Cost Effectiveness, Diabetes, HIV, Hypertension, Maternal Child Health, Tuberculosis
Conditions
Keywords
HIV treatment and prevention, Tuberculosis, Community health campaign, PrEP
Brief summary
The SEARCH study aims to test evidenced-based innovative community based interventions that lead to the elimination of HIV in rural communities in East Africa using a multi-disease approach. The first phase of the study will quantify the impact of early HIV diagnosis using a streamlined and immediate ART (antiretroviral therapy). The second phase of the study, will quantify the impact of targeted Pre-Exposure Prophylaxis (PrEP) in the context of universal treatment and streamlined care. The study intervention is designed to improve the entire continuum of care, to reduce structural barriers for all populations including those most at risk.
Detailed description
The SEARCH study aims to test evidenced-based innovative community based interventions that lead to the elimination of HIV in rural communities in East Africa using a multi-disease approach. The first phase of the study will quantify the impact of early HIV diagnosis using a streamlined and immediate ART (antiretroviral therapy). The second phase of the study, will quantify the impact of targeted Pre-Exposure Prophylaxis (PrEP) in the context of universal treatment and streamlined care. The study intervention is designed to improve the entire continuum of care, to reduce structural barriers for all populations including those most at risk.
Interventions
OTHERUniversal ART in a streamlined care model
immediate ART start for all HIV+ in community with streamlined care
OTHERAnnual Community Health Campaigns
HIV and multi-disease testing for all community members
OTHERTargeted PrEP and Targeted testing interventions
OTHERBaseline community-based HIV and multi-disease testing
HIV and multi-disease testing for all community members at baseline only
Sponsors
Infectious Diseases Research Collaboration, Uganda
Makerere University
Kenya Medical Research Institute
Gilead Sciences
World Bank
National Institute of Allergy and Infectious Diseases (NIAID)
United States President's Emergency Plan for AIDS Relief
Bill and Melinda Gates Foundation
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
Community Level Inclusion Criteria: * Non-adjacent geopolitical units in south-western and eastern Uganda and western Kenya. * Most recent census population between 9,000 and 11,000 individuals. * Served by an ART providing health center. * Community leader commitment for study participation and implementation. * Accessibility to health center via a maintained transportation route. * Community location with sufficient distance from other potential study communities to limit contamination of intervention or control conditions (buffer zone) Individual Level Inclusion Criteria: * Residency of individual in community, defined as present in household for at least 6 months of the calendar year. Community Level
Exclusion criteria
* Presence of ongoing community-based ART intervention strategies that provide treatment outside of the current in-country treatment guidelines. * An urban setting defined as a city with a population of 100,000 or more inhabitants. * Absence of a health center able to provide ART.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative HIV Incidence | 3 years follow up | Cumulative 3 year HIV incidence in men and women ages ≥15 years after the start of Phase I intervention. Mean was calculated as the average across clusters of the cluster-level cumulative incidence. |
| HIV Incidence | 3 years follow up | HIV incidence rate in men and women ages ≥15 years after the start of Phase II intervention (started after 3 years of Phase I). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HIV-free Infant Survival | 3 years follow up | Probability of an infant born to an HIV+ mother remaining alive and HIV uninfected. Mean was calculated as the average across clusters of the cluster-level cumulative incidence. |
| Percent of HIV+ Adults With HIV RNA <=500 c/mL | 3 years follow up | Percent of HIV+ adults with HIV RNA \<=500 c/mL. Mean was calculated as the average across clusters of the cluster-level cumulative incidence. |
| Time in Care for HIV+ Adults With Baseline Viremia | 3 years follow up | Percent of time spent actively engaged in HIV care among HIV+ adults with baseline viremia |
| Cumulative Incidence of ART-initiation | 3 years follow up | Proportion of baseline HIV+ ART-naive persons who initiate ART Mean was calculated as the average across clusters of the cluster-level cumulative incidence. |
| Hypertension Control | 3 years follow up | hypertension control (greater than or equal to 140 mg Hg systolic or 90 mg Hg diastolic after 3 repeated readings) at year 3 among adults aged \>= 30 years with hypertension. Mean was calculated as the average across clusters of the cluster-level cumulative incidence. |
| Adherence to PrEP Treatment | 3 years follow up | Number of patients with adherence to PrEP treatment (self reported adherence at \>=1 visit) |
| Incident TB Associated With HIV | 3 years follow up | Cumulative incidence of TB or death due to illness among HIV+ population. Mean was calculated as the average across clusters of the cluster-level cumulative incidence. |
| Year 3 Viremia Among ART-experienced Persons With Baseline Viremia | 3 years follow up | Plasma HIV RNA \<400 cps/ml Mean was calculated as the average across clusters of the cluster-level cumulative incidence. |
