RESUMEN
BACKGROUND & OBJECTIVES: As India and other developing countries are scaling up isoniazid preventive therapy (IPT) for people living with HIV (PLHIV) in their national programmes, we studied the feasibility and performance of IPT in terms of treatment adherence, outcome and post-treatment effect when given under programmatic settings. METHODS: A multicentre, prospective pilot study was initiated among adults living with HIV on isoniazid 300 mg with pyridoxine 50 mg after ruling out active tuberculosis (TB). Symptom review and counselling were done monthly during IPT and for six-month post-IPT. The TB incidence rate was calculated and risk factors were identified. RESULTS: Among 4528 adults living with HIV who initiated IPT, 4015 (89%) successfully completed IPT. IPT was terminated in 121 adults (3%) due to grade 2 or above adverse events. Twenty five PLHIVs developed TB while on IPT. The incidence of TB while on IPT was 1.17/100 person-years (p-y) [95% confidence interval (CI) 0.8-1.73] as compared to TB incidence of 2.42/100 p-y (95% CI 1.90-3.10) during the pre-IPT period at these centres (P=0.017). The incidence of TB post-IPT was 0.64/100 p-y (95% CI 0.04-1.12). No single factor was significantly associated with the development of TB. INTERPRETATION & CONCLUSIONS: Under programmatic settings, completion of IPT treatment was high, adverse events minimal with good post-treatment protection. After ruling out TB, IPT should be offered to all PLHIVs, irrespective of their antiretroviral therapy (ART) status. Scaling-up of IPT services including active case finding, periodic counselling on adherence and re-training of ART staff should be prioritized to reduce the TB burden in this community.
Asunto(s)
Infecciones por VIH , Tuberculosis , Adulto , Antituberculosos/efectos adversos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Incidencia , India/epidemiología , Isoniazida/efectos adversos , Proyectos Piloto , Estudios Prospectivos , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Tuberculosis/prevención & controlRESUMEN
BACKGROUND & OBJECTIVES: Cardiovascular disease (CVD) risk with low high-density lipoprotein cholesterol (HDL-C) and high triglycerides is common in the general population in India. As nevirapine (NVP)-based antiretroviral therapy (ART) tends to increase HDL-C, gene polymorphisms associated with HDL-C metabolism in HIV-infected adults on stable NVP-based ART were studied. METHODS: A cross-sectional study was conducted between January 2013 and July 2014 among adults receiving NVP-based ART for 12-15 months. Blood lipids were estimated and gene polymorphisms in apolipoprotein C3 (APOC3), cholesteryl ester transfer protein (CETP) and lipoprotein lipase (LPL) genes were analyzed by real-time polymerase chain reaction. Framingham's 10-yr CVD risk score was estimated. Logistic regression was done to show factors related to low HDL-C levels. RESULTS: Of the 300 patients included (mean age: 38.6±8.7 yr; mean CD4 count 449±210 cell/µl), total cholesterol (TC) >200 mg/dl was observed in 116 (39%) patients. Thirty nine per cent males and 47 per cent females had HDL-C levels below normal while 32 per cent males and 37 per cent females had TC/HDL ratio of 4.5 and 4.0, respectively. Body mass index [adjusted odds ratio (aOR)=1.70, 95% confidence interval (CI) 1.01-2.84, P=0.04] and viral load (aOR=3.39, 95% CI: 1.52-7.52, P=0.003) were negatively associated with serum HDL-C levels. The 10-yr risk score of developing CVD was 11-20 per cent in 3 per cent patients. Allelic variants of APOC3 showed a trend towards low HDL-C. INTERPRETATION & CONCLUSIONS: High-risk lipid profiles for atherosclerosis and cardiovascular disease were common among HIV-infected individuals, even after 12 months of NVP-based ART. Targeted interventions to address these factors should be recommended in the national ART programmes.
