Clinical trial NCT05048472: East Africa Point of Care Viral Load Study
Official title: Implementation of Point of Care HIV Viral Load Monitoring to Improve Viral Load Suppression Among Children and Adolescents Living With HIV in East Africa
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: HIV
Viral Load
Point of Care Monitoring
Keywords: Children
Adolescents
East Africa
Lead sponsor: MRC/UVRI and LSHTM Uganda Research Unit
Sponsor class: OTHER
Collaborators: name: Karolinska Institutet
name: Kilimanjaro Christian Medical Centre, Tanzania
name: Amsterdam Institute for Global Health and Development
name: National Institute for Medical Research, Tanzania
name: Kenya Medical Research Institute
name: University of Rwanda
First posted: 2021-09-17
Enrollment: 1440
Sex: ALL
Minimum age (years): 6
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Intervention arm will use point of care viral load monitoring (Abbott PoC devices) while the control arm will use the standard of care (centralized viral load monitoring).
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of the project is to examine the feasibility, acceptability, and effectiveness of using point of care viral load (PoC VL) monitoring to improve viral load suppression among children and adolescents (age ≤19 years) living with HIV in Kenya, Rwanda, Tanzania and Uganda.

Detailed description: Main Study Aims:

i) To determine the effectiveness of PoC VL monitoring in improving viral suppression among children and youth living with HIV in East Africa.

ii) To evaluate feasibility and acceptability of using PoC VL monitoring among children and adolescents living with HIV in East Africa.

Objectives of Aim 1:

Primary objective i. To estimate the effect of PoC VL monitoring on viral load suppression among children and adolescents living with HIV in East Africa at 6 and 12 months of follow-up.

Secondary objectives i. To describe the effect of PoC VL monitoring on the proportion of children and adolescents living with HIV that experiences virological rebound after initial suppression within 6 and 12 months of follow-up.

ii. To describe the effect of PoC VL monitoring on time to initiation of intensive adherence counselling following virological failure among children and adolescents living with HIV.

iii. To estimate the effect of PoC VL monitoring on the proportion of children and adolescents living with HIV that experiences change of antiretroviral therapy (ART) regimen within 6 and 12 months of follow-up.

iv. To determine the effect of PoC VL monitoring on the proportion of children and adolescents living with HIV that is retained in care at 6 and 12 months.

Objectives of Aim 2 i. To assess the acceptability of the implementation and scale-up of PoC VL testing and monitoring from the perspective of children, adolescents and their caregivers.

ii. To assess the critical determinants that may affect the implementation of PoC VL testing and monitoring from the perspective of healthcare workers and policy makers.

iii. To assess potential barriers and facilitators to implementation and scale-up of PoC VL testing and monitoring among children and adolescents living with HIV.

iv. To assess the incremental cost-effectiveness of PoC VL from a modified societal perspective using established models, with data collected alongside the implementation of the intervention combined with data estimated based on existing studies.

Design: A cluster randomized controlled trial with 10 intervention clusters and 10 control clusters.

Study Sites: Twenty (20) health facilities spread across 4 countries as follows: Uganda (6), Kenya (4), Tanzania (6), and Rwanda (4).

Population: The study will be conducted among three population sub-groups

1. Study population 1: children and adolescents (≤19 years) living with HIV in participating countries in East Africa.
2. Study population 2: Care givers/ guardians and treatment supporters of children and adolescents living with HIV in participating countries in East Africa
3. Study population 3: Health care workers attending to children and adolescents living with HIV, and policy makers.

Study Intervention: PoC VL monitoring using the Abbott platform Control: Standard-of-care / centralized HIV VL monitoring

Duration: The whole project will take 48 months including 24 months of data collection. Each participant will be followed up for a minimum of 12 months and maximum 24 months.

Sample size The study will enroll 1440 children and youth (0-24years); with 720 in 10 intervention clusters and 720 in 10 control clusters (72 participants per cluster). The effect of the intervention and 95% confidence intervals (CIs) will be estimated using cluster-level summary methods and a power of 80%. To ensure equal distribution of the participants across the ages, we aim to split the enrollment proportionally according to the cluster sizes into three age groups of (0-5 years, 6-12 years and 13-19 years).

Statistical Analysis Aim 1

To investigate the effect of the intervention on viral suppression our analysis will be carried out at the cluster level as follows:

* Reduce clusters to independent observations and provide summary statistics by comparing those in the intervention arm to those in the non-intervention arm.
* Use fixed effects regression to take into account unobserved time-invariant heterogeneity and the treatment effects across the clusters
* Analyze the main outcome (viral suppression) using time to event comparison of the two arms from enrollment to failure or completion of the follow-up time (2 years).

