Effect of ready-to-use supplementary food on mortality in severely immunocompromised HIV-infected individuals in Africa initiating antiretroviral therapy (REALITY): an open-label, parallel-group, randomised controlled trial

Abstract

SummaryBackgroundIn sub-Saharan Africa, severely immunocompromised HIV-infected individuals have a high risk of mortality during the first few months after starting antiretroviral therapy (ART). We hypothesise that universally providing ready-to-use supplementary food (RUSF) would increase early weight gain, thereby reducing early mortality compared with current guidelines recommending ready-to-use therapeutic food (RUTF) for severely malnourished individuals only.MethodsWe did a 2 × 2 × 2 factorial, open-label, parallel-group trial at inpatient and outpatient facilities in eight urban or periurban regional hospitals in Kenya, Malawi, Uganda, and Zimbabwe. Eligible participants were ART-naive adults and children aged at least 5 years with confirmed HIV infection and a CD4 cell count of fewer than 100 cells per μL, who were initiating ART at the facilities. We randomly assigned participants (1:1) to initiate ART either with (RUSF) or without (no-RUSF) 12 weeks' of peanut-based RUSF containing 1000 kcal per day and micronutrients, given as two 92 g packets per day for adults and one packet (500 kcal per day) for children aged 5–12 years, regardless of nutritional status. In both groups, individuals received supplementation with RUTF only when severely malnourished (ie, body-mass index [BMI] <16–18 kg/m2 or BMI-for-age Z scores <–3 for children). We did the randomisation with computer-generated, sequentially numbered tables with different block sizes incorporated within an online database. Randomisation was stratified by centre, age, and two other factorial randomisations, to 12 week adjunctive raltegravir and enhanced anti-infection prophylaxis (reported elsewhere). Clinic visits were scheduled at weeks 2, 4, 8, 12, 18, 24, 36, and 48, and included nurse assessment of vital status and symptoms and dispensing of all medication including ART and RUSF. The primary outcome was mortality at week 24, analysed by intention to treat. Secondary outcomes included absolute changes in weight, BMI, and mid-upper-arm circumference (MUAC). Safety was analysed in all randomly assigned participants. Follow-up was 48 weeks. This trial is registered with ClinicalTrials.gov (NCT01825031) and the ISRCTN registry (43622374).FindingsBetween June 18, 2013, and April 10, 2015, we randomly assigned 1805 participants to treatment: 897 to RUSF and 908 to no-RUSF. 56 (3%) were lost-to-follow-up. 96 (10·9%, 95% CI 9·0–13·1) participants allocated to RUSF and 92 (10·3%, 8·5–12·5) to no-RUSF died within 24 weeks (hazard ratio 1·05, 95% CI 0·79–1·40; log-rank p=0·75), with no evidence of interaction with the other randomisations (both p>0·7). Through 48 weeks, adults and adolescents aged 13 years and older in the RUSF group had significantly greater gains in weight, BMI, and MUAC than the no-RUSF group (p=0·004, 0·004, and 0·03, respectively). The most common type of serious adverse event was specific infections, occurring in 90 (10%) of 897 participants assigned RUSF and 87 (10%) of 908 assigned no-RUSF. By week 48, 205 participants had serious a...

Mortality in a Cohort of HIV-Infected Children: A 12-Month Outcome of Antiretroviral Therapy in Makurdi, Nigeria

“…In addition, other measures that have been proven to reduce mortality in severely immunocompromised HIV-infected individuals initiating ART in Africa can also reduce further the mortality seen in our setting, and can also be applied [61, 62]. These measures include the use of ready-to-use supplementary food (RUSF) and an enhanced anti-infection prophylaxis (EAIP).…”

“…These measures include the use of ready-to-use supplementary food (RUSF) and an enhanced anti-infection prophylaxis (EAIP). The EAIP comprises trimethoprim-sulfamethoxazole plus 12 weeks of isoniazid-pyridoxine, 12 weeks of fluconazole, 5 days of azithromycin, and a single dose of albendazole against mortality from tuberculosis, cryptococcal infection, oral/oesophageal candidiasis, and severe bacterial infections [61, 62]. …”

Prevalence of malnutrition and associated factors among adult patients on Antiretroviral Therapy follow up care in Jimma Medical Center, Southwest Ethiopia

“…Despite improvement in treatment coverage over time (14), treatment effectiveness remains low due to factors such as non-adherence, quality and nutritional status of patients (15,16). The probability of mortality is highest among patients with poor nutritional status, as malnutrition is the cause for damage in the immune system and subsequent susceptibility to illnesses (17).…”

Nutritional support to reduce mortality in patients with HIV?

“…10,11 In Ethiopia, RUSF with micronutrients at a concentration of one reference nutrient intake, compared with unsupplemented HIVinfected patients, was associated with a considerable increase in lean mass in a subgroup of patients with viral suppression, 12 but not in those without viral suppression, suggesting that reduction of inflammation might have contributed to the beneficial effects in the viral-suppressed subgroup. Thus, similar mechanisms might underlie the results of Mallewa and colleagues' trial 5 and previous trials. [6][7][8] In the light of these findings, should nutritional supplementation continue to be encouraged in patients starting ART?…”

“…However, two key questions are which patients should receive supplements and when. The evidence from Mallewa and colleagues' study 5 suggests that low CD4 cell counts should not be used as an indicator for supplementation, while findings from other studies indicate that low BMI could be used as a marker. 7,12 Future studies should investigate the appropriate timing for initiating nutritional support in HIV-infected patients when inflammation has reduced, to help provide a scientific basis for further trials of nutritional interventions in improving health of HIV-infected patients.…”