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Non-viral opportunistic infections in new users of tumour necrosis factor inhibitor therapy: results of the SAfety Assessment of Biologic ThERapy (SABER) study.
Baddley JW, Winthrop KL, Chen L, Liu L, Grijalva CG, Delzell E, Beukelman T, Patkar NM, Xie F, Saag KG, Herrinton LJ, Solomon DH, Lewis JD, Curtis JR
(2014) Ann Rheum Dis 73: 1942-8
MeSH Terms: Adult, Aged, Antirheumatic Agents, Arthritis, Rheumatoid, Autoimmune Diseases, Biological Products, Biological Therapy, Female, Humans, Immunocompromised Host, Immunosuppressive Agents, Male, Middle Aged, Opportunistic Infections, Retrospective Studies, Tumor Necrosis Factor-alpha, United States
Show Abstract · Added July 27, 2018
OBJECTIVES - To determine among patients with autoimmune diseases in the USA whether the risk of non-viral opportunistic infections (OI) was increased among new users of tumour necrosis factor α inhibitors (TNFI), when compared to users of non-biological agents used for active disease.
METHODS - We identified new users of TNFI among cohorts of rheumatoid arthritis (RA), inflammatory bowel disease and psoriasis-psoriatic arthritis-ankylosing spondylitis patients during 1998-2007 using combined data from Kaiser Permanente Northern California, two pharmaceutical assistance programmes for the elderly, Tennessee Medicaid and US Medicaid/Medicare programmes. We compared incidence of non-viral OI among new TNFI users and patients initiating non-biological disease-modifying antirheumatic drugs (DMARD) overall and within each disease cohort. Cox regression models were used to compare propensity-score and steroid- adjusted OI incidence between new TNFI and non-biological DMARD users.
RESULTS - Within a cohort of 33 324 new TNFI users we identified 80 non-viral OI, the most common of which was pneumocystosis (n=16). In the combined cohort, crude rates of non-viral OI among new users of TNFI compared to those initiating non-biological DMARD was 2.7 versus 1.7 per 1000-person-years (aHR 1.6, 95% CI 1.0 to 2.6). Baseline corticosteroid use was associated with non-viral OI (aHR 2.5, 95% CI 1.5 to 4.0). In the RA cohort, rates of non-viral OI among new users of infliximab were higher when compared to patients newly starting non-biological DMARD (aHR 2.6, 95% CI 1.2 to 5.6) or new etanercept users (aHR 2.9, 95% CI 1.5 to 5.4).
CONCLUSIONS - In the USA, the rate of non-viral OI was higher among new users of TNFI with autoimmune diseases compared to non-biological DMARD users.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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Brief report: incidence of selected opportunistic infections among children with juvenile idiopathic arthritis.
Beukelman T, Xie F, Baddley JW, Chen L, Delzell E, Grijalva CG, Mannion ML, Patkar NM, Saag KG, Winthrop KL, Curtis JR, SABER Collaboration
(2013) Arthritis Rheum 65: 1384-9
MeSH Terms: Adolescent, Antirheumatic Agents, Arthritis, Juvenile, Child, Coccidiosis, Cohort Studies, Comorbidity, Databases, Factual, Female, Herpes Zoster, Humans, Immunosuppressive Agents, Incidence, Male, Opportunistic Infections, Salmonella Infections, United States
Show Abstract · Added July 27, 2018
OBJECTIVE - To compare incidence rates of selected opportunistic infections among children with and children without juvenile idiopathic arthritis (JIA).
METHODS - Using U.S. national Medicaid administrative claims data from 2000 through 2005, we identified a cohort of children with JIA based on physician diagnosis codes and dispensed medications. We also identified a non-JIA comparator cohort of children diagnosed as having attention deficit hyperactivity disorder (ADHD). We defined 15 types of opportunistic infection using physician diagnosis or hospital discharge codes; criteria for 7 of these types also included evidence of treatment with specific antimicrobial agents. We calculated infection incidence rates. The rates in the ADHD comparator cohort were standardized to the age, sex, and race distribution of the JIA cohort. We calculated incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs) to compare infection rates.
