI/mL) was 15.5 percent (100/636). The association of hypothyroidism in the independent analysis showed significant relation only for the use of nevirapine (RR 1.6; CI 95 percent 1.1- 2.34) and stavudine (RR 1.5; CI 95 percent, 1 - 2.3). Conclusions: The prevalence of hypothyroidism was surprisingly high among the studied population.
Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Hipotireoidismo/induzido quimicamente , Nevirapina/efeitos adversos , Estavudina/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Estudos de Coortes , Colômbia , Estudos Transversais , Hospitais Universitários , Hipotireoidismo/diagnóstico , Tireotropina/sangue , Carga ViralRESUMO
IMPORTANCE OF THE FIELD: The nucleoside reverse transcriptase inhibitors (NRTIs) are used in antiretroviral therapy worldwide for the treatment of HIV infections. These drugs act by blocking reverse transcriptase enzyme activity, causing pro-viral DNA chain termination. As a consequence, NRTIs could cause genomic instability and loss of heterozygosity. AREAS COVERED IN THIS REVIEW: This review highlights the toxic and genotoxic effects of NRTIs, particularly lamivudine (3TC) and stavudine (d4T) analogues. In addition, a battery of short-term in vitro and in vivo systems are described to explain the potential genotoxic effects of these NRTIs as a single drug or a complexity of highly active antiretroviral therapy. WHAT THE READER WILL GAIN: The readers will gain an understanding of a secondary effect that could be induced by 3TC and d4T treatments. TAKE HOME MESSAGE: Considering that AIDS has become a chronic disease, more comprehensive toxic genetic studies are needed, with particular attention to the genetic alterations induced by NRTIs. These alterations play a primary role in carcinogenesis and are also involved in secondary and subsequent steps of carcinogenesis.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Aberrações Cromossômicas/efeitos dos fármacos , Lamivudina/efeitos adversos , Mutação , Inibidores da Transcriptase Reversa/efeitos adversos , Estavudina/efeitos adversos , Adulto , Animais , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/toxicidade , Criança , Ensaios Clínicos como Assunto , Cricetinae , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Haplorrinos , Humanos , Lamivudina/administração & dosagem , Lamivudina/farmacocinética , Lamivudina/toxicidade , Camundongos , Testes de Mutagenicidade , Ratos , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/farmacocinética , Inibidores da Transcriptase Reversa/toxicidade , Estavudina/administração & dosagem , Estavudina/farmacocinética , Estavudina/toxicidadeRESUMO
OBJECTIVES: To compare carotid intima-media thickness (cIMT) of children and adolescents with and without HIV infection and to determine associations among independent socio-demographic, clinical or cardiovascular variables and cIMT in HIV-infected children and adolescents. PATIENTS AND METHODS: This is a matched case-control study comparing 83 HIV-infected and 83 healthy children and adolescents. Clinical and laboratorial parameters, cIMT and echocardiogram were measured. RESULTS: The cIMT was higher in HIV-infected individuals (median 480 microm; interquartile range 463-518 microm) compared with controls (426 microm; range 415-453 microm, P<0.001). In addition, the HIV-infected group showed higher levels of high-sensitive C-reactive protein (medians 1.0 mg/l vs. 0.4 mg/l, P<0.001), glycated hemoglobin (6.1+/-0.9 vs. 5.7+/-0.8%, P=0.028) and triglycerides (medians 0.9 vs. 0.8 mmol/l, P=0.031). Finally, this group showed lower levels of total and high-density lipoprotein-cholesterol. After multivariate analysis, increased cIMT was positively associated with stavudine use [odds ratio (OR): 18.9, P=0.005], left atrial/aorta index (OR: 15.6, P=0.019), suprailiac skinfold (OR: 7.9, P=0.019), tachypnea (OR: 5.9, P=0.031), CD8 lymphocyte count (OR: 5.7, P=0.033) and CD4 T-lymphocyte count (OR: 5.5, P=0.025). cIMT increment was negatively associated with total cholesterol (OR: 0.2, P=0.025) and with CD8 zenith (OR: 0.1, P=0.007). CONCLUSION: In this sample of children and adolescents, having HIV infection was associated with increased cIMT and elevated prevalence of cardiovascular risk factors. These findings suggest that this group should be included in cardiovascular prevention programs.
