Clinical trial NCT03995953: Integrated Care Delivery of HIV Prevention and Treatment in AGYW in Zambia
Official title: Developing and Testing a Multi-level Package of Interventions for an Integrated Care Delivery Model of HIV Prevention and Treatment Targeting Adolescent Girls in Zambia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV
Keywords: HIV prevention
HIV treatment
Zambia
Lead sponsor: RTI International
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Population Council
name: University of North Carolina, Chapel Hill
First posted: 2019-06-24
Enrollment: 1123
Sex: FEMALE
Minimum age (years): 10
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Zones, with their respective clinics, will be randomized into three groups (zones with integrated wellness care (IWC) clinics and (Support for HIV Integrated Education, Linkages to care, and Destigmatization) SHIELD intervention, zones with only SHIELD intervention, and control zones with no intervention at the clinic or community levels) to assess the impact of offering IWC clinics coupled with the SHIELD intervention compared to the standard of care. In each clinic zone, the study team will use stratified random sampling, using age-group strata drawn from the sampling frame previously established, to select AGYW for the HIV-/u and HIV+ study cohorts. The sample size was calculated assuming conventional specifications (power = .80, alpha = .05, two-sided tests) and based on the primary endpoints.
Primary purpose: PREVENTION

Brief summary: The study team will test a multilevel package of interventions to connect adolescent girls and young women (AGYW) with a source of regular care to provide a sustainable platform for successful implementation of regular human immunodeficiency virus (HIV) testing and support for linkage to care, retention in care, and adherence to antiviral treatment. Interventions will include integrated wellness care (IWC) clinics and the SHIELD intervention (Support for HIV Integrated Education, Linkages to care, and Destigmatization) to educate and empower AGYW and their families, and to create community-based youth clubs to foster peer support. A cluster randomized controlled trial will be implemented with 6 geographic regions randomized into 3 groups: zones with IWC clinics and SHIELD intervention, zones with only SHIELD intervention, and control zones with no intervention. HIV testing will be assessed among the SHIELD only HIV negative or unknown (HIV-/u) cohort and retention in care along with viral load suppression will be primarily assessed in the IWC clinics and SHIELD HIV positive (HIV+) cohort. In-depth interviews and surveys will be used to gather staff and stakeholder feedback following the trial. Cost-effectiveness of the interventions and budgetary impacts will be assessed through using a cost assessment tool.

Detailed description: The overall goal of this study is to develop and test a multilevel package of interventions to connect adolescent girls and young women (AGYW) of ages 10-24 in Zambia with a source of regular care to provide a sustainable platform for successful implementation of regular HIV testing and support for linkage to care, retention in care, and adherence to antiviral treatment. To meet the overall goal, the study team will adapt prior tools to create integrated wellness care (IWC) clinics and the SHIELD intervention (Support for HIV Integrated Education, Linkages to care, and Destigmatization) to educate and empower AGYW and their families, and to create community-based youth clubs to foster peer support. The researchers will test the hypothesis that the combination of IWC clinics, age-appropriate SHIELD interventions for AGYW and their families, and peer support will increase HIV testing, retention in care, and viral load suppression compared to the current standard-of-care clinical services with or without the SHIELD intervention.

Interventions

The SHIELD intervention is based on social cognitive theory, which posits that positive behavior change requires knowledge and skills to increase behavioral capability, development of self-efficacy to increase the belief that one can achieve the desired outcomes, and social support to provide positive reinforcement and develop positive outcomes expectations. The researchers will develop a three-session, six-module program for AGYW that increases knowledge, skills, and self-efficacy to engage along the HIV prevention and care continuum, and a two-session, four-module program for family members to increase social support. Intervention content for both AGYW and families will be tailored for five distinct groups to reflect development stage and AGYW's HIV status. Modules will be adapted from existing evidence-based interventions, such as Stepping Stones and Families Matter! based on community advisory board (CAB) and youth advisory board (YAB) input and formative research with AGYW, caregivers, and community leaders. Modules will address HIV prevention and treatment, general wellness and sexual and reproductive health (SRH), approaches to combat stigma and discrimination, and skills for better communication, and include new content on health service availability and access to increase self-efficacy in seeking health care services. In addition to the education modules, we will establish youth clubs for the five distinct groups by adapting those created for a prior initiative. Youth clubs will be facilitated by peer navigators, who will be AGYW aged 16 to 24 years, and trained in participant confidentiality, AGYW rights, basic counseling skills, overview of SRH and HIV continuum of care, processes of referral and linkages for health services, recruitment strategies, and study aims.

