A Multisectoral Strategy to Address Persistent Drivers of the HIV Epidemic in East Africa (SAPPHIRE)

• ClinicalTrials.gov Identifier: NCT04810650
• Recruitment Status: Recruiting
• First Posted: March 23, 2021
• Last Update Posted: April 23, 2021
• Sponsor: University of California, San Francisco
• Collaborators: Infectious Diseases Research Collaboration, Uganda; Makerere University; Kenya Medical Research Institute; University of California, Berkeley; University of Massachusetts, Amherst; University College, London; University of Pennsylvania; National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute of Mental Health (NIMH); National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): University of California, San Francisco

Study Description

Brief Summary:

The overall objective is to determine to reduce HIV incidence and to improve community health with multi-sector, scalable interventions. This study will consist of two phases: Phase A, in which randomized trials will assess effectiveness, fidelity and cost and improve context-specific "fit" of prevention and treatment interventions. Combining effectiveness with implementation, costing and modelling outcomes, Phase A will optimize intervention packages with context specific adaptations in structured consultation with stakeholders. Phase B, which will evaluate the effects of these optimized dynamic prevention and treatment packages, alone and in combination, on prevention coverage, population-level suppression, and HIV incidence, as well as other health outcomes, in a balanced, community randomized 2x2 factorial design. This clinicaltrial.gov registration is for Phase A.

Condition or disease	Intervention/treatment	Phase
HIV; Hypertension; Alcohol Drinking; Maternal Child Health; Cost Effectiveness; Adolescent Behavior	Other: Mobile Travel Pack; Other: Alcohol Counselling; Other: Hypertension Linkage; Other: PrEP/PEP at Outpatient Clinics; Other: PrEP/PEP at Antenatal/FP Clinics; Other: PrEP/PEP at Households; Other: Youth Hubs; Other: Standard of Care	Not Applicable

Detailed Description:

In the "optimization" Phase A, the study will conduct randomized trials to assess effectiveness, fidelity and cost and improve context-specific "fit" of prevention and treatment interventions. Phase A will evaluate dynamic treatment packages tailored to the needs of heavy alcohol users and mobile populations. Phase A will evaluate dynamic choice prevention delivered in the context of antenatal/family planning clinics, the outpatient department, in youth hubs, and in the community delivered by village health teams. Phase A will evaluate a linkage intervention for patients with hypertension. Combining effectiveness with implementation, costing and modelling outcomes, the study will optimize intervention packages with context-specific adaptations in structured consultation with stakeholders.

In the "evaluation" Phase B, the study will evaluate the effects of Dynamic Prevention and Dynamic Treatment intervention packages based on data from Phase A and new advances from outside the study, alone and in combination, on prevention coverage, population-level viral suppression, and HIV incidence, as well as other health outcomes, in a 2x2 balanced, community randomized factorial design. Phase B will measure outcomes within longitudinal cohorts of residents living within study communities. Phase B will evaluate population-level intervention implementation outcomes, elucidate mechanisms of action and component intervention effects, and estimate incremental costs and gains. Finally, the study will use the HIV Synthesis Model to model outcomes and costs of Phase B results over a period of decades to inform policy and stakeholder decisions to adopt successful strategies to achieve and sustain HIV epidemic control.