Assuntos
Doenças das Artérias Carótidas/complicações , Infecções por HIV/complicações , Adolescente , Proteína C-Reativa/análise , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Doenças das Artérias Carótidas/patologia , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Inibidores da Transcriptase Reversa/efeitos adversos , Estavudina/efeitos adversos , Túnica Íntima/patologia , Túnica Média/patologiaRESUMO
AIM: This study investigated the incidence of pancreatitis and its association with antiretroviral therapy (ART), focussing on stavudine and didanosine. METHODS: EuroSIDA has collected information on pancreatitis since Summer 2001. All identified cases have been verified by the coordinating centre. Individuals were followed from June 2001 or the date of entry into EuroSIDA (whichever occurred later) until a diagnosis of pancreatitis or the last study visit. Factors associated with pancreatitis were investigated using Poisson regression. Cumulative lengths of exposure to didanosine without stavudine, stavudine without didanosine, stavudine with didanosine, and other ART were time-updated variables. Treatment variables were fitted with a 6-month time lag. RESULTS: There were 43 (nine presumptive) pancreatic events in 9678 individuals during 33 742 person-years (incidence 1.27/1000 person-years). The incidence among those with no, 2 or less and over 2 years' exposure to ART including stavudine and didanosine was 1.24, 1.73 and 0.78/1000 person-years, respectively. In multivariable analysis, higher baseline CD4 cell counts were associated with a decreased risk of pancreatitis. There was no evidence of an association of pancreatitis with cumulative exposure to didanosine and stavudine, didanosine without stavudine, stavudine without didanosine, or other ART. CONCLUSION: We observed a low overall rate of pancreatitis in the years 2001-2006, and did not find an association of an increased incidence of pancreatitis with cumulative exposure to antiretroviral agents generally, and to didanosine and stavudine in particular.
Assuntos
Antirretrovirais/efeitos adversos , Infecções por HIV/complicações , HIV , Pancreatite/epidemiologia , Adulto , Antirretrovirais/uso terapêutico , Argentina/epidemiologia , Linfócitos T CD4-Positivos/imunologia , Estudos de Casos e Controles , Didanosina/efeitos adversos , Didanosina/uso terapêutico , Quimioterapia Combinada , Europa (Continente)/epidemiologia , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Israel/epidemiologia , Linfopenia , Masculino , Pessoa de Meia-Idade , Pancreatite/induzido quimicamente , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Fatores de Risco , Estavudina/efeitos adversos , Estavudina/uso terapêuticoRESUMO
BACKGROUND: Study 903 is a phase 3 trial with a completed 144-week, double-blind phase comparing tenofovir DF (TDF) with stavudine (d4T), in combination with lamivudine (3TC) and efavirenz (EFV), and an ongoing 336-week open-label extension phase. METHOD: Patients in 3 countries completing the d4T treatment phase were allowed to switch d4T to TDF and receive once-daily TDF+3TC+EFV in the extension phase. RESULTS: At the time of switch, 100% and 99% of patients (n = 85; 60% male, 64% White; mean age 37 years; mean CD4 = 650 cells/mm3) had HIV RNA <400 and <50 copies/mL. At 144 weeks after the switch, 89% (missing = failure) had HIV RNA <400 copies/mL and 87% had HIV RNA <50 copies/mL. Mean CD4 cell count increased 155 cells/mm3. No patient had virologic failure. Significant decreases from switch to week 144 in mean fasting total cholesterol (-22 mg/dL, p < .0001) and triglycerides (-78 mg/dL, p < .0001) were observed. Mean limb fat increased significantly from 4.5 kg to 5.8 kg, 144 weeks after switch (p < .0001). CONCLUSION: In virologically suppressed patients, switching d4T to TDF as part of a once-daily regimen with 3TC and EFV resulted in maintenance of virologic suppression and continued CD4 cell increases through 144 weeks, with significant improvements in metabolic parameters.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Organofosfonatos/uso terapêutico , Estavudina/uso terapêutico , Adenina/efeitos adversos , Adenina/uso terapêutico , Tecido Adiposo , Adulto , Alcinos , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Argentina , Benzoxazinas/efeitos adversos , Brasil , Contagem de Linfócito CD4 , Colesterol/sangue , Ciclopropanos , República Dominicana , Feminino , Humanos , Lamivudina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Organofosfonatos/efeitos adversos , Placebos/administração & dosagem , Estavudina/efeitos adversos , Tenofovir , Triglicerídeos/sangue , Carga ViralRESUMO
