CHIPS data finds response to HAART varies with age in children

The Collaborative HIV Paediatric Study (CHIPS) is a multicentre cohort of children in the UK and Ireland participating in PENTA trials since 1996.

A study reported in the 24 September issue of AIDS evaluates the effect of age, pre-HAART CD4 percentage (CD4%) and plasma HIV-1 RNA on response to highly active antiretroviral therapy (HAART) in treatment naïve children.

The investigators reported that on 1 June 2003, 692 children had enrolled in CHIPS and 462 had received HAART. Of these 324 were drug naïve when initiating HAART regimens and 265 (82%) had both CD4 and viral load values pre-HAART and therefore eligible for this evaluation.

Seventy-seven (29%) children were less than 2 years old. 39 (17%) under one year, 49 (18%) were over 9 years. One hundred and thirty-eight children (52%) had CD4% of 15% or lower at HAART initiation.

The investigators reported that at 6 months, 181 (86%) of children had higher CD4% than at baseline. In univariate and multivariate analyses, adjusted for confounding factors, 10% CD4% increase was more likely at younger age [OR 0.84 per year, p=0.001] and lower pre-HAART CD4% [OR, 0.67 per 5% higher, p=0.001), but was not related to pre-HAART viral load. Effects of AIDS stage, calendar year of HAART initiation or HAART regimen were not significant

Younger age was also associated with a higher chance of achieving CD4% of >30% at 6 months. Children starting with a four drug regimen were more likely to achieve CD4% >30% at 6 months at all ages (OR, 5.48; 95% CI, 1.18-25.5; p=0.03).

Conversely older children were more likely to achieve HIV-1 RNA suppression, <400 copies/ml at 6 months (p= 0.03), and this was unrelated to pre-HAART HIV-1 RNA or CD4%. Children initiating HAART with 4 drugs had a greater likelihood of suppression (adjusted OR, 3.07; 95% CI, 1.04-9.08; p=0.04). Only 57 (27%) children achieved HIV-1 RNA <50 copies at 6 months and the likelihood was also greater in older children (OR, 1.09 per year of age; 95% CI, 1.01-1.18; p=0.02).

CD4% and HIV-1 RNA results were available for 149 children at 24 months and the investigators report that predictors were similar to 6 months results for CD4% increases over 10% at 24 months (overall rate 62% vs 38% at 6 months): initiation of HAART at younger age (OR, 0.87 per year, p=0.02) or with lower CD4% (OR, 0.60 per 5% higher baseline, p=0.0001). There were no predicting factors for viral load suppression <400 copies/ml at 24 months (overall rate 54% vs 60% at 6 months).

The authors write: “The findings from our study suggest that there are critical differences in the predictors of immunological and virological responses to HAART in previously untreated children and adults. Specifically, in children there are substantial and opposed effects of age on immunological and virological response, and a lack of association between response and pre-HAART HIV-1 RNA. these results may help inform the timing of initiation of HAART in children: this is likely to be a compromise between improved immunological and poorer virological response (potentially driving the development of resistance) at younger ages, versus the need to avoid clinical disease progression before starting HAART at older ages with poorer immunological and improved virological response.” They add “Longer follow up is required to determine whether children with low CD4% prior to HAART are able to normalise CD4 values and improve the quality of immune response.”

Walker SA, Doerholt K, Sharland M et al. Response to highly active antiretroviral therapy varies with age: the UK and Ireland Collaborative HIV Paediatric Study. AIDS 2004, 18:1915–1924.