HIV Prevention
Conditions
Keywords
Kenya, adolescent girls and young women (AGYW), HIV pre-exposure prophylaxis (PrEP) delivery, HIV self-testing delivery
Brief summary
Few young women at risk of HIV infection are initiating pre-exposure prophylaxis (PrEP) for HIV prevention in Kenya, thus we propose refining and testing a new model to increase PrEP initiation among young women at high HIV risk that has never been explored: enhanced peer PrEP referral with HIV self-test (HIVST) delivery. We conducted formative research to design of a model that is acceptable to young women and feasible to implement in Kenya. In this study, we will refine this model where young (≥16 to 24 years) female PrEP users refer their peers to PrEP and deliver HIVSTs in a pilot study and then test the refined model in a hybrid effectiveness-implementation trial. We hypothesize that relative to standard informal word-of-month peer PrEP referral (currently ongoing in Kenya), enhanced peer PrEP referral with HIVST delivery will increase PrEP initiation, continuation, and adherence among peers; have high fidelity; and be low cost.
Detailed description
HIV PrEP is highly effective, but uptake remains low among young women in Africa, one of the populations at greatest HIV risk. In Kenya, one of the target groups for HIV incidence reduction is young women (16-24 years), who account for 33% of the total of new HIV infections yet comprise only 10% of the population. Barriers to PrEP initiation for this population are multi-faceted and include institutional (e.g., stigma associated with use) and intra-personal (e.g., lack of PrEP knowledge or self-efficacy) barriers. Thus, innovative PrEP delivery models that can overcome these barriers are needed. The opinion of peers often influences the behaviors and preferences of young women, including those related to health and health care. Most young women who have initiated PrEP in Kenya to date have done so because of informal peer referral, thus peer referral enhanced with training and HIVST delivery has the potential to increase PrEP initiation among members of this population. HIVST is a new technology that has the potential to enhance peer PrEP referral. Much of the emphasis on HIVST to date has been on identifying new individuals living with HIV and facilitating linkage to treatment, but most individuals who self-test will test negative and may be interested in starting prevention services, like PrEP. We hypothesize that an enhanced peer PrEP referral model with HIVST delivery can increase PrEP initiation among young Kenyan women at HIV risk compared to standard informal peer PrEP referral. We conducted formative qualitative research to inform the design of such a model and propose refining this model in a pilot study with 16 young female PrEP users (i.e., peer providers or index peers) who will be encouraged to referred up to four peer (i.e., peer clients or referred peers; =64 in total) using the defined implementation strategies (i.e., formalized training on PrEP and HIVST, and HIVST delivery). At one month, we will measure model adoption (e.g., peer referral, PrEP initiation) and feasibility (e.g., peer follow up) using survey data and qualitatively measure model acceptability using focus group discussions (FDGs) with index and referred peers (4-5 FDGs, 3-6 women/FDG). We will incorporate findings from the pilot into a refined version of the enhanced peer PrEP referral with HIVST delivery model and test this compared to standard peer PrEP referral in hybrid effectiveness-implementation cluster-randomized controlled trial (cRCT). In our cRCT, we will randomize 80 index peers to either: 1) enhanced peer PrEP referral, where they are encouraged to refer 4 peer (i.e., referred peers) to PrEP using an educational brochure, HIVSTs (2/peer), and a MOH-style referral slip, or 2) standard peer PrEP referral, where they are encouraged to refer 4 peer clients to PrEP using word-of-mouth, as is ongoing in Kenya, and a MOH-style referral slip. All trial outcomes will be measured among referred peers, as reported by index peers, three months later. Effectiveness outcomes will include PrEP initiation \[primary\], PrEP continuation (any refilling), and recent HIV testing (past 3 months); self-reported PrEP adherence will be assessed among referred peers reached for follow-up. Implementation outcomes will include model acceptability, fidelity, and costs. The results from this cRCT will address one of the greatest challenges to PrEP scale-up today and inform an R01 proposal for a community-randomized trial and budget impact analysis.
