ABSTRACT
BACKGROUND: Currently, there is no validated method for estimating antimicrobial consumption in the neonatal population, as it exists for adults using Defined Daily Doses (DDD). In neonatology, although there are different methods, each one with advantages and disadvantages, there is no unified criterion for use. The aim of this study is to validate the neonatal DDD designed as a new standardised form of antimicrobial consumption over this population. METHODS: The validation of the neonatal DDD, Phase II of the research project, was carried out through a descriptive observational study. Periodic cut-offs were performed to collect antimicrobial prescriptions of neonates admitted to the neonatology and intensive care units of nine Spanish hospitals. The data collected included demographic variables (gestational age, postnatal age, weight and sex), antimicrobial dose, frequency and route of administration. The selection of the optimal DDD value takes into account power value, magnitude obtained from the differences in the DDD, statistical significance obtained by the Wilcoxon test and degree of agreement in the stipulated doses. RESULTS: Set of 904 prescriptions were collected and finally 860 were analysed based on the established criteria. The antimicrobials were mostly prescribed in the intensive care unit (63.1%). 32 different antimicrobials were collected, and intravenous administration was the most commonly used route. Neonatal DDD were defined for 11 different antimicrobials. A potency > 80% was obtained in 7 antibiotics. The 57.1% of the selected DDD correspond to phase I and 21.4% from phase II. CONCLUSION: DDD validation has been achieved for the majority of intravenously administered antimicrobials used in clinical practice in the neonatal population. This will make it possible to have an indicator that will be used globally to estimate the consumption of antimicrobials in this population, thus confirming its usefulness and applicability.
ABSTRACT
BACKGROUND: Antimicrobial defined daily dose (DDD), a standardized metric to assess antimicrobial consumption in adult population, has limitations hampering its use in neonatal patients. This study proposes an alternative DDD design applicable for neonates. METHODS: Neonates (<1 month-old) from 6 Spanish hospitals during a 12-months period were included. Weight and weeks gestational age of each neonate were the variables collected. DDD (g) for each antimicrobial was calculated by multiplying the obtained weight times the recommended dose (mg/kg) of the antimicrobial for the most common infectious indication selected by the Delphi method. RESULTS: A total of 4820 neonates were included. Mean age was 36.72 weeks of gestational age and Mean weight was 2.687kg. Standardized DDD (intravenous; oral route) for representative antimicrobials were: Amoxicillin (0.08; 0.08), amoxicillin-clavulanic acid (0.27; 0.08), ampicillin (0.27; x), cloxacillin (0.13; 0.13), penicillin G sodium (0.12), cefazolin (0.13), cefuroxime (0.27; x), cefotaxime (0.27), ceftazidime (0.27), ceftriaxone (0.13), cefepime (0.27) piperacillin-tazobactam (0.54), aztreonam (0.24), azithromycin (0.03; 0.03), clindamycin (0.04; 0.04), amikacin (0.04), gentamicin (0.01), metronidazole (0.04; 0.08), ciprofloxacin (0.04; 0.05), levofloxacin (x;x), fluconazole (0.02; 0.02), itraconazole (0.01; 0.01), fosfomycin (0.27). Restricted antimicrobials: meropenem (0.11), teicoplanin (0.02), vancomycin (0.08; 0.11), linezolid (0.08; 0.08), daptomycin (x), amphotericin B liposomal (0.01). CONCLUSIONS: A useful method for antimicrobial DDD measurement in neonatology has been designed to monitor antimicrobial consumption in hospital settings. It should be validated in further studies and thereby included in the design for neonatal antimicrobial stewardship programs in the future.