Formative Research

To inform the adaptation of existing materials and new content for the SHIELD intervention, the study team will conduct formative research with AGYW, their parents, and community leaders to explore their perceptions of HIV, stigma, and social support. The study team will conduct in-depth interviews (IDI) and focus group discussions (FGD) with AGYWs to explore their knowledge about HIV and the perceived importance of prevention, testing, and antiretroviral therapy (ART) adherence (as applicable). The study team will examine barriers and facilitators to HIV care or prevention, with a focus on the types of stigma experienced and social support. The study team will also explore AGYW's knowledge of availability of health services and their preferences for service delivery, which will also inform the discrete choice experiment (DCE) attributes and levels. The researchers will conduct focus group discussions (FGDs) with parents and other caregivers of HIV-uninfected AGYW, and FGDs with caregivers of HIV-infected AGYW, to discuss participant's views about their daughters' access to SRH services and HIV care, the stigma that AGYW and their families experience when AGYW use these services, and barriers to and facilitators of family support for AGYW's access to care. Finally, the research team will conduct IDIs with community stakeholders such as health care providers, church leaders, and teachers to explore their views on how best to reduce stigma within their communities.

Findings from the formative research will help to identify content that should be adapted or added to the SHIELD intervention to address locally relevant barriers to HIV prevention, testing, treatment, and care. The researchers will review the findings and develop draft training modules and the youth club protocols. The modules will be tested with participants from each AGYW cohort, families of HIV-uninfected AGYW, and families of HIV-infected AGYW to fine-tune content and delivery. The data from this pre-testing phase will be used to make final revisions to the intervention content, manual, and training materials in preparation for the trial implementation.

IWC Clinic Intervention

IWC clinics will be created within health facilities where AGYWs can receive sexual and reproductive health services, including HIV testing and treatment, family planning, sexually transmitted disease screening and treatment, and human papilloma virus (HPV) vaccination. IWC clinics will be established in existing government health facilities and will follow the model of the cervical cancer screening clinics. SOPs will be developed to include HIV, HPV vaccination, and SRH clinical guidelines specific to the AGYW, care pathways mapped out for common problems or conditions, procedures to maintain patient privacy, quality assurance checklists, and details on documentation and data capture (pre-programed computer tablets will be used to enter study data). The researchers will also map out the physical structure and layout of the room for the IWC to ensure ergonomics in patient care processes and offer privacy for physical exams. The study team will explore the best options for placement of the IWC clinic within the health facilities with the use of at least two rooms: one devoted to the intake process and another for medical examinations. To accommodate AGYW who are generally not available to attend clinics during work or school hours, the IWC operational hours will include early morning, late evening, and weekend hours. Given this proposed schedule, it may be possible to share space with the cervical cancer screening clinic, which generally has at least two dedicated rooms and operates on a more conventional workday schedule.

IWC clinic and health center staff will be trained to ensure that staff offer holistic HIV and SRH services, including family planning, sexually transmitted infection diagnosis and treatment, and condom promotion, in a nonjudgmental and friendly manner. This training will include learning the standard operating procedures (SOPs), gaining hands-on experience by shadowing nurses based at the same facility to understand clinic procedures, and stigma training that can give staff the skills to create a stigma-free health facility.

Discrete Choice Experiment (DCE)

A DCE along with a supplemental survey will be administered to systematically evaluate preferences for HIV clinical care services. AGYW will be asked to choose among constructed scenarios with varying combinations of key attributes relevant to HIV and other clinical care services (for example, service availability, wait time, operating hours, provider type, and protection of privacy); choosing not to attend the clinic will also be an option. To permit use in a low-literacy environment and to ensure an AGYW-tailored approach, the attributes and levels will be converted into graphics. The DCE selection will generate 200 possible scenarios based on attributes and levels. To select a fractional set of scenarios (target of 128 profiles), the study team will employ a randomized design process that ensures that respondents see well-balanced and near-orthogonal fractions of the full-choice design (eight choice decisions per respondent).

The study team plans to perform sub-analyses by age group and HIV status to assess differences by developmental stage and have ensured that the sample size of 1,000 HIV-/u (approximately 330 in three groups) and 800 HIV+ (400 in 2 groups) will be adequate to perform the planned analysis. In addition to the choice tasks, the study team will administer a supplemental survey to obtain demographics, socioeconomic status, reproductive history, access to care, attitudes towards using formal medical care, and stigma associated with HIV diagnosis. The findings from the DCE will be supplemented with information gained from other qualitative (interviews and focus groups) and quantitative (patient supplemental survey) data collection to ensure a comprehensive and context-based interpretation of the results. These findings will be used to tailor the services, hours of operation, and overall structure of the IWC clinic-based intervention.

