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ABSTRACT: Immune reconstitution inflammatory syndrome (IRIS) is an important complication of HAART in sub-Saharan Africa, where opportunistic infections (OIs) including mycobacteria and cryptococcus are common. The immune system's role in HIV infected patients is complex with cytokine expression strongly influencing HIV infection and replication.
We determined the expression patterns of 10 cytokines by Luminex multi-analyte profiling in 17 IRIS nested case-control pairs participating in a prospective South African cohort initiating anti-retroviral therapy.
Interferon-gamma (IFN-γ) expression was significantly elevated in IRIS cases compared to controls (median 9.88 pg/ml versus 2.68 pg/ml, respectively, P = 0.0057), while other cytokines displayed non-significant differences in expression. Significant correlation was observed between IL-6, IL-10, and IFN-γ expression in the IRIS patients.
Significantly increased expression levels of IFN-γ suggest that this cytokine possibly plays a role in IRIS pathology and is a potential diagnostic marker.
AIDS Research and Therapy 10/2010; 7:36. · 2.54 Impact Factor
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ABSTRACT: There are limited data on acute HIV infection (AHI) prevalence during pregnancy. Malawian pregnant women admitted in the third trimester and meeting eligibility criteria underwent dual HIV rapid antibody testing. AHI prevalence was retrospectively detected through HIV RNA pooling of seronegative plasma. Among 3,825 pregnant women screened, dual HIV rapid testing indicated that 30.2% were HIV positive, 69.7% were HIV negative, and 0.1% were indeterminate. Sensitivity and specificity of dual rapid testing was 99.0% and 98.7%, respectively. Of 2,666 seronegative specimens, 2,327 had samples available for HIV RNA pooling; 5 women (0.21%) (95% confidence interval, 0.03-0.40%) had AHI with a median peripartum viral load of 1,324,766 copies/mL. Pregnant women are at risk for AHI, warranting counseling of all women and their sexual partners about incident HIV during pregnancy. Dual HIV rapid tests have high sensitivity and specificity. HIV testing should be repeated in the third trimester and/or at delivery.
Diagnostic microbiology and infectious disease 04/2010; 66(4):356-60. · 2.45 Impact Factor
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AIDS (London, England) 09/2008; 22(13):1689-90. · 4.91 Impact Factor
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ABSTRACT: To determine the incidence, clinical manifestations, risk factors and outcome of immune reconstitution inflammatory syndrome (IRIS) in South Africa.
Prospective surveillance cohort and nested case-control study in a large, University hospital-based antiretroviral therapy (ART) clinic.
A total of 423 ART-naive HIV-infected South African patients were followed for signs and symptoms IRIS during the first 6 months of ART. We also performed a nested case-control study with controls matched to IRIS cases on ART duration.
During the first 6 months of ART, 44 (10.4%) patients experienced IRIS for an overall incidence rate of 25.1 cases per 100 patient-years. Diagnoses included tuberculosis (18/44, 41%), abscess formation and suppurative folliculitis (8/44, 18.2%), varicella zoster (6/44, 13.6%), herpes simplex (4/44, 9.1%), cryptococcal meningitis (3/44, 6.8%), molluscum contagiosum (3/44, 6.8%), and Kaposi's sarcoma (2/44, 4.5%). Median IRIS onset was 48 days (interquartile range, 29-99) from ART initiation. In comparison with controls, IRIS cases had significantly lower CD4 cell counts at baseline (79 versus 142 cells/microl; P = 0.02) and at IRIS diagnosis (183 versus 263 cells/microl; P = 0.05), but similar virological and immunological response to ART. In multivariable analyses, higher baseline CD4 cell count was protective of developing IRIS (HR 0.72 per 50 cells/microl increase). Most IRIS cases were mild, with ART discontinued in three (6.8%) patients, corticosteroids administered to four (9.1%) patients, and hospitalization required in 12 (27.3%) patients. Two deaths were attributable to IRIS.
