RESUMEN
BACKGROUND: HIV infection affects millions of people globally. Currently, although several drugs have brought an improvement in the quality and life expectancy of these individuals, they are accompanied by several adverse effects. OBJECTIVE: To conduct a systematic review of studies examining the relationship between antiretroviral therapy (ART) uses and secondary dyslipidemia. METHODS: The review followed the criteria defined by PRISMA. Only articles that completely evaluated the lipid profile were included, which consisted of total cholesterol (TC), triglycerides (TG), and LDL cholesterol (LDL-c), HDL cholesterol (HDL-c). RESULTS: It was observed that the use of nucleoside and non-nucleoside reverse transcriptase inhibitor (NNRTI and NNRTI respectively) drugs and protease inhibitors are the most used in ART and are associated with changes in lipid profiles. The main changes observed were increases in TC, TG, and LDL-c in addition to a decrease in HDL-c. These patients had a higher risk of developing cardiovascular disease not only due to the use of therapy, but also due to the presence of other comorbidities evaluated in these studies, such as obesity, diabetes, and hypertension. The increase in age, the difference between genders, CD4 T-cell count, and viral load, were observed as risk factors for worsening dyslipidemia. CONCLUSION: According to the findings of this study, anti-HIV therapy is linked to dyslipidemia, which may or may not be the primary cause, and is frequently connected with a number of metabolic problems that can exacerbate the illness.
Asunto(s)
Dislipidemias , Infecciones por VIH , Adulto , Humanos , Femenino , Masculino , Terapia Antirretroviral Altamente Activa/efectos adversos , LDL-Colesterol/uso terapéutico , Inhibidores de la Transcriptasa Inversa/efectos adversos , HDL-Colesterol/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Dislipidemias/inducido químicamente , Dislipidemias/complicaciones , Dislipidemias/tratamiento farmacológico , Triglicéridos/uso terapéutico , Inhibidores de Proteasas/uso terapéuticoRESUMEN
BACKGROUND: It is well known that people living with HIV (PLWH) is in higher risk for the development of depression and it has also been suggested that the use of efavirenz into the antiretroviral regimens increases even that risk. OBJECTIVE: To evaluate the effect of efavirenz-containing antiretroviral regimens on the development of depression in newly ART initiated HIV patients in Ecuador. METHODS: In a prospective cohort study from June 2016 to May 2017, all newly HIV diagnosed patients at the HIV/AIDS Unit of the Hospital Eugenio Espejo in Quito, Ecuador were evaluated using the Hamilton Rating Scale for Depression followed by a second assessment 8-12 weeks after antiretroviral therapy containing efavirenz was initiated. RESULTS: A total of 79 patients, mainly males younger than 35 years were studied. Majority of them were on TDF/FTC/EFV. Initial score in Hamilton Rating Scale revealed that less than 30% had no depression symptoms while almost 40% had mild depression. However, in the second assessment, 22.6% of the subjects had a score in the Hamilton Rating Scale compatible with severe or very severe depression (RR 1.58, 95% CI 1.09 to 2.28; p = 0.05). CONCLUSION: In our cohort study, depression was much higher in patients on Efavirenz-containing treatments. Therefore, assessment for depression must be essential as part of follow-up in these patients.
