- What is ARROW?
- How long will ARROW go on?
- What are the criteria to be included in ARROW?
- What are the objectives of ARROW?
- Why test a clinical monitoring strategy in an African trial?
- How is the safety of the patients on anti-HIV drugs monitored?
- What drugs will be given to children in ARROW?
- What are the options for children who want to leave ARROW and continue to receive anti HIV drugs?
- Is there any assurance of provision of anti-HIV drugs after ARROW?
- How is ARROW similar to the DART trial?
- How will the benefits and risks of taking part in ARROW be explained to the children/carers?
- Why are the clinic visits once a month?
- Can other tests be requested outside of the routine tests?
- How can participants (or their community representatives) interact with trial investigators in ARROW?
- Who can be contacted for further queries about ARROW?
- Why are some children taking a fourth drug for the first 36 weeks?
Q.1 What is ARROW?
ARROW is short for “AntiRetroviral Research fOr Watoto”. Watoto means children in Swahili.
It is a randomised controlled clinical trial designed to assess two different management strategies for giving first line anti-HIV medicines. It is being carried out in Uganda and Zimbabwe in collaboration with the UK.
Q.2 How long will ARROW go on?
ARROW is a 5 year trial, recruiting for 18 months to the end of 2008 with follow up for a further 31/2 years to mid 2012.
Q.3 What are the criteria to be included in ARROW?
See Eligibility Criteria.
Q.4 What are the objectives of ARROW?
ARROW has two main aims: to find out whether anti-HIV drugs can be given safely and effectively without doing regular blood tests to monitor how children are doing on HIV treatment; 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.
ARROW is also investigating a number of other aspects relating to HIV treatment, including adherence to treatment (i.e. whether the children are taking the pills as prescribed) and the appropriate doses (pharmacokinetics) of these anti-HIV medicines.
Q.5 Why test a clinical monitoring strategy in an African trial?
Anti-HIV drugs are becoming increasingly available across Africa but it is not clear how these drugs can be provided safely outside centres of excellence in large cities where substantial resources are available.
Currently, doctors use regular laboratory tests, usually every 12 weeks, to see how well the medicines are working. However, these laboratory tests are expensive, not widely available and require skilled technicians.
There is reason to believe that with good clinical care many laboratory tests for possible drug toxicity would only need to be carried out if there were clinical symptoms present. However, it is also possible that some toxicities would only be detected too late using such an approach.
In ARROW we are evaluating how many laboratory tests are ordered if this is only done when there is clinical concern. But by still doing all the tests in all patients we can also find out how many serious toxicities might be missed. In ARROW, such serious laboratory results are provided to the doctors of children who are routinely being treated by the clinical assessment only.
It is only by doing such a randomised study that we can determine which, if any routine tests are needed to ensure safety and also when best to test (how soon after starting a drug) and how often.
The results will inform how much money should be spent on laboratory facilities, tests, equipment and staff compared to spending on doctors, nurses, pharmacists and drugs. With billions of US$ being spent each year across Africa it is vital that we know how to spend this money to the greatest benefit.
Q.6 How is the safety of the patients on anti-HIV drugs monitored?
All participants in ARROW are monitored in the same way. They routinely visit the clinic once a month but can attend the clinic at any time if the need arises. On a scheduled visit they are seen by the counsellors and nurses, who evaluate them and may recommend them to see a doctor. Otherwise they routinely see a doctor every three months. On a routine visit, they have blood taken to monitor how well they are doing on treatment. 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.
A small group of independent experts regularly monitors the results of the two groups. If either group were clearly doing worse, they would recommend closing the trial.
Q.7 What drugs will be given to children in ARROW?
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. This is detailed further in the trial schema.
Q.8 What are the options for children who want to leave ARROW and continue to receive anti HIV drugs?
In both Uganda and Zimbabwe there are now national programmes for the provision of free anti-HIV drugs. If a person should choose to leave ARROW they would have the same priority for acceptance onto such programmes as other people living with HIV/AIDS that have already had anti-HIV treatment. There is also the option to purchase these drugs but this would not be realistic for many ARROW participants.
Q.9 Is there any assurance of provision of anti-HIV drugs after ARROW?
The governments of Uganda and Zimbabwe have made written commitments that participants of ARROW will be able to access anti-HIV drugs under national programmes after the end of the trial.
Q.10 How is ARROW similar to the DART trial?
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 antiretroviral drugs may also provide extra information about how the medicines are working.
Q.11 How will the benefits and risks of taking part in ARROW be explained to the children/carers?
All carers and children being screened for ARROW are given information on the study objectives and procedures involved. This is generally done by a team of trained counsellors and nurses who provide them with a detailed information sheet (approved by ethics committees) to take home. They are then asked to return about 2 weeks later to enrol in the study, to give them plenty of time to consider and discuss ARROW with family or friends. At the enrolment visit there is further opportunity to ask any questions. Once all concerns have been addressed, carers and children (where appropriate) will then sign a formal trial consent form.
Q.12 Why are the clinic visits once a month?
The patients are routinely scheduled to visit the clinic once a month, but in cases where they are sick, they are seen promptly when they come, or if they are unable to travel a home visitor will go and assess their situation at home. This allows for more effective monitoring of adherence, side effects and any disease progression.
Q.13 Can other tests be requested outside of the routine tests?
In both groups the doctors can request for other tests than the routine ones. These may include imaging tests like X-rays, ultrasound scans, CT scans, and any other tests deemed necessary for the management of the patient. The only tests not available for clinical management are HIV viral load tests for all patients and CD4 tests in children being treated by clinical assessment only.
Q.14 How can participants (or their community representatives) interact with trial investigators in ARROW?
ARROW participants visit the ARROW clinic every 4 weeks and they always see at least a nurse. They also have access to counsellors and doctors whenever they need it. They are always free to raise any concerns or to ask any questions they have. Queries can be passed up to ARROW Principal Investigators if needed.
The ARROW trial management group are keen to communicate all aspects of the trial to the wider community in an open, clear and understandable manner.
Q.15 Who can be contacted for further queries about ARROW?
Please send any queries to firstname.lastname@example.org
Q.16 Why are some children taking a fourth drug for the first 36 weeks?
The rationale for using a fourth drug for the first 36 weeks is that children may do better in the long term compared to starting on a standard 3 drug regimen. There have been no randomised trials comparing 4 versus 3 drug regimens in children.