Clinical patterns, prevalence and factors associated with immune reconstitution syndrome in children on HAART attending Joint Clinical Resarch Centre
No Thumbnail Available
Date
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Description
A thesis submitted in partial fulfillment of the requirements for the award of the Master of Medicine Degree of Makerere University.
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 I-Iuman 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 focused 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. Objective: To describe the clinical pattern, prevalence and factors associated with IRIS in HIV infected children on HAART attending the Joint Clinical Research Center. Methods: This was a cross-sectional study of 162 HIV infected children aged less than 18 years who had been on HAART for at least 2 weeks to 6 months. This study was carried out at three Joint Clinical Research Centers. 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 function 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 consent from the care takers and assent from older children was obtained. Data was entered using EPI-DA TA 2.1 b 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 analysed, with a male: female ratio of 1.4: I, 50.6%, 39.5%, and 9.9% from Mengo, Mbale, and Fort Portal respectively. They were aged 0.5 to 18 years with a median age of 6years (Interquartile range= 2.5-11 years). At initiation of HAART 72.8 %were in WHO stage III/IV indicating severe immunosuppression. There was no 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 occurrence 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 contangiosum, Tinea umblicatus. Factors associated with IRIS were male sex, presence of a cough for at least 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 (CI: 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 centers 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 minimize non-adherence at this early stage. A large study is needed to determine the predictors of IRIS in children.
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 I-Iuman 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 focused 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. Objective: To describe the clinical pattern, prevalence and factors associated with IRIS in HIV infected children on HAART attending the Joint Clinical Research Center. Methods: This was a cross-sectional study of 162 HIV infected children aged less than 18 years who had been on HAART for at least 2 weeks to 6 months. This study was carried out at three Joint Clinical Research Centers. 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 function 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 consent from the care takers and assent from older children was obtained. Data was entered using EPI-DA TA 2.1 b 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 analysed, with a male: female ratio of 1.4: I, 50.6%, 39.5%, and 9.9% from Mengo, Mbale, and Fort Portal respectively. They were aged 0.5 to 18 years with a median age of 6years (Interquartile range= 2.5-11 years). At initiation of HAART 72.8 %were in WHO stage III/IV indicating severe immunosuppression. There was no 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 occurrence 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 contangiosum, Tinea umblicatus. Factors associated with IRIS were male sex, presence of a cough for at least 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 (CI: 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 centers 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 minimize non-adherence at this early stage. A large study is needed to determine the predictors of IRIS in children.
Keywords
Active Antiretroviral Therapy (HAART), Opportunistic infections, Acquired Immune Deficiency Syndrome (AIDS), Mortality, HIV patients, Joint Clinical Research Centre, Uganda