The study team will conduct pilot testing to assess the SOPs in practice, and review the patient flow and interaction with the IWC staff. The study team will recruit a sample of AGYW from the clinic catchment area to receive services at one of the IWC clinics. Each AGYW will be offered HPV vaccination, counseling for HIV testing, and SRH services; the AGYW will also be encouraged to discuss additional health care needs. Those who choose to receive HPV vaccination will be given a follow-up appointment so the study team can also monitor the process of providing the second vaccine dose (second dose will be provided at 6 weeks or 6 months, depending on the 2- or 3-dose schedule; AGYW will be followed to ensure they complete the required doses, but only the 6-week dosage will be included in the pilot study). The study team will use time and motion methodology to monitor the AGYW interaction and activities at the clinic from initial check-in to the end of the visit; the data will be used to assess patient wait times and disruptions in the patient flow. This information, along with the feedback from the AGYW (who will undergo a short interview at the end of the first visit) and the IWC nurse and peer navigator team (interviewed at the completion of all pilot test visits), will help identify any changes that need to be incorporated to improve the care processes. The SOPs will be revised by incorporating lessons from the pilot testing, and the nurses will receive additional training when necessary.

Cohort recruitment and sampling frame

Identify AGYW to establish a sampling frame. In collaboration with the Ministry of Health (MOH), we will identify six health centers or clinics that provide HIV services and cervical cancer screening in Lusaka district. The study team will identify AGYW for inclusion in the catchment areas of these clinics, zones immediately surrounding the clinics. To avoid potential cross-contamination, the study team will select clinic zones that are not contiguous. The AGYW recruited using this approach will serve as the cohort for conducting the DCE and the sampling frame for random selection to participate in the cluster randomized trial. The sample sizes required for these follow-on assessments were taken into account in determining the size of the initial HIV-/u and HIV+ cohorts, and the feasibility of recruiting the targeted number of AGYW is based on prior and ongoing studies conducted by the grant team. The systematic approach to establishing the sampling frame will provide discrete, non-duplicated individuals (the participant list will be updated daily); reduce selection bias by ensuring a more representative sampling for the cluster randomized trial; and also, if necessary, allow for adjustments in the random selection process so AGYW cohorts are similar.

To identify the HIV-/u cohort, the study team will map out each neighborhood and households within the clinic catchment area with the assistance of the local Neighborhood Health Committees, the community liaisons attached to the clinics, and the outreach staff from the cervical cancer program. Peer Navigators (PNs) will visit each household, beginning with residential areas closest to the clinics, to identify eligible AGYW and recruit them to participate in the study. Participants will be notified of their rights, that questions regarding HIV status will be discussed, and that their refusal to participate will not affect their access to health care or other services. All AGYW 18 years of age and older will provide written informed consent in their preferred language, and parental consent will be obtained for participants under 18 years of age followed by assent from these minors. The study team will include one AGYW per household and enroll AGYW on a continual basis until desired enrollment targets are reached. Participants in the HIV-/u cohort must (a) be female; (b) be 10 to 20 years of age; and (c) self-report their HIV status as negative or unknown (no HIV testing within the past 6 months).

The study team has selected the 10 to 20 age group because this is the highest-priority cohort and because prevention interventions are best targeted to this age group, as high-risk young women older than 20 years are likely to be HIV positive already. Additional inclusion criteria include (d) is not pregnant, does not suspect she is pregnant, and does not express desire to become pregnant over the next 18 months; (e) is willing to sign a release for medical records (to obtain clinic data on service use); (f) plans to reside in the current location for the next 18 months; and (g) has not been part of the other planned formative research activities. The study team is excluding pregnant AGYW because their motivations and health-seeking behaviors are likely to change during pregnancy, they require specialized antenatal care, and they are not eligible for the HPV vaccine that will be offered to the IWC clinic participants. All pregnant AGYW identified during the study will be offered assistance to obtain care at appropriate antenatal clinics. The study team will recruit 160 to 170 adolescent girls from each clinic catchment area, with equal numbers in 10 to 12, 13 to 15, and 16 to 20 age ranges, for a total of 1,000 girls.

For the HIV+ cohort, to maintain confidentially, the study team will request that health providers and community outreach staff at target clinics, along with staff from community-based testing centers, approach eligible HIV+ AGYW who reside in the clinic catchment area (identified through patient record review). The use of community outreach staff will allow targeting AGYW who are HIV+ but not receiving treatment. Those who voluntarily indicate that they are HIV positive during recruitment of the HIV-/u cohort will also be given the opportunity to enroll in the HIV+ cohort when eligible. Participants who are female, 16 to 24 years of age, and diagnosed with HIV within the past 3 years (to target relatively recently diagnosed AGYW at the time of recruitment) will be eligible for inclusion in the study. The study team will continue enrollment until the enrollment target is reached. Those who receive a new HIV+ diagnosis during the 3-month recruitment time frame will also be included. In Zambia, sexual acts with adolescents younger than 16 years, even if consensual, are considered criminal. Given the possible negative repercussions that AGYW may experience should they be reported and our desire to maintain a trusting relationship with the communities that are served, the study team will not recruit adolescent girls aged 15 years and younger for the HIV+ cohort. The study team will enroll a total of 800 HIV+ AGYW, targeting a similar number (130 to 140) from each clinic zone with equal representation among those 16 to 20 and 21 to 24 years of age. The additional inclusion criteria will also be applied to the HIV+ cohort.

