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

The overall goal of the Partners Scale Up Project is to serve as a catalyst for expansion of PrEP delivery in public HIV clinics in Kenya and to document best practices for PrEP delivery. The specific aims are:

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 this design, each step provides data for both pre-implementation (baseline) and implementation periods, and data analysis proceeds by comparing time points across steps in baseline versus implementation periods. In collaboration with the Kenya MOH, PrEP delivery was introduced in public health HIV clinics in a staged fashion, with ongoing intensive technical assistance and monitoring and evaluation conducted to rigorously assess how PrEP delivery is being implemented. PrEP provision including behavior risk assessment, demand creation, and retention activities are conducted by public health staff, with no additional resources provided by the project team. 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.

HIV-uninfected individuals with HIV-positive sexual partners became eligible for PrEP per the Kenya national guidelines on use of antiretroviral drugs for treatment and prevention of HIV released in 2016 [16]. A national PrEP implementation framework and service provider toolkit was developed by the Kenya MOH [19], with contribution from the Partners Scale Up Project team. PrEP rollout nationally in Kenya was officially launched in May 2017 and is expanding at a variety of care centers, aimed at providing HIV prevention to key populations [19]. Kenya guidelines specifically recommend PrEP for HIV-uninfected members of HIV-serodiscordant couples until the HIV-infected partner achieves viral suppression with effective ART, in serodiscordant couples desiring safer conception or if otherwise meeting behavioral criteria for individuals to receive PrEP (e.g., additional sexual partners of positive or unknown HIV serostatus, sex work).

The Partners Scale Up Project is being implemented in 24 Comprehensive Care Clinics (the term used for public health HIV clinics) in two geographical regions of Kenya: Central and Nairobi regions, herein referred to as Central (Kiambu, Kirinyaga, Murang’a, Nairobi, Nyeri counties) and Nyanza, herein referred to as Western (Homa Bay, Kisumu, Migori, Siaya counties). High-volume clinics with established ART programs were identified. Final participating clinics were then selected in consultation with MOH/National AIDS & STI Control Programme (NASCOP) and county health authorities prior to project initiation and reflect the Kenya Ministry of Health HIV priority areas based on HIV prevalence, diversity, and health care settings (Fig. 1). Lessons learnt from the pioneering 24 clinics will be used to inform dissemination of PrEP implementation nationally, including in regions where the project did not initially operate.

Beginning February 2017, we implemented a stepped-wedge trial design to randomly assign 24 HIV care clinics to scaled implementation of PrEP integrated in HIV clinics for couples. During the project pre-implementation period, PrEP was sanctioned as part of  standard of care by the Kenya national guidelines but there were no systematic approaches in place for implementation in clinical settings. The project intervention is to be a catalytic force to integrate PrEP delivery in public HIV clinics nationally and the intervention package includes staff training, clinic streamlined access to PrEP commodity from Kenya Medical Supply Authority (KEMSA), and ongoing PrEP technical assistance. Prior to randomization, the 24 clinics were stratified by region (12 Central, 12 Western), and each clinic was randomized to the order in which it would start implementing PrEP delivery. The randomization process was conducted at a public event attended by national and county health representatives. Facility leadership picked the order of initiation from an opaque bag containing numbered balls labeled from 1 to 12. Following randomization, the implementation was rolled out in groups of two to four clinics (Fig. 2). Program indicators to measure number of serodiscordant couples newly identified through couples HIV testing, number of HIV-uninfected individuals initiating PrEP, and number of HIV-infected individuals newly initiating ART are obtained monthly from all participating clinics starting 1 month prior to the project initiation.

Using 24 clinics with a baseline period, two to four clinics implementing at each step, and 50 at-risk HIV-uninfected persons initiating PrEP per clinic every 6 months (200 couples on average per site overall, 4800 total), the trial is estimated to have > 90% power to detect a minimum 10% difference in the number of at-risk HIV-uninfected individuals initiating PrEP (defined below as Reach) after implementing the intervention, with a two-sided alpha of 0.05. This difference was conservatively chosen, recognizing that as interventions move to scale their impact is often diminished (a “voltage drop” along successive steps of an implementation cascade [20]).

PrEP has regulatory and normative guidance sanction in Kenya and has been defined as part of standard care, in part based on a series of clinical trials and implementation studies done in Kenyan populations [12, 21‐29]. Thus, the intention of the Partners Scale Up Project is to study the process of integrating PrEP services for HIV-serodiscordant couples in HIV clinics and not the PrEP medication itself. PrEP delivery activities are fully conducted by MOH staff in accordance with Kenyan national guidelines; project staff conduct technical assistance and monitoring and evaluation activities to characterize the implementation processes, define facilitators and barriers, and measure uptake, adherence, and costs. The components of the implementation (intervention) package (i.e., activities conducted by the project) include (1) health care provider training on clinical delivery of integrated PrEP and ART for couples, (2) development of operational tools for PrEP delivery, (3) monitoring and evaluation and implementation process evaluation, (4) economic evaluations, and (5) stakeholder and community engagement.

Key quantitative program implementation outcomes will include (a) Reach, defined as the number of at-risk persons initiating PrEP; (b) Effectiveness, defined as the number of HIV-uninfected on PrEP partners staying HIV-uninfected and adherence to PrEP as measured by tenofovir levels in DBS; and (c) Adoption, measured by PrEP continuation, number of serodiscordant couples newly identified through couples HIV testing. HIV risk profiles of PrEP initiators will be characterized using a validated risk score for HIV-serodiscordant couples [31], which we will use to further predict HIV incidence in the absence of intervention [14]. Monitoring and evaluation will measure patient, provider, and clinic level factors influencing delivery including clinic innovations, adaptations, barriers, and facilitators of PrEP implementation and opportunities for efficiency.

The project uses multiple data sources (Table 2) that will robustly synthesize and triangulate PrEP delivery processes to identify contextually relevant strategies for successful implementation, as well as practical difficulties in adoption, integration, and maintenance to inform wider implementation.

All abstracted health and patient data are handled in a secure and confidential way through adherence to institutional policies and procedures for securely storing, maintaining, and updating health record information. All health records and patient data are securely stored on password-protected and encrypted servers, and these data will not be released externally except under specific data-sharing agreements. All study results will be presented in aggregate, and no individual patient or provider will be identifiable.

This protocol was registered with ClinicalTrials.​gov on February 14, 2017 (NCT03052010). Amendments to the study protocol will require approval from the Scientific and Ethics Review Unit of the Kenya Medical Research Institute and the Human Subjects Division of the University of Washington. Any amendments will be communicated via trial registration updates and reported in any published manuscripts associated with the study as necessary.

The study team for this award is committed to public dissemination of results of clinical trial to local stakeholders in Kenya, the global scientific community, and global policymakers. Dissemination of study results will follow principles of good participatory practice. Results will be published in conference abstracts and peer-reviewed journals. Study results will be disseminated through presentations to global and local stakeholders and policymakers in Kenya, including working in close collaboration with the Kenyan Ministry of Health to help foster immediate translational impact. Authorship eligibility will be determined according to the International Committee of Medical Journal Editors recommendations.

The project was activated in February 2017 and implementation is currently ongoing and expected to end in 2021.