Mixed method Analysis Aim 2 Acceptability and feasibility will be investigated using a combined qualitative and quantitative approach, consisting of thematic content analyses of observations, in-depth interviews and focus group discussions, triangulated and generalized with descriptive statistics of survey data. As part of the feasibility study, the impact of a range of values in sensitivity analyses using each of the respective sites' 2020 per capita Gross Domestic Product (GDP) as a benchmark cost-effectiveness threshold will be evaluated to be able to estimate the incremental cost-effectiveness of the POC VL compared to the standard of care. Quality adjusted life years (QALYS) will be calculated based on weights derived from the Global Burden of Disease.

Eligibility criteria: Inclusion Criteria:

* Age 6 months - 19 years
* Documented evidence of HIV infection
* Receiving ART for treatment of HIV infection for at least 6 months.
* Has had a detectable VL of \>1000 copies/ml in the last 6 months.
* Guardian, parent or legal representative able and willing to give voluntary consent and sign/mark an informed consent document.
* Willing and able to comply with protocol requirements/study procedures.

Exclusion Criteria:

* Any medical conditions that require pausing of ART for more than three months.
* Potential participant already enrolled in another study which may interfere with the study outcome or participation as per investigator's judgement.
* Child or adolescent already enrolled and completed follow up in the current study.
* Any medical or other condition in the potential participant or their parent/ guardian that precludes provision of informed consent/ assent or that may hinder achieving study objectives as per investigator's judgement.