Interventions
BEHAVIORALEnhanced peer PrEP referral + HIVST delivery
After a brief training, young female PrEP users will be encouraged to refer up to 4 peers to PrEP using strategies gained from the training, PrEP educational materials (i.e., brochures), HIVST kits (2 kits/peer = 8 kits total), and Kenya MOH-style referral cards.
Sponsors
National Institute of Mental Health (NIMH)
Fred Hutchinson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
The pilot study will be a single group model (anticipated N=104), and the RCT will be a parallel model (anticipated N=400).
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 24 Years
Healthy volunteers
Yes
Inclusion criteria
For peer providers (qualitative data, pilot): * Age ≥16 to 24 years\* * Female * Have been on PrEP for a minimum of three months * Good adherence to PrEP (i.e., self-report take PrEP all the time) * Willing to disclose PrEP use to their peers * Able to identify up to 4 peers at risk of HIV infection * Willing to participate in training with study counselors on PrEP referral and HIVST use * Willing to refer peers to PrEP and deliver HIVSTs * Able and willing to provide written informed consent * Per the discretion of the site investigator, no clear risks of social harm or inability otherwise to reasonably conduct HIVST at home in the context of PrEP delivery For peer providers (cRCT): * Age ≥16 to 24 years\* * Female * Must have refilled or initiated PrEP (i.e., been dispensed PrEP) * Not currently enrolled in an HIV study * Able to identify up to 4 peers with recent self-reported behaviors associated with risk of HIV acquisition * Willing to participate in training with study counselors on PrEP referral and HIVST use * Willing to refer peers to PrEP and deliver HIVSTs * Able and willing to provide written informed consent * Willing to provide contact information for follow-up * Willing to engage in all research activities including completion of questionnaires * Per the discretion of the site investigator, no clear risks of social harm or inability otherwise to reasonably conduct HIVST at home in the context of PrEP delivery For peer clients (pilot, RCT): * Age ≥16 to 24 years\* * Female * Referred by peer (i.e., a PrEP users) to initiate PrEP * Able and willing to provide informed consent * NOTE: We will only enroll young women ≥16 to 17 years into the study if they are emancipated minors and thus able to legally provide consent for participation in research. Kenyan law acknowledges women ages 14 to 17 who have become pregnant as emancipated minors. The PHRD site/UW collaboration has successfully enrolled emancipated minors into a number of prior studies, including PrEP clinical trials. In addition, Kenya's national policy guidelines explicitly permit PrEP use in this age group.
Exclusion criteria
For peer providers (qualitative data, pilot): * Age ≥16 or \>24 years * Male * Have not used PrEP for a minimum of three months * Not willing to disclose PrEP use to their peers * Not able to identify up to 4 peers at risk of HIV infection * Not willing to participate in training with study counselors on PrEP referral and HIVST use * Not willing to refer peers to PrEP and deliver HIVSTs * Not able and willing to provide written informed consent For peer providers (cRCT): * Age ≥16 or \>24 years * Male * Have not used PrEP * Currently enrolled in an HIV study * Not able to identify up to 4 peers at risk of HIV infection * Illiterate * Not willing to participate in training with study counselors on PrEP referral and HIVST use * Not willing to refer peers to PrEP and deliver HIVSTs * Not able and willing to provide written informed consent For peer clients (pilot, cRCT): * Age ≥16 or \>24 years * Male * Not referred by peer (i.e., a PrEP users) to initiate PrEP * Not able and willing to provide written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| cRCT: PrEP Initiation | 3 months | Number of referred peers that initiated PrEP, among all referred peers, as reported by index peers. |
| Pilot: PrEP Initiation, as Reported by Referred Peers | 1 month | Number of referred peers that initiated PrEP, among eligible referred peers who enrolled and completed follow-up, as reported by referred peers. |
| Pilot: PrEP Initiation, as Reported by Index Peers | 1 month | Number of referred peers that initiated PrEP, among all eligible referred peers, as reported by index peers. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| cRCT: PrEP Adherence | 3 months | A 0-100 point PrEP adherence score derived from the validated three-item Wilson et al Adherence scale with higher scores indicating higher adherence, among referred peers who enrolled and completed follow-up, as reported by referred peers. |
| cRCT: PrEP Continuation (Index Peers) | 3 months | Number of index peers that returned to a clinic to refill PrEP in the past 3 months. |
| Pilot: PrEP Referral | 1 month | Number of referred peers referred to PrEP, among all referred peers, as reported by index peers. |
| Pilot: HIVST Use | 1 month | Number of referred peers that used HIVST, among referred peers who enrolled and completed follow-up, as reported by referred peers. |