Asunto(s)
Alquinos/efectos adversos , Benzoxazinas/efectos adversos , Ciclopropanos/efectos adversos , Depresión/inducido químicamente , Depresión/epidemiología , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Transcriptasa Inversa/efectos adversos , Adulto , Fármacos Anti-VIH/efectos adversos , Depresión/clasificación , Ecuador/epidemiología , Femenino , Infecciones por VIH/complicaciones , Humanos , Masculino , Estudios Prospectivos , Adulto JovenRESUMEN
Non-nucleoside reverse transcription inhibitor (NNRTI)-containing antiretroviral therapy (ART) for the prevention of mother to child transmission (PMTCT) of human immunodeficiency virus (HIV) has led to dramatic reductions in perinatal HIV infection in resource-constrained settings. Nonetheless, PMTCT programs are complicated by repeat pregnancies, in which long-term or repeat exposures to PMTCT regimens over time may lead to the acquisition of HIV drug resistance mutations, and consequent treatment failure. In this study, we retrospectively assessed the effectiveness of the NNRTI-based PMTCT protocol from 2008 to 2010 in The Bahamas National HIV/AIDS Program. We show that women who had been in repeat pregnancies and those who were already prescribed ART at conception were at increased risk of virologic failure, relative to treatment-inexperienced women and primigravida, respectively (AOR 3.1, 95% CI: 1.3-7.1, p = .008 and AOR 5.0, 95% CI: 1.8-14.1, p = .002). In addition, women undergoing treatment at conception were more likely to possess HIVDR mutations relative to treatment-naive women (AOR 447.1, 95% CI: 17.9-11,173.5, p = .001). Therefore, individual treatment history is a key metric determining the effectiveness of current and future PMTCT interventions. The implications of this to PMTCT programmatic success in light of the most recent WHO guidelines are discussed.
Asunto(s)
Terapia Antirretroviral Altamente Activa/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Inhibidores de la Transcriptasa Inversa/efectos adversos , Adulto , Estudios Transversales , Femenino , Infecciones por VIH/transmisión , Humanos , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/virología , Estudios Retrospectivos , Inhibidores de la Transcriptasa Inversa/clasificación , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Factores de Riesgo , Carga ViralRESUMEN
OBJECTIVES: Neuropsychiatric adverse effects (NPAE) related to efavirenz, mainly dizziness, is detrimental to human immunodeficiency virus (HIV) treatment. Our study aims at evaluating if zidovudine use potentiates the risk of dizziness related to efavirenz when used together and whether there are significant differences in over time distribution of this NPAE and others relatively frequents regarding efavirenz regimen without zidovudine. METHODS: Human immunodeficiency virus-infected patients under efavirenz-containing different therapy were enrolled. A retrospective analysis of official medical records was accomplished to collect clinical data regarding NPAE occurrence and severity. Univariate statistic and statistical model based on survival analyses were performed. KEY FINDINGS: One hundred sixty-two patients were included, of these seventy-seven (47.5%) had NPAE reported, such as dizziness (more frequent), depression and insomnia. Univariate statistical analysis demonstrated that the combined use of efavirenz with zidovudine increased the NPAE risk (OR: 2.5; P-value: 0.008), mainly dizziness risk (OR: 3.5; P-value: 0.009) and survival analysis showed that such combination is associated with dizziness occurrence faster (HR: 2.9; P-value: 0.02). CONCLUSIONS: The results may contribute to clarify the dizziness occurrence dynamics in therapy with efavirenz and zidovudine by identifying susceptibilities and assisting in the choice of combined antiretroviral therapy.
Asunto(s)
Alquinos/efectos adversos , Fármacos Anti-VIH/efectos adversos , Benzoxazinas/efectos adversos , Ciclopropanos/efectos adversos , Mareo/inducido químicamente , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Transcriptasa Inversa/efectos adversos , Zidovudina/efectos adversos , Adulto , Brasil , Depresión/inducido químicamente , Quimioterapia Combinada/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trastornos del Inicio y del Mantenimiento del Sueño/inducido químicamente , Análisis de Supervivencia , Factores de TiempoRESUMEN
OBJECTIVES: The aim of the review was to elucidate the adverse effects of chronic treatment with the main subclasses of highly active antiretroviral therapy (HAART). METHODS: A systematic review was carried out using the methods recommended in the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P). Searches of articles in MEDLINE, SCIELO, Web of Science and LILACS were conducted from January to October 2018 based on the following descriptors and keywords: 'HIV' [AND]; 'AIDS' [OR]; 'HAART' [AND]; 'Highly Active Antiretroviral Therapy' [OR]; 'Adverse Effects' [AND]. All articles selected described the biochemical changes produced by, and the main adverse effects of, using one or more of the following HAART subclasses: nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and other new drugs. The selected articles included patients living with HIV (PLWH) initiating or continuing any type of HAART. The results are presented qualitatively and discussed. RESULTS: Twenty-one articles found in the searches were selected for the review, and they included a total of 5626 participants. Seven of the studies investigated mainly NRTIs, three studies mainly NNRTIs, eight studies predominantly PIs, and three studies other antiretroviral drugs as the main treatment. The most common adverse effects on biochemical parameters were the emergence of anaemia for NRTIs as well as NNRTIs and PIs, and plasma lipid alterations caused by their prolonged use. In general, it was found that biological differences among individuals can cause differences in adverse effects, such as virological and treatment failure. CONCLUSIONS: One or more occurrences of adverse effects of the chronic utilization of drugs were found for all subclasses of HAART, and certain combinations of drugs from different subclasses were also found to be associated with adverse events.