Primary outcomes:
measure: The proportion of children and adolescents living with HIV that achieves viral suppression at 6 and 12 months of follow-up.
timeFrame: 36 months
measure: The time between enrolment into the study and viral suppression.
timeFrame: 36 months
Secondary outcomes:
measure: The proportion of children and adolescents living with HIV that experiences virological rebound after initial suppression within 6 and 12 months of follow-up
timeFrame: 36 months
measure: The time between enrolment into the study and initiation of intensive adherence counselling following virological failure.
timeFrame: 36 months
measure: The proportion of children and adolescents living with HIV that experiences change of ART regimen within 6 and 12 months of follow-up
timeFrame: 36 months
measure: The proportion of children and adolescents living with HIV that is retained in care at 6 and 12 months.
timeFrame: 36 months
Other outcomes:
measure: The proportion of children, adolescents and their care givers who accept implementation of PoC VL testing and monitoring
timeFrame: 36 months
measure: The number of factors which may affect the implementation of PoC VL testing and monitoring from the perspective of healthcare workers and policy makers.
timeFrame: 24 months
measure: The number of potential barriers and facilitators to implementation and scale-up of PoC VL testing and monitoring identified by children and adolescents living with HIV.
timeFrame: 36 months
measure: The incremental cost-effectiveness of PoC VL from a modified societal perspective
timeFrame: 36 months
Locations:
city: Kisumu
country: Kenya
facility: Kenya Medical Research Institute
city: Entebbe
country: Uganda
facility: MRC/UVRI and LSHTM
city: Entebbe
country: Uganda
facility: Unhro/ Uvri
Study officials:
affiliation: London School of Hygiene and Tropical Medicine
name: Pontiano Kaleebu
role: PRINCIPAL_INVESTIGATOR
References:
citation: Joint United Nations Programme on, H.A. and H.I.V.A. Joint United Nations Programme on, 90-90-90: an ambitious treatment target to help end the AIDS epidemic. Geneva: UNAIDS
citation: UNAIDS UNAIDS data 2020. Annual Report, 2020.
citation: Joint United Nations Programme on, H.A., Fast-track: ending the AIDS epidemic by 2030. Geneva: UNAIDS.
citation: Humphrey JM, Genberg BL, Keter A, Musick B, Apondi E, Gardner A, Hogan JW, Wools-Kaloustian K. Viral suppression among children and their caregivers living with HIV in western Kenya. J Int AIDS Soc. 2019 Apr;22(4):e25272. doi: 10.1002/jia2.25272.
citation: Agolory S, de Klerk M, Baughman AL, Sawadogo S, Mutenda N, Pentikainen N, Shoopala N, Wolkon A, Taffa N, Mutandi G, Jonas A, Mengistu AT, Dzinotyiweyi E, Prybylski D, Hamunime N, Medley A. Low Case Finding Among Men and Poor Viral Load Suppression Among Adolescents Are Impeding Namibia's Ability to Achieve UNAIDS 90-90-90 Targets. Open Forum Infect Dis. 2018 Aug 11;5(9):ofy200. doi: 10.1093/ofid/ofy200. eCollection 2018 Sep.
citation: Gill MM, Hoffman HJ, Bobrow EA, Mugwaneza P, Ndatimana D, Ndayisaba GF, Baribwira C, Guay L, Asiimwe A. Detectable Viral Load in Late Pregnancy among Women in the Rwanda Option B+ PMTCT Program: Enrollment Results from the Kabeho Study. PLoS One. 2016 Dec 22;11(12):e0168671. doi: 10.1371/journal.pone.0168671. eCollection 2016.
citation: Ntlantsana V, Hift RJ, Mphatswe WP. HIV viraemia during pregnancy in women receiving preconception antiretroviral therapy in KwaDukuza, KwaZulu-Natal. South Afr J HIV Med. 2019 Apr 10;20(1):847. doi: 10.4102/sajhivmed.v20i1.847. eCollection 2019.
citation: Bulage L, Ssewanyana I, Nankabirwa V, Nsubuga F, Kihembo C, Pande G, Ario AR, Matovu JK, Wanyenze RK, Kiyaga C. Factors Associated with Virological Non-suppression among HIV-Positive Patients on Antiretroviral Therapy in Uganda, August 2014-July 2015. BMC Infect Dis. 2017 May 3;17(1):326. doi: 10.1186/s12879-017-2428-3.
citation: Nabukeera S, Kagaayi J, Makumbi FE, Mugerwa H, Matovu JKB. Factors associated with virological non-suppression among HIV-positive children receiving antiretroviral therapy at the Joint Clinical Research Centre in Lubowa, Kampala Uganda. PLoS One. 2021 Jan 27;16(1):e0246140. doi: 10.1371/journal.pone.0246140. eCollection 2021.
citation: RBC, Rwanda Population-based HIV Impact Assessment, R.B. Centre, Editor. 2020, RPHIA 2018-2019.
citation: UNAIDS, Understanding fastâ€ track: Accelerating action to end the AIDS epidemic by 2030. 2015, UNAIDS Geneva.
citation: Mwau M, Syeunda CA, Adhiambo M, Bwana P, Kithinji L, Mwende J, Oyiengo L, Sirengo M, Boeke CE. Scale-up of Kenya's national HIV viral load program: Findings and lessons learned. PLoS One. 2018 Jan 11;13(1):e0190659. doi: 10.1371/journal.pone.0190659. eCollection 2018.
citation: El-Sadr WM, Rabkin M, Nkengasong J, Birx DL. Realizing the potential of routine viral load testing in sub-Saharan Africa. J Int AIDS Soc. 2017 Nov;20 Suppl 7(Suppl 7):e25010. doi: 10.1002/jia2.25010. No abstract available.
citation: Mangone E, C.C., Johns B, Mudhune V, & Avila C, Economic Evaluation of Nationally Scaled Point-of-Care Diagnostic Platforms for Viral Load Monitoring in Kenya, U. Report, Editor. 2018.