Asunto(s)
Terapia Antirretroviral Altamente Activa , HDL-Colesterol/sangre , Infecciones por VIH/tratamiento farmacológico , Nevirapina/administración & dosificación , Adulto , Apolipoproteína C-III/sangre , Proteínas de Transferencia de Ésteres de Colesterol/sangre , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/virología , Humanos , Lipoproteína Lipasa/sangre , Masculino , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
BACKGROUND: WHO recommends the use of a simplified symptom-based algorithm for screening for tuberculosis (TB) among people living with HIV (PLHIV). We assessed the feasibility and effectiveness of this algorithm and determined the prevalence and incidence of TB among PLHIV attending antiretroviral treatment (ART) centres in India. METHODS: We did a prospective multicentric implementation research study in four states of India. To rule out TB, we administered the WHO symptom-screen algorithm to all PLHIV every month for 6 months. If they were found to be symptomatic any time during this period, they were referred for investigations for TB. A case of TB diagnosed during the first month of screening was taken as a prevalent case while those detected TB in the subsequent 5 months were considered cases of incident TB. We calculated the incidence rate using the person-years method. Results . Between May 2012 and October 2013, a total of 6099 adults and 1662 children living with HIV were screened for TB at the ART centres of four states. Of the 6099 adult PLHIV, 1815 (30%) had at least one symptom suggestive of TB, of whom only 634 (35%) were referred for investigations of TB. Of those referred, 97 (15%) PLHIV were diagnosed with TB. Overall, the prevalence of undiagnosed TB was 0.84 person-years and in the subsequent period, the incidence of TB was 2.4/100 person-years (95% CI 1.90-3.10). Among 1662 children, 434 (26%) had at least one symptom suggestive of TB. But only 57 (13%) children were referred for investigations of TB and 13 (23%) of them were diagnosed with TB. The prevalence of TB among children was 0.5% and its incidence among them was 2.7/100 person-years (95% CI 1.60-4.30). CONCLUSION: Prevalence and incidence of TB is high among PLHIV attending ART centres. This emphasizes the need to strengthen regular screening for symptoms of TB and further referral of those symptomatic for diagnosis of TB.
Asunto(s)
Infecciones por VIH/complicaciones , Tamizaje Masivo/métodos , Tuberculosis/diagnóstico , Adolescente , Adulto , Niño , Estudios de Factibilidad , Femenino , Infecciones por VIH/inmunología , Humanos , Incidencia , India/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Tuberculosis/epidemiología , Tuberculosis/inmunologíaRESUMEN
We compared the pharmacokinetics of rifampicin (RMP) during daily and intermittent (thrice weekly) anti-tuberculosis treatment in human immunodeficiency virus infected tuberculosis patients. Patients treated with a thrice-weekly regimen had significantly lower plasma peak concentration, area under the time concentration curve from 0 to 24 h and higher oral clearance of RMP than those treated with the daily regimen. The median values were respectively 3.7 and 6.4 µg/ml (P < 0.001), 20.7 and 29.4 µg/ml.h (P = 0.03) and 21.7 and 15.3 ml/min (P = 0.03).
Asunto(s)
Antituberculosos/administración & dosificación , Infecciones por VIH/complicaciones , Rifampin/administración & dosificación , Rifampin/farmacocinética , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto , Recuento de Linfocito CD4 , Esquema de Medicación , Femenino , Humanos , India , Masculino , Estudios ProspectivosRESUMEN
The objective of this report was to study the pharmacokinetics of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) in HIV-infected children with tuberculosis (TB) treated with a thrice-weekly anti-TB regimen in the government program in India. Seventy-seven HIV-infected children with TB aged 1 to 15 years from six hospitals in India were recruited. During the intensive phase of TB treatment with directly observed administration of the drugs, a complete pharmacokinetic study was performed. Drug concentrations were measured by high-performance liquid chromatography. A multivariable regression analysis was done to explore the factors impacting drug levels and treatment outcomes. The proportions of children with subnormal peak concentrations (Cmax) of RMP, INH, and PZA were 97%, 28%, and 33%, respectively. Children less than 5 years old had a lower median Cmax and lower exposure (area under the time-concentration curve from 0 to 8 h [AUC0-8]) of INH (Cmax, 2.5 versus 5.1 µg/ml, respectively [P=0.016]; AUC0-8, 11.1 versus 22.0 µg/ml·h, respectively [P=0.047[) and PZA (Cmax, 34.1 versus 42.3 µg/ml, respectively [P=0.055]; AUC0-8, 177.9 versus 221.7 µg/ml·h, respectively [P=0.05]) than those more than 5 years old. In children with unfavorable versus favorable outcomes, the median Cmax of RMP (1.0 versus 2.8 µg/ml, respectively; P=0.002) and PZA (31.9 versus 44.4 µg/ml, respectively; P=0.045) were significantly lower. Among all factors studied, the PZA Cmax influenced TB treatment outcome (P=0.011; adjusted odds ratio, 1.094; 95% confidence interval, 1.021 to 1.173). A high proportion of children with HIV and TB had a subnormal RMP Cmax. The PZA Cmax significantly influenced treatment outcome. These findings have important clinical implications and emphasize that drug doses in HIV-infected children with TB have to be optimized.
