Integrating PrEP delivery in public health family planning clinics: a protocol for a pragmatic stepped wedge cluster randomized trial in Kenya

Kenneth K Mugwanya, Daniel Matemo, Caitlin W Scoville, Kristin M Beima-Sofie, Allison Meisner, Dickens Onyango, Mary Mugambi, Erika Feutz, Cole Grabow, Ruanne Barnabas, Bryan Weiner, Jared M Baeten, John Kinuthia, FP Plus Team, Kenneth K Mugwanya, Daniel Matemo, Caitlin W Scoville, Kristin M Beima-Sofie, Allison Meisner, Dickens Onyango, Mary Mugambi, Erika Feutz, Cole Grabow, Ruanne Barnabas, Bryan Weiner, Jared M Baeten, John Kinuthia, FP Plus Team

Abstract

Background: Adolescent girls and young women account for a disproportionate fraction of new HIV infections in Africa and are a priority population for HIV prevention, including provision of pre-exposure prophylaxis (PrEP). Anchoring PrEP delivery to care settings like family planning (FP) services that women already access routinely may offer an efficient platform to reach HIV at-risk women. However, context-specific implementation science evaluation is needed.

Methods: The Family Planning Plus Project is a prospective, pragmatic implementation evaluation, designed as a stepped wedge, cluster randomized trial, at 12 clinics in Kenya. In collaboration with the Kenya Ministry of Health and Kisumu County Department of Health, we will introduce integration of HIV risk screening and PrEP delivery in public health FP clinics. The core multifaceted implementation strategies to integrate PrEP in FP clinics will include: (1) PrEP delivery by existing FP clinic staff, (2) health provider training, (3) PrEP technical assistance to coach and mentor providers, (4) joint supervision with Kisumu County health officials, and (5) stakeholder engagement. All core components of PrEP delivery-including screening for HIV risk, HIV testing, dispensing, adherence and risk reduction counseling, assessment of side effects, and provision of refills, or safety assessment-will be conducted by existing FP clinic staff as part of a standard care service package. The goal is to catalyze sustainable scale-up within existing infrastructures beyond the project. We will rigorously evaluate implementation outcomes and impact, using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework, and we will use Organizational Readiness for Implementing Change (ORIC) and the Consolidated Framework for Implementation Science Research (CFIR) to assess readiness to implement and contextual enablers and barriers of implementation, including how clinics innovate efficient delivery systems.

Discussion: Anchoring PrEP delivery to existing FP systems and staffing has tremendous potential to address barriers that women face in accessing HIV prevention and PrEP care, including lack of time, cost, and stigma of visiting a facility solely for HIV prevention. The FP Plus Project will initiate preparation for full-scale and sustainable model of integration of comprehensive HIV prevention services, including PrEP implementation, in public health FP clinics in low-income settings. Trial registration Registered with ClinicalTrials.gov on December 14, 2020: NCT04666792.

Conflict of interest statement

All authors declare no competing interests

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Schematic of stepped-wedge cluster randomized trial design.