citation: Zhang J, Lan T, Lu Y. Translating in vitro diagnostics from centralized laboratories to point-of-care locations using commercially-available handheld meters. Trends Analyt Chem. 2020 Mar;124:115782. doi: 10.1016/j.trac.2019.115782. Epub 2019 Dec 23.
citation: Boeke CE, Joseph J, Atem C, Banda C, Coulibaly KD, Doi N, Gunda A, Kandulu J, Kiernan B, Kingwara L, Maokola W, Maparo T, Mbaye RN, Mtumbuka E, Mziray J, Ngugi C, Nkakulu J, Nzuobontane D, Okomo Assoumo MC, Peter T, Rioja MR, Sacks JA, Simbi R, Vojnov L, Khan SA. Evaluation of near point-of-care viral load implementation in public health facilities across seven countries in sub-Saharan Africa. J Int AIDS Soc. 2021 Jan;24(1):e25663. doi: 10.1002/jia2.25663.
citation: Moyo S, Mohammed T, Wirth KE, Prague M, Bennett K, Holme MP, Mupfumi L, Sebogodi P, Moraka NO, Boleo C, Maphorisa CN, Seraise B, Gaseitsiwe S, Musonda RM, van Widenfelt E, Powis KM, Gaolathe T, Tchetgen Tchetgen EJ, Makhema JM, Essex M, Lockman S, Novitsky V. Point-of-Care Cepheid Xpert HIV-1 Viral Load Test in Rural African Communities Is Feasible and Reliable. J Clin Microbiol. 2016 Dec;54(12):3050-3055. doi: 10.1128/JCM.01594-16. Epub 2016 Oct 12.
citation: Bwana P, Ageng'o J, Danda J, Mbugua J, Handa A, Mwau M. Performance and usability of mPIMA HIV 1/2 viral load test in point of care settings in Kenya. J Clin Virol. 2019 Dec;121:104202. doi: 10.1016/j.jcv.2019.104202. Epub 2019 Oct 23.
citation: Drain PK, Dorward J, Violette LR, Quame-Amaglo J, Thomas KK, Samsunder N, Ngobese H, Mlisana K, Moodley P, Donnell D, Barnabas RV, Naidoo K, Abdool Karim SS, Celum C, Garrett N. Point-of-care HIV viral load testing combined with task shifting to improve treatment outcomes (STREAM): findings from an open-label, non-inferiority, randomised controlled trial. Lancet HIV. 2020 Apr;7(4):e229-e237. doi: 10.1016/S2352-3018(19)30402-3. Epub 2020 Feb 24.
citation: Nicholas S, Poulet E, Wolters L, Wapling J, Rakesh A, Amoros I, Szumilin E, Gueguen M, Schramm B. Point-of-care viral load monitoring: outcomes from a decentralized HIV programme in Malawi. J Int AIDS Soc. 2019 Aug;22(8):e25387. doi: 10.1002/jia2.25387.
citation: Villa G, Abdullahi A, Owusu D, Smith C, Azumah M, Sayeed L, Austin H, Awuah D, Beloukas A, Chadwick D, Phillips R, Geretti AM. Determining virological suppression and resuppression by point-of-care viral load testing in a HIV care setting in sub-Saharan Africa. EClinicalMedicine. 2020 Jan 5;18:100231. doi: 10.1016/j.eclinm.2019.12.001. eCollection 2020 Jan.
citation: Bowen DJ, Kreuter M, Spring B, Cofta-Woerpel L, Linnan L, Weiner D, Bakken S, Kaplan CP, Squiers L, Fabrizio C, Fernandez M. How we design feasibility studies. Am J Prev Med. 2009 May;36(5):452-7. doi: 10.1016/j.amepre.2009.02.002.
citation: Fleuren MA, Paulussen TG, Van Dommelen P, Van Buuren S. Towards a measurement instrument for determinants of innovations. Int J Qual Health Care. 2014 Oct;26(5):501-10. doi: 10.1093/intqhc/mzu060. Epub 2014 Jun 20.
citation: Sekhon M, Cartwright M, Francis JJ. Acceptability of health care interventions: A theoretical framework and proposed research agenda. Br J Health Psychol. 2018 Sep;23(3):519-531. doi: 10.1111/bjhp.12295. Epub 2018 Feb 16. No abstract available.
citation: Baral S, Logie CH, Grosso A, Wirtz AL, Beyrer C. Modified social ecological model: a tool to guide the assessment of the risks and risk contexts of HIV epidemics. BMC Public Health. 2013 May 17;13:482. doi: 10.1186/1471-2458-13-482.
citation: Fazeli PL, Turan JM, Budhwani H, Smith W, Raper JL, Mugavero MJ, Turan B. Moment-to-moment within-person associations between acts of discrimination and internalized stigma in people living with HIV: An experience sampling study. Stigma Health. 2017 Aug;2(3):216-228. doi: 10.1037/sah0000051. Epub 2016 Aug 8.
citation: WHO, Child and Adolescent Health and Development, in Progress Report, W.H. Organization, Editor. 2006.
citation: Decety J. Empathy in Medicine: What It Is, and How Much We Really Need It. Am J Med. 2020 May;133(5):561-566. doi: 10.1016/j.amjmed.2019.12.012. Epub 2020 Jan 15.
citation: Mariani D, de Azevedo MCVM, Vasconcellos I, Ribeiro L, Alves C, Ferreira OC Jr, Tanuri A. The performance of a new point-of-care HIV virus load technology to identify patients failing antiretroviral treatment. J Clin Virol. 2020 Jan;122:104212. doi: 10.1016/j.jcv.2019.104212. Epub 2019 Nov 9.
citation: Meggi B, Bollinger T, Zitha A, Mudenyanga C, Vubil A, Mutsaka D, Nhachigule C, Mabunda N, Loquiha O, Kroidl A, Jani IV. Performance of a True Point-of-Care Assay for HIV-1/2 Viral Load Measurement at Antenatal and Postpartum Services. J Acquir Immune Defic Syndr. 2021 May 1;87(1):693-699. doi: 10.1097/QAI.0000000000002621.
citation: Vasconcellos I, Mariani D, Azevedo MCVM, Ferreira OC Jr, Tanuri A. Development and validation of a simple and rapid way to generate low volume of plasma to be used in point-of-care HIV virus load technologies. Braz J Infect Dis. 2020 Jan-Feb;24(1):30-33. doi: 10.1016/j.bjid.2019.10.010. Epub 2019 Nov 21.