Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An emergence of drug-resistant tuberculosis (DR-TB) in settings affected by human immunodeficiency virus (HIV) and tuberculosis (TB) has been observed. We investigated the prevalence of DR-TB in P1041, a multicentered, randomised, double-blind trial which compared the administration of isoniazid (INH) to placebo, in HIV-exposed, non-infected and -infected African infants in the absence of any documented TB exposure. The prevalence of multidrug-resistant TB (MDR-TB) was 22.2% (95%CI 8.5-45.8) and INH monoresistance 5.6% (95%CI 0.1-27.6) among culture-confirmed cases, with all MDR-TB occurring in a single site. There was no association between INH treatment or placebo group, or between HIV infection status, and DR-TB prevalence. There was a high prevalence of DR-TB among HIV-exposed and -infected children. Surveillance of DR-TB among children in high-burden TB-HIV settings should be routine.
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PMID:High prevalence of drug resistance amongst HIV-exposed and -infected children in a tuberculosis prevention trial. 2223 19

Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide and the main cause of death in correctional facilities in middle- and low-income countries. Due to the closed environment and the concentration of individuals with TB-related risk factors, effective measures are required to control TB in such settings. Isoniazid preventive therapy (IPT) represents an effective and cost-effective measure. Despite international recommendations that IPT be integral to TB control, it is seldom deployed. A systematic review of interventions used to assess IPT initiation and completion in correctional facilities was conducted using published studies from two biomedical databases and relevant keywords. Additional references were reviewed, resulting in 18 eligible studies. Most (72%) studies were conducted in the United States and in jail settings (60%), with the main objective of improving completion rates inside the facility or after release. Studies that provided data about initiation and completion rates showed poor success in correctional facilities. Adverse consequences and treatment interruption ranged from 1% to 55% (median 5%) in reported studies; hepatotoxicity was the most prevalent adverse reaction. Despite its accelerating effect on the development of active TB, information on human immunodeficiency virus (HIV) status was provided in only half of the studies. Among the four studies where IPT effectiveness was assessed, the results mirror those described in community settings. Future studies require thorough assessments of IPT initiation and completion rates and adverse effects, particularly in low- and middle-income countries and where comorbid viral hepatitis may contribute significantly to outcomes, and in settings where TB and HIV are more endemic.
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PMID:Isoniazid preventive therapy in correctional facilities: a systematic review. 2241 Jan 1

Tuberculosis (TB) is the most common opportunistic infection in human immunodeficiency virus (HIV)-infected patients and the emergence of drug-resistant tuberculosis (DR-TB) is a growing problem in resource-limited settings. Adequate infrastructure for testing drug sensitivity and sufficient evidence of first-line resistance are currently unavailable in Nigeria. We collected sputum samples from HIV-infected patients enrolled in the Harvard PEPFAR/APIN Plus program over 12 months at two PEPFAR antiretroviral therapy (ART) clinics in the southwest and north central regions in Nigeria. Smear-positive sputum samples were submitted for GenoType MTBDRplus testing (n = 415); mutations were confirmed through sequencing. Our results show high rates of DR-TB in Nigerian HIV-infected individuals (7.0% for rifampin [RIF] and 9.3% for RIF or isoniazid [INH]). Total RIF resistance indicative of MDR-TB in treatment-naive patients was 5.52%, far exceeding the World Health Organization predictions (0 to 4.3%). RIF resistance was found in 6/213 (2.8%) cases, INH resistance was found in 3/215 (1.4%) cases, and MDR-TB was found in 8/223 (3.6%) cases. We found significantly different amounts of DR-TB by location (18.18% in the south of the country versus 3.91% in the north central region [P < 0.01]). Furthermore, RIF resistance was genetically distinct, suggesting possible location-specific strains are responsible for the transmission of drug resistance (P < 0.04). Finally, GenoType MTBDRplus correctly identified the drug-resistant samples compared to sequencing in 96.8% of cases. We found that total DR-TB in HIV-infection is high and that transmission of drug-resistant TB in HIV-infected patients in Nigeria is higher than predicted.
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PMID:Genetic determinants of drug-resistant tuberculosis among HIV-infected patients in Nigeria. 2274 Jul 9

