Response to highly active antiretroviral therapy varies with age: the UK and Ireland Collaborative HIV Paediatric Study.
Walker AS., Doerholt K., Sharland M., Gibb DM., Collaborative HIV Paediatric Study (CHIPS) Steering Committee None.
OBJECTIVE: To evaluate the effect of age, CD4 percentage (CD4%) and plasma HIV-1 RNA on response to highly active antiretroviral therapy (HAART) in previously untreated children. DESIGN: Cohort study. METHODS: We examined the association between age at HAART initiation, and CD4 and HIV-1 RNA response using logistic and Cox regression, adjusting for sex, route of infection and pre-HAART values. RESULTS: CD4% increases of > 10% at 6 months were more likely in younger children [odds ratio (OR), 0.84 per year, P < 0.001] and those with lower pre-HAART CD4% (OR, 0.67 per 5% higher, P < 0.001), but were not related to pre-HAART HIV-1 RNA (P = 0.6). In contrast, HIV-1 RNA suppression < 400 copies/ml at 6 months was more likely in older children (OR, 1.09 per year, P = 0.03), and was unrelated to pre-HAART HIV-1 RNA or CD4% (P > 0.3). CD4% was still increasing during the second year following HAART initiation (60% followed > 24 months). Longer-term increases in CD4% occurred faster, and decreases in HIV-1 RNA occurred more slowly in younger children. The median time to CD4% >/= 30% after initiating HAART with CD4% </= 25% was under 12 months for children under 2 years irrespective of pre-HAART CD4%, and increased progressively in older children and as CD4% decreased. CONCLUSIONS: Children respond immunologically to HAART irrespective of pre-HAART HIV-1 RNA or clinical status. However, immunological response is better in younger children and those with lowest CD4%, whereas younger children have poorer virological response, increasing the risk of resistance. Differences in response to HAART according to age and underlying risk of disease progression should be considered when initiating HAART in children.