| cRCT: Recent HIV Testing | 3 months | Number of referred peers who tested for HIV (any form, including HIVST) since peer PrEP referral, among all referred peers, as reported by index peers. |
| cRCT: PrEP Continuation (Referred Peers) | 3 months | Number of referred peers that returned to a clinic to refill PrEP since referral, among all referred peers, as reported by index peers. |
Other
| Measure | Time frame | Description |
|---|---|---|
| cRCT: HIVST Use | 3 months | Number of referred peers in the enhanced group that used HIVST, among referred peers in the enhanced group who enrolled and completed follow-up, as reported by referred peers in the enhanced group. |
| cRCT: Materials Received | 3 months | Number of referred peers that received the intervention or standard-of-care materials, among referred peers who enrolled and completed follow-up, as reported by referred peers. |
| cRCT: Acceptability of Intervention Model | 3 months | Number of referred peers and index peers who agree/strongly agree (on a 5-point Likert scale) to statements adapted from the Theoretical Framework of Acceptability. |
| cRCT: Appropriateness of Intervention Model | 3 months | Number of referred peers and index peers who agree/strongly agree (on a 5-point Likert scale) to statements adapted from the Appropriateness of Intervention Measure instrument. |
| cRCT: Feasibility of Intervention Model | 3 months | Normal of referred peers and index peers who agree/strongly agree (on a 5-point Likert scale) to statements adapted from the Feasibility of Intervention Measure instrument. |
| cRCT: Linkage to Care | 3 months | Number of referred peers that went to a clinic to access HIV prevention or treatment services, among referred peers who enrolled and completed follow-up, as reported by referred peers. |
| cRCT: PrEP Referral | 3 months | Median number of referred peers referred to PrEP services by each index peer. |
Countries
Kenya
Participant flow
Recruitment details
To identify index peers for recruitment, we reviewed the records of public clinics and research programs delivering PrEP in the region and called adolescent girls and young women (AGYW) who met the study eligibility criteria. Referred peers were recruited by index peers, who were given instructions to only recruit peers between 16 to 24 years who they thought might benefit from PrEP.
Pre-assignment details
In both the pilot and the 2-arm cRCT, index peers (k) referred their peers to HIV services (i.e., referred peers, n). At follow-up, index peers reported outcomes for all the referred peers (started). At follow up, some of the referred peers were also enrolled (completed). Thus, some outcomes are measured among index peers, referred peers who started (as reported by index peers), and referred peers who completed (as reported by referred peers). Enrollment totals reflect those who completed.
Participants by arm
| Arm | Count |
|---|---|
| Pilot: Index Peers (k) Index peers who received formalized training on PrEP referral strategies and HIV self-testing. | 16 |
| Pilot: Referred Peers (n) Referred peers recruited by index peers whom we were able to reach for follow-up (completed enrollment). | 30 |
| cRCT: Enhanced Group; Index Peers (k) Index peers assigned to the enhanced peer referral group. | 40 |
| cRCT: Standard Group; Index Peers (k) Index peers assigned to the standard peer referral group. | 42 |
| cRCT: Enhanced Group; Referred Peers (n) Referred peers recruited by index peers in the enhanced peer referral group whom we were able to reach for follow-up (completed enrollment). | 55 |
| cRCT: Standard Group; Referred Peers (n) Referred peers recruited by index peers in the standard peer referral group whom we were able to reach for follow-up (completed enrollment). | 28 |
| Total | 211 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 26 | 0 | 0 | 72 | 69 |
| Overall Study | Not Eligible to Enroll | 0 | 0 | 0 | 0 | 10 | 7 |
Baseline characteristics
| Characteristic | Pilot: Index Peers (k) | Total | cRCT: Standard Group; Referred Peers (n) | cRCT: Enhanced Group; Referred Peers (n) | cRCT: Standard Group; Index Peers (k) | cRCT: Enhanced Group; Index Peers (k) | Pilot: Referred Peers (n) |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 23 years | 22 years | 22 years | 22 years | 22 years | 22 years | 21 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 211 Participants | 28 Participants | 55 Participants | 42 Participants | 40 Participants | 30 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 16 Participants | 211 Participants | 28 Participants | 55 Participants | 42 Participants | 40 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 30 | 0 / 40 | 0 / 42 | 0 / 55 | 0 / 28 |
| other Total, other adverse events | 0 / 16 | 0 / 30 | 1 / 40 | 1 / 42 | 0 / 55 | 0 / 28 |
| serious Total, serious adverse events | 0 / 16 | 0 / 30 | 0 / 40 | 0 / 42 | 0 / 55 | 0 / 28 |
Outcome results
Primary
cRCT: PrEP Initiation
Number of referred peers that initiated PrEP, among all referred peers, as reported by index peers.
