REALITY
Reduction of EArly mortaLITY in HIV-infected adults and children starting antiretroviral therapy
Can early mortality in those starting ART with severe immunodeficiency be reduced?
What was this study about?
A randomised controlled trial to investigate three methods to reduce early mortality in adults, adolescents and children aged 5 years or older starting antiretroviral therapy (ART) with severe immuno-deficiency.
The three methods were:
- increasing the potency of ART with a 12 week induction period using 4 antiretroviral (ARV) drugs from 3 classes (rather than standard 3 ARVs from 2 classes)
- augmented prophylaxis against opportunistic/bacterial infections and helminths for 12 weeks
- macronutrient intervention using ready-to-use supplementary food for 12 weeks.
What difference did this study make?
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.
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.
REALITY found adding an extra ART drug for the first 12 weeks of treatment did not reduce deaths. People who the extra ART drug did have faster declines in HIV viral load, but there were no significant differences in deaths within 24 weeks of starting treatment. Nor were there differences in clinical disease progression or side-effects.
While the rapid reduction in viral loads did not lead to a reduction in deaths, it may have potential for reducing onward transmission of the disease. This might be particularly useful for women who are identified as HIV-infected during pregnancy, to prevent the virus being passed to their baby.
REALITY found that people in the group who received supplementary food gained about 1kg more weight than people in the group who did not receive supplementary food. But this increase in weight did not lead to improvements in grip strength, or reduce deaths. It also made no difference to how much virus people had in their blood.
These results suggest that, for adults without severe malnutrition, supplementary feeding is not necessary in addition to a healthy balanced diet for those initiating ART with very low CD4 counts. The ready-to-use supplementary food is relatively expensive, so it is useful to know that it is not universally needed for people without severe malnutrition.
Type of study
Randomised trial
Contact details
Who funded the study?
Department for International Development, UK (DFID), the Wellcome Trust and the Medical Research Council (MRC) UK. Additional funding support was provided by the PENTA foundation.
When did it take place?
Recruitment began in June 2013 and completed in April 2015. The last patient last visit was in March 2016.
Where did it take place?
Joint Clinical Research Centre (JCRC), Kampala, Uganda (Coordinating centre only – not recruiting patients); JCRC Fort Portal, Uganda; JCRC Mbarara, Uganda; JCRC Mbale, Uganda; JCRC Gulu, Uganda; University of Zimbabwe Clinical Research Centre (UZCRC), Harare, Zimbabwe; University of Malawi, Department of Medicine, Blantyre, Malawi; Moi University Clinical Research Centre (MUCRC), Eldoret, Kenya; KEMRI Wellcome Trust Centre, Kilifi, Kenya
Who was included?
1805 HIV-infected patients including adults, adolescents and children aged 5 years or older with low CD4 counts (<100 cells/mm3) about to initiate combination antiretroviral therapy (ART).