Adedeji Majekodunmi
University College London
Objectives: The aim objective of this project is to investigate the effect of HCV infection on long term immune reconstitution of CD4 T cells in HIV infected children across Europe who are on anti-retroviral therapy (ART).
Methods: In a recent model developed by Lewis et al[1], it was shown that immune reconstitution in children commenced on antiretroviral therapy followed an asymptotic recovery in the first 5 yrs (zij = asyi – (asyi – inti)e-c*t + εij)[1]. However, when this model was applied to a new cohort of HIV infected children who are also coinfected with hepatitis C, a linear mixed effect model was preferentially chosen as it provided a much better fit. The data analysed was a retrospective observational data collected from 8 European paediatric HIV cohorts included in the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC). The children were aged btw 18 months and 25yrs and had acquired HIV/HCV infection maternally or in childhood.
Analysis was done using the principles of mixed effect modelling in R (nlme).
Results: Coinfected children appear to have higher cd4 z-scores throughout the first 5 yrs of treatment. However, this was only statistically significant in the Ukraine cohort ( p < 0.001).
Covariate analysis revealed that age at start of antiretroviral therapy and HCV status both had significant interactions with the initial cd4 z-score (intercept) of the model (p < 0.001, 0.022). Age at start of antiretroviral therapy also had a significant impact on the rate of increase of cd4 z score over a 5 yr period (p = 0.0016). Older children have lower cd4 z-scores compared to their younger counterparts.
Conclusions: Coinfected children from Ukraine appear to have a significantly higher cd4 z-score at start of ART. This is an unexpected finding when compared with coinfected adults who are known to have lower cd4 recovery profiles[2]. A possible explanation for this could be additional homeostatic mechanisms in repopulating T cells in children. However, larger studies are needed to fully characterize immune profiles of these patients.
References:
[1] Lewis et al- Age and CD4 count at initiation of antiretroviral therapy in HIV-infected children: effects on long-term T-cell reconstitution, J. Infect. Dis. Feb 2012.
[2] Van Griensven et al- Hepatitis B/C Co-infection among HIV-infected Adults while on Antiretroviral Treatment: Long-Term Survival, CD4 Cell Count Recovery and Antiretroviral Toxicity in Cambodia, PLOS One, Vol. 9, Feb 2014.
[3] Claret-Teruel et al- Impact of HIV coinfection on the progression of mother- to-child transmitted HCV infection. Paed. Infect. Dis. Journal. Vol. 30, 2011.
Reference: PAGE 23 (2014) Abstr 3310 [www.page-meeting.org/?abstract=3310]
Poster: Drug/Disease modeling - Infection