These national clinical guidelines outlining the screening, prophylaxis and critical information required prior to initiating anti-TNF-alpha treatment have been approved by the Danish Society for Gastroenterology. Anti-TNF-alpha therapy is widely used in gastroenterology (for inflammatory bowel disease), rheumatology (for rheumatoid arthritis, psoriatic arthritis and spondyloarthropathies) and dermatology (for psoriasis). With this background, the Danish Society for Gastroenterology established a group of experts to assess evidence for actions recommended before treatment with anti-TNF-alpha agents. Screening should take place for both active tuberculosis and latent tuberculosis. Screening must evaluate the risk of hepatitis B exposure/infection and that of other viral infections such as human immunodeficiency virus (HIV) and varicella zoster virus (VZV). The assessment should include a history of previous malignancies (cases of malignant disease within 5 years of anti-TNF-alpha treatment should be carefully considered). The physical examination should include lung/heart auscultation and lymph node examination, and the paraclinical investigations should include chest X-rays and laboratory tests, including an interferon gamma release assay, a hepatitis B test, an HIV test and, when prior VZV infection is uncertain, a VZV antibody test. Prophylaxis: Isoniazid should be administered in cases of suspected latent TB infection. Antiviral treatment is recommended in HBsAg-positive patients at the start of anti-TNF-alpha treatment. Before anti-TNF-alpha therapy, vaccination with 23-valent pneumococcal vaccine is recommended, and HBV vaccination may be considered in seronegative patients. Annual vaccination against seasonal influenza is recommended. Human papilloma virus vaccination should be administered in accordance with the guidelines of the National Board of Health of Denmark. In patients without a prior VZV infection, VZV vaccination may be considered. Information for patients: Anti-TNF-alpha treatment results in a generally increased risk of infection and latent tuberculosis flare-up. Women are advised to comply with the national guidelines for screening for cervical cancer, and their HPV immunisation status should be clarified. An increased risk of lymphoma with biological therapy in combination with thiopurines should be mentioned. Patients are advised to seek medical advice in case of herpes zoster infection.
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PMID:Guidelines for screening, prophylaxis and critical information prior to initiating anti-TNF-alpha treatment. 2275 56

Drug-resistant strains of Mycobacterium tuberculosis have emerged as a major threat to global tuberculosis control. Despite the availability of curative antituberculosis therapy for nearly half a century, inappropriate and inadequate treatment has allowed M. tuberculosis to acquire resistance to our most important antituberculosis drugs. The epidemic of drug-resistant tuberculosis has spread quickly in some areas due to the convergence of resistant strains of M. tuberculosis in high-risk patients (e.g., those with human immunodeficiency virus/acquired immunodeficiency syndrome) and high-risk environments (e.g., hospitals and prisons). The World Health Organization (WHO) estimates that there were 650,000 cases of multidrug resistant tuberculosis (MDR-TB) in 2010, defined as strains that are resistant to at least isoniazid (INH) and rifampicin (RIF). Globally, WHO estimates that 3.7% of new tuberculosis cases and 20% of re-treatment cases have MDR-TB. By the end of 2012, 84 countries had reported at least one case of extensively drug resistant strains (XDR-TB), which are MDR-TB strains that have acquired additional resistance to fluoroquinolones and at least one second-line injectable. Recently, cases of "totally drug resistant" tuberculosis have been reported. It is estimated that only 10% of all MDR-TB cases are currently receiving therapy and only 2% are receiving quality-assured drugs. This article reviews the management of MDR and XDR-TB and highlights the updated 2011 WHO guidelines on the programmatic management of drug-resistant tuberculosis.
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PMID:Management of multidrug resistant tuberculosis. 2346 5

Isoniazid preventive therapy (IPT) with antiretroviral therapy (ART) reduces incident tuberculosis among patients infected with the human immunodeficiency virus. We describe IPT use among patients on ART at two primary care clinics in South Africa. Of 597 participants interviewed, 100 (16.8%) reported IPT use; 73.4% (365/497) with no reported IPT use were eligible for IPT. IPT use was associated with age <35 years (aOR 1.90, 95%CI 1.18-3.06), and receiving care at one clinic as opposed to the other (aOR 4.72, 95%CI 2.69-7.93). The high proportion of patients on ART eligible for IPT represents a missed opportunity for IPT scale-up.
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PMID:Isoniazid preventive therapy use among patients on antiretroviral therapy: a missed opportunity. 2467 May 68

The Arkansas colorimetric method monitors adherence to isoniazid (INH) by the detection of INH metabolites in urine. Urine samples 4 h after INH administration in 31 human immunodeficiency virus infected children receiving daily or thrice weekly INH preventive therapy were Arkansas test-positive for 29/31 (94%), while acetylisoniazid (AcINH) was detected in 30/31 (97%) using mass spectrometry. At 24, 48 and 72 h, only 78%, 23% and 0 samples, respectively, were Arkansas-positive, while INH or AcINH was detected in respectively 94%, 69% and 33%. The Arkansas test reliably predicted INH ingestion at a clinic visit 4 h after morning doses, but did not perform well at 24 h.
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PMID:Isoniazid/acetylisoniazid urine concentrations: markers of adherence to isoniazid preventive therapy in children. 2490 87

