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Immune reconstitution inflammatory syndrome in human immunodeficiency virus-infected children in Peru.

ABSTRACT: Immune reconstitution inflammatory syndrome (IRIS) after initiating highly active antiretroviral therapy (HAART) has not been widely studied in children, especially in resource-poor settings.Retrospective cohort study of HIV-infected children initiating HAART between 2001 and 2006 at a tertiary pediatric hospital in Lima, Peru. Charts were reviewed for 1 year after HAART initiation. IRIS was defined as a HAART-associated adverse event caused by an infectious or inflammatory condition in patients with documented virologic or immunologic success.Ninety-one children (52% female) received HAART for at least 1 year. Median age at initiation was 5.7 years; 91% were ART naive and 73% had CDC stage C disease. The incidence of IRIS was 19.8 events per 100 person years (95% CI: 11.5-28.0). Median time to IRIS was 6.6 weeks after HAART initiation (range: 2-32 weeks). There were 18 IRIS events, 11 unmasking and 7 paradoxical. These included associations with Mycobacterium tuberculosis in 4 cases, Bacillus Calmette Guerin lymphadenitis in 1 case, varicella zoster virus in 6 cases and herpes simplex labialis in 6 cases. Children who developed IRIS had a higher baseline HIV viral load (P = 0.02) and an indicator of malnutrition (P = 0.007) before HAART initiation.IRIS occurred in 20% of HIV-infected children starting HAART in Peru and was associated with more advanced disease and malnutrition. Future research is needed to examine specific risk factors associated with pediatric IRIS to allow prompt identification and treatment of IRIS.

SUBMITTER: Wang ME

PROVIDER: S-EPMC3514443 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Immune reconstitution inflammatory syndrome in human immunodeficiency virus-infected children in Peru.

Wang Marie E ME Castillo Maria E ME Montano Silvia M SM Zunt Joseph R JR

The Pediatric infectious disease journal 20091001 10

<h4>Background</h4>Immune reconstitution inflammatory syndrome (IRIS) after initiating highly active antiretroviral therapy (HAART) has not been widely studied in children, especially in resource-poor settings.<h4>Methods</h4>Retrospective cohort study of HIV-infected children initiating HAART between 2001 and 2006 at a tertiary pediatric hospital in Lima, Peru. Charts were reviewed for 1 year after HAART initiation. IRIS was defined as a HAART-associated adverse event caused by an infectious or ...[more]

PMID: 19687769

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Project description:BackgroundExtensive immunopathology occurs in human immunodeficiency virus (HIV)/tuberculosis (TB) coinfection, but the underlying molecular mechanisms are not well-defined. Excessive matrix metalloproteinase (MMP) activity is emerging as a key process but has not been systematically studied in HIV-associated TB.MethodsWe performed a cross-sectional study of matrix turnover in HIV type 1 (HIV-1)-infected and -uninfected TB patients and controls, and a prospective cohort study of HIV-1-infected TB patients at risk of TB immune reconstitution inflammatory syndrome (TB-IRIS), in Cape Town, South Africa. Sputum and plasma MMP concentrations were quantified by Luminex, plasma procollagen III N-terminal propeptide (PIIINP) by enzyme-linked immunosorbent assay, and urinary lipoarabinomannan (LAM) by Alere Determine TB LAM assay. Peripheral blood mononuclear cells from healthy donors were cultured with Mycobacterium tuberculosis and extracellular matrix in a 3D model of TB granuloma formation.ResultsMMP activity differed between HIV-1-infected and -uninfected TB patients and corresponded with specific TB clinical phenotypes. HIV-1-infected TB patients had reduced pulmonary MMP concentrations, associated with reduced cavitation, but increased plasma PIIINP, compared to HIV-1-uninfected TB patients. Elevated extrapulmonary extracellular matrix turnover was associated with TB-IRIS, both before and during TB-IRIS onset. The predominant collagenase was MMP-8, which was likely neutrophil derived and M. tuberculosis-antigen driven. Mycobacterium tuberculosis-induced matrix degradation was suppressed by the MMP inhibitor doxycycline in vitro.ConclusionsMMP activity in TB differs by HIV-1 status and compartment, and releases matrix degradation products. Matrix turnover in HIV-1-infected patients is increased before and during TB-IRIS, informing novel diagnostic strategies. MMP inhibition is a potential host-directed therapy strategy for prevention and treatment of TB-IRIS.

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Immune reconstitution inflammatory syndrome in human immunodeficiency virus-infected children in Peru.

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Immune reconstitution inflammatory syndrome in human immunodeficiency virus-infected children in Peru.

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