IRIS may affect 10% of patients initiating ART in Africa, particularly those with advanced immunosuppression, but severe, life-threatening IRIS is uncommon.
AIDS (London, England) 04/2008; 22(5):601-10. · 4.91 Impact Factor
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ABSTRACT: Smoking tobacco is disproportionably common among HIV-infected patients in the highly active antiretroviral therapy (HAART) era.
An observational cohort study of 300 HIV-positive patients receiving care between 1996 and 2005 examined the effect of smoking on pneumonia risk. Multivariable analyses assessed the association between smoking and pneumonia risk and identified independent predictors of pneumonia during the HAART era.
Current smoking was common (67%). Eighty-two patients (27%) experienced 119 pneumonia episodes during 2151 patient-years of follow-up, with 7.2 episodes/100 person-years among smokers and 2.9 episodes/100 person-years among non-smokers (unadjusted incidence rate ratio (IRR): 2.50 (95% CI: 1.58, 4.09). Adjustment for age and HIV RNA level resulted in an IRR of 1.77 (95% CI: 0.98, 3.21). No prior antiretroviral therapy use (P-value <0.001), higher HIV RNA level (P-value = 0.01), lower CD4 count (P-value = 0.01), younger age (P-value = 0.01), and alcohol use (P-value = 0.04) were independent predictors of pneumonia. HAART use decreased pneumonia risk (IRR 0.28, 95% CI: 0.18, 0.44).
While HIV-positive smokers had over a 2-fold increase in the rate of pneumonia, the trend did not reach statistical significance in multivariable models. Clinical factors such as HAART, alcohol use and immunological status are important in pneumonia risk.
The Open Respiratory Medicine Journal 01/2008; 2:22-8.
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ABSTRACT: The immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients initiating antiretroviral therapy (ART) results from restored immunity to specific infectious or non-infectious antigens. A paradoxical clinical worsening of a known condition or the appearance of a new condition after initiating therapy characterizes the syndrome. Potential mechanisms for the syndrome include a partial recovery of the immune system or exuberant host immunological responses to antigenic stimuli. The overall incidence of IRIS is unknown, but is dependent on the population studied and its underlying opportunistic infectious burden. The infectious pathogens most frequently implicated in the syndrome are mycobacteria, varicella zoster, herpesviruses, and cytomegalovirus (CMV). No single treatment option exists and depends on the underlying infectious agent and its clinical presentation. Prospective cohort studies addressing the optimal screening and treatment of opportunistic infections in patients eligible for ART are currently being conducted. These studies will provide evidence for the development of treatment guidelines in order to reduce the burden of IRIS. We review the available literature on the pathogenesis and epidemiology of IRIS, and present treatment options for the more common infectious manifestations of this diverse syndrome and for manifestations associated with a high morbidity.
AIDS Research and Therapy 02/2007; 4:9. · 2.54 Impact Factor
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ABSTRACT: Cellulitis caused by Mycobacterium avium-intracellulare has rarely been described. Mycobacterium avium-intracellulare is a rare cause of septic arthritis after intra-articular injection, though the causative role of injection is difficult to ascertain in such cases.
A 57-year-old with rheumatoid arthritis treated with prednisone and azathioprine developed bilateral painful degenerative shoulder arthritis. After corticosteroid injections into both acromioclavicular joints, he developed bilateral cellulitis centered over the injection sites. Skin biopsy showed non-caseating granulomas, and culture grew Mycobacterium avium-intracellulare. Joint aspiration also revealed Mycobacterium avium-intracellulare infection.
Although rare, skin and joint infections caused by Mycobacterium avium-intracellulare should be considered in any immunocompromised host, particularly after intra-articular injection. Stains for acid-fast bacilli may be negative in pathologic samples even in the presence of infection; cultures of tissue specimens should always be obtained.
BMC Infectious Diseases 02/2007; 7:9. · 3.12 Impact Factor