Subject(s)
Anti-Infective Agents , Antimicrobial Stewardship , Anti-Bacterial Agents/therapeutic use , Ceftriaxone , Ciprofloxacin , Humans , Infant , Infant, NewbornSubject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Ampicillin/therapeutic use , Bronchiectasis , Pulmonary Disease, Chronic Obstructive , Administration, InhalationABSTRACT
BACKGROUND: Antimicrobial defined daily dose (DDD), a standardized metric to assess antimicrobial consumption in adult population, has limitations hampering its use in neonatal patients. This study proposes an alternative DDD design applicable for neonates. METHODS: Neonates (<1 month-old) from 6 Spanish hospitals during a 12-months period were included. Weight and weeks gestational age of each neonate were the variables collected. DDD (g) for each antimicrobial was calculated by multiplying the obtained weight times the recommended dose (mg/kg) of the antimicrobial for the most common infectious indication selected by the Delphi method. RESULTS: A total of 4820 neonates were included. Mean age was 36.72 weeks of gestational age and Mean weight was 2.687kg. Standardized DDD (intravenous; oral route) for representative antimicrobials were: Amoxicillin (0.08; 0.08), amoxicillin-clavulanic acid (0.27; 0.08), ampicillin (0.27; x), cloxacillin (0.13; 0.13), penicillin G sodium (0.12), cefazolin (0.13), cefuroxime (0.27; x), cefotaxime (0.27), ceftazidime (0.27), ceftriaxone (0.13), cefepime (0.27) piperacillin-tazobactam (0.54), aztreonam (0.24), azithromycin (0.03; 0.03), clindamycin (0.04; 0.04), amikacin (0.04), gentamicin (0.01), metronidazole (0.04; 0.08), ciprofloxacin (0.04; 0.05), levofloxacin (x;x), fluconazole (0.02; 0.02), itraconazole (0.01; 0.01), fosfomycin (0.27). Restricted antimicrobials: meropenem (0.11), teicoplanin (0.02), vancomycin (0.08; 0.11), linezolid (0.08; 0.08), daptomycin (x), amphotericin B liposomal (0.01). CONCLUSIONS: A useful method for antimicrobial DDD measurement in neonatology has been designed to monitor antimicrobial consumption in hospital settings. It should be validated in further studies and thereby included in the design for neonatal antimicrobial stewardship programs in the future.
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PURPOSE: The successful use of nadolol as an alternative to propranolol therapy in three cases of infantile hemangioma is reported. SUMMARY: Infantile hemangioma is a benign vascular neoplastic disorder that affects up to 10% of newborns and can lead to deformity or local complications in severe cases. Propranolol, administered alone or in combination with corticosteroids, is increasingly used to treat infantile hemangioma, but its ability to cross the blood-brain barrier and potentially cause central nervous system adverse effects has prompted research on alternative ß-blocker therapies for the disorder that have more favorable safety profiles, including nadolol. This article describes the use of nadolol to treat three pediatric patients with a buccal or genital hemangioma who developed adverse reactions (mainly, irritability and sleep disturbances) or resistance to initial treatment with propranolol. The patients were 10 months, 12 months, and 4 years of age, respectively, when hemangioma treatment was initiated. The results of nadolol therapy were favorable, with involution of lesions and gradual disappearance of propranolol-associated adverse effects occurring in all three cases. As with any use of ß-blocker therapy in a pediatric patient, a cardiac workup is advised before the start of nadolol therapy; blood pressure and heart rate monitoring should be performed at one and two hours after the first dose and continued during dose escalation. CONCLUSION: Nadolol was an effective alternative to propranolol in three pediatric patients with hemangiomas.
Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Hemangioma/drug therapy , Nadolol/therapeutic use , Skin Neoplasms/drug therapy , Blood Pressure/drug effects , Child, Preschool , Female , Heart Rate/drug effects , Hemangioma/pathology , Humans , Infant , Propranolol/therapeutic use , Skin Neoplasms/pathology , Treatment OutcomeSubject(s)
Anti-HIV Agents/administration & dosage , HIV Infections/drug therapy , HIV Protease Inhibitors/administration & dosage , Lopinavir/administration & dosage , Oligopeptides/administration & dosage , Pyridines/administration & dosage , Ritonavir/administration & dosage , Adolescent , Atazanavir Sulfate , Child , Female , HIV-1/isolation & purification , Humans , Male , RNA, Viral/blood , Treatment Outcome , Viral LoadABSTRACT
BACKGROUND: Sustained virologic response to peginterferon plus ribavirin reduces liver-related complications and mortality in patients co-infected with HIV and hepatitis C virus. Therefore, the presence of any barriers to start hepatitis C virus therapy should be identified and eliminated in order to recruit all eligible patients. METHODS: Cross-sectional study. In a HIV referral clinic we assessed the proportion of patients eligible for hepatitis C virus evaluation and treatment according to consensus guidelines. RESULTS: We identified 134 patients with hepatitis C virus and HIV co-infection. Twenty-one patients were excluded from the analysis due to never attending the HIV clinic (n=12) or having hepatitis C virus RNA not detectable (n=9). In the remaining 113 patients, only 61% had identification of hepatitis C virus genotype and quantification of hepatitis C viral load. Thirty-six patients started peginterferon plus ribavirin, and 16 (44%) achieved sustained virologic response. Seventy-seven patients did not receive treatment for hepatitis C virus due to the presence of medical contraindications (n=22), provider barriers (n=15), or patient barriers (n=40). Multivariate analysis identified lower education degree (odds ratio: 4.53; 95% confidence intervals: 1.36-15.16, p=0.014) and patient civil status single, separated or widower (odds ratio: 4.81; 95% confidence intervals: 1.54-14.99, p=0.007) as the independent determinants associated to not initiating therapy for hepatitis C virus infection in patients with barriers. CONCLUSION: A minor proportion of HIV-infected patients received appropriate assessment and treatment for hepatitis C virus infection. Social disadvantages require multidisciplinary models of health care to improve hepatitis C virus treatment initiation and success.
Subject(s)
Antiviral Agents/therapeutic use , HIV Infections/diagnosis , HIV Infections/drug therapy , Hepacivirus/isolation & purification , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Adult , Cross-Sectional Studies , Drug Therapy, Combination , Educational Status , Female , HIV Infections/epidemiology , Hepatitis C/epidemiology , Humans , Interferon alpha-2 , Interferon-alpha/administration & dosage , Male , Medical Records , Middle Aged , Polyethylene Glycols/administration & dosage , Recombinant Proteins , Ribavirin/administration & dosage , Risk Assessment , Risk Factors , Spain/epidemiology , Statistics, NonparametricABSTRACT
BACKGROUND: We incorporated the latest available information to evaluate the net benefit of using resistance testing in HIV-infected patients with virological failure. METHODS: Meta-analysis of randomized controlled trials comparing the clinical impact of selecting antiretroviral therapy according to results of resistance testing (phenotype or genotype) or according to the standard of care. The population studied included HIV-infected patients with virological failure. The outcome measures were the proportion of patients with HIV-RNA below the detection limit, and the decline in HIV-RNA and increase in CD4 lymphocyte count at the end of follow-up (< or = 24 weeks). Clinical trials were identified through searches in MEDLINE, EMBASE and proceedings from major infectious diseases meetings. RESULTS: Eight trials including a total of 1810 patients were eligible. Therapy guided by resistance testing resulted in a higher percentage of patients with HIV-1 RNA below the detection limit at the end of follow-up (< or = 24 weeks) as compared with the standard of care (40.2% vs. 32.9%). The pooled risk ratio was 1.23; 95% CI 1.09-1.40, p = 0.0009; test for heterogeneity I(2)=0%; p = 0.46). The number needed to treat [NNT] was 13 (95% CI: 9-25). Subgroup analysis showed greater benefits in therapy guided by genotype testing with expert interpretation, when compared with standard of care (NNT: 5; 95% CI: 3-9; p = 0.06). The heterogeneity among trials for evaluating HIV-1 RNA decline and CD4 lymphocyte cell count increase made unfeasible pooling the results across studies. CONCLUSION: Genotype testing with expert interpretation showed the greatest benefit for guiding therapy in patients with HIV infection and virological failure.