| Linkage to Care | 30 days after HIV test | Proportion of Persons Attending an HIV Clinic Visit by 30 Days After HIV Test Mean was calculated as the average across clusters of the cluster-level cumulative incidence. |
| HIV Incidence Rate | 3 years follow up | HIV incidence rates during the first and third year of follow up; Results from the Control arm are not provided because annual HIV incidence was not measured in the control arm (annual HIV testing was only conducted in the intervention arm). |
| Prevalence of Transmitted HIV Drug-resistance Mutations | Baseline | HIV NNRTI drug-resistance mutations found at baseline |
| Prevalence of Chronic Kidney Disease (CKD) | 3 years follow up | Percentage of participants with chronic kidney disease (CKD) |
| Total Costs of Programming (ART) | Follow up year 3 | Cost of ART streamlined care delivery amount HIV+ persons |
| Average Adults' on- and Off-farm Employment | 3 years follow up | HIV+ adults with on- and off-farm employment |
| Overall Mortality | 3 years follow up | Mortality risk among HIV+ population. Mean was calculated as the average across clusters of the cluster-level cumulative incidence. |
Countries
Kenya, Uganda
Participant flow
Recruitment details
32 communities were enrolled and randomized to the intervention and control (16 per arm in each stage). We enrolled 150,395 community residents aged 15+ years at study baseline in Stage 1. At the start of Stage 2, 184,091 community residents (including in-migrants) aged 15+ years were enrolled. The analytic population for each endpoint is detailed in the Outcomes section.
Participants by arm
| Arm | Count |
|---|---|
| Intervention Intervention arm first stage: Annual universal community- based HIV and multi-disease testing; ART eligibility for all HIV+; ART delivery using streamlined patient-centered care | 79,818 |
| Control Active Comparator arm first stage: Baseline universal community-based HIV and multi-disease testing; ART eligibility and delivery by country standard of care | 70,577 |
| Total | 150,395 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Stage 2 | DSMB design modification | 86,056 | 92,558 |
Baseline characteristics
| Characteristic | Intervention | Control | Total |
|---|---|---|---|
| Age, Customized 15-20 years | 20053 Participants | 16602 Participants | 36655 Participants |
| Age, Customized 21-49 years | 44047 Participants | 39975 Participants | 84022 Participants |
| Age, Customized >=50 years | 15718 Participants | 14000 Participants | 29718 Participants |
| Education Any secondary school or higher | 17266 Participants | 14408 Participants | 31674 Participants |
| Education Below primary school | 50912 Participants | 45691 Participants | 96603 Participants |
| Education Completed primary school | 11478 Participants | 10305 Participants | 21783 Participants |
| Household wealth index quintile Fifth, indicating most wealth | 21235 Participants | 15678 Participants | 36913 Participants |
| Household wealth index quintile First, indicating least wealth | 12078 Participants | 11876 Participants | 23954 Participants |
| Household wealth index quintile Fourth | 17384 Participants | 15703 Participants | 33087 Participants |
| Household wealth index quintile Second | 13474 Participants | 12652 Participants | 26126 Participants |
| Household wealth index quintile Third | 15448 Participants | 14371 Participants | 29819 Participants |
| Marital Status Married | 46684 Participants | 42502 Participants | 89186 Participants |
| Marital Status Single | 23692 Participants | 19392 Participants | 43084 Participants |
| Marital Status Widowed, divorced or separated | 9228 Participants | 8542 Participants | 17770 Participants |
| Marital status - polygamous marriage | 9575 Participants | 9210 Participants | 18785 Participants |
| Occupation Formal sector | 19753 Participants | 15733 Participants | 35486 Participants |
| Occupation High-risk informal sector | 3235 Participants | 4944 Participants | 8179 Participants |
| Occupation Low-risk informal sector | 48753 Participants | 42341 Participants | 91094 Participants |
| Occupation No job or disabled | 4261 Participants | 4215 Participants | 8476 Participants |
| Occupation Other | 3595 Participants | 3201 Participants | 6796 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 79818 Participants | 70577 Participants | 150395 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Residents living with HIV | 7212 Participants | 6317 Participants | 13529 Participants |
| Residents with prevalent hypertension | 5953 Participants | 5911 Participants | 11864 Participants |
| Sex: Female, Male Female | 43770 Participants | 38644 Participants | 82414 Participants |
| Sex: Female, Male Male | 36048 Participants | 31933 Participants | 67981 Participants |
| Stable residents | 76111 Participants | 67759 Participants | 143870 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1,217 / 79,818 | 18 / 5,447 |
| other Total, other adverse events | 80 / 1,671 | 17 / 5,447 |
| serious Total, serious adverse events | 89 / 1,671 | 50 / 5,447 |
Outcome results
Primary
Cumulative HIV Incidence
Cumulative 3 year HIV incidence in men and women ages ≥15 years after the start of Phase I intervention. Mean was calculated as the average across clusters of the cluster-level cumulative incidence.
