Giving a low-cost package of drugs to prevent infections among people starting HIV treatment with advanced disease saves lives. This finding from the REALITY trial was published yesterday in the New England Journal of Medicine.
Many people with HIV in Africa do not start antiretroviral therapy (ART) until their immune system has been badly damaged by the disease. People with low CD4 counts (a measure of the strength of the immune system) when they start HIV treatment are at a high risk of dying within the first few weeks of treatment. Around one in five people starting ART in Africa have CD4 cell counts of less than 100cells/mm 3, which is very low.
The REALITY trial looked at ways to reduce these deaths in the early stages of treatment. It tested three strategies, in addition to standard HIV treatment, for the first 12 weeks of treatment:
- Enhanced prophylaxis to prevent infections
- Increasing the potency of ART by adding the anti-HIV drug raltegravir to reduce the amount of virus in the blood faster
- Ready-to-Use Supplementary Food to improve nutritional status
The results published yesterday focus on the results of the enhanced prophylaxis comparison. In this comparison, people were randomised to receive either cotrimoxazole prophylaxis (an antibiotic that can be used to prevent bacterial infections) which is standard care, or cotrimoxazole plus a package of additional drugs:
- Isoniazid to prevent tuberculosis
- Fluconazole to prevent cryptococcal disease and candida
- Azithromycin to prevent bacterial and protozoal diseases
- Albendazole to treat worms
1,805 adults and children over 5 years of age from Kenya, Malawi, Uganda and Zimbabwe took part in the REALITY trial. All had CD4 counts under 100 cells and were starting Antretroviral medicines (ARVs). People who took part in the trial were followed up for 48 weeks.
REALITY found there were more than three fewer deaths for every hundred people treated in the group who had the enhanced prophylaxis than the group who had standard cotrimoxazole prophylaxis. Enhanced prophylaxis reduced the risk of death by 25%. People in the enhanced prophylaxis group were also less likely to have severe AIDS illnesses, abnormal test results or require admission to hospital.
REALITY prophylaxis film from MRC Clinical Trials Unit at UCL on Vimeo.
The drugs used in the enhanced prophylaxis package are all relatively low cost, costing less than $5 more than standard cotrimoxazole, per patient. Health economic analysis has found that the package is cost-effective in all the countries where the trial was carried out.
The researchers are now recommending that people in Africa starting HIV treatment with low CD4 counts should be given enhanced prophylaxis for the first few weeks of treatment.
The REALITY trial was led by the MRC Clinical Trials Unit at UCL, in collaboration with: Joint Clinical Research Centre (JCRC), Kampala, Fort Portal, Mbarara, Mbale, and Gulu, Uganda; University of Zimbabwe Clinical Research Centre (UZCRC), Harare, Zimbabwe; Malawi-Liverpool-Wellcome Trust Programme and Department of Medicine, University of Malawi, Blantyre, Malawi; Moi University Clinical Research Centre (MUCRC), Eldoret, Kenya; KEMRI Wellcome Trust Centre, Kilifi, Kenya; and London School of Hygiene and Tropical Medicine, London, UK.
The REALITY trial was funded by the Department for International Development, UK (DFID), the Wellcome Trust and the Medical Research Council (MRC) UK. Additional funding support is provided by the PENTA foundation. Drugs for the prophylaxis package were donated by Cipla. ARV drugs were donated by Gilead, Viiv, Merck and Cipla.