Should treatment be started in all newborns infected with HIV?

A report from the HIV Paediatric Prognostic Markers Collaborative Study Group, published in the 15 November 2003 issue of the Lancet, evaluated the risk of progression to AIDS – with regards to CD4% or viral load and age – of HIV-infected newborns in the first year of life [1].

This study performed a meta-analysis of pooled individual patient data for 3,941 children participating in 17 cohort studies and randomised trials conducted in Europe and the USA between 1983 and 2002, receiving either no therapy or zidovudine monotherapy. Separate analyses were undertaken to determine the 12-month predictive value of CD4% and viral load for death (in both the presence and absence of AIDS) and progression to AIDS.

The investigators reported that in analysis of the predictive value of CD4%, 997 children progressed to AIDS or died without an AIDS diagnosis, compared to 284 children analysed by viral load; the numbers of deaths were 568 and 129 respectively. They reported a sharp increase in risk of death among children above two years when CD4% fell below 10%, and a poorer prognosis in children below two years than older children with the same CD4%. Additionally they reported 917 AIDS events and that the relative frequency of these events was strongly age related. They cited an approximately three-fold higher risk of AIDS in a one year old child than in a five year old child and a difference of about six-fold for death.

For infants they reported very substantial rates of disease progression even at high CD4%: at six months for example a CD4% between 25% and 50% predicted a risk of developing AIDS within six months of between 25% and 13% and a risk of death between 8.5% and 4.1%

Viral load values greater than 100,000 copies/mL increased the risk of disease progression considerably at all ages but was a better predictor of disease progression at lower levels in older than in younger children. However, CD4 was a stronger predictor than both age and viral load.

The investigators noted: “The observation that neither CD4% nor viral load could identify children at low risk for disease progression lends some support to a universal treatment policy for infants, or at least the need for close observation to promptly detect clinical signs or symptoms preceding AIDS.” Current European guidelines recommend that paediatricians “consider” treatment for all children less than one year of age, differing from the US guidelines, which advocate treatment for all at this age.

In a commentary from Dr Elaine Abrams and Dr Louise Kuhn in the same issue, the authors commend the study group, stating that their findings “…confirm collective experience and worst fears…For children under one year of age, the risk of progression to AIDS or death remains unacceptably high, even when immune degradation and viraemia are moderately well contained. CD4 T cells gradually decrease during early childhood from high values at birth, while HIV-RNA levels increase progressively, peaking during the first three to six months of life before decreasing slowly thereafter. With these developmental changes, it is not surprising that these markers are less informative during the first years of life.”

The authors write that considering the findings from this study, arguments in favour of universal treatment for infants seem compelling and ask: “…is it feasible to treat children when they are most vulnerable and then stop treatment at a safer time?”