RESULTS - The JIA cohort included 8,503 children with 13,990 person-years of followup. The ADHD comparator cohort included 360,362 children with 477,050 person-years of followup. When all opportunistic infections were considered together as a single outcome, there were 42 infections in the JIA cohort (incidence rate 300 per 100,000 person-years; IRR 2.4 [95% CI 1.7-3.3] versus ADHD). The most common opportunistic infections among children with JIA were 3 cases of Coccidioides (incidence rate 21 per 100,000 person-years; IRR 101 [95% CI 8.1-5,319] versus ADHD), 5 cases of Salmonella (incidence rate 35 per 100,000 person-years; IRR 3.8 [95% CI 1.2-9.5]), and 32 cases of herpes zoster (incidence rate 225 per 100,000 person-years; IRR 2.1 [95% CI 1.4-3.0]).
CONCLUSION - Opportunistic infections are rare among children with JIA. Nevertheless, children with JIA had a higher rate of opportunistic infections, including an increased rate of Coccidioides, Salmonella, and herpes zoster compared to children with ADHD.
Copyright © 2013 by the American College of Rheumatology.
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Sulphadiazine-induced renal stones in a 63-year-old HIV-infected man treated for toxoplasmosis.
McGettigan BD, Hew M, Phillips E, McLean-Tooke A
(2012) BMJ Case Rep 2012:
MeSH Terms: AIDS-Related Opportunistic Infections, Antiprotozoal Agents, Diagnosis, Differential, HIV-1, Humans, Kidney Calculi, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Sulfadiazine, Toxoplasmosis, Cerebral
Show Abstract · Added March 30, 2020
A 63-year-old man was admitted for investigation of blurred vision and multiple ring-enhancing lesions on cranial MRI. Histopathological examination of tissue obtained at brain biopsy showed multiple Toxoplasma gondii cysts. He was started on a combination of sulphadiazine and pyrimethamine for cerebral toxoplasmosis and was subsequently diagnosed with HIV-1 infection. He then developed acute renal failure and flank pain and was diagnosed with bilateral vesico-uretric calculi requiring bilateral stent insertion. The retrieved renal calculi were negative for the common stones that are routinely tested for in our laboratory and had the macroscopic characteristics of a sulphadiazine stone. His renal failure responded to cessation of the sulphadiazine.
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Treatment of latent tuberculosis infection in HIV: shorter or longer?
Person AK, Sterling TR
(2012) Curr HIV/AIDS Rep 9: 259-66
MeSH Terms: AIDS-Related Opportunistic Infections, Anti-HIV Agents, Antitubercular Agents, Drug Administration Schedule, Drug Therapy, Combination, Female, Humans, Isoniazid, Latent Tuberculosis, Male, Rifampin, Time Factors, Treatment Outcome, Tuberculin Test, Tuberculosis, Multidrug-Resistant
Show Abstract · Added May 29, 2014
Nine months of daily isoniazid is efficacious in treating latent M. tuberculosis infection, but completion rates are low, limiting treatment effectiveness. In 2011, three important studies were published involving novel regimens for the treatment of latent M. tuberculosis infection. At least 36 months of isoniazid was more effective than 6 months of isoniazid in one study, but not in another-both of which were conducted among tuberculin skin test positive HIV-infected adults living in high tuberculosis incidence settings. Three months of once-weekly isoniazid plus rifapentine or twice-weekly isoniazid plus rifampin (both given under direct observation) resulted in tuberculosis rates similar to those seen with 6 months of isoniazid among HIV-infected persons in high tuberculosis incidence settings. Three months of once-weekly, directly-observed isoniazid plus rifapentine was at least as effective as 9 months of daily isoniazid among predominantly HIV-uninfected persons living in low and medium tuberculosis incidence countries. The 3-month once-weekly isoniazid plus rifapentine regimen demonstrates promise for treatment of latent M. tuberculosis infection in HIV-infected persons.
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Septicemia in patients with AIDS admitted to a university health system: a case series of eighty-three patients.
