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
Authors: Jane Mallewa, Alexander J Szubert, Peter Mugyenyi, Ennie Chidziva, Margaret J Thomason, Priscilla Chepkorir, George Abongomera, Keith Baleeta, Anthony Etyang, Colin Warambwa, Betty Melly, Shepherd Mudzingwa, Christine Kelly, Clara Agutu, Helen Wilkes, Sanele Nkomani, Victor Musiime, Abbas Lugemwa, Sarah L Pett, Mutsa Bwakura-Dangarembizi, Andrew J Prendergast, Diana M Gibb, A Sarah Walker, James A Berkley, Peter Mugyenyi, Cissy Kityo, Victor Musiime, Priscilla Wavamunno, Esther Nambi, Paul Ocitti, Milly Ndigendawani, Sheila Kabahenda, Mable Kemigisa, Juliet Acen, David Francis Olebo, Gordon Mpamize, Alex Amone, David Okweny, Andrew Mbonye, Florence Nambaziira, Angela Rweyora, Mary Kangah, Beatrice Kabaswahili, James Abach, George Abongomera, Joseph Omongin, Irene Aciro, Aleti Philliam, Beatrice Arach, Emmanuel Ocung, Geoffrey Amone, Peter Miles, Claudia Adong, Constance Tumsuiime, Patrick Kidega, Ben Otto, Florence Apio, Keith Baleeta, Andrew Mukuye, Mary Abwola, Fred Ssennono, David Baliruno, Stephen Tuhirwe, Ronald Namisi, Fredrick Kigongo, Dickson Kikyonkyo, Furaha Mushahara, David Okweny, Julian Tusiime, Alex Musiime, Agnes Nankya, Dickens Atwongyeire, Sowal Sirikye, Sula Myalo, Nelson Noowe, Abbas Lugemwa, Mariam Kasozi, Sandra Mwebe, Lorna Atwine, Tapson Senkindu, Ian Natuhurira, Chrispus Katemba, Emily Ninsiima, Moses Acaku, Joy Kyomuhangi, Rogers Ankunda, Deogratious Tukwasibwe, Lillian Ayesiga, James Hakim, Kusum Nathoo, Mutsa Bwakura-Dangarembizi, Andrew Reid, Ennie Chidziva, Tawand Mhute, Gloria Tinago, Joyline Bhiri, Shepherd Mudzingwa, Misheck Phiri, John Steamer, Ruth Nhema, Colin Warambwa, Godfrey Musoro, Shirley Mutsai, Beauty Nemasango, Columbus Moyo, Stuart Chitongo, Kennias Rashirai, Sydney Vhembo, Brian Mlambo, Sanele Nkomani, Buxton Ndemera, Marko Willard, Chipo Berejena, Yeukai Musodza, Patience Matiza, Boniface Mudenge, Vongai Guti, Anthony Etyang, Clara Agutu, Jay Berkley, Kathryn Maitland, Patricia Njuguna, Shalton Mwaringa, Timothy Etyang, Ken Awuondo, Stephen Wale, Jimmy Shangala, Jefwa Kithunga, Salim Mwarumba, Salma Said Maitha, Robert Mutai, Margaret Lozi Lewa, Gabriel Mwambingu, Alfred Mwanzu, Connie Kalama, Helen Latham, Joyce Shikuku, Amos Fondo, Anne Njogu, Connie Khadenge, Bryan Mwakisha, Abraham Siika, Kara Wools-Kaloustian, Winston Nyandiko, Priscilla Chepkorir-Cheruiyot, Allan Sudoi, Simon Wachira, Betty Meli, Mercy Karoney, Agnes Nzioka, Michael Tanui, Martha Mokaya, Wilson Ekiru, Chris Mboya, Dorothy Mwimali, Cecilia Mengich, Julie Choge, Wilfred Injera, Kennedy Njenga, Salinah Cherutich, Millicent Anyango Orido, Gerald Omondi Lwande, Peter Rutto, Alice Mudogo, Irene Kutto, Amina Shali, Linda Jaika, Hellen Jerotich, Mowlem Pierre, Jane Mallewa, Symon Kaunda, Joep Van Oosterhout, Bernadette O'Hare, Robert Heydermann, Carmen Gonzalez, Nettie Dzabala, Christine Kelly, Brigitte Denis, George Selemani, Linda Nyondo- Mipando, Emmie Chirwa, Peter Banda, Linley Mvula, Harrison Msuku, Milton Ziwoya, Yollam Manda, Simon Nicholas, Clemens Masesa, Thandi Mwalukomo, Lumbani Makhaza, Irene Sheha, Joseph Bwanali, Molly Limbuni, Diana M Gibb, Margaret J Thomason, Ann Sarah Walker, Sarah L Pett, Alexander J Szubert, Anna Griffiths, Helen Wilkes, Chathurika Rajapakse, Moira J Spyer, Andrew J Prendergast, Nigel Klein, Mary Rauchenberger, Nadine Van Looy, Emma Little, Keith Fairbrother, Frances Cowan, Janet Seeley, Sarah Bernays, Rachel Kawuma, Zivai Mupambireyi
Journal: The Lancet HIV (2018)

BackgroundIn 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 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).InterpretationIn 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.FundingJoint Global Health Trials Scheme (UK Medical Research Council, UK Department for International Development, and Wellcome Trust).