Data Collection Procedures

The study team will collect data from AGYW, their caregiver (identified by AGYW), clinical staff, and PNs electronically using computer tablets with pre-loaded software and instruments. Instruments will be available in English, Bemba, Nyanja, and Tonga as needed. To facilitate use by younger girls who may not be fully literate, the study team will include a voice-enabled component, which will allow AGYW to listen and respond to questions. In addition, AGYW can use the tablet, along with headphones, to self-administer the instrument to answer sensitive questions related to sexual risk and HIV status. All instruments for data collection will be created (with adjustments as needed for each AGYW age group) and pretested, using the same set of AGYW and caregivers selected for pretesting the SHIELD intervention. The study team will also identify five clinical staff and five PNs who will not be participating in the study to pretest provider specific data collection instruments. To ensure the highest level of fidelity and adherence to the protocol, all data collectors will receive in-depth training and monitoring. Additionally, the study team will be abstracting required data elements through clinic audit from the six clinic sites included in the study; the study team have the Zambian Ministry of Health's (MOH's) support to interact with clinic personnel and conduct record abstraction. The study team will perform pilot data abstraction to review quality of data at each site and conduct a series of trainings for clinic staff to address problems identified and implement procedures to ensure high-quality data are available for the study.

Eligibility criteria: Inclusion Criteria:

HIV negative or unknown cohort

* Female
* 10 to 20 years of age
* self-report HIV status as negative or unknown (no HIV testing within the past 6 months
* not pregnant, does not suspect pregnancy, and does not express a desire to become pregnant over the next 18 months
* is willing to sign a release for medical records (to obtain clinic data on service use)
* plans to reside in the current location for the next 18 months
* has not been part of the other planned formative research activities

HIV positive cohort

* Female
* 16 to 24 years of age
* diagnosed with HIV within the past 3 years or newly diagnosed at the time of the study
* not pregnant, does not suspect pregnancy, and does not express a desire to become pregnant over the next 18 months
* is willing to sign a release for medical records (to obtain clinic data on service use)
* plans to reside in the current location for the next 18 months
* has not been part of the other planned formative research activities

Exclusion Criteria:

* pregnant

Primary outcomes:
measure: HIV testing
timeFrame: 6 months
measure: HIV testing
timeFrame: 12 months
measure: Retention in care
timeFrame: 12 months
measure: Viral load suppression
timeFrame: 12 months
Secondary outcomes:
measure: HIV risk behavior - delay in first intercourse
timeFrame: Baseline
measure: HIV risk behavior - delay in first intercourse
timeFrame: 6 months
measure: HIV risk behavior - delay in first intercourse
timeFrame: 12 months
measure: HIV risk behavior - reduction in sexual partners
timeFrame: Baseline
measure: HIV risk behavior - reduction in sexual partners
timeFrame: 6 months
measure: HIV risk behavior - reduction in sexual partners
timeFrame: 12 months
measure: HIV risk behavior - increases in condom use
timeFrame: Baseline
measure: HIV risk behavior - increases in condom use
timeFrame: 6 months
measure: HIV risk behavior - increases in condom use
timeFrame: 12 months
measure: HIV early detection
timeFrame: 12 months
measure: Linkages to HIV care - enrollment at HIV clinic
timeFrame: 6 months
measure: Linkages to HIV care - enrollment at HIV clinic
timeFrame: 12 months
measure: Linkages to HIV care - ART initiation
timeFrame: 6 months
measure: Linkages to HIV care - ART initiation
timeFrame: 12 months
measure: Adherence to ART
timeFrame: 6 months
measure: Adherence to ART
timeFrame: 12 months
Other outcomes:
Locations:
city: Lusaka
country: Zambia
facility: Population Council
Study officials:
affiliation: RTI International
name: Sujha Subramanian, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Subramanian S, Edwards P, Roberts ST, Musheke M, Mbizvo M. Integrated Care Delivery for HIV Prevention and Treatment in Adolescent Girls and Young Women in Zambia: Protocol for a Cluster-Randomized Controlled Trial. JMIR Res Protoc. 2019 Oct 3;8(10):e15314. doi: 10.2196/15314.