Reduction of EArly mortaLITY in HIV-infected Adults and Children Starting Antiretroviral Therapy
REALITY
Reduction of Early mortALITY in HIV-infected African Adults and Children Starting Antiretroviral Therapy: a Randomised Controlled Trial
1 other identifier
interventional
1,805
4 countries
8
Brief Summary
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 are: (i) increasing the potency of ART with a 12 week induction period using 4 antiretroviral drugs from 3 classes (ii) augmented prophylaxis against opportunistic/bacterial infections and helminths for 12 weeks (iii) macronutrient intervention using ready-to-use supplementary food for 12 weeks.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2013
Typical duration for phase_3
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 7, 2013
CompletedFirst Posted
Study publicly available on registry
April 5, 2013
CompletedStudy Start
First participant enrolled
June 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2016
CompletedApril 20, 2016
April 1, 2016
2.8 years
January 7, 2013
April 19, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
All-cause mortality over the first 24 weeks after starting ART
Week 24
Secondary Outcomes (7)
48 week mortality (all-cause)
Week 48
Safety
Week 0-48
Hospital inpatient episodes and total days admitted
Week 0-48
Adherence to ART and acceptability of each strategy
Week 0-48
Endpoint relating to anti-infection intervention
0-48 weeks
- +2 more secondary outcomes
Study Arms (3)
Antiretroviral Therapy
EXPERIMENTALRaltegravir twice daily for 12 weeks from antiretroviral therapy (ART) initiation in addition to 3 standard ARVs (2NRTIs/1NNRTI) compared with 3 standard ARVs
Opportunistic Infection (OI) Prophylaxis
EXPERIMENTALImmediate isoniazid/pyridoxine and cotrimoxazole, plus 12 weeks fluconazole, 5 days azithromycin and a single dose of albendazole compared with immediate cotrimoxazole (if not already taking this) in all patients plus (not malawi)isoniazid/pyridoxine after 12 weeks.
Nutritional Support
EXPERIMENTALSupplementation with Ready to Use Supplementary Food (RUSF) for 12 weeks compared with supplementation for those with severe malnutrition as local practice.
Interventions
400mg twice daily for the first 12 weeks only in addition to 3 standard ARVs
300mg taken immediately in combination with cotrimoxazole
2x92g packets daily of high energy, low protein lipid-based paste for 12 weeks
Eligibility Criteria
You may qualify if:
- Aged 5 years or older
- Documented HIV infection by HIV ELISA or HIV rapid test
- Naive to ART
- CD4 T-cell count \<100 cells/mm3 on blood test taken at screening for REALITY
- Results of screening haematology and biochemistry tests available and no contraindications to planned ART according to national guidelines
- Patient/carer provide informed consent (and children \<18 years assent, as appropriate according to their age and knowledge of HIV status)
- The lower age limit is because CD4 counts are less reliable predictors of immunodeficiency under 5 years: CD4 counts are recommended by guidelines in older children.
- No patient with a CD4 count above 100 cells/mm3 should have ART delayed in order to subsequently meet eligibility criteria. Rather, patients eligible for REALITY will be those testing HIV positive for the first time with a low CD4 count (i.e. those delaying presentation to care), or those who have defaulted before initiating ART and only return to care at an advanced stage of immuno-deficiency.
You may not qualify if:
- Contraindications to any proposed antiretroviral drugs (including integrase inhibitors), isoniazid, fluconazole, albendazole or azithromycin
- Pregnant or breastfeeding or intending to become pregnant during the first 12 weeks of the study
- Ever known to have previously received single-dose nevirapine for prevention of mother-to-child transmission (mother or child).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Anna Griffiths, MRClead
- Department for International Development, United Kingdomcollaborator
- Wellcome Trustcollaborator
- Medical Research Councilcollaborator
- PENTA Foundationcollaborator
Study Sites (8)
Moi University Clinical Research Centre
Eldoret, Kenya
KEMRI Wellcome Trust Research Programme
Kilifi, Kenya
University of Malawi
Blantyre, Malawi
Joint Clinical Research Centre, Fort Portal
Fort Portal, Uganda
Joint Clinical Research Centre, Gulu
Gulu, Uganda
Joint Clinical Research Centre, Mbale
Mbale, Uganda
Joint Clinical Research Centre, Mbarara
Mbarara, Uganda
University of Zimbabwe Clinical Research Centre
Harare, Zimbabwe
Related Publications (4)
Kelly C, Tinago W, Alber D, Hunter P, Luckhurst N, Connolly J, Arrigoni F, Garcia Abner A, Kamn'gona R, Sheha I, Chammudzi M, Jambo K, Mallewa J, Rapala A, Mallon PWG, Mwandumba H, Klein N, Khoo S. Inflammatory pathways amongst people living with HIV in Malawi differ according to socioeconomic status. PLoS One. 2021 Aug 25;16(8):e0256576. doi: 10.1371/journal.pone.0256576. eCollection 2021.
PMID: 34432828DERIVEDKelly C, Tinago W, Alber D, Hunter P, Luckhurst N, Connolly J, Arrigoni F, Abner AG, Kamngona R, Sheha I, Chammudzi M, Jambo K, Mallewa J, Rapala A, Heyderman RS, Mallon PWG, Mwandumba H, Walker AS, Klein N, Khoo S. Inflammatory Phenotypes Predict Changes in Arterial Stiffness Following Antiretroviral Therapy Initiation. Clin Infect Dis. 2020 Dec 3;71(9):2389-2397. doi: 10.1093/cid/ciaa186.
PMID: 32103268DERIVEDKityo C, Szubert AJ, Siika A, Heyderman R, Bwakura-Dangarembizi M, Lugemwa A, Mwaringa S, Griffiths A, Nkanya I, Kabahenda S, Wachira S, Musoro G, Rajapakse C, Etyang T, Abach J, Spyer MJ, Wavamunno P, Nyondo-Mipando L, Chidziva E, Nathoo K, Klein N, Hakim J, Gibb DM, Walker AS, Pett SL; REALITY trial team. Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial. PLoS Med. 2018 Dec 4;15(12):e1002706. doi: 10.1371/journal.pmed.1002706. eCollection 2018 Dec.
PMID: 30513108DERIVEDMallewa J, Szubert AJ, Mugyenyi P, Chidziva E, Thomason MJ, Chepkorir P, Abongomera G, Baleeta K, Etyang A, Warambwa C, Melly B, Mudzingwa S, Kelly C, Agutu C, Wilkes H, Nkomani S, Musiime V, Lugemwa A, Pett SL, Bwakura-Dangarembizi M, Prendergast AJ, Gibb DM, Walker AS, Berkley JA; REALITY trial team. 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. Lancet HIV. 2018 May;5(5):e231-e240. doi: 10.1016/S2352-3018(18)30038-9. Epub 2018 Apr 10.
PMID: 29653915DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Diana M Gibb
Medical Research Council
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER GOV
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Trial Manager
Study Record Dates
First Submitted
January 7, 2013
First Posted
April 5, 2013
Study Start
June 1, 2013
Primary Completion
March 1, 2016
Study Completion
March 1, 2016
Last Updated
April 20, 2016
Record last verified: 2016-04