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Antituberculosos/farmacocinética , Antituberculosos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Tuberculosis/tratamiento farmacológico , Adolescente , Niño , Preescolar , Femenino , Humanos , India , Lactante , Isoniazida/farmacocinética , Isoniazida/uso terapéutico , Masculino , Pirazinamida/farmacocinética , Pirazinamida/uso terapéutico , Análisis de Regresión , Rifampin/farmacocinética , Rifampin/uso terapéutico , Resultado del TratamientoRESUMEN
SETTING: The currently recommended dosages of rifampicin (RMP), isoniazid (INH), pyrazinamide (PZA) and ethambutol in children are extrapolated from adult pharmacokinetic studies, and have not been adequately evaluated in children. OBJECTIVE: To describe the pharmacokinetics of RMP, INH and PZA given thrice weekly in children with tuberculosis (TB), and to relate pharmacokinetics to treatment outcomes. METHODS: Eighty-four human immunodeficiency virus negative children with TB aged 1-12 years in Chennai and Madurai, India, were recruited. Phenotypic INH acetylator status was determined. Nutritional status was assessed using Z scores. During the intensive phase of anti-tuberculosis treatment, a complete pharmacokinetic study was performed after directly observed administration of drugs. At 2 and 6 months, drug levels were measured 2 h post-dose. Drug concentrations were measured using high performance liquid chromatography and pharmacokinetic variables were calculated. Multivariable regression analysis was performed to explore factors impacting drug levels and treatment outcomes. RESULTS AND CONCLUSIONS: Children aged <3 years had significantly lower RMP, INH and PZA concentrations than older children, and 90% of all children had sub-therapeutic RMP Cmax (<8 µg/ml). Age, nutritional status and INH acetylator status influenced drug levels. Peak RMP and INH concentrations were important determinants of treatment outcome. Recommendations for anti-tuberculosis treatment in children should take these factors into consideration.
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Antituberculosos/farmacocinética , Isoniazida/farmacocinética , Pirazinamida/farmacocinética , Rifampin/farmacocinética , Acetilación , Factores de Edad , Antituberculosos/administración & dosificación , Antituberculosos/uso terapéutico , Niño , Preescolar , Cromatografía Líquida de Alta Presión , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , India , Lactante , Isoniazida/administración & dosificación , Isoniazida/uso terapéutico , Masculino , Análisis Multivariante , Estado Nutricional , Fenotipo , Pirazinamida/administración & dosificación , Pirazinamida/uso terapéutico , Análisis de Regresión , Rifampin/administración & dosificación , Rifampin/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento , Tuberculosis/tratamiento farmacológicoRESUMEN
We evaluated the effects of human immunodeficiency virus (HIV) disease on pharmacokinetics of antituberculosis medications by measuring concentrations of isoniazid and rifampin in blood and of pyrazinamide and ethambutol in urine. Peak concentration and exposure were reduced for rifampin, and rapid acetylators of isoniazid had lower drug levels. HIV and HIV-tuberculosis patients who have diarrhea and cryptosporidial infection exhibit decreased bioavailability of antituberculosis drugs.