Isoniazid preventive therapy (IPT) is the administration of isoniazid (INH) to people with latent tuberculosis (TB) infection (LTBI) to prevent progression to active TB disease. Despite being life-saving for human immunodeficiency virus (HIV)-infected persons who do not have active TB, IPT is poorly implemented globally due to misconceptions shared by healthcare providers and policy makers. However, amongst HIV-infected patients especially those living in resource-limited settings with a high burden of TB, available evidence speaks for IPT: Among HIV-infected persons, active TB- the major contraindication to IPT, can be excluded with symptom screening; chest X-ray and tuberculin skin testing are unreliable and often lead to logistic delays resulting in increased numbers of people with LTBI progressing to active TB; the use of IPT has not been found to increase the risk of the development of INH mono-resistance; IPT is cost-effective and cheaper than the cost of treating cases of active TB that would develop without IPT; ART and IPT have an additive effect on the prevention of TB, and both are safe and beneficial even in children. In order to sustain the recorded gains from ART scale-up and to further reduce TB-related morbidity and mortality, more efforts are needed to scale-up IPT implementation globally.
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PMID:Debunking the myths perpetuating low implementation of isoniazid preventive therapy amongst human immunodeficiency virus-infected persons. 2596 75

The direct inhibitory potential of twenty five anti-tuberculosis drugs on eight CYP-specific reactions in human liver microsomes was investigated to predict in vivo drug-drug interactions (DDIs) from in vitro data. Rifampicin, rifabutin, and thioacetazone inhibited one CYP reaction. Isoniazid and clofazimine had inhibitory effects on four CYP reactions, and rifapentine, ethionamide, and prothionamide widely inhibited CYP reactions. Based on the inhibition constant (Ki) and the therapeutic total inhibitor concentrations [I]max of eight drugs in human plasma, [I]max/Ki values were calculated to evaluate clinical DDIs. The [I]max/Ki values were 0.20 or less for rifampicin, rifabutin, and thioacetazone; 0.15-2.0 for isoniazid; 0.14-1.5 for rifapentine; 0.29-1.4 for ethionamide; 0.41-2.2 for prothionamide; and 0.12-6.3 for clofazimine. The highest [I]max/Ki values were 2.0 for isoniazid on CYP3A4 [testosterone (T)]; 1.5 for rifapentine on CYP3A4 [midazolam (M)]; 1.4 for ethionamide on CYP2C8; 2.2, 1.8, and 1.3 for prothionamide on CYP2B6, CYP2C19, and CYP2C8, respectively; and 6.3 and 5.7 for clofazimine on CYP3A4 (M) and CYP3A4 (T), respectively. These drugs with high [I]max/Ki values lead to clinical DDIs. Considering the drug regimens for tuberculosis (TB) and co-infection with TB and human immunodeficiency virus, the inhibitory potential for CYP3A4 and CYP2B6 is particularly important. These results suggest that clofazimine and prothionamide are likely to cause clinically relevant DDIs when co-administered with products metabolized by CYP3A4 and CYP2B6, respectively. Isoniazid and rifapentine may cause DDIs with drugs metabolized by CYP3A4.
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PMID:Inhibitory Potential of Twenty Five Anti-tuberculosis Drugs on CYP Activities in Human Liver Microsomes. 2609 99

Isoniazid preventive therapy is recommended in patients on antiretroviral treatment (ART) with latent tuberculous infection to prevent progression to active tuberculosis disease. Isoniazid (INH) inhibits cytochrome (CY) P3A4, which metabolises lopinavir (LPV). The administration of INH may cause higher LPV concentrations, which may increase LPV toxicity. LPV bioavailability is increased by co-formulated ritonavir (r), which may enhance the interaction of INH on LPV. We studied the effect of INH on LPV concentrations by administering INH for 7 days and performing intensive pharmacokinetic sampling in 16 human immunodeficiency virus infected patients established on LPV/r-based ART. INH did not significantly increase steady-state LPV area under the plasma concentration-time curve calculated for the 12 h-dosing interval.
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PMID:The pharmacokinetics of lopinavir/ritonavir when given with isoniazid in South African HIV-infected individuals. 2645 32


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