Time frame: 3 months
Population: Outcome only applies to cRCT referred peers.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| cRCT: Enhanced Group; Referred Peers (n) | cRCT: PrEP Initiation | 41 Participants |
| cRCT: Standard Group; Referred Peers (n) | cRCT: PrEP Initiation | 41 Participants |
Comparison: The sample size calculation was based on the primary PrEP initiation outcome at follow-up; 80 clusters (40 per study group) provided 80% power to detect a 17% difference in PrEP initiation between the enhanced (80%) and standard (63%) groups, assuming three referred peers per cluster (75% of those recommended), an intra-cluster correlation coefficient of 0.05, and an alpha level of 0.05.95% CI: [-26, 11]
Primary
Pilot: PrEP Initiation, as Reported by Index Peers
Number of referred peers that initiated PrEP, among all eligible referred peers, as reported by index peers.
Time frame: 1 month
Population: Outcome only applies to pilot referred peers. The denominator (n=55) excludes one referred peer reported as HIV-positive.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| cRCT: Enhanced Group; Referred Peers (n) | Pilot: PrEP Initiation, as Reported by Index Peers | 43 Participants |
Primary
Pilot: PrEP Initiation, as Reported by Referred Peers
Number of referred peers that initiated PrEP, among eligible referred peers who enrolled and completed follow-up, as reported by referred peers.
Time frame: 1 month
Population: Outcome only applies to pilot referred peers who enrolled and completed follow-up. The denominator (n=26) excludes four referred peers who were already/currently using PrEP at the time of referral.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| cRCT: Enhanced Group; Referred Peers (n) | Pilot: PrEP Initiation, as Reported by Referred Peers | 22 Participants |
Secondary
cRCT: PrEP Adherence
A 0-100 point PrEP adherence score derived from the validated three-item Wilson et al Adherence scale with higher scores indicating higher adherence, among referred peers who enrolled and completed follow-up, as reported by referred peers.
Time frame: 3 months
Population: Outcome only applies to cRCT referred peers who enrolled and completed follow-up.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| cRCT: Enhanced Group; Referred Peers (n) | cRCT: PrEP Adherence | 4.9 Scores on a scale |
| cRCT: Standard Group; Referred Peers (n) | cRCT: PrEP Adherence | 58.9 Scores on a scale |
95% CI: [-36.3, 2.5]
Secondary
cRCT: PrEP Continuation (Index Peers)
Number of index peers that returned to a clinic to refill PrEP in the past 3 months.
Time frame: 3 months
Population: Outcome only applies to cRCT index peers.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| cRCT: Enhanced Group; Referred Peers (n) | cRCT: PrEP Continuation (Index Peers) | 19 Participants |
| cRCT: Standard Group; Referred Peers (n) | cRCT: PrEP Continuation (Index Peers) | 28 Participants |
95% CI: [-40, 2]
Secondary
cRCT: PrEP Continuation (Referred Peers)
Number of referred peers that returned to a clinic to refill PrEP since referral, among all referred peers, as reported by index peers.