References

    1. UNAIDS. UNAIDS data 2018; 2018 [updated 2018; cited 2019 September 03]; Available from: .
    1. Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, Tappero JW, Bukusi EA, Cohen CR, Katabira E, Ronald A, Tumwesigye E, Were E, Fife KH, Kiarie J, Farquhar C, John-Stewart G, Kakia A, Odoyo J, Mucunguzi A, Nakku-Joloba E, Twesigye R, Ngure K, Apaka C, Tamooh H, Gabona F, Mujugira A, Panteleeff D, Thomas KK, Kidoguchi L, Krows M, Revall J, Morrison S, Haugen H, Emmanuel-Ogier M, Ondrejcek L, Coombs RW, Frenkel L, Hendrix C, Bumpus NN, Bangsberg D, Haberer JE, Stevens WS, Lingappa JR, Celum C, Partners PrEP Study Team Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367(5):399–410. doi: 10.1056/NEJMoa1108524.
    1. Choopanya K, Martin M, Suntharasamai P, Sangkum U, Mock PA, Leethochawalit M, Chiamwongpaet S, Kitisin P, Natrujirote P, Kittimunkong S, Chuachoowong R, Gvetadze RJ, McNicholl JM, Paxton LA, Curlin ME, Hendrix CW, Vanichseni S. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2013;381(9883):2083–2090. doi: 10.1016/S0140-6736(13)61127-7.
    1. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, Goicochea P, Casapia M, Guanira-Carranza JV, Ramirez-Cardich ME, Montoya-Herrera O, Fernandez T, Veloso VG, Buchbinder SP, Chariyalertsak S, Schechter M, Bekker LG, Mayer KH, Kallas EG, Amico KR, Mulligan K, Bushman LR, Hance RJ, Ganoza C, Defechereux P, Postle B, Wang F, McConnell JJ, Zheng JH, Lee J, Rooney JF, Jaffe HS, Martinez AI, Burns DN, Glidden DV. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363(27):2587–2599. doi: 10.1056/NEJMoa1011205.
    1. Kenya Ministry of Health. Demographic andHealth Survey; 2014 [updated 2014; cited 2019 August 30]; Available from: .
    1. O. Evidence for Contraceptive and H. I. V. O. T Consortium. HIV incidence among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a randomised, multicentre, open-label trial. Lancet. 2019;394(10195):303–313. doi: 10.1016/S0140-6736(19)31288-7.
    1. United Nations. The Millennium Development Goals Report; 2010 [updated 2010; cited 2019 September 03]; Available from: .
    1. Mugwanya KK, Pintye J, Kinuthia J, Abuna F, Lagat H, Begnel ER, Dettinger JC, John-Stewart G, Baeten JM, E. P. I. f. Y. W. Pr and P. Adolescents Integrating preexposure prophylaxis delivery in routine family planning clinics: a feasibility programmatic evaluation in Kenya. PLoS Med. 2019;16(9):e1002885. doi: 10.1371/journal.pmed.1002885.
    1. Kenya Ministry of Health. Kenya HIV prevention revolution road map: Count down to 2030; 2014 [updated 2014; cited 2017 December 12]; Available from: .
    1. Kenya Ministry of Health. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection in Kenya; 2016 [updated 2016; cited 2017 December 12]; Available from: .
    1. Baeten JM, Donnell D, Mugo NR, Ndase P, Thomas KK, Campbell JD, Wangisi J, Tappero JW, Bukusi EA, Cohen CR, Katabira E, Ronald A, Tumwesigye E, Were E, Fife KH, Kiarie J, Farquhar C, John-Stewart G, Kidoguchi L, Coombs RW, Hendrix C, Marzinke MA, Frenkel L, Haberer JE, Bangsberg D, Celum C, E. P. S. T. Partners Pr Single-agent tenofovir versus combination emtricitabine plus tenofovir for pre-exposure prophylaxis for HIV-1 acquisition: an update of data from a randomised, double-blind, phase 3 trial. Lancet Infect Dis. 2014;14(11):1055–1064. doi: 10.1016/S1473-3099(14)70937-5.
    1. Donnell D, Baeten JM, Bumpus NN, Brantley J, Bangsberg DR, Haberer JE, Mujugira A, Mugo N, Ndase P, Hendrix C, Celum C. HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention. J Acquir Immune Defic Syndr. 2014;66(3):340–348. doi: 10.1097/QAI.0000000000000172.