Structured stakeholder consultations are formally incorporated in the study design and leverage regular and ongoing collaborations the study team has with the HIV, non-communicable disease and general health leads in Kenya and Uganda Ministries of Health and PEPFAR implementing partners at the national and the regional level.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 3200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Phase A includes conducting parallel randomized trials to assess effectiveness, fidelity and cost and improve context-specific "fit" of prevention and treatment interventions.
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Multisectoral Strategy to Address Persistent Drivers of the HIV Epidemic in East Africa
• Actual Study Start Date: April 15, 2021
• Estimated Primary Completion Date: September 2023
• Estimated Study Completion Date: September 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dynamic Prevention Intervention	Other: PrEP/PEP at Outpatient Clinics; Intervention delivered at Outpatient Clinics: Counseling and education on and choice between prevention modalities (e.g. PrEP, PEP, condoms), choice of service location, provision of a clinical officer's or nurse's mobile telephone number for immediate PEP starts any day of the week, routine assessment of barriers to initiation or adherence to PrEP/PEP, including the offer of personalized potential solutions such as choice of in-clinic or offsite service delivery, psychologic supports for traumatic experiences, and offer of concurrent, additional health or prevention related services; Other: PrEP/PEP at Antenatal/FP Clinics; Intervention delivered at Antenatal/FP Clinics: Counseling and education on and choice between prevention modalities (e.g. PrEP, PEP, condoms), choice of service location, provision of a clinical officer's or nurse's mobile telephone number for immediate PEP starts any day of the week, routine assessment of barriers to initiation or adherence to PrEP/PEP, including the offer of personalized potential solutions such as choice of in-clinic or offsite service delivery, psychologic supports for traumatic experiences, and offer of concurrent, additional health or prevention related services; Other: PrEP/PEP at Households; Intervention delivered in community by village health team: Counseling and education on and choice between prevention modalities (e.g. PrEP, PEP, condoms), choice of service location, provision of a clinical officer's or nurse's mobile telephone number for immediate PEP starts any day of the week, routine assessment of barriers to initiation or adherence to PrEP/PEP, including the offer of personalized potential solutions such as choice of in-clinic or offsite service delivery, psychologic supports for traumatic experiences, and offer of concurrent, additional health or prevention related services; Other: Youth Hubs; Youth Hubs setting will integrate an HIV health curriculum into the routine meetings. A standard life-skills curriculum and activities to attract participation in the clubs will be augmented with additional units related to PrEP, PEP and HIV prevention and treatment.
Experimental: Dynamic Treatment Intervention	Other: Mobile Travel Pack; 1) Access to a mobility coordinator who will assist with transfers, rescheduling, and out-of-facility refills; 2) Provision of a "travel pack" with alternative ART packaging options (e.g. ziplock bags, envelopes, pill boxes), a packing list and mobility coordinator phone contact for unplanned travel; 3) Screening at every clinic visit for planned mobility; 4) Mobile number and mobile minutes for unexpected travel; 5) Provision of longer refills (up to 6-months) for planned travel; Other: Alcohol Counselling; 1) Two in-person alcohol counseling sessions with support from a clinical psychologist; 2) Monthly booster phone calls; Other: Hypertension Linkage; 1) Travel voucher (financial incentive) conditional on linkage to hypertensive care; 2) Phone call reminders for missed visits
Active Comparator: Control	Other: Standard of Care; HIV prevention and treatment standard of care

Outcome Measures

Primary Outcome Measures :

1. Number of participants with viral suppression defined by HIV RNA<400 cps/ml [ Time Frame: 48 weeks for all prevention and treatment interventions (with exception of Alcohol Counselling) ]
   Data collected from Ministry of Health medical records and pharmacy records
2. Number of participants with viral suppression defined by HIV RNA<400 cps/ml [ Time Frame: 24 weeks for Alcohol Counselling intervention ]
   Data collected from Ministry of Health medical records and pharmacy records
3. Prevention coverage defined as proportion of follow-up weeks at risk that the participant is protected from HIV infection with either PrEP or PEP among persons eligible by MoH criteria [ Time Frame: 48 weeks ]
   Primary definition of coverage will rely on clinical records and prescription refills and self report; individuals without PrEP or PEP records will be assumed to never have started either prevention modality.
4. Number of participants to linked to hypertension care by 30 days [ Time Frame: 48 weeks ]
   Linkage to hypertension care at the local government clinic within 30 days of screening positive for high blood pressure during community screening. The primary definition will rely on clinical records; individuals without records will be assumed to never have linked.

Secondary Outcome Measures :

1. Number of participants retained in care for Mobile Travel Pack intervention at 48 weeks [ Time Frame: 48 weeks ]
   Time retained in care (non-retention defined as the period of time following >2 weeks from a missed clinic visit until return to clinical care) and ART-covered time over 48 weeks
2. Number of participants who no longer meet definition of heavy alcohol use by self report and PEth validation while in Alcohol Counselling intervention [ Time Frame: 24 weeks ]
   Measured by self-report and corroborated by phosphatidylethanol [PEth], a valid biomarker of prior 2-3 weeks' alcohol consumption
3. Number of participants who no longer meet definition of heavy alcohol use by self report and PEth validation while in Alcohol Counselling intervention [ Time Frame: 48 weeks ]
   Measured by self-report and corroborated by phosphatidylethanol [PEth], a valid biomarker of prior 2-3 weeks' alcohol consumption
4. Number of participants retained in care in Alcohol Counselling intervention at 24 weeks [ Time Frame: 24 weeks ]
   Non-retention defined as the period of time following >2 weeks from a missed clinic visit until return to clinical care
5. Proportion of participants linking to hypertension care on the date of their scheduled appointment [ Time Frame: 3-months post-enrollment ]
   Proportion of participants linking to hypertension care on the date of their scheduled appointment
6. Number of participants with 'blood pressure control' in Hypertension Linkage intervention [ Time Frame: 3-months post-enrollment ]
   Blood pressure control defined as systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg

Eligibility Criteria

• Ages Eligible for Study: 15 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Individual Level Inclusion Criteria for Component Interventions

Dynamic Prevention: Outpatient and antenatal/FP clinics

1. Age ≥15 years
2. HIV-negative
3. Current or anticipated risk for HIV-infection

Dynamic Prevention: Households

1. Age > 15 years
2. HIV-negative
3. Current or anticipated risk for HIV-infection

Dynamic Prevention: Youth Hubs

1. Age ≥15 to ≤25 years
2. HIV-negative
3. Current or anticipated risk for HIV-infection
4. At least one of the following risk factors: School drop-out, prior pregnancy, transactional sex, orphanhood, or STI history

Dynamic Treatment: Mobile Travel Pack intervention

1. Age ≥15 years
2. HIV-positive
3. HIV RNA non-suppression (>400 c/mL in the prior 12 months) or missed 2 visits in past 12 months
4. Travel outside the community ≥2 times in past 12 months
5. Enrolled or new to care in a study clinic

Dynamic Treatment: Alcohol intervention

1. Age ≥18 years
2. HIV-positive
3. HIV RNA non-suppression (>400 c/mL in the prior 12 months) or missed clinic visits without return to care (>90 days) within past 6 months
4. Heavy alcohol use per AUDIT-C tool (scores of ≥4 for men, and ≥3 for women)
5. Enrolled or new to care in a study clinic

Dynamic Treatment: Hypertension Linkage Intervention

1. Age ≥25 years
2. Blood pressure ≥140/90 mmHg on three repeated measurements during community-based hypertension screening
3. Resident (by self-report) within catchment area of referral health center

Individual Level Exclusion Criteria for Component Interventions

Dynamic Prevention: Outpatient and antenatal/FP clinics

1. <15 years of age
2. Unable to provide consent or parental co-consent as per country guidelines
3. Participation in another Phase A RCT intervention component

Dynamic Prevention: Households

1. <15 years of age
2. unable to provide consent or parental co-consent as per country guidelines
3. Participation in another Phase A RCT intervention component

Dynamic Prevention: Youth Hubs

1. <15 or >25 years of age
2. Unable to provide consent or parental co-consent as per country guidelines
3. Participation in another Phase A RCT intervention component

Dynamic Treatment: Mobile Travel Pack intervention

1. <15 years of age
2. Participation in another Phase A RCT intervention component

Dynamic Treatment: Alcohol intervention

1. <18 years of age
2. Participation in another Phase A RCT intervention component

Dynamic Treatment: Hypertension Linkage Intervention

1. <25 years of age
2. Plan to out-migrate from the catchment area of referral health center within 30 days of screening visit
3. Already engaged in hypertensive care (by self-report)
4. Blood pressure measure of ≥180/110 mmHg during screening symptoms of hypertensive emergency

Contacts and Locations

Contacts

Contact: Tamara Clark, MHS; 628-206-8790; Tamara.Clark@ucsf.edu

Locations

Kenya

GPRT / SEARCH Office; Not yet recruiting

Kisumu, Kenya

Contact: James Ayeiko, MBChB, MPH, PhD +254-720-925262 jimayieko@gmail.com

Principal Investigator: Elizabeth Bukusi, MBChB, PhD

Uganda

IDRC Southwest Uganda; Recruiting

Mbarara, Uganda

Contact: Jane Kabami, MPH +256-706-315810 jkabami@idrc-uganda.org

Principal Investigator: Moses R Kamya, MBChB, PhD

Sponsors and Collaborators

University of California, San Francisco

Infectious Diseases Research Collaboration, Uganda

Makerere University

Kenya Medical Research Institute

University of California, Berkeley

University of Massachusetts, Amherst

University College, London

University of Pennsylvania

National Institute of Allergy and Infectious Diseases (NIAID)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

National Institute of Mental Health (NIMH)

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Diane Havlir, MD; University of California, San Francisco
• Principal Investigator: Moses Kamya, MBChB, PhD; Makerere University
• Principal Investigator: Maya Petersen, PhD; University of California, Berkeley

More Information

Additional Information:

SEARCH 

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT04810650
• Other Study ID Numbers: SAPPHIRE; U01AI150510 ( U.S. NIH Grant/Contract )
• First Posted: March 23, 2021
• Last Update Posted: April 23, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of California, San Francisco:

PrEP; PEP; HIV Treatment and Prevention; Community Health; Mobile Populations; Youth and Adolescents

Additional relevant MeSH terms:

Alcohol Drinking; Drinking Behavior