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Antibióticos Antituberculosos/farmacocinética , Infecciones por VIH/metabolismo , Rifampin/farmacocinética , Acetilación , Adulto , Antituberculosos/farmacocinética , Disponibilidad Biológica , Etambutol/farmacocinética , Heces/microbiología , Femenino , Infecciones por VIH/complicaciones , Humanos , Absorción Intestinal , Isoniazida/farmacocinética , Masculino , Persona de Mediana Edad , Fenotipo , Pirazinamida/farmacocinética , Tuberculosis/complicaciones , Tuberculosis/metabolismoRESUMEN
The absorption of rifampin, isoniazid, and D-xylose in patients with human immunodeficiency virus (HIV) infection and diarrhea, in patients with HIV infection and tuberculosis (TB), in patients with pulmonary TB alone, and in healthy subjects was studied. Percentage of dose of the drugs, their metabolites, and D-xylose excreted in urine were calculated. A significant reduction in the absorption of drugs and D-xylose in both the HIV infection/diarrhea and HIV infection/TB groups was observed (P<.05), and the correlation between them was significant. Our results indicate that patients with HIV infection and diarrhea and those with HIV infection and TB have malabsorption of rifampin and isoniazid.
Asunto(s)
Antibióticos Antituberculosos/farmacocinética , Infecciones por VIH/metabolismo , Isoniazida/farmacocinética , Rifampin/farmacocinética , Tuberculosis/metabolismo , Adolescente , Adulto , Infecciones por VIH/complicaciones , Humanos , Absorción Intestinal , Síndromes de Malabsorción , Masculino , Persona de Mediana Edad , Tuberculosis/complicaciones , Xilosa/farmacocinéticaRESUMEN
In most settings in India, private pharmacies dispense prescriptions for anti-tuberculosis drugs made out by private practitioners. In a cross-sectional study, we assessed the dispensing practices for tuberculosis and knowledge about the national tuberculosis programme of 300 pharmacies. In all, 2800 prescriptions were dispensed monthly by the pharmacies. Doctors' prescriptions were for durations of several months, but half of the patients bought drugs one dose at a time for self-administration. This practice might promote drug resistance. Although 95% of pharmacists were not aware of the existence of the tuberculosis programme, the majority (97%) were willing to learn and contribute towards tuberculosis control. The need and the potential of private pharmacies for participation in tuberculosis control are highlighted.
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Antituberculosos/administración & dosificación , Conocimientos, Actitudes y Práctica en Salud , Farmacias/normas , Sector Privado , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/prevención & control , Estudios Transversales , Prescripciones de Medicamentos , Femenino , Humanos , India , Masculino , Programas Nacionales de Salud/organización & administración , Farmacias/tendencias , Prevención Primaria/organización & administración , Competencia ProfesionalRESUMEN
Among 155 patients who were initiated on continuous ambulatory peritoneal dialysis (CAPD), 4 patients (2 men, 2 women) developed tuberculous peritonitis. They had been on PD for between 2 months and 84 months when they developed the peritonitis. The Mantoux test was negative in all of them. The diagnosis was made by a variety of means in the various cases: demonstration of Mycobacterium tuberculosis in the peritoneal cavity; presence of caseating granuloma in a peritoneal biopsy; Mycobacterium tuberculosis in a cold abscess adjacent to the peritoneal cavity; and demonstration of IS6110 and MPB64 genes of Mycobacterium tuberculosis by polymerase chain reaction (PCR) technique. Two of the patients developed ultrafiltration failure. Among 3 patients who were switched to hemodialysis, 2 died and 1 continues on maintenance dialysis. The last patient, whose catheter was removed, was reimplanted with a new catheter and continues on PD without ultrafiltration failure. Any patient with peritonitis unresponsive to conventional therapy should be investigated for tuberculous peritonitis. Institution of chemotherapy without delay will preserve peritoneal membrane integrity.