0846 Early antiretroviral therapy (ART) better than expectant therapy in HIV-infected infants

Current paediatric guidelines recommend the initiation of ART on the basis of low CD4 percentage or count, a high viral load or the presence of clinical symptoms i.e. treatment is not recommended for asymptomatic infants with apparently more robust immune systems and high CD4 values. However South African authors involved in the international CHER trial (Children with HIV Early Antiretroviral Therapy) have recently challenged these guidelines in the New England Journal of Medicine with data showing significantly improved outcome with early administration of ART to infants who do not meet current eligibility criteria. 377 infants with CD4 counts ≥25% were randomized at a median age of 7.4 weeks to one of 3 groups: one to receive deferred treatment on the basis of CD4 count and/or clinical deterioration, while the others were to receive one of two regimens until 1 or 2 years of age. ARTs used as first line were lopinavir-ritonavir, zidovudine and lamivudine. The results represent early outcomes and status following the study’s review board’s recommendations that patients in the deferred group be offered treatment. At a median follow up of 40 weeks the study has shown that mortality among the early intervention infants was 4% vs 16% for the deferred group, and disease progressed in 26% of deferred infants vs 6% in the early intervention groups. One-third of deferred infants had not yet qualified for treatment at the time of analysis and 15 of the 20 infants who died in the deferred group had not yet received ART. Failure to thrive was twice as frequent in the deferred group. Particlular note should perhaps be taken of the fact that the majority of infants in this study were ‘MTCT failures’ i.e. were products of monitored pregnancies and labours and had received ART according to protocols of the two study centres. Rapid progression among such infants has been reported, and the data presented strongly support the case for early intervention in such infants if not for all HIV-positive infants, irrespective of CD4 counts.

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