Reduction of Early mortaLITY in HIV-infected African adults and children starting antiretroviral therapy: REALITY trial
Lead Research Organisation:
University College London
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
People |
ORCID iD |
Publications
Kamau F
(2020)
Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV - pilot study
in Wellcome Open Research
Kelly C
(2020)
Inflammatory Phenotypes Predict Changes in Arterial Stiffness Following Antiretroviral Therapy Initiation.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Kelly C
(2019)
HIV-Related Arterial Stiffness in Malawian Adults Is Associated With the Proportion of PD-1-Expressing CD8+ T Cells and Reverses With Antiretroviral Therapy.
in The Journal of infectious diseases
Kityo C
(2018)
Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial.
in PLoS medicine
Post FA
(2018)
Causes and Timing of Mortality and Morbidity Among Late Presenters Starting Antiretroviral Therapy in the REALITY Trial.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Post FA
(2018)
Causes and Timing of Mortality and Morbidity Among Late Presenters Starting Antiretroviral Therapy in the REALITY Trial.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Siika A
(2018)
Late Presentation With HIV in Africa: Phenotypes, Risk, and Risk Stratification in the REALITY Trial.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Siika A
(2018)
Late Presentation With HIV in Africa: Phenotypes, Risk, and Risk Stratification in the REALITY Trial.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
| Description | THE COLLEGE OF MEDICINE University of Malawi |
| Organisation | University of Malawi |
| Department | College of Medicine |
| Country | Malawi |
| Sector | Academic/University |
| PI Contribution | TRACT and REALITY Trials Lablite Project (funded by DFid) |
| Collaborator Contribution | Clinical sites for TRACT and REALITY Trials Dignitas International are an IMplementation partner in the Lablite Project |
| Impact | publications from the Lablite Project REALITY TRial and TRACT trial ongoing |
| Start Year | 2012 |
| Description | University of Zimbabwe |
| Organisation | University of Zimbabwe |
| Country | Zimbabwe |
| Sector | Academic/University |
| PI Contribution | DART, ARROW, REALITY Trials funding and coordination by MRC CTU LAblite Project on enabling rollout of antiretroviral therapy. |
| Collaborator Contribution | Clinical sites for DART, ARROW, REALITY, PENTA 20(ODYSSEY) Trials Staff are partners in all aspects of reserach from design through to enrolling patients and writing results papers |
| Impact | DART and ARROW trials and substudy outcomes and implementation impact; ARROW young lives study and economic substudies REALITY trial ongoing LAblite Project outputs |
| Start Year | 2006 |
| Description | ESPID Plenary Lecture |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | I as invited and gave the plenary lecture at ESPID (European Society for Paediatric Infectious Diseases) which is an international conference addressing clinicians and policymakers. The talk ws well recieved to an audience of over 100 and which discussed the trials run from CTU, SHINE/CHAMP/SURE/STREAM/REALITY/CAPIT/ODYSSEY/ARROW Title of the talk: New ways of doing clinical trials in infectious diseases to maximise evidence generation |
| Year(s) Of Engagement Activity | 2019 |
| Description | ICASA 2015 - Intenational Conference on AIDS and STIs in Africa. Oral presentation. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Oral presentation; abstract Title: Sulfamethoxazole/Trimethoprim/Isoniazid/Pyridoxine scored tablets are bioequivalent to individual products and are acceptable to patients with advanced HIV infection in the REALITY trial Authors: Bwakura-Dangarembizi M2, Gibb DM1, Abhyankar D9, Agutu C3, Lugemwa A4, Abongomera G5, Miranda S6, Musiime V7, Mallewa J8, Siika A11, Baleeta K12, Mehta V9, Malhotra G9, Griffiths A1, Kityo C10, Maitland K3, Chidziva E2, Chepkorir P11, Szubert AJ1, Gogtay J9, Hakim J2 and the REALITY Trial Team Background Patients initiating ART with low CD4 counts benefit from isoniazid and cotrimoxazole prophylaxis, but these increase pill burden; stockouts of single formulations are also common. Methods: Sulfamethoxazole/Trimethoprim/Isoniazid/Pyridoxine (800/160/300/25mg) fixed-dose-combination (FDC) scored tablets (Cipla , India) were compared with Septrin®Forte (sulfamethoxazole-800mg/trimethoprim-160mg (GlaxoWellcome)) and Isoniazid-300mg (Sandoz) separate tablets in 28 healthy volunteers (18male; 10female) in an open-label, randomized, single-dose, two-treatment, two-period, 26-sample crossover pharmacokinetic bioequivalent study. Acceptability and adherence questionnaire data were collected in the ongoing, 2x2x2 factorial, REALITY randomised trial evaluating enhanced OI prophylaxis, 4-drug ART and enhanced nutrition for 12 weeks after ART initiation, in 1805 African adults/children(=5years) with CD4 <100cells/mm3. Within-individual data on FDC (weeks 12-24) vs cotrimoxazole alone (weeks 0-12) were compared in 319 patients; and in weeks 0-12 among those receiving FDC+fluconazole (for prophylaxis against cryptococcal disease) (n=543) vs cotrimoxazole (n=604). Results: Geometric mean test-to-reference ratios for sulfamethoxazole (AUC: 99.8% (90% CI 96.2%-103.5%) and Cmax: 103.2%(99.5%-107.0%)), trimethoprim (97.2%(93.7-100.9)%; 98.2%(93.4-103.3)%) and isoniazid 103.8%(99.5-108.3); 104.3%(95.1-114.4)) were well within required 80-125% range. In REALITY, acceptability was similar between FDC (12-24 weeks) and cotrimoxazole (0-12 weeks): 99.7% vs 99.4% reported none/not much daily-life interference; 95.6% vs 96.6% reported drugs were very easy/easy to take. Comparing groups (0-12 weeks) gave similar results: 500/543(92.1%) vs 565/604(93.5%),(p=0.8) reported taking medication was very easy/easy; 4.0% vs 3.9% reported missing =1 dose. Conclusions: Sulfamethoxazole/Trimethoprim/Isoniazid/Pyridoxine FDC tablets are bioequivalent to individual drugs (data submitted for WHO prequalification). They are acceptable, reduce pill burden and could improve adherence, in addition to simplifying drug distribution for programmes. |
| Year(s) Of Engagement Activity | 2015 |
| URL | http://icasa2015zimbabwe.org/ |
| Description | Media Publications |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Results reported from the REALITY trial in Paris for the IAS conference on HIV science where published by the British media. |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://www.theguardian.com/global-development/2017/jul/24/cocktail-of-drugs-could-prevent-10000-hiv... |
| Description | REALITY animation |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Animated version of the REALITY infographic |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://vimeo.com/226262006 |
| Description | REALITY briefing paper |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Briefing paper describing the enhanced prophylaxis results from the REALITY trial. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.ctu.mrc.ac.uk/13706/13710/reality_prophylaxis_briefing_paper_2017 |
| Description | REALITY film |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | One in five people starting HIV treatment in low and middle income countries have a low CD4 count (a measure of the strength of their immune system). This puts them at high risk of dying in the first few weeks of treatment. The REALITY trial tested giving people starting treatment with a low CD4 count an enhanced package of drugs to prevent infections. It found this package was highly effective at preventing deaths and illnesses. This film explores those results. |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://vimeo.com/225532382 |
| Description | REALITY infographic |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | An infographic summarising the results of the REALITY trial |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.ctu.mrc.ac.uk/12602/13005/REALITYinfographic140717.png |
