Impact of community engagement and social support on the outcomes of HIV-related meningitis clinical trials in a resource-limited setting
Authors: Kwizera Richard , Sadiq Alisat , Ndyetukira Jane Frances , Nalintya Elizabeth , Williams Darlisha , Rhein Joshua , Boulware David R. , Meya David B. ,   on behalf of the COAT and ASTRO trial teams, Meya David B. , Musubire Abdu , Nabeta Henry W. , Kambugu Andrew , Manabe Yukari C. , Ndyetukira Jane Francis , Ahimbisibwe Cynthia , Kugonza Florence , Sadiq Alisat , Kwizera Richard , Elbireer Ali , Lukande Robert , Akampurira Andrew , Wagubi Robert , Kajumbula Henry , Najjuka Grace , Nanteza Catherine , Namawejje Mariam , Ssennono Mark , Kiragga Agnes , Mpoza Edward , Kiggundu Reuben , Tugume Lillian , Ssebambulidde Kenneth , Kirumira Paul , Namuju Carolyne , Luggya Tony , Kaboggoza Julian , Laker Eva , Namudde Alice , Muzoora Conrad , Taseera Kabanda , Ndyatunga Liberica , Memela Brian , Noeme Busingye , Ninsiima Emily , Mwesigye James , Mushagara Rhina , Boulware David R. , Rolfes Melissa A. , Hullsiek Kathy Huppler , Williams Darlisha A. , Rajasingham Radha , Rhein Joshua , Lo Melanie W. , Nielsen Kirsten , Bergemann Tracy L. , Bohjanen Paul R. , Scriven James , Janoff Edward N. , Fossland Nicholas , Rani Monica , Carlson Renee , Birkenkamp Kate , Butler Elissa , McDonald Tami , Strain Anna , Wiesner Darin , von Hohenberg Maximilian , Vogt Ann , Botker Grant , Bahr Nathan , Yasukawa Kosuke , Baker Jason V. , Lofgren Sarah , Stadelman Anna , Bangdiwala Ananta S. , Schutz Charlotte , Thienemann Friedrich , Meintjes Graeme , Sigila Yolisa , Magwayi Monica , Hassanally Leya , Bicanic Tihana , Haddow Lewis J. 
Published: August 2020

Abstract
Background
Clinical trials remain the cornerstone of improving outcomes for HIV-infected individuals with cryptococcal meningitis. Community engagement aims at involving participants and their advocates as partners in research rather than merely trial subjects. Community engagement can help to build trust in communities where these trials are conducted and ensure lasting mutually beneficial relationships between researchers and the community. Similarly, different studies have reported the positive effects of social support on patient’s outcomes. We aimed to describe our approach to community engagement in Uganda while highlighting the benefits of community engagement and social support in clinical trials managing patients co-infected with HIV and cryptococcal meningitis.

Methods
We carried out community engagement using home visits, health talks, posters, music and drama. In addition, social support was given through study staff individually contributing to provide funds for participants’ food, wheel chairs, imaging studies, adult diapers, and other extra investigations or drugs that were not covered by the study budget or protocol. The benefits of this community engagement and social support were assessed during two multi-site, randomized cryptococcal meningitis clinical trials in Uganda.

Results
We screened 1739 HIV-infected adults and enrolled 934 with cryptococcal meningitis into the COAT and ASTRO-CM trials during the period October 2010 to July 2017. Lumbar puncture refusal rates decreased from 31% in 2010 to less than 1% in 2017. In our opinion, community engagement and social support played an important role in improving: drug adherence, acceptance of lumbar punctures, data completeness, rate of screening/referrals, reduction of missed visits, and loss to follow-up.

Conclusions
Community engagement and social support are important aspects of clinical research and should be incorporated into clinical trial design and conduct.

Trial registration
ClinicalTrials.gov number, NCT01075152 and NCT01802385.