Immune reconstitution inflammatory syndrome among HIV-infected South African infants initiating antiretroviral therapy

Abstract

Objectives To determine the incidence, clinical manifestations and risk factors for immune reconstitution inflammatory syndrome (IRIS) in young children initiating highly active antiretroviral therapy (HAART). Design A prospective cohort of antiretroviral-naïve HIV-infected children less than 24 months of age enrolled in a treatment strategies trial in Johannesburg, South Africa. Methods Among 169 HIV-infected children initiating HAART, April 2005 to November 2006, the records of 83 children suspected to have IRIS within 6 months of starting treatment were reviewed to determine whether they met criteria for IRIS. Seven were excluded due to incomplete follow-up. Pretreatment and post-treatment characteristics of children with and without IRIS were compared. Results Overall, 34/162 (21%) children developed IRIS at a median of 16 days (range 7–115 days) post-HAART initiation. Bacille Calmette-Guérin reaction was most common occurring in 24/34 (71%) children, primarily injection site lesions and/or ipsilateral axillary lymphadenitis with abscess. Other IRIS conditions (not mutually exclusive) included Mycobacterium tuberculosis (n = 12), cytomegalovirus pneumonia (n = 1), Streptococcus pneumonia sepsis (n = 1), and severe seborrheic dermatitis (n = 1). Children with IRIS were younger (median age 7 vs. 10 months, P = 0.007) with a lower CD4 cell percentage (median 13.9 vs. 19.2, P = 0.009) at HAART initiation than controls. After 24 weeks on HAART, 62% of IRIS cases vs. 28% of controls had HIV RNA more than 400 copies/ml (P = 0.001), odds ratio = 2.88 (95% confidence interval = 1.14–7.29) after adjusting for baseline factors. Conclusion Infants and young children with advanced HIV disease initiating HAART are at high risk for developing IRIS, leading to additional morbidity and possibly impairing virologic response to antiretroviral treatment.

Pharmacology and immuno-virologic efficacy of once-a-day HAART in African HIV-infected children: ANRS 12103 phase II trial

“…Its frequency (6%) was far lower than described in South Africa, 20 although some less severe cases of IRIS were probably missed in our study.…”

Dermatite seborreica

“…109,110 Furthermore, there have been reports of aggravation during immune reconstitution inflammatory syndrome and reports that antiretroviral treatment does not alter the prevalence or the course of SD. 111,112 With respect to histopathology, the findings of SD in HIV-positive patients are similar to those found in HIV-negative patients; however, there appears to be greater follicular involvement in the lesions and more plasmocytes in the inflammatory infiltrate in the HIVpositive patients. 17,78,101 The clinical appearance of SD is typical, affecting areas rich in sebaceous glands and accompanied or not by pruritus.…”

Rapid Development of Antiretroviral Drug Resistance Mutations in HIV-Infected Children Less Than Two Years of Age Initiating Protease Inhibitor-Based Therapy in South Africa

“…An ART strategies trial enrolled HIV-infected children between 6 and 104 weeks of age who were exposed to NVP for PMTCT and were either eligible for ART based on immunologic or clinical criteria (n = 254) or currently receiving a stable PI-based ART regimen (n = 69). [26][27][28] The study protocol was approved by the Columbia University Medical Center and University of the Witwatersrand Institutional Review Boards, and each participant's guardian provided signed informed consent. This analysis makes use of data from the observational prerandomization phase of the study only.…”