Reduction of EArly mortaLITY in HIV-infected Adults and Children Starting Antiretroviral Therapy (REALITY)
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.
Human Immunodeficiency Virus
Dietary Supplement: Ready to Use Supplementary Food
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Reduction of Early mortALITY in HIV-infected African Adults and Children Starting Antiretroviral Therapy: a Randomised Controlled Trial|
- All-cause mortality over the first 24 weeks after starting ART [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
- 48 week mortality (all-cause) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
- Safety [ Time Frame: Week 0-48 ] [ Designated as safety issue: Yes ]
- serious adverse events
- grade 4 adverse events
- adverse events leading to modification of ART or other study drugs
- Hospital inpatient episodes and total days admitted [ Time Frame: Week 0-48 ] [ Designated as safety issue: Yes ]
- Adherence to ART and acceptability of each strategy [ Time Frame: Week 0-48 ] [ Designated as safety issue: No ]Adherence to ART, OI drugs and RUSF will be assessed in all participants at each visit by pill counts and short nurse-administered questions. Every 12 weeks, a more detailed adherence questionnaire will be adminstered.
- Endpoint relating to anti-infection intervention [ Time Frame: 0-48 weeks ] [ Designated as safety issue: No ]Incidence of tuberculosis (TB), cryptococcal and candida disease, severe bacterial infections
- Endpoint relating to anti-malnutrition intervention [ Time Frame: 0-48 weeks ] [ Designated as safety issue: No ]BMI, weight and body fat assessed by bioimpedance analysis (BIA), height (in children) and grip strength
- Endpoint relating to anti-HIV intervention [ Time Frame: 0-48 weeks ] [ Designated as safety issue: No ]Changes in CD4 cell count
|Study Start Date:||June 2013|
|Estimated Study Completion Date:||March 2016|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Experimental: Antiretroviral Therapy
Raltegravir twice daily for 12 weeks from antiretroviral therapy (ART) initiation in addition to 3 standard ARVs (2NRTIs/1NNRTI) compared with 3 standard ARVs
400mg twice daily for the first 12 weeks only in addition to 3 standard ARVs
Experimental: Opportunistic Infection (OI) Prophylaxis
Immediate 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.
100mg once daily for 12 weeksDrug: Azithromycin
500mg once daily for 5 daysDrug: Albendazole
a single dose 400mgDrug: Isoniazid
300mg taken immediately in combination with cotrimoxazole
Experimental: Nutritional Support
Supplementation with Ready to Use Supplementary Food (RUSF) for 12 weeks compared with supplementation for those with severe malnutrition as local practice.
Dietary Supplement: Ready to Use Supplementary Food
2x92g packets daily of high energy, low protein lipid-based paste for 12 weeks
Other Name: RUSF
REALITY is a open-label randomised trial of 1800 adults, adolescents and children aged 5 years or more with low CD4 counts about to initiate ART.
The trial will have a factorial design with 3 randomisations, each to address one of the potential approaches to reduce early mortality in adults and children initiating ART with low CD4, namely:
- Raltegravir for 12 weeks from ART initiation in addition to 3 standard ART (3-drug 2-class) versus standard of care first-line 3-drug 2-class ART (choice according to national guidelines for ART initiation);
- Immediate enhanced opportunistic infections (OI) prophylaxis with isoniazid/pyridoxine and cotrimoxazole, plus 12 weeks fluconazole, 5 days azithromycin and a single dose of albendazole versus cotrimoxazole prophylaxis alone for the first 12 weeks followed by isoniazid and any prophylaxis and/or treatment prescribed at screening
- supplementation with Ready to Use Supplementary Food (RUSF) for 12 weeks versus standard of care nutritional support to those with poor nutritional status according to local guidelines.
All participants will receive cotrimoxazole throughout the trial.
The primary objective of the trial is to identify effective, safe and acceptable interventions to reduce early mortality (all-cause) in HIV-infected adults, adolescents, and older children (5 years or more) initiating ART.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01825031
|Moi University Clinical Research Centre|
|KEMRI Wellcome Trust Research Programme|
|University of Malawi|
|Joint Clinical Research Centre, Fort Portal|
|Fort Portal, Uganda|
|Joint Clinical Research Centre, Gulu|
|Joint Clinical Research Centre, Mbale|
|Joint Clinical Research Centre, Mbarara|
|University of Zimbabwe Clinical Research Centre|
|Study Director:||Diana M Gibb||Medical Research Council|