Expanded Social Network Recruitment to HIV Testing (E-SNRHT) Intervention to Locate Undiagnosed Cases and Reduce HIV-related Stigma

Study Overview. The primary goal of the proposed study is to conduct a site-randomized trial (with Department of Health \[DoH\] clinics in the Msunduzi region of KwaZulu-Natal, South Africa as sites) to evaluate the efficacy of an expanded social network recruitment to HIV testing (E-SNRHT) intervention that is designed to extend the reach of HIV testing and care to groups and individuals that have been "hard-to-reach" for HIV testing, and to address HIV-related stigma as a barrier to HIV testing. Thirty-two participating DoH clinics will be randomly assigned to either the E-SNRHT intervention condition or to the control condition using urbanicity-stratified random assignment. People with newly-diagnosed HIV (PNDH) will then be recruited at participating clinics as "seeds" (i.e., initial study participants). After conducting brief education to remind them of HIV transmission risks and how HIV transmits through networks, seed participants in the intervention arm only (i.e., seeds recruited from an intervention condition-assigned clinic) will be asked to recruit members of their expanded social networks (e.g., friends, family members, acquaintances) who they think may be at risk of having undiagnosed HIV infection, or may otherwise benefit from HIV testing. All recruited network members will be tested for HIV, and will then be referred to additional HIV services: (i) those who test positive for HIV will be referred to antiretroviral treatment (ART) and offered support with appointment scheduling and navigating the clinic system, and (ii) those who test negative for HIV will be offered support to schedule follow-up HIV testing at 3 months and 6 months post baseline. This intervention not only aims (a) to increase rates of HIV testing and care among groups who test at low rates in this setting (specifically to men, who test in Msunduzi area clinics at much lower rates than women); and (b) to locate previously undiagnosed cases of HIV at higher rates than business as usual clinic testing; but also aims (c) to reduce HIV-related stigma and increase HIV-related social support through the process of peer recruitment, which will facilitate and normalize conversations about HIV and related services among peer networks. All participants will be interviewed and assessed at baseline, and will also be asked to complete 6-month follow-up interviews. A subset of 50 participants who are network members will also be asked to participate in in-depth qualitative interviews about their experiences being recruited to HIV testing by peers and recruiting their peers to HIV testing. Implementation data will also be collected based on the RE-AIM implementation science framework, in order to evaluate implementation success on key RE-AIM outcomes.

Recruitment Coupons. All recruitment of participants' network members in the intervention condition will occur via the distribution of recruitment coupons by participants. Coupons will contain unique, confidential alpha-numeric codes which will not contain any identifying information about the participant, but which will be used to link participants' social network members to them for analytic purposes. To protect participants' privacy, coupons will state only that the study is about "community health." Coupon design and language (and all study materials and procedures) will be reviewed and approved by UIC's and HSRC's IRBs and HSRC's Community Advisory Board (CAB) that HSRC maintains in the study locality, comprised of diverse, representative community stakeholders. The PIs will meet several times with the CAB during the recruitment period to report recruitment rates by site, to ensure there are no concerns with variation in recruitment being indicative of participants' discomfort with recruitment procedures at some sites.

Number and Characteristics of Participants to Be Enrolled. A planned total of 2,480 human subjects will be involved in the proposed research. Of these, 560 will be "seed" participants (i.e., original trial participants) who are newly-diagnosed with HIV (NDH), recruited from "business as usual" HIV testing at 32 Department of Health (DoH) clinics in the Msunduzi region of KwaZulu-Natal, South Africa. The remaining 1,920 participants will be the expanded social network members of intervention arm seeds, who will be recruited to the study by seed participants.

The 32 Department of Health clinics included in the study will include 10 clinics in urban areas, 10 clinics in suburban areas, and 12 clinics in rural areas. These 32 clinics will be randomly assigned to the expanded social network recruitment to HIV testing (E-SNRHT) intervention condition or to the control condition using urbanicity-stratified random assignment to ensure that conditions are balanced within each urbanicity type, before participant enrollment begins. Seed participants and the network members they recruit will therefore be enrolled into the study condition (intervention or control condition) already assigned to the clinic at which they (the seeds) were diagnosed with HIV and recruited to the study.

A planned 15 seeds from each of the 16 intervention clinics and 20 seeds from each of the 16 control clinics (240 intervention seeds + 320 control seeds = 560 total seeds) will be recruited. Seeds recruited from intervention condition clinics will be asked to recruit their expanded social network members to the study, and seeds recruited from control condition clinics will not. Specifically, seeds recruited from intervention clinics will be shown a diagram of how HIV spreads through a community and reminded of potential HIV transmission risk behaviors, and then asked to recruit anyone they know (e.g., friends, family members) who they think might be at risk of having undiagnosed HIV infection, or who they think might otherwise benefit from being tested for HIV, regardless of whether or not they have engaged in any HIV risk behaviors together. By including expanded social network members who participants perceive to be at risk of having undiagnosed HIV infection, this approach aims to broaden the reach of HIV testing to people who have previously been "hard-to-reach" for HIV testing.

