Clinical trial NCT03508908: Tambua Mapema Plus - to Discover HIV Infection Early and Prevent Onward Transmission
Official title: Impact of a Novel HIV-1 RNA Testing Intervention to Detect Acute and Prevalent HIV Infection and Reduce HIV Transmission - Tambua Mapema Plus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: HIV testing
ART
partner notification
PrEP
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: University of Washington
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2018-04-26
Enrollment: 2887
Sex: ALL
Minimum age (years): 18
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of Patients With Newly Diagnosed HIV Infection at Care Seeking
timeFrame: 24 months
Secondary outcomes:
measure: Proportion of Newly Diagnosed Patients Linked to Care
timeFrame: 24 months
measure: Proportion of Named Partners Tested for HIV
timeFrame: 24 months
measure: Cost Effectiveness of Novel RNA Testing Intervention: Total Cost (Including Both Testing and HIV-positive Patient Management) Per Participant (Base Case Patient Modeled)
timeFrame: Data collected over 2 years, data is a predicted time point extrapolated to 10 years
measure: Cost Effectiveness of Novel RNA Testing Intervention: Disability-Adjusted Life Years (Base Case Patient Modeled)
timeFrame: Data collected over 2 years, data is a predicted time point extrapolated to 10years
Other outcomes:
Locations:
city: Kilifi
country: Kenya
facility: KEMRI Mtwapa
Study officials:
affiliation: University of Washington
name: SUSAN M GRAHAM, MD MPH PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Oxford
name: EDUARD J SANDERS, MD MPH PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Babigumira JB, Agutu CA, Hamilton DT, van der Elst E, Hassan A, Gichuru E, Mugo PM, Farquhar C, Ndung'u T, Sirengo M, Chege W, Goodreau SM, Sanders EJ, M Graham S. Testing strategies to detect acute and prevalent HIV infection in adult outpatients seeking healthcare for symptoms compatible with acute HIV infection in Kenya: a cost-effectiveness analysis. BMJ Open. 2022 Sep 29;12(9):e058636. doi: 10.1136/bmjopen-2021-058636.
citation: Agutu CA, Oduor TH, Hassan AS, Mugo PM, Chege W, de Wit TFR, Sanders EJ, Graham SM. Predictors of testing history and new HIV diagnosis among adult outpatients seeking care for symptoms of acute HIV infection in coastal Kenya: a cross-sectional analysis of intervention participants in a stepped-wedge HIV testing trial. BMC Public Health. 2022 Feb 11;22(1):280. doi: 10.1186/s12889-022-12711-1.
citation: Sanders EJ, Agutu C, van der Elst E, Hassan A, Gichuru E, Mugo P, Farquhar C, Babigumira JB, Goodreau SM, Hamilton DT, Ndung'u T, Sirengo M, Chege W, Graham SM. Effect of an opt-out point-of-care HIV-1 nucleic acid testing intervention to detect acute and prevalent HIV infection in symptomatic adult outpatients and reduce HIV transmission in Kenya: a randomized controlled trial. HIV Med. 2022 Jan;23(1):16-28. doi: 10.1111/hiv.13157. Epub 2021 Aug 25.
citation: Graham SM, Agutu C, van der Elst E, Hassan AS, Gichuru E, Mugo PM, Farquhar C, Babigumira JB, Goodreau SM, Hamilton DT, Ndung'u T, Sirengo M, Chege W, Sanders EJ. A Novel HIV-1 RNA Testing Intervention to Detect Acute and Prevalent HIV Infection in Young Adults and Reduce HIV Transmission in Kenya: Protocol for a Randomized Controlled Trial. JMIR Res Protoc. 2020 Aug 7;9(8):e16198. doi: 10.2196/16198.