Scale up of PrEP integrated in public health HIV care clinics: a protocol for a stepped-wedge cluster-randomized rollout in Kenya

Kenneth K Mugwanya, Elizabeth Irungu, Elizabeth Bukusi, Nelly R Mugo, Josephine Odoyo, Elizabeth Wamoni, Kenneth Ngure, Jennifer F Morton, Kathryn Peebles, Sarah Masyuko, Gena Barnabee, Deborah Donnell, Ruanne Barnabas, Jessica Haberer, Gabrielle O'Malley, Jared M Baeten, Partners Scale Up Team, Kenneth K Mugwanya, Elizabeth Irungu, Elizabeth Bukusi, Nelly R Mugo, Josephine Odoyo, Elizabeth Wamoni, Kenneth Ngure, Jennifer F Morton, Kathryn Peebles, Sarah Masyuko, Gena Barnabee, Deborah Donnell, Ruanne Barnabas, Jessica Haberer, Gabrielle O'Malley, Jared M Baeten, Partners Scale Up Team

Abstract

Background: Antiretroviral therapy (ART) for HIV-infected persons and pre-exposure prophylaxis (PrEP) for uninfected persons are extraordinarily effective strategies for HIV prevention. In Africa, the region which shoulders the highest HIV burden, HIV care is principally delivered through public health HIV care clinics, offering an existing platform to incorporate PrEP delivery and maximize ART and PrEP synergies. However, successfully bringing this integrated approach to scale requires an implementation science evaluation in public health settings.

Methods: The Partners Scale Up Project is a prospective, pragmatic implementation evaluation, designed as a stepped-wedge, cluster-randomized trial, operating at 24 clinics in Kenya. In collaboration with the Kenya Ministry of Health, we are catalyzing scaled implementation of PrEP delivery integrated in HIV care clinics. The intervention package includes staff training, clinic streamlined access to PrEP commodity from the Kenya Medical Supply Authority, and ongoing intensive technical assistance to rigorously assess how PrEP delivery is implemented. PrEP service delivery including retention efforts are conducted by the clinic staff with no additional resources from the project. Guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework and Consolidated Framework for Implementation Science Research, project progress and learning are documented through ongoing monitoring and process evaluations, including chart abstraction and individual and key informant interviews, to evaluate pragmatic rollout and understand barriers and facilitators for successful PrEP delivery in this setting. In this staged rollout design, each step provides data for both pre-implementation (baseline) and implementation periods, and we will compare time points across steps in the baseline versus implementation periods.

Discussion: Cost-effective delivery models are urgently needed to maximize the public health impact of PrEP and ART. The Partners Scale Up Project will set the stage for full-scale PrEP implementation fully run and owned by the Kenya Ministry of Health. The work combines nationally sponsored PrEP delivery with technical support and implementation science from academic partners, defining a new but sustainable paradigm for public health collaboration.

Trial registration: Registered with ClinicalTrials.gov on February 14, 2017: NCT03052010 .

Conflict of interest statement

Ethics approval and consent to participate

The protocol described herein was approved as a minimal risk study by the Scientific and Ethics Review Unit of the Kenya Medical Research Institute and the Human Subjects Division of the University of Washington. The research team meets weekly to study for executive as well as safety and quality management purposes. The project is subject to oversight by an independent data monitoring committee that periodically reviews data from the study, including project execution, adherence, HIV incidence, and serious adverse events. Review follows an unblinded fashion, consistent with the open-label, unblinded nature of the implementation project. Persons who participate in the planned qualitative interviews and the random blood draws provide written consent.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Clinical settings. Counties in Kenya with high and medium HIV incidence
Fig. 2
Fig. 2
Schema for the cluster-randomized stepped-wedge design