Nucleoside analog reverse transcriptase inhibitors (NRTI) have been used to treat HIV-infected patients for >10 years. Some severe adverse events have been attributed to mitochondrial dysfunction. Since 1991, cases of severe lactic acidosis have been reported in association with nucleoside therapy. Our objective was to report two cases of metabolic acidosis and hepatic steatosis in patients receiving stavudine (d4T) and to review the literature. A male and a female, 47 and 45 years of age, respectively, presented with abdominal pain, nausea, vomiting, and weakness after 9 and 6 months, respectively, of treatment with stavudine. At presentation, both patients had severe metabolic acidosis and liver failure. Ultrasonography showed hepatic steatosis (confirmed by biopsy in one case). All antiretroviral drugs were withdrawn and patients were treated with bicarbonate. Both patients developed fulminant liver dysfunction and multiple organ failure. We reviewed the literature and found 75 cases of lactic acidosis and hepatic steatosis associated with use of NRTI; 57 of these patients received d4T (76%). Of all cases reported in association with nucleoside therapy, 63% were females and mortality was 47%. General weakness, hepatic enzyme elevation, and liver steatosis are data that should alert physicians to this serious adverse event and to respond with prompt interruption of antiretroviral drugs and measurement of lactic acid in plasma. It is important to report serious adverse events in commercially released drugs to know prevalence in an exposed population. Physicians should be aware of risk and early signs of this serious adverse event.
Assuntos
Acidose Láctica/induzido quimicamente , Fármacos Anti-HIV/efeitos adversos , Fígado Gorduroso/induzido quimicamente , Inibidores da Transcriptase Reversa/efeitos adversos , Estavudina/efeitos adversos , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Evolução Fatal , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Transcriptase Reversa/uso terapêutico , Estavudina/uso terapêuticoRESUMO
Twenty-four subjects presenting at a single treatment center with primary HIV infection were enrolled in a pilot study aimed to establish the possible role of hydroxyurea in this setting. Study participants were randomly assigned to receive or not to receive hydroxyurea in addition to stavudine (d4T) plus didanosine (ddI) and nevirapine (NVP). Seventy-five percent of patients without hydroxyurea had plasma HIV RNA below 50 copies/mL at 48 weeks by both intention-to-treat (ITT) and on-treatment (OT) analysis in comparison with 50% (ITT) and 67% (OT) of patients with hydroxyurea (p >.1). A median increase of >200 cells/mm3 was observed from baseline to week 48 whether or not hydroxyurea was included in the regimen. Overall, in 12 patients treated with hydroxyurea, 33 adverse events were reported versus 19 reported for 12 patients who did not receive hydroxyurea (p <.05). Our results suggest that that adding hydroxyurea to a regimen of d4T plus ddI and NVP increases toxicity without improving the antiviral effect.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Hidroxiureia/efeitos adversos , Inibidores da Transcriptase Reversa/efeitos adversos , Adulto , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Didanosina/efeitos adversos , Didanosina/uso terapêutico , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Nevirapina/efeitos adversos , Nevirapina/uso terapêutico , Projetos Piloto , RNA Viral/sangue , Inibidores da Transcriptase Reversa/uso terapêutico , Estavudina/efeitos adversos , Estavudina/uso terapêutico , Viremia/tratamento farmacológicoRESUMO
We retrospectively reviewed the effects on the erythrocyte mean corpuscular volume (MCV) of the use of stavudine-including antiretroviral regimens in both zidovudine-naive and zidovudine-experienced HIV-infected patients. Macrocytosis was commonly observed among patients on stavudine-based regimens although the MCV usually stabilized at a lower level than that observed with zidovudine.
Assuntos
Anemia Macrocítica/induzido quimicamente , Fármacos Anti-HIV/efeitos adversos , Índices de Eritrócitos/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Estavudina/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , Feminino , Infecções por HIV/sangue , Humanos , Masculino , Estudos Retrospectivos , Estavudina/uso terapêuticoRESUMO
Type B lactic acidosis occurs without any evidence of cellular hypoxia and is associated with the use of drugs or toxins. We report a 36 years old woman with acquired immunodeficiency syndrome that was admitted to the hospital with a severe lactic acidosis. She had been treated with didanosine, stavudine and efavirenz for four months prior to admission. Despite the use of high bicarbonate doses and vasoactive drugs, the patient had a catastrophic evolution and died in shock and multiple organ failure, 68 hours after admission