Abstract:
Background In 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.
Methods We 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).
Findings Between 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 adverse events in both groups (p=0·81), and 181 had grade 4 adverse
events in the RUSF group compared with 172 in the non-RUSF group (p=0·45).
Interpretation In severely immunocompromised HIV-infected individuals, providing RUSF universally at ART
initiation, compared with providing RUTF to severely malnourished individuals only, improved short-term weight
gain but not mortality. A change in policy to provide nutritional supplementation to all severely immunocompromised
HIV-infected individuals starting ART is therefore not warranted at present.