Adedeji Majekodunmi
University College London
Objectives: The effect of HCV co-infection on CD4 T cell recovery in treated HIV-infected children is poorly understood. The main aim of this study is to investigate the significance of Hepatitis C virus (HCV) co-infection on CD4 T cell reconstitution of HIV-infected children undergoing anti-retroviral therapy. Secondly, to investigate the importance of other covariates on this relationship.
Methods: 78 age-matched European children selected from an observational study conducted by the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) were included into this study. The children were aged between 1month and 25 yrs and were all receiving antiretroviral therapy. There were a total of 39 Hepatitis C co-infected and 39 HIV mono-infected children who had CD4 counts measured over a 5 yr period. The CD4 counts were transformed into z scores to accommodate for age fluctuations in CD4 counts [3]. We fitted this longitudinal data using a recently developed exponential model containing three parameters and within the frame work of non-linear mixed effects modelling [1]. Estimates were obtained for pre-antiretroviral therapy z scores (intercept), long term antiretroviral therapy z scores (asymptote) and rate of increase in CD4 z scores (c). Covariates investigated include age at start of therapy, gender, aids status, hepatitis C status and country of origin.
Results: The analysis revealed that hepatitis C did not have a significant effect on immune reconstitution in these HIV-infected children undergoing therapy. This was confirmed using both univariate and multivariate analysis. In our HCV status-inclusive univariate model, the impact of HCV co-infection on either intercept or asymptote was not statistically different from zero (p = 0.3935 and p = 0.0951 respectively). As expected, younger children had a higher rate of CD4 T cell recovery (p = 0.0329) and higher pre-ART age-adjusted CD4 counts (p = 0.0021) compared to older children.
Conclusions: Our results are in agreement with a study published in 2007 looking at the impact of HCV on immune reconstitution in 44 Spanish children [2]. Although this Spanish study did not use a modelling based approach, they established that hepatitis C did not have a significant impact on CD4 T cell recovery in HIV-infected children receiving treatment.
References:
[1] Joanna Lewis, A. Sarah Walker, Hannah Castro, Anita De Rossi, Diana M. Gibb, Carlo Giaquinto, Nigel Klein and Robin Callard. Age and CD4 Count at Initiation of Antiretroviral Therapy in HIV-Infected Children: Effects on Long-term T-Cell Reconstitution, JID 2012 Feb 15;205(4):548-56.
[2] Micheloud D, Jensen J, Bellon JM, Gonzalez R, Mellado MJ, Navarro ML et al ; Spanish Group of Paediatric HIV Infection. Long-term response to highly active antiretroviral therapy in human immunodeficiency virus and hepatitis C virus coinfected children: 6 years of follow-up, Pediatr Infect Dis J. 2007 Nov;26(11):1061-4.
[3] Huenecke S, Behl M, Fadler C, Zimmermann SY, Bochennek K, Tramsen L et al. Age-matched lymphocyte subpopula- tion reference values in childhood and adolescence: ap- plication of exponential regression analysis, Eur J Haema- tol 2008; 80:532-9
Reference: PAGE 24 (2015) Abstr 3379 [www.page-meeting.org/?abstract=3379]
Poster: Drug/Disease modeling - Paediatrics