| Description | The 46th Union World Conference on Lung Health, Cape Town, 2-6 December 2015. Oral Presentation |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Abstract Title: Sulfamethoxazole/Trimethoprim/Isoniazid/Pyridoxine scored tablets are bioequivalent to individual products and are acceptable to patients with advanced HIV infection in the REALITY trial Authors: Gibb DM1, Bwakura-Dangarembizi M2, Abhyankar D9, Szubert AJ1, Agutu C3, Lugemwa A4, Abach J5, Kemigisa M6, Mallewa J8, Siika A10, Mukuye A11, Mehta V9, Malhotra G9, Nambi E10, Thomason M1, Pett S1, Berkley J3, Meli B10, Kityo C7, Nathoo K2, Musiime V7, Walker AS1, Gogtay J9 and the REALITY Trial Team Affiliations: 1MRC Clinical Trials Unit at UCL, London, UK; 2University of Zimbabwe, Harare, Zimbabwe; 3KEMRI Wellcome Trust Research Programme, Kilifi, Kenya; 4Joint Clinical Research Centre, Mbarara, Uganda; 5Joint Clinical Research Centre, Gulu, Uganda; 6Joint Clinical Research Centre, Fort Portal, Uganda; 7Joint Clinical Research Centre, Kampala, Uganda and Makerere University College of Health Sciences, Kampala, Uganda; 8University of Malawi, Blantyre, Malawi; 9Cipla Ltd., Mumbai, India; 10 Moi University Clinical Research Centre, Eldoret, Kenya, 11Joint Clinical Research Centre, Mbale, Uganda Background: HIV-infected patients initiating antiretroviral therapy (ART) with low CD4 counts particularly benefit from OI and anti-tuberculosis prophylaxis. However, individual drug formulations of isoniazid and cotrimoxazole add to the pill burden of ART and adherence difficulties early in treatment when mortality is highest; stockouts are also frequent in low-resource settings. Methods: Sulfamethoxazole/Trimethoprim/Isoniazid/Pyridoxine (800/160/300/25mg) fixed-dose-combination (FDC) scored tablets, made by Cipla, India, were evaluated for bioequivalence vs separate tablets of Septrin®Forte (sulfamethoxazole-800mg/trimethoprim-160mg (GlaxoWellcome)) and Isoniazid-300mg (Sandoz) in an open-label, randomized, single-dose, two-treatment, two-period, 26-sample crossover pharmacokinetic study. Acceptability and adherence questionnaire data were collected in the ongoing, 2x2x2 factorial, REALITY randomised trial evaluating 12-week enhanced OI prophylaxis, 4-drug ART and enhanced nutrition in 1805 African adults/children (=5years) with CD4 <100cells/mm3. Within-individual data on FDC (weeks 12-24) vs cotrimoxazole alone (weeks 0-12) were compared in 319 patients; and in weeks 0-12 among those receiving FDC+fluconazole (for prophylaxis against cryptococcal disease) (n=543) vs cotrimoxazole (n=604). Results: Among 28 fasting healthy subjects (18 male; 10 female; Mean(range) age 31(18-45)years; BMI 25.1+2.9), geometric mean test-to-reference ratios for sulfamethoxazole (AUC: 99.8% (90% CI 96.2%-103.5%) and Cmax: 103.2%(99.5%-107.0%)), trimethoprim (97.2%(93.7-100.9)%; 98.2%(93.4-103.3)%) and isoniazid 103.8%(99.5-108.3); 104.3%(95.1-114.4)) were well within required 80-125% range. In REALITY, no within-individual differences in acceptability were reported between FDC (12-24 weeks) vs cotrimoxazole (0-12 weeks): 99.7% vs 99.4% reported none/not much interference with everyday life and 95.6% vs 96.6% reported drugs were very easy/easy to take. Comparing groups over 0-12 weeks gave similar results: 500/543(92.1%) vs 565/604(93.5%) (p=0.8) reported taking medication was very easy/easy; 4.0% vs 3.9% reported missing =1 dose. Conclusions: Sulfamethoxazole/Trimethoprim/Isoniazid/Pyridoxine scored FDC tablets are bioequivalent to individual drugs; data have been submitted for WHO prequalification. They are acceptable, reduce pill burden and could improve adherence for adults/children =5 years, in addition to simplifying drug distribution for HIV programmes. |
| Year(s) Of Engagement Activity | 2015 |
| URL | http://capetown.worldlunghealth.org/ |