Haddy RI, Richmond BW, Trapse FM, Fannin KZ, Ramirez JA
(2012) J Am Board Fam Med 25: 318-22
MeSH Terms: AIDS-Related Opportunistic Infections, Acquired Immunodeficiency Syndrome, Adult, CD4 Lymphocyte Count, Escherichia coli, Female, Hospitals, Teaching, Humans, Kentucky, Male, Methicillin-Resistant Staphylococcus aureus, Mycobacterium avium, Pseudomonas aeruginosa, Risk Factors, Sepsis, Streptococcus pneumoniae
Show Abstract · Added March 30, 2020
BACKGROUND - Patients with AIDS incur higher rates of infection than the general population. However, little evidence exists to guide family physicians in selecting antibiotics for initial empiric therapy for suspected septicemia.
METHODS - We recorded the causative organisms of septicemia (defined here as bacteremia, fungemia, or both) in 83 patients with AIDS admitted to the teaching hospitals of the University of Louisville from 1996 to 2006. All patients fulfilled the requirements for a diagnosis of AIDS on the basis of the 1993 Centers for Disease Control criteria. In addition to the causative organism, demographic information, immunologic data, portal of entry, and mortality were collected.
RESULTS - Only 53% of the patients presented with fever and the median leukocyte count was 4400 cells/mm(3). The most common organisms causing septicemia were, in decreasing order, methicillin-sensitive Staphylococcus aureus (MRSA; n = 21; 21.4%), Mycobacterium avium complex (n = 10; 10.2%), coagulase-negative staphylococci (n = 9; 9.2%) and Streptococcus pneumoniae (n = 9; 9.2%). Other pathogens included Escherichia coli, Pseudomonas aeruginosa, and MRSA. Polymicrobial septicemia was identified in 12 cases (14.5% of the episodes). The portals of entry of the organism were (in decreasing order) primary, lung, intravascular line, and skin. The types of organisms found in patients with primary septicemia patterned those found overall. The mortality rate was 12.1%.
CONCLUSIONS - AIDS patients with septicemia may not present with the signs that would a non-AIDS patient with septicemia. On the basis of the range of organisms identified in this study, antibiotic coverage of AIDS patients with suspected septicemia, both in primary septicemia and septicemia overall, should take into consideration bacteremia with a wide range of organisms: Gram-positive organisms including MRSA and M. avium complex and Gram-negative organisms including Pseudomonas species. In addition, physicians should be aware that polymicrobial septicemia may be present.
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Contemporary profile of oral manifestations of HIV/AIDS and associated risk factors in a Southeastern US clinic.
Tamí-Maury I, Willig J, Vermund S, Jolly P, Aban I, Hill J, Wilson CM
(2011) J Public Health Dent 71: 257-64
MeSH Terms: AIDS-Related Opportunistic Infections, Acquired Immunodeficiency Syndrome, Adult, African Americans, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Candidiasis, Oral, Cohort Studies, Female, Follow-Up Studies, HIV Infections, HIV-1, Heterosexuality, Homosexuality, Male, Humans, Male, Mouth Diseases, Oropharynx, Pharyngeal Diseases, Prevalence, Retrospective Studies, Risk Factors, Sex Factors, Southeastern United States, Viral Load, Young Adult
Show Abstract · Added March 5, 2014
BACKGROUND - Introduction of highly active antiretroviral therapy (HAART) has resulted in a significant decrease of oral manifestations (OMs). The profile and risk factors for OM in those individuals initiating HAART remain understudied in the Southeast of the United States, region of increasing HIV prevalence.
OBJECTIVE - To determine clinical, socio-demographic, and laboratory characteristics associated with the presence of OM among patients initiating HAART.
METHODS - Retrospective review of electronically captured data from patients initiating HAART at a Southeastern US clinic. Prevalence was determined, and risk factors for overall OM, oropharyngeal candidiasis (OPC), and all other OM were evaluated using logistic regression.
RESULTS - In our sample (n = 744), majority of individuals were males (75 percent), African-American (50 percent), mean age of 39 years, 42 percent of which reported sex with men (MSM). Two hundred sixty-six had some type of OM. Compared with those without any OM, patients with OM had a lower mean baseline CD4+ T cells count (CD4 count) (331 ± 260 versus 179 ± 244 CD4 cells/mm(3) ) and higher mean baseline HIV-1 RNA viral load (4.0 ± 1.34 log(10) versus 4.6 ± 1.30 log(10) ) (P < 0.01). In the logistic regression models seeking to determine factors associated with an increased risk of OM and OPC, the only characteristic associated with the outcome was baseline CD4 value. Being male, African-American, and heterosexual showed a protective role for OM other than OPC.