Subject(s)
Anti-HIV Agents/pharmacology , Antiretroviral Therapy, Highly Active , Drug Resistance, Viral , HIV Infections/drug therapy , HIV-1/drug effects , Microbial Sensitivity Tests/methods , Virology/methods , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , Follow-Up Studies , Genotype , HIV-1/genetics , Humans , Phenotype , RNA, Viral/blood , Randomized Controlled Trials as Topic , Retrospective Studies , Risk Factors , Treatment Failure , Treatment Outcome , Viral LoadABSTRACT
Antecedentes. Hemos incorporado la información más reciente para evaluar el beneficio obtenido tras realizar pruebas de resistencia en pacientes con infección por virus de la inmunodeficiencia humana (VIH) y fracaso virológico. Métodos. Metaanálisis de ensayos clínicos aleatorizados que comparaban el impacto clínico de los cambios de tratamiento antirretroviral dirigidos según el test de resistencia (fenotipo o genotipo) o según las recomendaciones estándar. La población estudiada fue los pacientes con infección por VIH y fracaso virológico. Las medidas de desenlace analizadas fueron: la proporción de pacientes con ARN-VIH no detectable, descenso de ARN-VIH e incremento de linfocitos CD4 al final del seguimiento. Los ensayos clínicos fueron identificados en búsquedas realizadas en Medline, Embase y libros de congresos. Resultados. Identificamos 8 ensayos clínicos y un total de 1.810 pacientes. El tratamiento guiado por tests de resistencia incrementó la proporción de pacientes con ARN-VIH no detectable (40,2% frente a 32,9%) al final del seguimiento (<= 24 semanas). El riesgo relativo combinado fue 1,23 (intervalo de confianza del 95% [IC 95%]: 1,09 a 1,41; p = 0,0009); no hubo heterogeneidad entre los estudios (I 2 5 0%; p = 0,46). El número de pacientes necesario a tratar (NNT) fue de 13 (8 a 27). El análisis de subgrupos identificó un mayor beneficio cuando se utilizaron tests de resistencia genotípicos interpretados por expertos (NNT: 5; IC 95%: 3 a 9; p = 0,06). Hubo heterogeneidad significativa entre los estudios al evaluar la reducción de ARN-VIH y el incremento de linfocitos CD4, ello impidió combinar los resultados. Conclusión. En pacientes con infección por VIH y fracaso virológico el mayor beneficio correspondió al tratamiento guiado por los tests genotípicos de resistencia interpretados por expertos (AU)
Background. We incorporated the latest available information to evaluate the net benefit of using resistance testing in HIV-infected patients with virological failure. Methods. Meta-analysis of randomized controlled trials comparing the clinical impact of selecting antiretroviral therapy according to results of resistance testing (phenotype or genotype) or according to the standard of care. The population studied included HIV-infected patients with virological failure. The outcome measures were the proportion of patients with HIV-RNA below the detection limit, and the decline in HIV-RNA and increase in CD4 lymphocyte count at the end of follow-up (<= 24 weeks). Clinical trials were identified through searches in MEDLINE, EMBASE and proceedings from major infectious diseases meetings. Results. Eight trials including a total of 1810 patients were eligible. Therapy guided by resistance testing resulted in a higher percentage of patients with HIV-1 RNA below the detection limit at the end of follow-up (<= 24 weeks) as compared with the standard of care (40.2% vs. 32.9%). The pooled risk ratio was 1.23; 95% CI 1.09-1.40, p = 0.0009; test for heterogeneity I 2 5 0%; p = 0.46). The number needed to treat [NNT] was 13 (95% CI: 9-25). Subgroup analysis showed greater benefits in therapy guided by genotype testing with expert interpretation, when compared with standard of care (NNT: 5; 95% CI: 3-9; p = 0.06). The heterogeneity among trials for evaluating HIV-1 RNA decline and CD4 lymphocyte cell count increase made unfeasible pooling the results across studies. Conclusion. Genotype testing with expert interpretation showed the greatest benefit for guiding therapy in patients with HIV infection and virological failure (AU)
Subject(s)
Humans , Anti-HIV Agents/pharmacology , Antiretroviral Therapy, Highly Active , Drug Resistance, Viral , HIV Infections/drug therapy , Virology/methods , Microbial Sensitivity Tests/methods , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , Follow-Up Studies , Genotype , HIV-1/genetics , Phenotype , Treatment OutcomeABSTRACT
