OverviewARROW is a 5 year clinical trial of anti-HIV therapy in 1200 children with HIV or AIDS in Uganda and Zimbabwe. The trial aims to investigate two main questions: can anti-HIV drugs be given in the absence of routine laboratory tests, relying on clinical assessments instead; and whether starting children on 4 anti-HIV drugs for a short period of time before continuing with 3 drugs is better over the long term than starting on the standard 3 drugs.
Currently, doctors use regular laboratory tests, usually every 12 weeks, to see how well the medicines are working. However, these laboratory tests are both expensive and not widely available. In ARROW all children have these laboratory tests carried out but half of them (selected at random) do not have their results returned to their doctors throughout the trial, i.e. the clinical examination alone is used to make health management decisions. However, for these children, doctors are able to request (and see the results of) laboratory tests if there is a concern about the health of the child. In addition all test results are reviewed and returned for the doctor’s attention if they are considered severe.
The DART (Development of AntiRetroviral Therapy in Africa) makes the same comparison of monitoring strategies. The reason for studying this question in children as well is that the answers may be different compared to adults, because children’s immune systems behave differently. The way children’s growth responds to anti-HIV drugs may also provide extra information about how the medicines are working.
For the second question children are selected at random for one of three treatment groups. All three treatment groups include abacavir, lamivudine and either nevirapine (children under 3 years) or efavirenz (children over 3 years), a three medicine combination recommended by the World Health Organisation (WHO) guidelines. The first group contains just this treatment regimen for the entire trial. The other two groups both have a fourth anti-HIV drug, zidovudine for the first 36 weeks. After 36 weeks, one of these groups drops zidovudine and the other drops either nevirapine or efavirenz depending on which drug they are taking. The majority of the tablets being used in ARROW are scored and so can be easily snapped in half, aiding their use in children. This is detailed further in the trial schema.
The outcome of the trial will be assessed in terms of the development of new AIDS-defining illnesses or death. These events will be compared across the different groups.
All data are reviewed periodically by the Data Monitoring Committee (DMC) to ensure that it is safe to carry on with the trial. The DMC would recommend the trial should stop early if there is a difference between study groups indicating that one of the strategies is worse.