Time frame: 3 months
Population: Outcome only applies to cRCT referred peers.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| cRCT: Enhanced Group; Referred Peers (n) | cRCT: PrEP Continuation (Referred Peers) | 17 Participants |
| cRCT: Standard Group; Referred Peers (n) | cRCT: PrEP Continuation (Referred Peers) | 11 Participants |
95% CI: [-10, 13]
Secondary
cRCT: Recent HIV Testing
Number of referred peers who tested for HIV (any form, including HIVST) since peer PrEP referral, among all referred peers, as reported by index peers.
Time frame: 3 months
Population: Outcome only applies to cRCT referred peers.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| cRCT: Enhanced Group; Referred Peers (n) | cRCT: Recent HIV Testing | 125 Participants |
| cRCT: Standard Group; Referred Peers (n) | cRCT: Recent HIV Testing | 56 Participants |
95% CI: [24, 54]
Secondary
Pilot: HIVST Use
Number of referred peers that used HIVST, among referred peers who enrolled and completed follow-up, as reported by referred peers.
Time frame: 1 month
Population: Outcome only applies to pilot referred peers who enrolled and completed follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| cRCT: Enhanced Group; Referred Peers (n) | Pilot: HIVST Use | 29 Participants |
Secondary
Pilot: PrEP Referral
Number of referred peers referred to PrEP, among all referred peers, as reported by index peers.
Time frame: 1 month
Population: Outcome only applies to pilot referred peers.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| cRCT: Enhanced Group; Referred Peers (n) | Pilot: PrEP Referral | 56 Participants |
Other Pre-specified
cRCT: Acceptability of Intervention Model
Number of referred peers and index peers who agree/strongly agree (on a 5-point Likert scale) to statements adapted from the Theoretical Framework of Acceptability.
Time frame: 3 months
Other Pre-specified
cRCT: Appropriateness of Intervention Model
Number of referred peers and index peers who agree/strongly agree (on a 5-point Likert scale) to statements adapted from the Appropriateness of Intervention Measure instrument.
Time frame: 3 months
Other Pre-specified
cRCT: Feasibility of Intervention Model
Normal of referred peers and index peers who agree/strongly agree (on a 5-point Likert scale) to statements adapted from the Feasibility of Intervention Measure instrument.
Time frame: 3 months
Other Pre-specified
cRCT: HIVST Use
Number of referred peers in the enhanced group that used HIVST, among referred peers in the enhanced group who enrolled and completed follow-up, as reported by referred peers in the enhanced group.
Time frame: 3 months
Population: We do not include the arm/group cRCT: Standard group; referred peers (n) here because this outcome only applies to referred peers in the enhanced group. Referred peers in the standard group did not receive HIVST as part of the intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| cRCT: Enhanced Group; Referred Peers (n) | cRCT: HIVST Use | 54 Participants |
Other Pre-specified
cRCT: Linkage to Care
Number of referred peers that went to a clinic to access HIV prevention or treatment services, among referred peers who enrolled and completed follow-up, as reported by referred peers.
Time frame: 3 months
Population: Outcome only applies to cRCT referred peers who enrolled and completed follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| cRCT: Enhanced Group; Referred Peers (n) | cRCT: Linkage to Care | 17 Participants |
| cRCT: Standard Group; Referred Peers (n) | cRCT: Linkage to Care | 17 Participants |
Other Pre-specified
cRCT: Materials Received
Number of referred peers that received the intervention or standard-of-care materials, among referred peers who enrolled and completed follow-up, as reported by referred peers.
Time frame: 3 months
Population: Outcome only applies to cRCT referred peers who enrolled and completed follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| cRCT: Enhanced Group; Referred Peers (n) | cRCT: Materials Received | 46 Participants |
| cRCT: Standard Group; Referred Peers (n) | cRCT: Materials Received | 24 Participants |
Other Pre-specified
cRCT: PrEP Referral
Median number of referred peers referred to PrEP services by each index peer.
Time frame: 3 months
Population: Outcome only applies to cRCT index peers.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| cRCT: Enhanced Group; Referred Peers (n) | cRCT: PrEP Referral | 4.0 referred peers |
| cRCT: Standard Group; Referred Peers (n) | cRCT: PrEP Referral | 3.0 referred peers |
95% CI: [-0.2, 1.1]