BACKGROUND AND OBJECTIVE: To describe the immunological, virological and clinical outcomes of HIV-infected patients who stop antiretroviral therapy (ART) and to identify the factors related to durability. PATIENTS AND METHOD: Retrospective study of patients who interrupt therapy after six months without clinical events, level of CD4+ > or = 500 cells/microl and HIV RNA > or = 5,000 copies/ml (3.7 log10). RESULTS: In October 2004, 44 patients were included, 32 (72%) of them were stables after one year of ART cessation (group A) and 12 (28%) patients had to restart therapy due to a decreased CD4+ count < 300 cells/microl (group B). Both groups were compared. CD4 cell count nadir (414 cells/microl [199] versus 171 cells/microl [107]; p = 0.000) and CD4+ count level at time of ART stop (920 [302] cells/microl versus 633 cells/microl [177] p = 0.004) showed differences with statistical significance. The most important CD4+ count fall was observed at third month after stopping ART; 588 cells/microl (288) on group A and 382 cells/microl (167) on group B. The mean time without ART was 27 months on group A and 7 months on group B. Two patients had acute retroviral syndrome, and one had Pneumocystis jiroveci pneumonia. Cholesterol levels were 199 mg/dl (42) and triglycerides 257 mg/dl (271) on ART and during interruption decreased to 155 (38) and 165 (122) mg/dl respectively. After multivariate analysis, a CD4+ count nadir > 200 cells/microl (p = 0,0005; OR = 0,12; 95% CI, 0.036-0,398) and a CD4+ count at time of ART stop > 800 cells/microl (p = 0,04; OR: 0,11; CI 95%: 0,015-0,936) were independently related to durability of therapy interruption. CONCLUSIONS: Prolonged discontinuation of ART guided by CD4+ response causes a low morbi-mortality. The cell count CD4+ nadir and the CD4+ count at time of ART cessation are protective factors of durability. An improvement of metabolic parameters is observed during the discontinuation of ART.
Subject(s)
Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/virology , Withholding Treatment/statistics & numerical data , Adult , Anti-Retroviral Agents/adverse effects , CD4 Antigens/drug effects , CD4 Antigens/immunology , Cell Count , Chronic Disease , Female , HIV Infections/epidemiology , HIV Infections/immunology , Humans , Male , RNA, Viral/drug effects , RNA, Viral/immunology , Retrospective Studies , Retroviridae Infections/epidemiology , Retroviridae Infections/immunologyABSTRACT
Fundamento y objetivo: Describir la evolución inmunológica, virológica y clínica de los pacientes con infección crónica por el virus de la inmunodeficiencia humana (VIH) que suspenden el tratamiento antirretroviral (TAR) de forma prolongada e identificar los factores asociados con la durabilidad de la interrupción. Pacientes y método: Estudio retrospectivo de pacientes que suspenden el TAR tras haber alcanzado recuento de linfocitos CD4+ mayor o igual a 500 células/µl, carga viral del VIH menor o igual a 5.000 copias/ml (3,7 log10) y estabilidad clínica durante al menos 6 meses. Resultados: En octubre de 2004 se incluyeron 44 pacientes; 32 (72%) de ellos continuaban estables sin TAR tras el primer año de interrupción (grupo A) y 12 (28%) pacientes habían precisado reiniciarlo por disminución de los linfocitos CD4+ por debajo de 300 células/µl (grupo B). Entre ambos grupos se observaron diferencias estadísticamente significativas en el nadir de linfocitos CD4+, media (desviación estándar) de 414 (199) células/µl frente a 171 (107) células/µl (p = 0,000) y en los recuentos de linfocitos CD4+ en el momento de la suspensión de TAR, 920 (302) células/µl frente a 633 (177) células/µl (p = 0,004). Tras la interrupción del TAR el descenso más acusado de CD4+ se observó al tercer mes: 588 (288) células/µl para el grupo A y 382 (167) células/µl para el grupo B. La duración media de la interrupción fue de 27 meses en el grupo A y 7 meses en el grupo B. Dos pacientes presentaron síndrome retroviral agudo y otro una neumonía por Pneumocystis jiroveci. Los valores de colesterol con TAR fueron de 199 (42) mg/dl y los de triglicéridos de 257 (271) mg/dl disminuyeron significativamente