HIV Infections
Conditions
Keywords
HIV testing, ART, partner notification, PrEP
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.
Interventions
DIAGNOSTIC_TESTHIV-1 RNA testing
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.
Sponsors
University of Washington
National Institute of Allergy and Infectious Diseases (NIAID)
University of Oxford
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 39 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Newly Diagnosed HIV Infection at Care Seeking | 24 months | Primary endpoints for the HIV-1 RNA testing intervention include the proportion of participants with newly diagnosed prevalent or AHI at care seeking. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Newly Diagnosed Patients Linked to Care | 24 months | Secondary endpoints for the linkage to care intervention include the proportion of newly diagnosed patients captured in the HIV care cascade. |
| Proportion of Named Partners Tested for HIV | 24 months | Proportion of named partners tested for HIV in each period |
| Cost Effectiveness of Novel RNA Testing Intervention: Total Cost (Including Both Testing and HIV-positive Patient Management) Per Participant (Base Case Patient Modeled) | Data collected over 2 years, data is a predicted time point extrapolated to 10 years | 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. |
| Cost Effectiveness of Novel RNA Testing Intervention: Disability-Adjusted Life Years (Base Case Patient Modeled) | Data collected over 2 years, data is a predicted time point extrapolated to 10years | 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. |
Countries
Kenya
Participant flow
Recruitment details
We identified the participating health facilities (three in Kilifi county; three in Mombasa county) due to their size, location (within 20 km of our KEMRI Research Clinic), patient volume (\> 500 patients aged 18-39 years seen over 3 months) and willingness to collaborate with the research team. All clinics served general population patients; the four public facilities included offered limited programming for key populations. Some sites had minor delays in starting an intervention period.
Pre-assignment details
We used a modified stepped-wedge design to evaluate outcomes before and after intervention delivery. Six clinics each had two phases (observation and intervention), for 12 clinic periods. Each clinic period lasted 6 months or until 250 participants were recruited, except first clinic period (3 months of observation, 125 participants). The order in which clinics were active was randomized such that only 2 clinics provided the intervention at a given time (due to limited testing platforms).
Participants by arm
| Arm | Count |
|---|---|
| Observation Period 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. | 1,374 |
| Intervention Period 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.
HIV-1 RNA testing: 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. | 1,500 |
| Observation Period Partners Consented for testing at week 6 | 3 |
| Intervention Period Partners Consented for testing and follow-up as soon as possible after diagnosis of the index patient | 10 |
| Total | 2,887 |
Baseline characteristics
| Characteristic | Total | Observation Period | Intervention Period | Observation Period Partners | Intervention Period Partners |
|---|---|---|---|---|---|
| Age, Continuous | 25 years | 25 years | 26 years | 32.6 years | 32.4 years |
| HIV testing history Missing | 7 Participants | 0 Participants | 0 Participants | 0 Participants | 7 Participants |
| HIV testing history Never tested for HIV | 303 Participants | 147 Participants | 153 Participants | 1 Participants | 2 Participants |
| HIV testing history Tested for HIV in past 12 months | 1064 Participants | 499 Participants | 563 Participants | 1 Participants | 1 Participants |
| HIV testing history Tested for HIV over 12 months ago | 1513 Participants | 728 Participants | 784 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2887 Participants | 1374 Participants | 1500 Participants | 3 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Kenya | 2887 participants | 1374 participants | 1500 participants | 3 participants | 10 participants |
| Sex: Female, Male Female | 1778 Participants | 886 Participants | 887 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 1109 Participants | 488 Participants | 613 Participants | 1 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1,374 | 0 / 1,500 | 0 / 3 | 0 / 10 |
| other Total, other adverse events | 0 / 1,374 | 0 / 1,500 | 0 / 3 | 0 / 10 |
| serious Total, serious adverse events | 0 / 1,374 | 0 / 1,500 | 0 / 3 | 0 / 10 |
Outcome results
Primary
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.
Time frame: 24 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adult Outpatients With Symptoms of Acute HIV Infection | Proportion of Patients With Newly Diagnosed HIV Infection at Care Seeking | Acute HIV infection | 2 Participants |
| Adult Outpatients With Symptoms of Acute HIV Infection | Proportion of Patients With Newly Diagnosed HIV Infection at Care Seeking | HIV-positive | 50 Participants |
| Adult Outpatients With Symptoms of Acute HIV Infection | Proportion of Patients With Newly Diagnosed HIV Infection at Care Seeking | HIV-negative | 2822 Participants |
| Observation Phase | Proportion of Patients With Newly Diagnosed HIV Infection at Care Seeking | Acute HIV infection | 0 Participants |
| Observation Phase | Proportion of Patients With Newly Diagnosed HIV Infection at Care Seeking | HIV-positive | 13 Participants |
| Observation Phase | Proportion of Patients With Newly Diagnosed HIV Infection at Care Seeking | HIV-negative | 1361 Participants |
| Intervention Phase | Proportion of Patients With Newly Diagnosed HIV Infection at Care Seeking | HIV-positive | 37 Participants |
| Intervention Phase | Proportion of Patients With Newly Diagnosed HIV Infection at Care Seeking | HIV-negative | 1461 Participants |
| Intervention Phase | Proportion of Patients With Newly Diagnosed HIV Infection at Care Seeking | Acute HIV infection | 2 Participants |
Secondary
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.
Time frame: Data collected over 2 years, data is a predicted time point extrapolated to 10years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adult Outpatients With Symptoms of Acute HIV Infection | Cost Effectiveness of Novel RNA Testing Intervention: Disability-Adjusted Life Years (Base Case Patient Modeled) | 0.2140 index |
| Observation Phase | Cost Effectiveness of Novel RNA Testing Intervention: Disability-Adjusted Life Years (Base Case Patient Modeled) | 0.1598 index |
Comparison: Cost (in US dollars) per DALY averted (Intervention referenced to Observation)
Secondary
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.
Time frame: Data collected over 2 years, data is a predicted time point extrapolated to 10 years
Population: The total cost (including both testing and HIV-positive patient management) per participant(base case patient modeled) is derived from the model where a measure of dispersion was not an output of the model.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adult Outpatients With Symptoms of Acute HIV Infection | Cost Effectiveness of Novel RNA Testing Intervention: Total Cost (Including Both Testing and HIV-positive Patient Management) Per Participant (Base Case Patient Modeled) | 47.24 US dollars |
| Observation Phase | Cost Effectiveness of Novel RNA Testing Intervention: Total Cost (Including Both Testing and HIV-positive Patient Management) Per Participant (Base Case Patient Modeled) | 214.91 US dollars |
Secondary
Proportion of Named Partners Tested for HIV
Proportion of named partners tested for HIV in each period
Time frame: 24 months
Population: In each period, trial participants who were newly diagnosed with HIV infection were offered assisted partner notification services and asked to report partners. Named partners who were successfully contacted were offered HIV testing and, if willing, provided informed consent for testing and documentation of the test result as part of this trial. Not all named partners were consented. Tested partners were referred to an observational HIV or PrEP cohort according to their status.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adult Outpatients With Symptoms of Acute HIV Infection | Proportion of Named Partners Tested for HIV | 3 Participants |
| Observation Phase | Proportion of Named Partners Tested for HIV | 10 Participants |
Secondary
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.
Time frame: 24 months
Population: newly diagnosed participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adult Outpatients With Symptoms of Acute HIV Infection | Proportion of Newly Diagnosed Patients Linked to Care | 9 Participants |
| Observation Phase | Proportion of Newly Diagnosed Patients Linked to Care | 33 Participants |