CONCLUSION - OM continues to be common despite HAART. General OM and OPC were closely associated with a low baseline CD4 count. Knowledge of risk factors for OM can potentially help clinicians target oral evaluation of HIV-positive individuals.
© 2011 American Association of Public Health Dentistry.
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Phase II AIDS Malignancy Consortium trial of topical halofuginone in AIDS-related Kaposi sarcoma.
Koon HB, Fingleton B, Lee JY, Geyer JT, Cesarman E, Parise RA, Egorin MJ, Dezube BJ, Aboulafia D, Krown SE
(2011) J Acquir Immune Defic Syndr 56: 64-8
MeSH Terms: AIDS-Related Opportunistic Infections, Administration, Topical, Adult, Antineoplastic Agents, Female, Humans, Male, Middle Aged, Piperidines, Quinazolinones, Sarcoma, Kaposi, Single-Blind Method, Young Adult
Show Abstract · Added March 5, 2014
Using a novel blinded intrapatient vehicle control design, we conducted a phase II study of topically administered halofuginone, an angiogenesis inhibitor that inhibits collagen type-I and matrix metalloproteinases (MMPs), in patients with AIDS-related Kaposi sarcoma. Serial Kaposi sarcoma biopsies assessed treatment effects on angiogenic factors and Kaposi sarcoma herpesvirus-latency associated nuclear antigen-1 (KSHV-LANA). We observed marked heterogeneity of KSHV-LANA expression. Although the small number of subjects whose response could be evaluated precluded definitive assessment of halofuginone's efficacy, we observed a significant decrease in type-I collagen only in halofuginone-treated lesions, but no effect on MMP-2. The trial design is applicable to future studies of topical agents.
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Initiation of rheumatoid arthritis treatments and the risk of serious infections.
Grijalva CG, Kaltenbach L, Arbogast PG, Mitchel EF, Griffin MR
(2010) Rheumatology (Oxford) 49: 82-90
MeSH Terms: Antirheumatic Agents, Arthritis, Rheumatoid, Dose-Response Relationship, Drug, Glucocorticoids, Hospitalization, Humans, Immunosuppressive Agents, Methotrexate, Opportunistic Infections, Pneumonia, Risk Assessment, Tennessee, Tumor Necrosis Factor-alpha
Show Abstract · Added December 10, 2013
OBJECTIVE - In clinical trials of RA patients on traditional DMARDs, the addition of TNF-alpha antagonists increased infections compared with addition of placebo. Our objective was to compare serious infections following initiation of different RA regimens. Prior comparative studies of DMARD initiation have yielded conflicting results.
METHODS - We estimated hospitalization rates for infections following initiation of TNF-alpha antagonists, other DMARDs and oral glucocorticoids in Tennessee Medicaid-enrolled RA patients (1995-2005). Exposure time was measured using pharmacy information and infections were identified using validated definitions. Initiation of RA regimens was compared using Cox regression models with MTX as the reference. Sensitivity analyses excluded glucocorticoid users, applied a first exposure carried forward approach, restricted observations to 2002-05 and first episodes of use and explored effects of unmeasured confounders.
RESULTS - We identified 28 906 new episodes of medication use, including TNF-alpha antagonists (8%), MTX alone (15%) and glucocorticoids alone (57%). Compared with MTX initiation, TNF-alpha antagonist initiation did not significantly increase the risk of hospitalizations for pneumonia [adjusted hazard ratio (aHR) 1.61; 95% CI 0.85, 3.03] or any infection (aHR 1.31; 95% CI 0.78, 2.19). Initiation of LEF, SSZ or HCQ did not increase serious infections, compared with MTX. Both initiation and concurrent glucocorticoid use were associated with a dose-dependent increase in serious infections. Sensitivity analyses showed consistent results.
CONCLUSIONS - Compared with initiation of MTX alone, initiation of TNF-alpha antagonists was not associated with a large increase in the risk of serious infections. Glucocorticoid use was associated with a dose-dependent increase in the risk of these infections.