Time frame: 3 years follow up
Population: Baseline HIV- stable adult (15+years) residents
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention | Cumulative HIV Incidence | 0.77 cumulative events per 100 persons |
| Control | Cumulative HIV Incidence | 0.81 cumulative events per 100 persons |
Comparison: Comparison of Phase 1 arms95% CI: [0.77, 1.17]
Primary
HIV Incidence
HIV incidence rate in men and women ages ≥15 years after the start of Phase II intervention (started after 3 years of Phase I).
Time frame: 3 years follow up
Population: Intervention population consists of persons aged 15+ years who initiated PrEP in Phase II intervention communities. The comparator population consists of propensity score matched historical controls from Phase I intervention communities. HIV testing was not comprehensively conducted during Phase 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention | HIV Incidence | 0.35 Incident HIV per 100 person-year |
| Control | HIV Incidence | 0.92 Incident HIV per 100 person-year |
95% CI: [0.09, 0.75]
Secondary
Adherence to PrEP Treatment
Number of patients with adherence to PrEP treatment (self reported adherence at \>=1 visit)
Time frame: 3 years follow up
Population: Persons who initiated PrEP eligible for a follow-up visit. No data were collected for the second stage in the control arm due to DSMB approved design modification.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Adherence to PrEP Treatment | 3282 Participants |
Secondary
Average Adults' on- and Off-farm Employment
HIV+ adults with on- and off-farm employment
Time frame: 3 years follow up
Population: Subsample of baseline HIV+ working-age adults (18-65)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention | Average Adults' on- and Off-farm Employment | 85.5 cumulative events per 100 persons |
| Control | Average Adults' on- and Off-farm Employment | 82.4 cumulative events per 100 persons |
Secondary
Cumulative Incidence of ART-initiation
Proportion of baseline HIV+ ART-naive persons who initiate ART Mean was calculated as the average across clusters of the cluster-level cumulative incidence.
Time frame: 3 years follow up
Population: Baseline HIV+ without previous or current ART
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention | Cumulative Incidence of ART-initiation | 83 cumulative events per 100 persons |
| Control | Cumulative Incidence of ART-initiation | 50 cumulative events per 100 persons |
Secondary
HIV-free Infant Survival
Probability of an infant born to an HIV+ mother remaining alive and HIV uninfected. Mean was calculated as the average across clusters of the cluster-level cumulative incidence.
Time frame: 3 years follow up
Population: Infants born in study period to women with HIV
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention | HIV-free Infant Survival | 96.7 cumulative events per 100 persons |
| Control | HIV-free Infant Survival | 93.6 cumulative events per 100 persons |
Secondary
HIV Incidence Rate
HIV incidence rates during the first and third year of follow up; Results from the Control arm are not provided because annual HIV incidence was not measured in the control arm (annual HIV testing was only conducted in the intervention arm).
Time frame: 3 years follow up
Population: HIV-negative adults in stage 1 intervention arm who had repeat HIV testing
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention | HIV Incidence Rate | 0.43 per 100 person-years |
| Control | HIV Incidence Rate | 0.31 per 100 person-years |
Secondary
Hypertension Control
hypertension control (greater than or equal to 140 mg Hg systolic or 90 mg Hg diastolic after 3 repeated readings) at year 3 among adults aged \>= 30 years with hypertension. Mean was calculated as the average across clusters of the cluster-level cumulative incidence.
Time frame: 3 years follow up
Population: Hypertensive adults (aged 30+) at year 3
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention | Hypertension Control | 47 cumulative events per 100 persons |
| Control | Hypertension Control | 37 cumulative events per 100 persons |
Secondary
Incident TB Associated With HIV
Cumulative incidence of TB or death due to illness among HIV+ population. Mean was calculated as the average across clusters of the cluster-level cumulative incidence.
Time frame: 3 years follow up
Population: Adults without active TB and with HIV at baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention | Incident TB Associated With HIV | 3.7 cumulative events per 100 persons |
| Control | Incident TB Associated With HIV | 4.6 cumulative events per 100 persons |
Secondary
Linkage to Care
Proportion of Persons Attending an HIV Clinic Visit by 30 Days After HIV Test Mean was calculated as the average across clusters of the cluster-level cumulative incidence.
Time frame: 30 days after HIV test
Population: Persons testing HIV+ and not in care
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention | Linkage to Care | 41 cumulative events per 100 persons |
| Control | Linkage to Care | 24 cumulative events per 100 persons |
Secondary
Overall Mortality
Mortality risk among HIV+ population. Mean was calculated as the average across clusters of the cluster-level cumulative incidence.
Time frame: 3 years follow up
Population: Known HIV+ at baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention | Overall Mortality | 3.0 cumulative events per 100 persons |
| Control | Overall Mortality | 3.9 cumulative events per 100 persons |
Secondary
Percent of HIV+ Adults With HIV RNA <=500 c/mL
Percent of HIV+ adults with HIV RNA \<=500 c/mL. Mean was calculated as the average across clusters of the cluster-level cumulative incidence.
Time frame: 3 years follow up
Population: HIV+ adults at year 3, including those out of care or without a prior HIV diagnosis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention | Percent of HIV+ Adults With HIV RNA <=500 c/mL | 79 cumulative events per 100 persons |
| Control | Percent of HIV+ Adults With HIV RNA <=500 c/mL | 68 cumulative events per 100 persons |
Secondary
Prevalence of Chronic Kidney Disease (CKD)
Percentage of participants with chronic kidney disease (CKD)
Time frame: 3 years follow up
Population: participants (age \>=18) who had a home visit during follow up year 3
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Prevalence of Chronic Kidney Disease (CKD) | 361 Participants |
| Control | Prevalence of Chronic Kidney Disease (CKD) | 248 Participants |
Secondary
Prevalence of Transmitted HIV Drug-resistance Mutations
HIV NNRTI drug-resistance mutations found at baseline
Time frame: Baseline
Population: ART naive HIV+ persons at baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Prevalence of Transmitted HIV Drug-resistance Mutations | 8 Participants |
| Control | Prevalence of Transmitted HIV Drug-resistance Mutations | 11 Participants |
Secondary
Time in Care for HIV+ Adults With Baseline Viremia
Percent of time spent actively engaged in HIV care among HIV+ adults with baseline viremia
Time frame: 3 years follow up
Population: HIV+ adults linked to care with baseline HIV RNA \>=500 c/mL
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention | Time in Care for HIV+ Adults With Baseline Viremia | 81 percentage of days |
| Control | Time in Care for HIV+ Adults With Baseline Viremia | 73 percentage of days |
Secondary
Total Costs of Programming (ART)
Cost of ART streamlined care delivery amount HIV+ persons
Time frame: Follow up year 3
Population: Units are Intervention clinics using streamlined care; participants are HIV+ with at least one streamlined care visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention | Total Costs of Programming (ART) | 291 USD per person year |
| Control | Total Costs of Programming (ART) | 221 USD per person year |
Secondary
Year 3 Viremia Among ART-experienced Persons With Baseline Viremia
Plasma HIV RNA \<400 cps/ml Mean was calculated as the average across clusters of the cluster-level cumulative incidence.
Time frame: 3 years follow up
Population: HIV+ ART experienced adults linked to care with baseline HIV RNA \>=500 c/mL
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention | Year 3 Viremia Among ART-experienced Persons With Baseline Viremia | 67 cumulative events per 100 persons |
| Control | Year 3 Viremia Among ART-experienced Persons With Baseline Viremia | 47 cumulative events per 100 persons |