durante el primer año de seguimiento hasta alcanzar 155 (38) y 165 (122) mg/dl respectivamente. Tras un análisis multivariante, un nadir de linfocitos CD4+ mayor de 200 células/µl (p = 0,0005; odds ratio [OR] = 0,12; intervalo de confianza [IC] del 95% 0,036-0,398) y un valor de linfocitos CD4+ superior a 800 c/µl en el momento de la interrupción de TAR (p = 0,04; OR = 0,11; IC del 95%, 0,015-0,936) se asociaron, de forma independiente, a mayor durabilidad de la suspensión del tratamiento. Conclusiones: Las interrupciones prolongadas del TAR guiadas por la respuesta de linfocitos CD4+ son una estrategia terapéutica que conlleva una baja morbimortalidad. El nadir de linfocitos CD4+ y el valor de linfocitos CD4+ en el momento de la interrupción del TAR pueden predecir la durabilidad de la suspensión. Se observa una mejoría metabólica durante el período libre de TAR
Background and objective: To describe the immunological, virological and clinical outcomes of HIV-infected patients who stop antiretroviral therapy (ART) and to identify the factors related to durability. Patients and method: Retrospective study of patients who interrupt therapy after six months without clinical events, level of CD4+ >= 500 cells/µl and HIV RNA >= 5.000 copies/ml (3,7 log10). Results: In October 2004, 44 patients were included, 32 (72%) of them were stables after one year of ART cessation (group A) and 12 (28%) patients had to restart therapy due to a decreased CD4+ count 200 cells/µl (p = 0,0005; OR = 0,12; 95% CI, 0.036-0,398) and a CD4+ count at time of ART stop > 800 cells/µl (p = 0,04; OR: 0,11; CI 95%: 0,015-0,936) were independently related to durability of therapy interruption. Conclusions: Prolonged discontinuation of ART guided by CD4+ response causes a low morbi-mortality. The cell count CD4+ nadir and the CD4+ count at time of ART cessation are protective factors of durability. An improvement of metabolic parameters is observed during the discontinuation of ART
Subject(s)
Male , Female , Adult , Humans , Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , Drug Administration Schedule , Antiretroviral Therapy, Highly Active/methods , Anti-HIV Agents/therapeutic use , Viral Load/statistics & numerical data , Retrospective Studies , CD4 Antigens/analysisABSTRACT
BACKGROUND AND OBJECTIVE: Dyslipidemia, insulin resistance and body fat redistribution are respectively short and long-term complications of protease inhibitor-containing antiretroviral regimens. To establish whether differences in the type of antiretroviral therapy (protease-containing or protease-sparing) or the presence and severity of body fat redistribution, explained differences in cardiovascular risk, we undertook a cross-sectional study. PATIENTS AND METHOD: The study was carried out in 219 consecutive HIV-infected patients attending an outpatient HIV clinic between February and April, 2002. Age, sex, smoking status, weight, height, waist circumference, blood pressure, antihypertensive treatment, total cholesterol, HDL cholesterol, triglycerides, and glucose concentrations, in addition to changes in body fat distribution were measured in 31 HIV-infected patients with no antiretroviral therapy, 35 HIV-infected patients treated with protease inhibitor-sparing regimens, and 153 HIV-infected patients treated with protease inhibitor-containing regimens. A ten-year cardiovascular disease risk was estimated according to the Framingham score. RESULTS: Patients treated with protease inhibitor-containing regimens as well as patients treated with protease inhibitor-sparing agents showed higher concentrations of cholesterol (p < 0.001), triglycerides (p = 0.004), glucose (p = 0.028), and greater changes in body fat distribution (p = 0.001) than patients with no antiretroviral therapy. An abnormal body fat distribution score was more strongly associated (p < 0.001) with the estimated 10-year cardiovascular disease risk than the type of HAART (p = 0.036). Ten-year cardiovascular disease risk increased linearly from 7.48% to 11.16% and to 19.50% in patients with no or mild, moderate and severe lipodystrophy scores, respectively. CONCLUSIONS: The results of this study encourage the use of cardiovascular preventive strategies in HIV-infected patients with severe lipodystrophy.