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13 MeSH Terms
Normal chest radiography in pulmonary tuberculosis: implications for obtaining respiratory specimen cultures.
Pepper T, Joseph P, Mwenya C, McKee GS, Haushalter A, Carter A, Warkentin J, Haas DW, Sterling TR
(2008) Int J Tuberc Lung Dis 12: 397-403
MeSH Terms: AIDS-Related Opportunistic Infections, Adult, Cohort Studies, Female, HIV Infections, Humans, Male, Mass Chest X-Ray, Middle Aged, Mycobacterium tuberculosis, Retrospective Studies, Sputum, Tuberculosis, Pulmonary
Show Abstract · Added March 13, 2015
SETTING - Urban tuberculosis (TB) clinic, Nashville, Tennessee, USA.
OBJECTIVE - Chest radiographs (CXRs) help in the diagnosis of pulmonary TB, but may be normal. Mycobacterium tuberculosis in culture is diagnostic of TB, but cultures are not routinely obtained in resource-poor settings. We examined rates and risk factors for pulmonary TB associated with normal CXR.
DESIGN - An observational cohort study was performed among all respiratory culture-positive TB cases referred to the Nashville Health Department from October 1992 to July 2003. Clinical factors, demographics and underlying medical conditions were assessed.
RESULTS - Of 601 study patients, 53 (9%) had normal CXRs: 31/138 (22%) were human immunodeficiency virus (HIV) infected and 22/463 (5%) were non-HIV-infected/unknown (P<0.001). Among HIV-infected patients, normal CXR was more likely in persons with renal failure (13% vs. 3%, P=0.048). Among non-HIV-infected/unknown patients, normal CXR was more likely in those who were asymptomatic at presentation (32% vs. 13%, P=0.022). In multivariable logistic regression analysis, HIV infection was associated with an increased risk of normal CXR (odds ratio [OR] 6.61, P<0.0001); factors associated with reduced risk were dyspnea (OR 0.24, P=0.026), positive sputum smear (OR 0.45, P=0.028) and cough (OR 0.48, P=0.038).
CONCLUSIONS - The rate of normal CXR among persons with culture-confirmed pulmonary TB was high. Respiratory specimen cultures should be obtained in TB suspects with a normal CXR, particularly HIV-infected persons.
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13 MeSH Terms
Drug hypersensitivity in HIV.
Phillips E, Mallal S
(2007) Curr Opin Allergy Clin Immunol 7: 324-30
MeSH Terms: AIDS-Related Opportunistic Infections, Anti-HIV Agents, Anti-Infective Agents, Dideoxynucleosides, Drug Hypersensitivity, Genetic Predisposition to Disease, HIV Infections, HLA-B Antigens, Humans, Reverse Transcriptase Inhibitors, Trimethoprim, Sulfamethoxazole Drug Combination
Show Abstract · Added March 30, 2020
PURPOSE OF REVIEW - Drug hypersensitivity has been reported to occur 100 times more commonly in those living with HIV. In the first decade of HIV treatment, this mainly involved drugs used to treat HIV-related infections but now primarily includes drugs used to treat HIV. This review focuses on the current knowledge of the epidemiology, pathophysiology and clinical features of drug hypersensitivity reactions of drugs used in the management of the HIV-infected patient.
RECENT FINDINGS - Our understanding of the immunogenetics and host predisposition to drug hypersensitivity has been advanced considerably by the antiretroviral drugs abacavir and nevirapine. The association of abacavir hypersensitivity reaction with HLA-B*5701 has been particularly important and provides a basis for genetic screening in the clinic setting.
SUMMARY - The increased predisposition of drug hypersensitivity disease in HIV will continue to provide a fertile ground for study of the diverse and complex processes that drive its pathophysiology. Our knowledge of drug hypersensitivity will also increase as the expanding armentarium of antiretroviral therapy is applied to more diverse populations in the developing world. The potential for widespread implementation of HLA-B*5701 screening for abacavir hypersensitivity will set an important precedent for bringing individualized medicine to the clinic and the use of genetic testing to improve drug safety.
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