References

    1. Piot P, Bartos M, Larson H, Zewdie D, Mane P. Coming to terms with complexity: a call to action for HIV prevention. Lancet. 2008;372(9641):845–859. doi: 10.1016/S0140-6736(08)60888-0.
    1. Chemaitelly H, Cremin I, Shelton J, Hallett TB, Abu-Raddad LJ. Distinct HIV discordancy patterns by epidemic size in stable sexual partnerships in sub-Saharan Africa. Sex Transm Infect. 2012;88(1):51–57. doi: 10.1136/sextrans-2011-050114.
    1. Eyawo O, de Walque D, Ford N, Gakii G, Lester RT, Mills EJ. HIV status in discordant couples in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10(11):770–777. doi: 10.1016/S1473-3099(10)70189-4.
    1. Celum C, Baeten JM. Serodiscordancy and HIV prevention in sub-Saharan Africa. Lancet. 2013;4(13):60147–60146.
    1. Grabbe KL, Bunnell R. Reframing HIV prevention in sub-Saharan Africa using couple-centered approaches. JAMA. 2010;304(3):346–347. doi: 10.1001/jama.2010.1011.
    1. Murnane PM, Celum C, Mugo N, Campbell JD, Donnell D, Bukusi E, et al. Efficacy of preexposure prophylaxis for HIV-1 prevention among high-risk heterosexuals: subgroup analyses from a randomized trial. AIDS. 2013;27(13):2155–2160. doi: 10.1097/QAD.0b013e3283629037.
    1. Curran K, Baeten JM, Coates TJ, Kurth A, Mugo NR, Celum C. HIV-1 prevention for HIV-1 serodiscordant couples. Curr HIV/AIDS Rep. 2012;9(2):160–170. doi: 10.1007/s11904-012-0114-z.
    1. Lingappa JR, Kahle E, Mugo N, Mujugira A, Magaret A, Baeten J, et al. Characteristics of HIV-1 discordant couples enrolled in a trial of HSV-2 suppression to reduce HIV-1 transmission: the Partners Study. PLoS One. 2009;4(4):e5272. doi: 10.1371/journal.pone.0005272.
    1. Lingappa JR, Lambdin B, Bukusi EA, Ngure K, Kavuma L, Inambao M, et al. Regional differences in prevalence of HIV-1 discordance in Africa and enrollment of HIV-1 discordant couples into an HIV-1 prevention trial. PLoS One. 2008;3(1):e1411. doi: 10.1371/journal.pone.0001411.
    1. Medley A, Baggaley R, Bachanas P, Cohen M, Shaffer N, Lo YR. Maximizing the impact of HIV prevention efforts: interventions for couples. AIDS Care. 2013;25(12):1569–1580. doi: 10.1080/09540121.2013.793269.
    1. Ware NC, Wyatt MA, Haberer JE, Baeten JM, Kintu A, Psaros C, et al. What's love got to do with it? Explaining adherence to oral antiretroviral pre-exposure prophylaxis for HIV-serodiscordant couples. J Acquir Immune Defic Syndr. 2012;59(5):463–468. doi: 10.1097/QAI.0b013e31824a060b.
    1. Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367(5):399–410. doi: 10.1056/NEJMoa1108524.
    1. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365(6):493–505. doi: 10.1056/NEJMoa1105243.
    1. Baeten JM, Heffron R, Kidoguchi L, Mugo NR, Katabira E, Bukusi EA, et al. Integrated delivery of antiretroviral treatment and pre-exposure prophylaxis to HIV-1–serodiscordant couples: a prospective implementation study in Kenya and Uganda. PLoS Med. 2016;13(8):e1002099. doi: 10.1371/journal.pmed.1002099.
    1. World Health Organization . Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV. Geneva: WHO; 2015. p. 78.
    1. Kenya Ministry of Health . Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection in Kenya. 2016.
    1. Glasgow RE, Vogt TM, Boles SM. Evaluating the public health impact of health promotion interventions: the RE-AIM framework. Am J Public Health. 1999;89(9):1322–1327. doi: 10.2105/AJPH.89.9.1322.
    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. Implement Sci. 2009;4:50. doi: 10.1186/1748-5908-4-50.
    1. Kenya Ministry of Health. Framework for implementation of pre-exposure prophylaxis of HIV in Kenya. 2017.
    1. Glasgow RE, Eckstein ET, Elzarrad MK. Implementation science perspectives and opportunities for HIV/AIDS research: integrating science, practice, and policy. J Acquir Immune Defic Syndr. 2013;63(Suppl 1):S26–S31. doi: 10.1097/QAI.0b013e3182920286.
    1. Baeten JM, Donnell D, Mugo NR, Ndase P, Thomas KK, Campbell JD, et al. 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, et al. 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, et al. 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, et al. 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, et al. 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. 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;214:1050–7. doi: 10.1093/infdis/jiw125.
    1. Mugwanya KK, Wyatt C, Celum C, Donnell D, Kiarie J, Ronald A, et al. 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, et al. 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. Anderson PL, Glidden DV, Liu A, Buchbinder S, Lama JR, Guanira JV, et al. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med. 2012;4(151):151ra125. doi: 10.1126/scitranslmed.3004006.
    1. Kahle EM, Hughes JP, Lingappa JR, John-Stewart G, Celum C, Nakku-Joloba E, et al. An empiric risk scoring tool for identifying high-risk heterosexual HIV-1-serodiscordant couples for targeted HIV-1 prevention. J Acquir Immune Defic Syndr. 2013;62(3):339–347. doi: 10.1097/QAI.0b013e31827e622d.
    1. Sherr K, Gimbel S, Rustagi A, Nduati R, Cuembelo F, Farquhar C, et al. Systems analysis and improvement to optimize pMTCT (SAIA): a cluster randomized trial. Implement Sci. 2014;9:55. doi: 10.1186/1748-5908-9-55.
    1. Report AVAC. Research & reality. New York: AVAC; 2013. p. 2013.
    1. Jilcott S, Ammerman A, Sommers J, Glasgow RE. Applying the RE-AIM framework to assess the public health impact of policy change. nn Behav Med. 2007;34(2):105–114. doi: 10.1007/BF02872666.
    1. Stoutenberg M, Galaviz KI, Lobelo F, Joy E, Heath GW, Hutber A, et al. A pragmatic application of the RE-AIM framework for evaluating the implementation of physical activity as a standard of care in health systems. Prev Chronic Dis. 2018;15:E54. doi: 10.5888/pcd15.170344.
    1. Kirk MA, Kelley C, Yankey N, Birken SA, Abadie B, Damschroder L. A systematic review of the use of the Consolidated Framework for Implementation Research. Implement Sci. 2016;11:72. doi: 10.1186/s13012-016-0437-z.
    1. VanDevanter N, Kumar P, Nguyen N, Nguyen L, Nguyen T, Stillman F, et al. Application of the Consolidated Framework for Implementation Research to assess factors that may influence implementation of tobacco use treatment guidelines in the Viet Nam public health care delivery system. Implement Sci. 2017;12(1):27. doi: 10.1186/s13012-017-0558-z.

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