Subject(s)
Anti-HIV Agents/adverse effects , Cardiovascular Diseases/epidemiology , HIV-Associated Lipodystrophy Syndrome/complications , Adult , Aged , Cardiovascular Diseases/etiology , Cross-Sectional Studies , Female , HIV Infections/complications , HIV Infections/drug therapy , HIV Protease Inhibitors/adverse effects , HIV-Associated Lipodystrophy Syndrome/etiology , Humans , Male , Middle Aged , Risk FactorsABSTRACT
We examined the risk and determinants of developing severe liver toxicity in 108 HIV-infected patients showing adherence to nevirapine- and efavirenz-containing regimens. Between January 1997 and December 2000, 70 patients were treated with nevirapine- and 38 patients with efavirenz-containing regimens, for a median period of 127 days (interquartile range 65-240). Severe liver toxicity was defined as grade 3-4 elevations (>5 x upper limit of normal) of aminotransferases AST or ALT. A total of 22 (20%) patients showed severe liver toxicity, 17 of them were treated with nevirapine- and five with efavirenz-containing regimens (relative risk [RR]: 1.85, 95% confidence intervals [CIs] 0.74-4.61; P=not significant). Multivariate analysis showed the association of severe liver toxicity with hepatitis C antibody positive (RR 7.64; 95% CI: 1.48-39.52; P=0.01), nevirapine- or efavirenz-containing regimens combined with a protease inhibitor (RR: 3.07, 95% CI: 1.01-9.32, P=0.04) and alcohol intake greater than 40 g per day (RR: 3.09, 95% CI: 1.27-7.54, P=0.01). These findings have potential implications for selecting and monitoring antiretroviral therapy in HIV-infected patients with hepatitis C virus coinfection and for avoiding alcohol intake during antiretroviral therapy.
Subject(s)
Anti-HIV Agents/adverse effects , Chemical and Drug Induced Liver Injury , HIV Infections/drug therapy , Nevirapine/adverse effects , Oxazines/adverse effects , Adult , Alanine Transaminase/blood , Alcoholism/blood , Alcoholism/complications , Alkynes , Benzoxazines , Cohort Studies , Cyclopropanes , Drug Therapy, Combination , Female , HIV Infections/complications , HIV Protease Inhibitors/adverse effects , Hepatitis C Antibodies/blood , Hepatitis C, Chronic/complications , Humans , Liver Diseases/blood , Male , Multivariate Analysis , Reverse Transcriptase Inhibitors/adverse effects , Risk , Risk Factors , Transaminases/bloodABSTRACT
FUNDAMENTO: Valoración de la respuesta inmunológica, virológica y clínica de pacientes con infección por el VIH que inician tratamiento antirretroviral con inhibidores de la proteasa (IP) en un hospital comarcal. Identificar los factores asociados a la aparición de infecciones. PACIENTES Y MÉTODO: Análisis retrospectivo de pacientes en tratamiento antirretroviral, valorando los recuentos de linfocitos CD4+, carga viral ARN-VIH (Amplicor) y aparición de infecciones durante el primer año de tratamiento con IP (Grupo A), y estudio comparativo con los datos analíticos y clínicos de estos mismos pacientes durante el año previo a la introducción de los IP (grupo B).RESULTADOS: Se incluyeron 134 pacientes en el grupo A y 84 en el B. El nadir de CD4+ fue de 169 × 106/l. Después de 6 meses de tratamiento con IP, la media de CD4+ aumentó de 217 a 355 × 106/l y la mediana de carga viral ARN-VIH descendió de 88.000 copias/ml (14.000485.000) a menos de 400 copias/ml (menos de 400-9.000). El 60 por ciento de los pacientes presentaban menos de 400 copias/ml. La incidencia de infecciones no oportunistas en los grupos A y B no se modificó (36 frente a 43 por ciento, p = NS). Sin embargo el grupo tratado con IP presentó una incidencia significativamente menor de infecciones oportunistas (el 15 frente al 30 por ciento) (OR: 0,41 [IC, 0,21-0,81]; p = 0,007), particularmente neumonía por Pneumocystis carinii y toxoplasmosis. En el análisis multivariado incluyendo linfocitos CD4+, carga viral, nadir de CD4+ y grupo de riesgo, únicamente el nadir de CD4+ superior a 100 × 106/l se asoció con una menor probabilidad de desarrollar infecciones oportunistas (OR: 0,2 [IC, 0,1-0,7]; p = 0,001).CONCLUSIONES: El tratamiento antirretroviral con IP consigue una mejoria inmunológica y virológica y reduce significativamente la incidencia de infecciones oportunistas. El nadir de linfocitos CD4+ superior a 100 × 106/l supone un marcador de buen pronóstico durante el primer año con IP, independientemente de la respuesta obtenida (AU)
