To further elucidate the immunopathogenesis of immune restoration diseases (IRD) in HIV patients responding to antiretroviral therapy and determine whether IRD associated with different opportunistic pathogens involve distinct immunopathological mechanisms.
DNA samples from patients with a range of IRD were typed for polymorphic loci in genes encoding immune-mediators.
PCR-restriction fragment length polymorphism assays were used to type loci in the and genes. Alleles of a microsatellite in the CD30 promoter were determined by capillary electrophoresis.
Only 8% of patients with IRD associated with a herpesvirus infection carried IL12B-3'UTR*2, compared with 42-54% of patients with other or no IRD. Patients with IRD arising from mycobacterial infection rarely carried IL6-174*C (36% versus 61-71%) and never carried TNFA-308*2 (0% versus 23-52%). TNFA-308*2 was carried by 52% of patients who experienced IRD associated with a herpesvirus infection, as several patients with exacerbations of cytomegalovirus retinitis carried this as part of a HLA-A2,B44 haplotype. Polymorphisms in and showed no distinct patterns.
Distinct cytokine-mediated mechanisms contribute to IRD initiated by herpesvirus and mycobacterial infections.
"IL-12 and IL-18 influence the induction of Th1 cytokine responses. Carriage of IL12B (3' UTR)*C was more common in Caucasian HIV-positive patients without neuropathy  and without CMV retinitis experienced after commencement of ART , suggesting a protective role in both cases. "
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Animal and in vitro models of HIV-associated sensory neuropathy suggest an inflammatory etiology. Previous genetic association studies of HIV-SN have been in small Caucasian or Asian cohorts. We assessed cytokine single nucleotide polymorphisms (SNPs) in a Black Southern African cohort.
342 black HIV-positive Southern Africans were recruited. 190 individuals had HIV-associated sensory neuropathy and 152 did not. DNA samples from all participants were genotyped for cytokine SNPs identified in studies of HIV disease and/or neuropathy.
IL4-590*T associated with an increased prevalence of HIV-SN including following correction for age, height and CD4 T-cell count. No other cytokine SNPs assessed displayed an association.
We identified a novel association between IL4-590*T and HIV-SN in African HIV-positive patients which warrants further investigation.
"Rarely, termination of ART is required. Risk factors for IRIS include lower CD4 cell count, higher viral load at start of treatment, rapidity of viral load decline; bacillary and antigen load (disseminated tuberculosis) at initiation, starting highly active ART closer to starting ATT, and genetic predisposition (HLA B-44)111–113. Although the pathophysiology of IRIS is incompletely understood, it is associated with an exuberant production of cytokines, such as IFN-γ or a lack of inhibitory immune responses114. "
[Show abstract][Hide abstract] ABSTRACT: Human immunodeficiency virus (HIV) associated tuberculosis (TB) remains a major global public health challenge, with an estimated 1.4 million patients worldwide. Co-infection with HIV leads to challenges in both the diagnosis and treatment of tuberculosis. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDR-TB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. Because of the poor performance of sputum smear microscopy in HIV-infected patients, newer diagnostic tests are urgently required that are not only sensitive and specific but easy to use in remote and resource-constrained settings. The treatment of co-infected patients requires antituberculosis and antiretroviral drugs to be administered concomitantly; challenges include pill burden and patient compliance, drug interactions, overlapping toxic effects, and immune reconstitution inflammatory syndrome. Also important questions about the duration and schedule of anti-TB drug regimens and timing of antiretroviral therapy remain unanswered. From a programmatic point of view, screening of all HIV-infected persons for TB and vice-versa requires good co-ordination and communication between the TB and AIDS control programmes. Linkage of co-infected patients to antiretroviral treatment centres is critical if early mortality is to be prevented. We present here an overview of existing diagnostic strategies, new tests in the pipeline and recommendations for treatment of patients with HIV-TB dual infection.
The Indian Journal of Medical Research 12/2011; 134(6):850-65. DOI:10.4103/0971-5916.92630 · 1.40 Impact Factor
"However, our report is relatively low as compared with studies done in Thailand and Texas. Our low rate of MTB infection might be explained partly due to genetic polymorphism and racial differences of the study subjects . And the nature of retrospective studies that may result differences in documenting and interpreting data in different settings also might play a role in variation of IRD reports. "
[Show abstract][Hide abstract] ABSTRACT: Highly active antiretroviral therapy (HAART) improves the immune function and decreases morbidity, mortality and opportunistic infections (OIs) in HIV-infected patients. However, since the use of HAART, immune restoration disease (IRD) has been described in association with many OIs. Our objective was to determine the proportion of IRD, changes in CD4+ T-cell count and possible risk factors of IRD in HIV-infected patients.
A retrospective study of all HIV- infected patients starting HAART between September 1, 2005 and August 31, 2006 at Zewditu memorial hospital HIV clinic, Addis Ababa, Ethiopia was conducted. All laboratory and clinical data were extracted from computerized clinic records and patient charts.
A total of 1166 HIV- infected patients with mean ± SD age of 36 ± 9.3 years were on HAART. IRD was identified in 170 (14.6%) patients. OIs diagnosed in the IRD patients were tuberculosis (66.5%, 113/170), toxoplasmosis (12.9%, 22/170), herpes zoster rash (12.9%, 22/170), Pneumocystis jirovecii pneumonia (4.1%, 7/170), and cryptococcosis (3.5%, 6/170). Of the 170 patients with IRD, 124 (72.9%) patients developed IRD within the first 3 months of HAART initiation. Low baseline CD4+ T-cell count (odds ratio [OR], 3.16, 95% confidence interval [CI], 2.19-4.58) and baseline extra pulmonary tuberculosis (OR, 7.7, 95% CI, 3.36-17.65) were associated with development of IRD. Twenty nine (17.1%) of the IRD patients needed to use systemic anti-inflammatory treatment where as 19(11.2%) patients required hospitalization associated to the IRD occurrence. There was a total of 8 (4.7%) deaths attributable to IRD.
The proportion and risk factors of IRD and the pattern of OIs mirrored reports from other countries. Close monitoring of patients during the first three months of HAART initiation is important to minimize clinical deterioration related to IRD.
AIDS Research and Therapy 12/2010; 7(1):46. DOI:10.1186/1742-6405-7-46 · 1.46 Impact Factor
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