Asunto(s)
Terapia Antirretroviral Altamente Activa/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Ensayos Clínicos como Asunto , Humanos , Inhibidores de Proteasas/efectos adversos , Inhibidores de Proteasas/uso terapéutico , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Limited data exist on efavirenz pharmacokinetics in HIV-positive pregnant women and neonatal washout. METHODS: HIV-infected pregnant women receiving 600 mg efavirenz once daily had intensive steady-state 24-h pharmacokinetics profiles during the second trimester (2T), third trimester (3T) and 6-12 weeks postpartum (PP). Maternal and umbilical cord blood samples were drawn at delivery and neonatal washout pharmacokinetics were determined. Therapeutic targets were the estimated 10th percentile efavirenz area under the concentration-time curve (AUC) in non-pregnant historical controls (40.0 µgâ¢h/ml) and a trough concentration (C24 h) of 1 µg/ml. Data were prospectively collected within two trials: IMPAACT P1026s (United States) and PANNA (Europe). RESULTS: Among 42 women studied, 15, 42 and 40 had efavirenz pharmacokinetic data available in 2T, 3T and PP, respectively. Median (range) 3T age 33 (20.7-43.5) years, weight 74 (50-132) kg and gestational age 33.4 (28.4-37.9 weeks). Efavirenz AUC during the 3T (60 µgâ¢h/ml) was similar to that reported in non-pregnant adults (58 µgâ¢h/ml). Exposure in the 2T was lower, but within the 0.80-1.25 range. C24 concentrations during pregnancy were lower compared to historical controls on 600 mg efavirenz, however, they were similar to the C24 concentrations after equally potent dose of 400 mg efavirenz. Cord blood/maternal plasma concentration ratio (range) was 0.67 (0.36-0.95). Among 23 infants with washout data available, median (interquartile range) elimination half-life was 65.6 h (40.6-129). HIV RNA viral loads at delivery were <400 and <50 copies/ml for 96.7% and 86.7% of women, respectively. In 3T and PP, respectively, 8/41 (19%) and 6/40 (15%) had AUC below target; 7/41 (17%) and 3/39 (8%) had C24 below target. CONCLUSIONS: Efavirenz exposure was similar during pregnancy compared with PP, C24 was in line with C24 after 400 mg equipotent efavirenz dosing. Efavirenz readily crossed the placenta and infant elimination half-life was over twice that of maternal participants. Clincaltrials.gov identifiers: NCT00825929 and NCT00042289.
Asunto(s)
Benzoxazinas/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Transcriptasa Inversa/farmacocinética , Adolescente , Adulto , Alquinos , Terapia Antirretroviral Altamente Activa , Benzoxazinas/administración & dosificación , Benzoxazinas/efectos adversos , Niño , Preescolar , Ciclopropanos , Monitoreo de Drogas , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/diagnóstico , Infecciones por VIH/virología , Humanos , Lactante , Recién Nacido , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Inhibidores de la Transcriptasa Inversa/efectos adversos , Resultado del Tratamiento , Adulto JovenAsunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Pirimidinas/administración & dosificación , Infecciones por VIH/prevención & control , VIH-1 , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Pirimidinas/efectos adversos , Vagina , Infecciones por VIH/epidemiología , Método Doble Ciego , Estudios Multicéntricos como Asunto , Factores de Edad , Cooperación del Paciente , Ensayos Clínicos Fase III como Asunto , Inhibidores de la Transcriptasa Inversa/efectos adversos , África Austral/epidemiología , Farmacorresistencia Viral , Ensayos Clínicos Controlados no Aleatorios como AsuntoRESUMEN
Objectives: There are limited data regarding efavirenz pharmacogenetics in admixed populations. The Brazilian population is highly admixed. In a Brazilian cohort, we sought to characterize associations between efavirenz adverse effects (all-cause and CNS) and polymorphisms in seven genes known or suspected to affect efavirenz metabolism and transport. Methods: We studied 225 HIV-positive individuals who had been prescribed efavirenz-containing regimens at a hospital in Rio de Janeiro, Brazil. Eighty-nine cases had efavirenz adverse effects, including 43 with CNS adverse effects, while 136 controls had no adverse effect of any antiretroviral after treatment for at least 6 months. A total of 67 candidate polymorphisms in ABCB1, CYP2A6, CYP2B6, CYP3A4, CYP3A5, NR1I2 and NR1I3 genes were selected for association analysis. Admixture was assessed using 28 ancestry-informative polymorphisms previously validated for the Brazilian population. Associations were evaluated with logistic regression models adjusted for sex and genetic ancestry. Results: There was extensive African, European and Native American admixture in the cohort. Increased all-cause adverse effects were associated with the CYP2B6 genotype combination 15582CC-516TT-983TT (OR = 7.26, P = 0.003) and with the CYP2B6 slow metabolizer group 516TT or 516GT-983CT (OR = 3.10, P = 0.04). CNS adverse effects were nominally associated with CYP3A4 rs4646437 (OR = 4.63, P = 0.014), but not after adjusting for multiple comparisons. Conclusions: In a highly admixed Brazilian cohort, the CYP2B6 slow metabolizer genotype was associated with an increased risk of efavirenz adverse effects.
Asunto(s)
Benzoxazinas/efectos adversos , Benzoxazinas/metabolismo , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Infecciones por VIH/tratamiento farmacológico , Inactivación Metabólica/genética , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/metabolismo , Adulto , Anciano , Alquinos , Benzoxazinas/administración & dosificación , Brasil , Receptor de Androstano Constitutivo , Ciclopropanos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Inhibidores de la Transcriptasa Inversa/administración & dosificaciónRESUMEN
OBJECTIVE: To evaluate the prevalence of adverse drug reactions (ADR) and associated factors during the use of Highly Active Antiretroviral Therapy (HAART) in patients initiating treatment. METHODS: This is a cross-sectional analysis of a prospective study conducted in three public referral services specialized in HIV/AIDS care in Belo Horizonte, Brazil. Self-reported ADR and explanatory variables were obtained from face-to-face interview and from Information Systems. Associated factors with ADR were evaluated by logistic regression in SPSS software v.22. RESULTS: We included 399 patients, of which 85.5% reported at least one and 72.7% up to 5 ADRs after HAART initiation. Neurological reactions were the most frequent, with self-reported ADRs being distinct according to HAART regimen used. The global model showed higher chance of ADRs among females (OR = 3.52) and illicit drug users (OR = 2.28). Lower chance of ADRs was found for patients aged > 33 years (OR = 0.37), DTG/TDF/3TC users (OR = 0.41), and higher physical domain of quality of life (OR = 0.78). The model restricted to patients using the single-tablet regimen EFV/TDF/3TC showed lower ADRs among patients with CD4+ T lymphocyte count > 200 cells/mm3 (OR = 0.23) and higher independence domain of quality of life (OR = 0.74). The model restricted to DTG/TDF/3TC and to other regimens showed lower ADRs with higher physical domain of quality of life (OR = 0.74 and OR = 0.55, respectively). CONCLUSIONS: The prevalence of self-reported ADRs to first-line antiretroviral regimens was high and patients using DTG/TDF/3TC had a smaller number of ADRs. In addition to HAART regimen, sociodemographic, clinical, and quality of life characteristics were associated with ADRs.
Asunto(s)
Terapia Antirretroviral Altamente Activa/efectos adversos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Adolescente , Adulto , Anciano , Alquinos , Benzoxazinas/efectos adversos , Brasil , Estudios Transversales , Ciclopropanos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/administración & dosificación , Inhibidores de Integrasa VIH/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Humanos , Lamivudine/efectos adversos , Masculino , Persona de Mediana Edad , Oxazinas , Piperazinas , Estudios Prospectivos , Piridonas , Calidad de Vida , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Tenofovir/efectos adversos , Adulto JovenRESUMEN
This study aimed to identify the 516 G>T polymorphism of the CYP2B6 gene and evaluate its influence on central nervous system (CNS) side effect development in HIV-positive individuals undergoing Efavirenz (EFV) treatment in a population from southern Brazil. Additionally, we performed a survey on the clinical and epidemiological characteristics of our sample. In addition to medical records evaluation, whole blood of 89 individuals was analyzed for viral load, T lymphocyte count (CD4+ and CD8+), and the polymorphism. Considering the side effects of the CNS reported by individuals but without considering the genetic variables, no statistically significant association was noted between the adverse effects and the antiretroviral treatment (including or not EFV). In addition, no statistically significant difference was noted for the influence of genotype on the viral load or the number of T lymphocytes (CD4+ and CD8+) among individuals undergoing EFV treatment. This is the first study that investigated the impact of the 516 G>T polymorphism of the CYP2B6 gene among HIV-positive individuals from southern Brazil. Its clinical significance indicates the need for prospective studies in this population.
Asunto(s)
Benzoxazinas/efectos adversos , Sistema Nervioso Central/efectos de los fármacos , Citocromo P-450 CYP2B6/genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Polimorfismo Genético/genética , Inhibidores de la Transcriptasa Inversa/efectos adversos , Adulto , Alquinos , Benzoxazinas/uso terapéutico , Relación CD4-CD8 , Ciclopropanos , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Carga ViralRESUMEN
ABSTRACT This study aimed to identify the 516 G>T polymorphism of the CYP2B6 gene and evaluate its influence on central nervous system (CNS) side effect development in HIV-positive individuals undergoing Efavirenz (EFV) treatment in a population from southern Brazil. Additionally, we performed a survey on the clinical and epidemiological characteristics of our sample. In addition to medical records evaluation, whole blood of 89 individuals was analyzed for viral load, T lymphocyte count (CD4+ and CD8+), and the polymorphism. Considering the side effects of the CNS reported by individuals but without considering the genetic variables, no statistically significant association was noted between the adverse effects and the antiretroviral treatment (including or not EFV). In addition, no statistically significant difference was noted for the influence of genotype on the viral load or the number of T lymphocytes (CD4+ and CD8+) among individuals undergoing EFV treatment. This is the first study that investigated the impact of the 516 G>T polymorphism of the CYP2B6 gene among HIV-positive individuals from southern Brazil. Its clinical significance indicates the need for prospective studies in this population.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Polimorfismo Genético/genética , Infecciones por VIH/genética , Infecciones por VIH/tratamiento farmacológico , Sistema Nervioso Central/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Benzoxazinas/efectos adversos , Citocromo P-450 CYP2B6/genética , Estudios Prospectivos , Relación CD4-CD8 , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Carga Viral , Benzoxazinas/uso terapéutico , GenotipoRESUMEN
BACKGROUND: For second-line antiretroviral therapy, WHO recommends a boosted protease inhibitor plus nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs). However, concerns about toxicity and cross-resistance motivated a search for regimens that do not contain NRTIs. We aimed to assess whether boosted lopinavir plus raltegravir would be non-inferior to boosted lopinavir plus NRTIs for virological suppression in resource-limited settings. METHODS: A5273 was a randomised, open-label, phase 3, non-inferiority study at 15 AIDS Clinical Trials Group (ACTG) research sites in nine resource-limited countries (three sites each in India and South Africa, two each in Malawi and Peru, and one each in Brazil, Kenya, Tanzania, Thailand, and Zimbabwe). Adults with plasma HIV-1 RNA concentrations of at least 1000 copies per mL after at least 24 weeks on a regimen based on a non-NRTI inhibitor were randomly assigned (1:1) to receive oral ritonavir-boosted lopinavir (100 mg ritonavir, 400 mg lopinavir) plus 400 mg raltegravir twice a day (raltegravir group) or to ritonavir-boosted lopinavir plus two or three NRTIs selected from an algorithm (eg, zidovudine after failure with tenofovir and vice versa; NRTI group). Randomised group assignment was done with a computer algorithm concealed to site personnel, and stratified by HIV-1 RNA viral load, CD4 cell count, and intention to use zidovudine, with the groups balanced by each site. The primary endpoint was time to confirmed virological failure (two measurements of HIV-1 RNA viral load >400 copies per mL) at or after week 24 in the intention-to-treat population. Non-inferiority (10% margin) was assessed by comparing the cumulative probability of virological failure by 48 weeks. This trial was registered with ClinicalTrials.gov, NCT01352715. FINDINGS: Between March 13, 2012, and Oct 2, 2013, we randomly assigned 515 participants: 260 to the raltegravir group and 255 to the NRTI group; two participants in the raltegravir group and one in the NRTI group were excluded from analyses because of ineligibility. By the end of follow-up (October, 2014), 96 participants had virological failure (46 in the raltegravir group and 50 in the NRTI group). By 48 weeks, the cumulative probability of virological failure was 10·3% (95% CI 6·5-14·0) in the raltegravir group and 12·4% (8·3-16·5) in the NRTI group, with a weighted difference of -3·4% (-8·4 to 1·5), indicating that raltegravir was non-inferior, but not superior, to NRTIs. 62 (24%) participants in the raltegravir group and 81 (32%) in the NRTI group had grade 3 or higher adverse events; 19 (7%) and 29 (11%), respectively, had serious adverse events. Three participants in each group died, all from HIV-related causes. INTERPRETATION: In settings with extensive NRTI resistance but no available resistance testing, our data support WHO's recommendation for ritonavir-boosted lopinavir plus NRTI for second-line antiretroviral therapy. Ritonavir-boosted lopinavir plus raltegravir is an appropriate alternative, especially if NRTI use is limited by toxicity. FUNDING: National Institutes of Health.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Recursos en Salud/economía , Raltegravir Potásico/uso terapéutico , Adulto , África del Sur del Sahara , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa , Brasil/epidemiología , Recuento de Linfocito CD4 , Farmacorresistencia Viral , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , VIH-1/genética , Recursos en Salud/provisión & distribución , Accesibilidad a los Servicios de Salud/economía , Humanos , India/epidemiología , Lopinavir/administración & dosificación , Lopinavir/efectos adversos , Lopinavir/uso terapéutico , Malaui/epidemiología , Masculino , Área sin Atención Médica , Perú/epidemiología , ARN Viral/sangre , Raltegravir Potásico/administración & dosificación , Raltegravir Potásico/efectos adversos , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Tailandia/epidemiología , Carga ViralRESUMEN
Dear Editor, The prevalence of type 2 diabetes (DM-2) in HIV-infected patients and the concomitant use of metformin (MTF) and non-nucleoside reverse transcriptase inhibitors (NRTI) is rising. Through inhibition of NADH dehydrogenase and DNA pol-γ, both drugs hinder oxidative phosphorylation that may lead to lactic acidosis (LA). Among NRTIs, abacavir and tenofovir have the lowest mitochondrial toxicity, with only a few LA cases reported2-4. We describe here a case of MTF-associated LA (MALA) secondary to the interaction with NRTI.