    1. Donnell D, Baeten JM, Kiarie J, Thomas KK, Stevens W, Cohen CR, McIntyre J, Lingappa JR, Celum C, H. S. V. H. I. V. T. S. T. Partners in Prevention Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet. 2010;375(9731):2092–2098. doi: 10.1016/S0140-6736(10)60705-2.
    1. Heffron R, Mugo N, Were E, Kiarie J, Bukusi EA, Mujugira A, Frenkel LM, Donnell D, Ronald A, Celum C, Baeten JM, E. P. S. T. Partners Pr Preexposure prophylaxis is efficacious for HIV-1 prevention among women using depot medroxyprogesterone acetate for contraception. AIDS. 2014;28(18):2771–2776. doi: 10.1097/QAD.0000000000000493.
    1. Ngure K, Heffron R, Curran K, Vusha S, Ngutu M, Mugo N, Celum C, Baeten JM, I knew I would be safer Experiences of Kenyan HIV serodiscordant couples soon after pre-exposure prophylaxis (PrEP) initiation. Aids Patient Care Stds. 2016;30(2):78–83. doi: 10.1089/apc.2015.0259.
    1. Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, Tappero JW, Bukusi EA, Cohen CR, Katabira E, Ronald A, Tumwesigye E, Were E, Fife KH, Kiarie J, Farquhar C, John-Stewart G, Kakia A, Odoyo J, Mucunguzi A, Nakku-Joloba E, Twesigye R, Ngure K, Apaka C, Tamooh H, Gabona F, Mujugira A, Panteleeff D, Thomas KK, Kidoguchi L, Krows M, Revall J, Morrison S, Haugen H, Emmanuel-Ogier M, Ondrejcek L, Coombs RW, Frenkel L, Hendrix C, Bumpus NN, Bangsberg D, Haberer JE, Stevens WS, Lingappa JR, Celum C. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367(5):399–410. doi: 10.1056/NEJMoa1108524.
    1. Mugwanya K, Baeten J, Celum C, Donnell D, Nickolas T, Mugo N, et al. Low risk of proximal tubular dysfunction associated with emtricitabine-tenofovir disoproxil fumarate preexposure prophylaxis in men and women. J Infect Dis. 2016.
    1. Mugwanya KK, Wyatt C, Celum C, Donnell D, Kiarie J, Ronald A, Baeten JM, E. P. S. T. Partners Pr Reversibility of glomerular renal function decline in HIV-uninfected men and women discontinuing emtricitabine-tenofovir disoproxil fumarate pre-exposure prophylaxis. J Acquir Immune Defic Syndr. 2016;71(4):374–380. doi: 10.1097/QAI.0000000000000868.
    1. Mugwanya KK, Wyatt C, Celum C, et al. Changes in glomerular kidney function among hiv-1–uninfected men and women receiving emtricitabine–tenofovir disoproxil fumarate preexposure prophylaxis: A randomized clinical trial. JAMA Intern Med. 2015;175(2):246–254. doi: 10.1001/jamainternmed.2014.6786.
    1. Mugwanya KK, Hendrix CW, Mugo NR, Marzinke M, Katabira ET, Ngure K, Semiyaga NB, John-Stewart G, Muwonge TR, Muthuri G, Stergachis A, Celum CL, Baeten JM. Pre-exposure prophylaxis use by breastfeeding HIV-uninfected women: a prospective short-term study of antiretroviral excretion in breast milk and infant absorption. PLOS Med. 2016;13(9):e1002132. doi: 10.1371/journal.pmed.1002132.
    1. Kenya Ministry of Health. Framework for Implementation of Pre-Exposure Prophylaxis of HIV in Kenya; 2017 [updated 2017; cited]; Available from: Available at: . Accessed August 03, 2017.
    1. Shea CM, Jacobs SR, Esserman DA, Bruce K, Weiner BJ. Organizational readiness for implementing change: a psychometric assessment of a new measure. Implementation Sci. 2014;9(1):7. doi: 10.1186/1748-5908-9-7.
    1. Damschroder LJ, Aron DC, Keith RE, Kirsh SR, Alexander JA, Lowery JC. Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science. Implementation Sci. 2009;4(1):50. doi: 10.1186/1748-5908-4-50.
    1. Grol R, Grimshaw J. From best evidence to best practice: effective implementation of change in patients' care. Lancet. 2003;362(9391):1225–1230. doi: 10.1016/S0140-6736(03)14546-1.
