PMID- 31260455 OWN - NLM STAT- MEDLINE DCOM- 20200218 LR - 20231012 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 14 IP - 7 DP - 2019 TI - A prospective study of the immune reconstitution inflammatory syndrome (IRIS) in HIV-infected children from high prevalence countries. PG - e0211155 LID - 10.1371/journal.pone.0211155 [doi] LID - e0211155 AB - BACKGROUND: The immune reconstitution inflammatory syndrome (IRIS) in HIV-infected infants and young children is relatively understudied in regions endemic for HIV and TB. We aimed to describe incidence, clinical features and risk factors of pediatric IRIS in Sub-Saharan Africa and India. METHODS AND FINDINGS: We conducted an observational multi-centred prospective clinical study from December 2010 to September 2013 in children <72 months of age recruited from public antiretroviral programs. The main diagnostic criterion for IRIS was a new or worsening inflammatory event after initiating antiretroviral therapy (ART). Among 198 participants, median age 1.15 (0.48; 2.21) years, 38 children (18.8%) developed 45 episodes of IRIS. Five participants (13.2%) had two IRIS events and one (2.6%) had 3 events. Main causes of IRIS were BCG (n = 21; 46.7%), tuberculosis (n = 10; 22.2%) and dermatological, (n = 8, 17.8%). Four TB IRIS cases had severe morbidity including 1 fatality. Cytomegalovirus colitis and cryptococcal meningitis IRIS were also severe. BCG IRIS resolved without pharmacological intervention. On multivariate logistic regression, the most important baseline associations with IRIS were high HIV viral load (likelihood ratio [LR] 10.629; p = 0.0011), recruitment at 1 site (Stellenbosch University) (LR 4.01; p = 0.0452) and CD4 depletion (LR 3.4; p = 0.0654). Significantly more non-IRIS infectious and inflammatory events between days 4 and 17 of ART initiation were noted in cases versus controls (35% versus 15.2%: p = 0.0007). CONCLUSIONS: IRIS occurs commonly in HIV-infected children initiating ART and occasionally has severe morbidity. The incidence may be underestimated. Predictive, diagnostic and prognostic biomarkers are needed. FAU - Cotton, Mark F AU - Cotton MF AUID- ORCID: 0000-0003-2559-6034 AD - Department of Pediatrics & Child Health, Stellenbosch University, Tygerberg, South Africa. FAU - Rabie, Helena AU - Rabie H AD - Department of Pediatrics & Child Health, Stellenbosch University, Tygerberg, South Africa. FAU - Nemes, Elisa AU - Nemes E AD - South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease & Molecular Medicine and Division of Immunology, Pathology, University of Cape Town, Cape Town, South Africa. FAU - Mujuru, Hilda AU - Mujuru H AD - Department of Pediatrics, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe. FAU - Bobat, Raziya AU - Bobat R AD - Department of Pediatrics & Child Health, University of KwaZulu-Natal, Durban, South Africa. FAU - Njau, Boniface AU - Njau B AD - Kilimanjaro Christian Medical Centre, Moshi, Tanzania. FAU - Violari, Avy AU - Violari A AD - Department of Pediatrics & Child Health, Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa. FAU - Mave, Vidya AU - Mave V AD - BJ Medical College, Pune, India. FAU - Mitchell, Charles AU - Mitchell C AD - Department of Pediatric Immunology, University of Miami, Miami, FL, United States of America. FAU - Oleske, James AU - Oleske J AD - Department of Pediatrics & Child Health, Rutgers New Jersey Medical School, Newark, NJ, United States of America. FAU - Zimmer, Bonnie AU - Zimmer B AD - Frontier Science & Technology Research Foundation, Amherst, NY, United States of America. FAU - Varghese, George AU - Varghese G AD - Department of Pediatrics & Child Health, University of Miami Miller School of Medicine, Miami, FL, United States of America. FAU - Pahwa, Savita AU - Pahwa S AD - Department of Pediatrics & Child Health, University of Miami Miller School of Medicine, Miami, FL, United States of America. CN - P1073 team LA - eng GR - HHSN275201800001C/HD/NICHD NIH HHS/United States GR - UM1 AI068632/AI/NIAID NIH HHS/United States GR - UM1 AI069453/AI/NIAID NIH HHS/United States GR - UM1 AI068616/AI/NIAID NIH HHS/United States GR - U01 AI069521/AI/NIAID NIH HHS/United States GR - UM1 AI069521/AI/NIAID NIH HHS/United States GR - UM1 AI069436/AI/NIAID NIH HHS/United States GR - HHSN275201800001I/HD/NICHD NIH HHS/United States GR - UM1 AI106716/AI/NIAID NIH HHS/United States GR - U01 AI069436/AI/NIAID NIH HHS/United States PT - Clinical Trial PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, N.I.H., Extramural DEP - 20190701 PL - United States TA - PLoS One JT - PloS one JID - 101285081 SB - IM MH - Africa South of the Sahara/epidemiology MH - Child, Preschool MH - *Colitis/epidemiology/immunology MH - Cryptococcus/immunology MH - Cytomegalovirus/immunology MH - *Cytomegalovirus Infections/epidemiology/immunology MH - Female MH - *HIV Infections/epidemiology/immunology MH - HIV-1/immunology MH - Humans MH - *Immune Reconstitution Inflammatory Syndrome/epidemiology/immunology MH - Incidence MH - India/epidemiology MH - Infant MH - Male MH - *Meningitis, Cryptococcal/epidemiology/immunology MH - Prevalence MH - Prospective Studies PMC - PMC6602181 COIS- The authors have declared that no competing interests exist. EDAT- 2019/07/02 06:00 MHDA- 2020/02/19 06:00 PMCR- 2019/07/01 CRDT- 2019/07/02 06:00 PHST- 2018/09/23 00:00 [received] PHST- 2019/05/31 00:00 [accepted] PHST- 2019/07/02 06:00 [entrez] PHST- 2019/07/02 06:00 [pubmed] PHST- 2020/02/19 06:00 [medline] PHST- 2019/07/01 00:00 [pmc-release] AID - PONE-D-18-27720 [pii] AID - 10.1371/journal.pone.0211155 [doi] PST - epublish SO - PLoS One. 2019 Jul 1;14(7):e0211155. doi: 10.1371/journal.pone.0211155. eCollection 2019.