Clinical pattern, prevalence and factors associated with immune reconstitution syndrone in children on HAART attending joint clinical research institute.

Abstract

INTRODUCTION: The introduction of highly active antiretroviral therapy (HAART) has markedly decreased the rate of opportunistic infections, the progression to acquired immune deficiency syndrome (AIDS) and overall mortality among human immune deficiency virus (HIV) infected people. However, certain patients deteriorate after starting HAART despite decreasing viral load and raising CD=4 cell counts with a paradoxical emergence of certain opportunistic infections. This is immune reconstitution inflammatory syndrome (IRIS). The clinical deterioration after the initiation of HAART may result from restored immunity. IRIS can manifest a wide variety of clinical symptoms, depending on the target of the inflammatory response. Most studies on IRIS have focussed on adults and there is very little information about IRIS in children. Establishing the magnitude and factors associated with IRIS is important in order to put in place preventive strategies. OBJECTIVES: To describe the clinical pattern, prevalence and factors associated with IRIS in HIV infected children on HAART attending the joint clinical research centre.

METHODS: This was a cross sectional study of 162 HIV infected children aged less than 18 years who had been on HAART for atleast two weeks to 6 months. This study was carried out at three joint clinical research centres. We assessed the baseline clinical and laboratory data prior to initiation of HAART, and these parameters were also determined on recruitment. Laboratory investigations performed included full blood count, erythrocyte sedimentation rate, C reactive protein, liver function and renal funation tests, CD4+, CD8+ counts and percentages, CD4+: CD8+ ratio and viral loads. These were compared with the baseline investigations to confirm an IRIS episode using diagnostic criteria adopted from the diagnostic IRIS criteria by French et al 2004. Patients were enrolled from December 2006 to October 2007 after informed conscent from the care takers and assent from older children was obtained. Data was entered using EPI-DATA M2.1b and analyzed using SPSS. Chi-squared tests, bivariate analysis and simple logistic regression were used to test for factors associated with IRIS. Multivariate logistic regression analysis was used to determine factors independently associated with IRIS. RESULTS: One sixty two children were analyzed, with a male: female ratio of 1.4:1, 50.6%, 39.5% and 99% from mengo, mbale and fort portal respectively. They were aged 0.5 to 18 years with a median age of 6 years (Interquartile range= 2.5-11 years). At initiation of HAART 72.8% were in WHO stage III/IV indicating severe immunosuppression. There wasno interruption of HAART and 90.7% (147) were on an NNRTI based regimen. The prevalence of IRIS was 38.3% and the commonest time of occurance was less than I month. The median age of the children with IRIS was 6.75 years and the prevalence was highest (46.4%) in 5-12 year age group. The clinical pattern was diverse with TB-IRIS (29%) commonest. Others included worsening or resurgence of otitis media, extensive dermatological manifestations such as Kaposi sarcoma, molluscum contangiossumm tinea umblicatus. Factors associated with IRIS were male sex, presence of a cough for atleat 7 days or more at interview, CD+8 absolute counts at interview less than 1000 cells, and a low baseline CD4+%<15%p-value 0.027; OR =3.09 (C1:1.14-8.36). CONCLUSIONS: The prevalence of IRIS among children attending JCRC was 38.3% Children with IRIS presented with a wide spectrum of conditions with TB-IRIS being the most prevalent. Male children, low baseline CD4+% less than 15% at HAART initiation, CD8+ absolute counts at interview less than 1000 cells and a cough persisting beyond one week at interview were factors associated with IRIS in this study. RECOMMENDATIONS: HIV treating centre should re-enforce TB diagnosis and its treatment in their patients prior to initiation of HAART. Since IRIS events are common and are more likely to occur in the first month of commencing HAART, there is need to increase awareness of this condition among health care providers and caretakers of the children so as to minimise non-adherence at its early stage. A large study is needed to determine the predictors of IRIS in children.