    1. Rowe AK, de Savigny D, Lanata CF, Victora CG. How can we achieve and maintain high-quality performance of health workers in low-resource settings? Lancet. 2005;366(9490):1026–1035. doi: 10.1016/S0140-6736(05)67028-6.
    1. Fernandez ME, Walker TJ, Weiner BJ, Calo WA, Liang S, Risendal B, Friedman DB, Tu SP, Williams RS, Jacobs S, Herrmann AK, Kegler MC. Developing measures to assess constructs from the Inner Setting domain of the Consolidated Framework for Implementation Research. Implement Sci. 2018;13(1):52. doi: 10.1186/s13012-018-0736-7.
    1. Golovaty I, Sharma M, Van Heerden A, van Rooyen H, Baeten JM, Celum C, Barnabas RV. Cost of integrating noncommunicable disease screening into home-based HIV testing and counseling in South Africa. J Acquir Immune Defic Syndr. 2018;78(5):522–526. doi: 10.1097/QAI.0000000000001713.
    1. Irungu EM, Sharma M, Maronga C, Mugo N, Ngure K, Celum C, Barnabas RV, Baeten J, Heffron R. The incremental cost of delivering PrEP as a bridge to ART for HIV serodiscordant couples in public HIV care clinics in Kenya. AIDS Res Treat. 2019;2019:4170615.
    1. Phillips AN, Cambiano V, Nakagawa F, Bansi-Matharu L, Wilson D, Jani I, Apollo T, Sculpher M, Hallett T, Kerr C, van Oosterhout JJ, Eaton JW, Estill J, Williams B, Doi N, Cowan F, Keiser O, Ford D, Hatzold K, Barnabas R, Ayles H, Meyer-Rath G, Nelson L, Johnson C, Baggaley R, Fakoya A, Jahn A, Revill P. Cost-per-diagnosis as a metric for monitoring cost-effectiveness of HIV testing programmes in low-income settings in southern Africa: health economic and modelling analysis. J Int AIDS Soc. 2019;22(7):e25325. doi: 10.1002/jia2.25325.
    1. Roberts DA, Barnabas RV, Abuna F, Lagat H, Kinuthia J, Pintye J, Bochner AF, Forsythe S, Gomez GB, Baeten JM, John-Stewart G, Levin C. The role of costing in the introduction and scale-up of HIV pre-exposure prophylaxis: evidence from integrating PrEP into routine maternal and child health and family planning clinics in western Kenya. J Int AIDS Soc. 2019;22(Suppl 4):e25296.
    1. Hughes JP, Granston TS, Heagerty PJ. Current issues in the design and analysis of stepped wedge trials. Contemp Clin Trials. 2015;45(Pt A):55–60. doi: 10.1016/j.cct.2015.07.006.
    1. Hussey MA, Hughes JP. Design and analysis of stepped wedge cluster randomized trials. Contemp Clin Trials. 2007;28(2):182–191. doi: 10.1016/j.cct.2006.05.007.
    1. Yelland LN, Salter AB, Ryan P. Performance of the modified Poisson regression approach for estimating relative risks from clustered prospective data. Am J Epidemiol. 2011;174(8):984–992. doi: 10.1093/aje/kwr183.
    1. Hemming K, Eldridge S, Forbes G, Weijer C, Taljaard M. How to design efficient cluster randomised trials. BMJ. 2017;358:j3064. doi: 10.1136/bmj.j3064.
    1. Simoni JM, Beima-Sofie K, Amico KR, Hosek SG, Johnson MO, Mensch BS. Debrief reports to expedite the impact of qualitative research: do they accurately capture data from in-depth interviews? AIDS Behav. 2019;23(8):2185–2189. doi: 10.1007/s10461-018-02387-3.
    1. Skillman M, Cross-Barnet C, Friedman Singer R, Rotondo C, Ruiz S, Moiduddin A. A framework for rigorous qualitative research as a component of mixed method rapid-cycle evaluation. Qual Health Res. 2019;29(2):279–289. doi: 10.1177/1049732318795675.
    1. Vindrola-Padros C, Johnson GA. Rapid techniques in qualitative research: a critical review of the literature. Qual Health Res. 2020;30(10):1596–1604. doi: 10.1177/1049732320921835.
    1. Hsieh HF, Shannon SE. Three approaches to qualitative content analysis. Qual Health Res. 2005;15(9):1277–1288. doi: 10.1177/1049732305276687.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe