Tambua Mapema Plus - to Discover HIV Infection Early and Prevent Onward Transmission

Study Overview
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Brief Summary
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This study will assess the impact of an HIV-1 RNA testing intervention targeting adult patients aged 18-39 years who seek urgent care for symptoms at primary care facilities and meet specific risk criteria for acute HIV infection. All newly diagnosed HIV-infected patients in the intervention arm will be linked to care and offered both immediate treatment and assisted partner notification. Partners will also be tested using the HIV testing intervention, and pre-exposure prophylaxis will be offered to uninfected individuals with HIV-infected partners. The cost-effectiveness of this intervention will be evaluated.

Detailed Description
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This is a proof-of-concept study comparing outcomes of a health facility-based acute HIV infection (AHI) and prevalent HIV testing intervention using point of care HIV-1 RNA detection, combined with assisted partner services (aPS) and follow-up in an antiretroviral therapy (ART) cohort for all newly diagnosed individuals and follow-up in a pre-exposure prophylaxis (PrEP) cohort for the uninfected partners of newly diagnosed individuals, compared to standard care. Study Design: Randomized stepped-wedge study with prospective cohort follow-up of all individuals newly diagnosed with acute or prevalent HIV infection and of up to 300 identified partners of these persons. Individuals enrolled in the observation phase will be compared to those enrolled in the intervention phase at each facility, after undergoing the following procedures in each phase. Study Population: The study population will be recruited from among male and female adult patients who present for care at 6 public or private outpatient clinics in coastal Kenya. Eligibility criteria for the HIV-1 RNA testing intervention include: 1) age from 18-39 years; 2) not previously diagnosed with HIV infection; and 3) a score ≥2 on our AHI risk score algorithm. Eligibility criteria for partners of newly diagnosed cases with acute or prevalent HIV infection include: 1) age over 18 years; and 2) not previously diagnosed with HIV infection. Sample Size: 3,175 study participants total, including 2,875 participants in the stepped-wedge study (1,375 in the observation period and 1,500 in the intervention period). We estimate that approximately 2% of participants in the observation period (n=28) and approximately 5% of participants in the intervention period (n=75) will test positive for HIV infection and continue in the study. We estimate that up to 300 partners of newly diagnosed individuals will be offered enrollment and tested for HIV using standard tests (observation period) or HIV-1 RNA testing (intervention period). Participating Sites: Kenya Medical Research Institute (KEMRI)-Wellcome Trust Programme, Kilifi, Kenya with stepped wedge trial implementation at 6 community health facilities (2-4 public, 2-4 private) and ART and PrEP cohort follow-up at the KEMRI Research Clinic in Mtwapa, Kenya. Schedule of Procedures: Individuals eligible for the HIV-1 RNA testing intervention will be offered enrollment when they seek care at one of the study facilities, with testing taking place on that same day. For individuals with negative test results for both acute and prevalent HIV infection, no further follow-up will occur. One 6-week follow-up visit will occur after testing for all individuals who are newly diagnosed with HIV. Procedures for the aPS intervention, the ART cohort, and the PrEP cohort are detailed in this protocol. Study Duration: Study enrollment will occur over 24 months. Following enrollment and study procedures (1-2 hours of time), all participants who test negative for HIV infection will have no further visits. All participants newly diagnosed with HIV will have a 6-week follow-up visit. All participants who enroll in the ART or PrEP cohort will be followed for a total of 12 months. Intervention: Testing for acute and prevalent HIV infection, followed by partner notification services and immediate ART (provided by the Kenyan Ministry of Health) for newly diagnosed individuals and PrEP (provided by Gilead) for uninfected partners in serodiscordant relationships.

Official Title
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Impact of a Novel HIV-1 RNA Testing Intervention to Detect Acute and Prevalent HIV Infection and Reduce HIV Transmission - Tambua Mapema Plus

Conditions
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HIV Infections

Intervention / Treatment
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* Diagnostic Test: HIV-1 RNA testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age from 18-39 years; not previously diagnosed with HIV infection; and a score ≥2 on our risk score algorithm to identify persons at higher risk for AHI, with scoring as follows: age 18-29 years (1), fever (1), fatigue (1), body pains (1), diarrhea (1), sore throat (1), and genital ulcer disease (GUD) (3). Eligibility criteria for partners of newly diagnosed cases with prevalent or acute HIV include: age over 18 years; and not previously diagnosed HIV infection. Exclusion Criteria: Patients not meeting inclusion criteria or those who are not willing or able to participate (e.g., due to illness or time constraints, or at the discretion of the study clinician) will be excluded. Individuals at high risk for Intimate Partner Violence (IPV) are excluded from the aPS intervention, but eligible for all other components of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This trial will use a modified stepped wedge design to evaluate the yield of the HIV-1 RNA testing intervention at 6 public or private health facilities in Kenya, before (1,375 patients) and after (1,500 patients) intervention delivery. This study will be conducted in two phases (observation phase and intervention phase) at each site.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Observation Period<br>HIV testing will only be done if ordered by the primary care clinician. Individuals diagnosed with HIV who have not yet notified partners will be offered assisted partner notification at a 6-week visit. | |
| Active Comparator: Intervention Period<br>Combination intervention with HIV-1 RNA testing followed by rapid tests if positive for HIV diagnosis, immediate ART if diagnosed, assisted partner notification with HIV-1 RNA testing of partners, and PrEP for uninfected partners in discordant relationships. | Diagnostic Test: HIV-1 RNA testing<br>* During the intervention period, a blood sample will be obtained and tested for AHI using point-of-care Xpert® HIV Qual assay (Cepheid, Sunnyvale, California, USA). Individuals who test positive will undergo rapid tests to differentiate acute from prevalent HIV infection. Newly diagnosed individuals will be offered immediate ART and assisted partner notification with the HIV-1 RNA testing intervention delivered to partners following the same approach.<br>* Other names: Xpert HIV-1 RNA testing;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With Newly Diagnosed HIV Infection at Care Seeking | Primary endpoints for the HIV-1 RNA testing intervention include the proportion of participants with newly diagnosed prevalent or AHI at care seeking. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Newly Diagnosed Patients Linked to Care | Secondary endpoints for the linkage to care intervention include the proportion of newly diagnosed patients captured in the HIV care cascade. | 24 months | 
| Proportion of Named Partners Tested for HIV | Proportion of named partners tested for HIV in each period | 24 months | 
| Cost Effectiveness of Novel RNA Testing Intervention: Total Cost (Including Both Testing and HIV-positive Patient Management) Per Participant (Base Case Patient Modeled) | Model outputs will include an analysis of the cost effectiveness of the novel testing intervention assessing several parameters of the HIV prevention and care cascade using stochastic, agent-based mathematical modelling. The population of interest modeled was 18- to 39-year-old heterosexuals in Kenya. The age range coincides with the sampled population in this study (NCT03508908) which provided the majority of the parameters for the networks and behavioral modules in the simulation. The observations from this study were weighted to match the sex and age composition reported in the Kenya Fact and Figures 2015 published by the Kenya National Bureau of Statistics. Additional model parameters were drawn from the literature on HIV infection, prevention, and treatment in Kenya.The analysis was conducted over a time horizon of 10 years, consistent with the mathematical model. 10,000 base-case patients (simulations) were run. | Data collected over 2 years, data is a predicted time point extrapolated to 10 years | 
| Cost Effectiveness of Novel RNA Testing Intervention: Disability-Adjusted Life Years (Base Case Patient Modeled) | Disability-adjusted Life Year (DALY) is an index calculated as the sum of years of life lost (YLL) plus the years lost due to disability (YLD), where 1 DALY represents one lost year of healthy life. The higher the DALY index value, the worse the outcome, where there is no theoretical minimum ore maximum index value. the sampled population in this study (NCT03508908) which provided the majority of the parameters for the networks and behavioral modules in the simulation. The observations from this study were weighted to match the sex and age composition reported in the Kenya Fact and Figures 2015 published by the Kenya National Bureau of Statistics. Additional model parameters were drawn from the literature on HIV infection, prevention, and treatment in Kenya. The analysis was conducted over a time horizon of 10 years, consistent with the mathematical model. 10,000 base-case patients (simulations) were run. | Data collected over 2 years, data is a predicted time point extrapolated to 10years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV testing, ART, partner notification, PrEP