A large study of immediate versus deferred antiretroviral treatment in South African infants has found a significant advantage to immediate treatment after just eight months of follow-up, and researchers monitoring the trial have decided that the `deferred treatment` arm of the study should be closed and all children not yet receiving treatment should be evaluated to determine whether they should start antiretroviral therapy.
The trial, called the Children with HIV Early Antiretroviral Therapy (CHER) study, has been halted following an interim review of data from the trial conducted by the study’s Data and Safety Monitoring Board.
The study has two parts – one for infants with relatively good immune function and one for infants with more advanced HIV disease. The change to the study is taking place in the arm that is recruiting HIV-diagnosed infants with relatively good immune function (a CD4 percentage above 25%).
In this arm of the study, infants have been randomised to one of three treatment strategies: immediate treatment lasting until the infant’s first birthday (approximately 40 weeks); immediate treatment lasting until the infant’s second birthday (approximately 96 weeks), or treatment deferred until the infant's CD4 cell percentage declines below 25 or they develop clinical symptoms of HIV disease.
All children in the study receive first-line treatment with AZT, 3TC and lopinavir/ritonavir (Kaletra).
The aim of the study is to determine whether a limited period of treatment in the first years of life can delay the need for long-term, indefinite antiretroviral therapy in infants infected with HIV by their mothers. The study is comparing this approach with the deferred treatment approach. In children with more advanced HIV disease, all children are receiving immediate treatment, but are being randomised to stop at their first or second birthday.
When they looked at the data after an average 32 weeks follow-up in the study, researchers found a significant advantage to early treatment for children with relatively preserved immune function. Ninety-six per cent of infants who received immediate treatment were still alive at this point, compared to 84% of children who received deferred treatment.
Based on this finding, the DSMB recommended that no additional infants be placed in the deferred-treatment arm of the study, and infants in this arm be evaluated for potential initiation of ARV therapy. The DSMB also recommended that the two immediate therapy arms evaluating early ARV treatment in HIV-infected infants for defined lengths of time (to first or second birthdays) continue (planned follow-up for each infant in the study is a minimum 3.5 years from study entry).
The NIAID-sponsored "Children with HIV Early Antiretroviral Therapy" (CHER) study, which began enrollment in July 2005, is being conducted at two locations in South Africa. It is coordinated by an international team from the Perinatal HIV Research Unit in Johannesburg, South Africa; the Children's Infectious Diseases Clinical Research Unit in Cape Town, South Africa; the Medical Research Council Clinical Trials Unit in London and NIAID's Division of AIDS.
Further results of the study will be presented as a late breaker at the Fourth International AIDS Society Conference on HIV Treatment and Pathogenesis on Wednesday July 24th.