Network member recruitment will follow a "two steps" algorithm for the E-SNRHT intervention arm, meaning that all participants who are recruited by intervention seeds (i.e., Step 1 network members) will also be asked to help the study recruit additional people they know who they think would benefit from HIV testing (i.e., Step 2 network members). If network members are not PNDH (i.e., people with undiagnosed HIV who are first diagnosed by the study team during the study), recruitment will end with Step 2 network members. However, a "2-steps from any PNDH" algorithm will also be used, such that if a Step 1 or Step 2 individual is found to be NDH, recruitment of people in his or her network will continue until two steps have been completed without recruiting another PNDH. This algorithm will maximize E-SNRHT's ability to locate PNDH and link them to care.

The Investigative Team's previous 2022-2023 pilot study of the intervention found an average network size of 6.5 network members for each seed. To account for the extension of network recruitment beyond Step 2 for networks that recruit PNDH (i.e., to account for the "2-steps from any PNDH" algorithm described above, which was not used in the pilot), total expected enrollment has been based on an average expected total network size of 8 network members per seed. The total approximate N of network members = 8 network members x 15 seeds x 16 sites = 1,920. The total anticipated sample is thus 2,480 (1,920 network members + 240 intervention seeds + 320 control seeds).

As stated above, participants will be recruited from clinics in the Msunduzi region. This region is comprised mostly of isiZulu- and English-speaking populations of Zulu heritage, but includes some areas with large English-speaking white and Indian populations. It is characterized by high HIV prevalence and incidence, high rates of unemployment, and low per capita income. Based on pilot data, up to 33% of network members are expected to be people living with HIV (15% PNDH \[i.e., people with previously undiagnosed HIV infection who will be diagnosed during the study\], plus up to 18% who were diagnosed with HIV before study participation, since participants are recruiting people they perceive to be at high risk for HIV but whose status they do not know).

Testing. At the time of the baseline interview, rapid HIV tests will be conducted for all network members. Before reviewing the results of the HIV test, pre-test counseling will be provided. After providing participants with their HIV test results, additional post-test counseling will also be provided. All participants who receive positive HIV test results will also receive a second, confirmatory HIV rapid test. All participants (including all seeds in both study arms) with diagnosed HIV infection will then be asked to provide a 5 milliliter (mL) blood sample for conducting a laboratory test of HIV viral load. Participants with diagnosed HIV infection will also be asked for 5 mL whole blood samples at the time of their 6-month follow-up interviews, for the purpose of measuring changes in viral load.

Referrals to Treatment or Additional HIV Testing. All participants who test positive for HIV will be referred to HIV treatment. After their interviews, E-SNRHT intervention arm participants who have been diagnosed with HIV (or were already aware that they were living with HIV) will be assisted by study referral staff in making clinic appointments. They will be given phone and email information to reach referral staff any time they need help in navigating the process of working with clinics to receive care. Approximately 2 months after their initial positive test, referral staff will contact them again to ask if they want additional help making follow-up appointments. All intervention arm participants who test negative for HIV at baseline will also be encouraged by study referral staff to schedule follow-up HIV testing appointments at a DoH clinic at 3-month intervals. All intervention arm participants will be assisted by study referral staff in making clinic appointments (for regular testing if they tested negative for HIV during the study, or for treatment if they have diagnosed HIV infection).

Baseline Quantitative Interviews. All participants will be interviewed about their sociodemographic characteristics, sexual and drug use behaviors during the last six months, previous use of HIV-related health services including antiretroviral therapy (ART - which is relevant since some network members may have long-diagnosed HIV infection), experiences of stigma and social support, and their perception of the level of HIV stigma in their communities. Audio computer-assisted structured interviewing (ACASI) will be u sed to ask questions about sensitive topics such as drug use and sexual behavior, such that participants will not have to answer these questions out loud.

Intervention arm participants who are asked to recruit network members (i.e., seeds and Step 1 network members) will be asked about the targeted members of their social networks who they will help recruit to the study. As described above, they will be asked to enumerate people in their expanded social networks (i.e., friends, family, peers, etc.) to recruit to the study who they believe might be at risk of having undiagnosed HIV infection, or would benefit from HIV testing. Participants asked to recruit others will be asked about the nature (i.e., type) and strength of their relationships to the network members they enumerate and plan to recruit, as well as about their basic descriptive characteristics like gender and approximate age. Their network members who enroll will also be asked about their relationship to the person who recruited them to the study.

All instruments

• Individual-level experiences of HIV-related social support [Срок оценки: baseline and 6-month follow-up]
• Participant antiretroviral treatment (ART) initiation [Срок оценки: 6-month follow-up]
• Clinic-level rates of antiretroviral treatment (ART) initiation [Срок оценки: 6-month follow-up]
• Participant HIV viral suppression [Срок оценки: 6-month follow-up]
• Clinic-level HIV rates of viral suppression [Срок оценки: 6-month follow-up]