Asunto(s)
Acidosis Láctica/inducido químicamente , Hipoglucemiantes/efectos adversos , Metformina/efectos adversos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Adulto , Terapia Antirretroviral Altamente Activa/efectos adversos , Terapia Antirretroviral Altamente Activa/métodos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Interacciones Farmacológicas , Infecciones por VIH/tratamiento farmacológico , Humanos , Hipoglucemiantes/administración & dosificación , Masculino , Metformina/administración & dosificación , Inhibidores de la Transcriptasa Inversa/administración & dosificaciónRESUMEN
BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) [also called drug-induced hypersensitivity syndrome (DIHS)] includes severe reactions to drugs that need to be promptly recognized by physicians. AIM: To explore heterogeneity in the clinical presentation of DRESS/DIHS at a large academic hospital in Latin America, using the criteria defined by the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) scoring system. METHODS: A retrospective medical record review of 60 patients with diagnostic suspicion of DRESS/DIHS admitted to our hospital between July 2008 and April 2012 was performed, including demographic data, clinical features, laboratory findings and treatment. RESULTS: Of the 60 patients, 27 fulfilled the criteria for DRESS/DIHS. Maculopapular exanthema (85.1%), fever (96.2%) and hepatic involvement (85.1%) were the most common features. Anticonvulsants were the most common causal drugs (77.7%); Phenytoin was the most common individual drug (44.4%), followed by carbamazepine (29.6%). All patients were treated initially with prednisone 1 mg/kg/day. Mortality rate was 4%. CONCLUSION: The major findings of this study (to our knowledge the largest collection of data on DRESS/DIHS in Latin America) include a positive statistical association between presence of atypical lymphocytes and higher levels of alanine aminotransferase (P < 0.001) and reinforce the importance of anticonvulsants in the pathogenesis of this severe reaction.
Asunto(s)
Síndrome de Hipersensibilidad a Medicamentos/patología , Eosinofilia/inducido químicamente , Adolescente , Adulto , Anciano , Alanina Transaminasa/análisis , Antiinfecciosos/efectos adversos , Anticonvulsivantes/efectos adversos , Niño , Síndrome de Hipersensibilidad a Medicamentos/etiología , Síndrome de Hipersensibilidad a Medicamentos/metabolismo , Síndrome de Hipersensibilidad a Medicamentos/mortalidad , Exantema/inducido químicamente , Femenino , Fiebre/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Adulto JovenRESUMEN
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.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Autoanticuerpos/aislamiento & purificación , Hipotiroidismo/epidemiología , Yoduro Peroxidasa/inmunología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Estavudina/uso terapéutico , Enfermedades de la Tiroides/epidemiología , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Adulto , Antirretrovirales/uso terapéutico , Enfermedades Asintomáticas/epidemiología , Enfermedades Asintomáticas/terapia , Recuento de Linfocito CD4 , Estudios Transversales , Didanosina/uso terapéutico , Femenino , Humanos , Hipotiroidismo/inducido químicamente , Hipotiroidismo/inmunología , Masculino , Prevalencia , Inhibidores de la Transcriptasa Inversa/efectos adversos , Estavudina/efectos adversos , Enfermedades de la Tiroides/tratamiento farmacológicoRESUMEN
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. .
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Autoanticuerpos/aislamiento & purificación , Hipotiroidismo/epidemiología , Yoduro Peroxidasa/inmunología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Estavudina/uso terapéutico , Enfermedades de la Tiroides/epidemiología , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Antirretrovirales/uso terapéutico , Enfermedades Asintomáticas/epidemiología , Enfermedades Asintomáticas/terapia , Estudios Transversales , Didanosina/uso terapéutico , Hipotiroidismo/inducido químicamente , Hipotiroidismo/inmunología , Prevalencia , Inhibidores de la Transcriptasa Inversa/efectos adversos , Estavudina/efectos adversos , Enfermedades de la Tiroides/tratamiento farmacológicoRESUMEN
According to evidence from randomized controlled trials and epidemiological data, the antiretroviral treatment (ART) of choice has consisted of the combination of 2 nucleoside analog reverse-transcriptase inhibitors (NRTI) plus 1 non-nucleoside analog reverse-transcriptase inhibitor (NNRTI) or a protease inhibitor (PI) for more than 17 years. There are several unresolved issues, notably the toxocity associated with NRTI, especially thymidine analogs, and the possibility of cross resistance, which may affect subsequent treatment. The development of new antiretroviral drugs with simpler dosing regimens and lower toxicity has led to evaluation of innovative strategies such as dual therapy for initial ART in treatment-naive, with the aim of preventing long-term toxicity and increasing treatment adherence. Despite encouraging results, some combinations have proven unsatisfactory. The strategies with favorable results to date consist of twice-daily lopinavir/ritonavir (LPV/r)-based regimens, those in the PROGRESS (LPV/r + raltegravir) and GARDEL (LPV/r + lamivudine) trials, and the combination of darunavir and raltegravir (NEAT 001 trial), although the latter observed a higher tendency (statistically nonsignificant) to virological failure in the dual combination arm. These trials were based on the use of NRTI-sparing regimens consisting of 2-3 fully- active agents for highly-active ART in treatment-naïve HIV-positive patients. Recent studies provide evidence supporting the use of NRTI-sparing regimens in HIV-infected patients with failure to an initial NNRTI-based ART regimen. The present review will discuss only LPV/r-based innovative strategies in initial ART regimens.
Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Lopinavir/uso terapéutico , Ritonavir/uso terapéutico , Terapias en Investigación , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Combinación de Medicamentos , Inhibidores de Integrasa VIH/administración & dosificación , Inhibidores de Integrasa VIH/efectos adversos , Inhibidores de Integrasa VIH/uso terapéutico , Inhibidores de la Proteasa del VIH/administración & dosificación , Humanos , Lopinavir/administración & dosificación , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Ritonavir/administración & dosificaciónRESUMEN
HIV/AIDS patients are probably more predisposed to vitamin E deficiency, considering that they are more exposed to oxidative stress. Additionally, there are an extensive number of drugs in the highly active antiretroviral therapy (HAART) regimens that may interfere with vitamin E concentrations. The objective of this study was to compare serum concentrations of alpha-tocopherol in 182 HIV/AIDS patients receiving different HAART regimens. The patients were divided into three groups according to regimen: nucleoside analog reverse-transcriptase inhibitors (NRTIs) + non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs); NRTIs + protease inhibitors + ritonavir; NRTIs + other classes. Alpha-tocopherol was assessed by high-performance liquid chromatography. Multiple linear regression analysis was used to evaluate the effects of HAART regimen, time of use, and compliance with the regimen on alpha-tocopherol concentrations. Alpha-tocopherol concentrations were on average 4.12 µmol/L lower for the NRTIs + other classes regimen when compared to the NRTIs + NNRTIs regimen (p = 0.037). A positive association (p < 0.001) was observed between alpha-tocopherol and cholesterol concentrations, a finding due, in part, to the relationship between liposoluble vitamins and lipid profile. This study demonstrated differences in alpha-tocopherol concentrations between patients using different HAART regimens, especially regimens involving the use of new drugs. Long-term prospective cohort studies are needed to monitor vitamin E status in HIV/AIDS patients since the beginning of treatment.
Asunto(s)
Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Deficiencia de Vitamina E/etiología , alfa-Tocoferol/sangre , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adulto , Fármacos Anti-VIH/uso terapéutico , Colesterol/sangre , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/complicaciones , Inhibidores de la Proteasa del VIH/efectos adversos , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Ritonavir/efectos adversos , Ritonavir/uso terapéutico , Vitamina E/sangre , Deficiencia de Vitamina E/sangreRESUMEN
The aim of the present study was to investigate the association between polymorphism in the interleukin-10 gene promoter at position -1082 in human immunodeficiency virus-infected patients who had presented allergic reaction due to efavirenz. The study included 63 patients treated at the Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil. Twenty-one patients who had presented allergic reaction to efavirenz were compared to 42 patients with no allergic reaction following exposure to this drug. Blood samples were collected for DNA extraction and submitted to the restriction fragment length polymorphism - polymerase chain reaction technique. The -1082AA genotype was significantly more frequent in allergic patients as compared to non-allergic patients (p=0.019; χ(2)=5.534; OR=3.625; 95% CI=1.210-10.860). Likewise the allele IL-10 -1082A was identified significantly more often among efavirenz allergic patients than in the non-allergic group (p=0.009; χ(2)=6.787; OR=3.029; 95% CI=1.290-7.111). These findings suggest that the polymorphism in the interleukin-10 gene promoter -1082G/A can be related to the development of allergic reactions to efavirenz.