Peer Delivered HIV/Syphilis Self-Testing With Assisted Partner Notification Services

Men who engage in sexual relations with other men (MSM)(1) are disproportionately affected by HIV and syphilis. Globally, gay men and other men who have sex with men have 28 times greater risk of HIV acquisition than adult men (15-49 years) in the general population.(2). Syphilis and HIV disproportionately affect MSM because of sexual network dynamics that include high-risk sexual practices and multiple sex partners.(3,4). HIV and syphilis co-infection is common because syphilis and HIV have similar modes of transmission(5,6). Having syphilis is associated with a 3-fold increased risk of HIV acquisition.(7,8); syphilis also increases the risk of HIV transmission and disease progression(9). The resurgence of syphilis among MSM globally(10,11) is attributed to increasing rates of risky sexual behaviors, such as anonymous sex, oral and anal condomless sex, sex with multiple partners, and/or sex under the influence of drugs(5,12). In 2013, the United States estimated that 46% of MSM with primary and secondary syphilis had HIV, compared to 8% of heterosexual men and 6% of women.(6). In sub-Saharan Africa, 6% of new HIV infections occurred among MSM in 2021(13). In Uganda, HIV prevalence among MSM was 13.2% in 2012 compared to 4.7% in similarly-aged males. (14,15).. Of the 41,655 syphilis cases reported in the United States in 2020, 43% were among MSM(16). In 2016, syphilis prevalence among MSM in Uganda was estimated at 9.0%(17) compared with 5.8% in males aged 15-64 years(14,15). Ugandan national 2020 guidelines for HIV prevention and care recommend annual STI testing as a strategy for STI prevention among MSM and their sexual networks, but uptake of facility-based STI testing is low (32%) of the estimated MSM population in Kampala. (14,15) ,(18). To achieve the WHO Global Health Sector Strategy goal of reducing syphilis incidence by 90% by 2030(19), and the first UNAIDS 95-95-95 goal of 95% of persons with HIV knowing their status by 2025(20), scaling up HIV/syphilis testing is critical to reaching undiagnosed MSM.

1.2. HIV/syphilis testing is the entry point to treatment and prevention services The World Health Organization (WHO) recommends dual HIV/syphilis testing for MSM.(21). Increasing testing coverage is key to reaching the first UNAIDS 95-95-95 target and reducing disease incidence.(13,20). Early detection, timely linkage to care and other prevention services, and identification of sexual contacts reduced HIV transmission by 89% among MSM in Bangkok.(22). However, current testing strategies in sub-Saharan Africa only reach men who are not at high risk of HIV and/or already tested for HIV and are thus low yield: 2.4% HIV positivity for provider-initiated testing, 2.9% positivity for voluntary counseling and testing, and 3.1% positivity for mobile testing approaches.(7). Thus, identifying high-yield strategies for dual HIV/syphilis testing that effectively reach MSM in the riskiest sexual networks is key.(23). In Uganda, HIV/syphilis testing uptake is still low among MSM despite efforts to scale up prevention services for this population.(23). A recent bio-behavioral survey in 2020 estimated that there were 202,343 undiagnosed HIV infections in Uganda, of which 44% were in men, mostly MSM and their sexual contacts.(24). Data on syphilis test uptake and coverage among MSM in Uganda are lacking.(15). In contrast, syphilis test coverage among pregnant women attending antenatal clinics is \>80%(25). This high coverage is part of a comprehensive dual HIV/syphilis elimination strategy using the SD BIOLINE HIV/syphilis Duo assay.(26,27). This assay is available at health facilities that are not friendly to MSM because of stigma and discrimination. Decentralized testing and community-based approaches could improve dual HIV/syphilis test uptake in this population.

1.3. Self-testing is feasible and acceptable to MSM Self-administered HIV self-tests (HIVST) and syphilis self-tests (permit the user to interpret test results by themselves in private (28). A scoping review of 11 studies in sub-Saharan Africa found that HIVST was feasible and acceptable to MSM (29). Studies among MSM in China(30,31) have shown that syphilis self-testing may increase testing frequency by empowering MSM to test and reducing the impact of structural barriers(32), but data from sub-Saharan Africa are limited. Combining HIVST and syphilis self-testing with peer delivery offers a unique opportunity to reach MSM with user-friendly technology in their communities. This strategy could overcome some of the barriers associated with facility-based testing, and promote early diagnosis and linkage to prevention services. As demonstrated with at-home COVID-19 testing, HIV and syphilis self-testing could sustain testing services when health facilities are inaccessible or inconvenient(33).

1.4. Peer-delivered self-tests can efficiently reach MSM and their social networks Peer approaches are recommended by the WHO for HIV testing.(30,34) and can be leveraged for dual HIV/syphilis testing. Peer delivery is a person-centered approach that could maximize the coverage, effectiveness, efficiency, and impact of HIV/syphilis services for MSM in Uganda. Peers are non-clinically trained persons with similar background characteristics to the beneficiary population. (34). Peer-led outreach services reach more MSM than traditional approaches by generating demand in the community and tapping into MSM social networks.(35,36). In Zimbabwe, peer-delivered syphilis self-testing was highly acceptable (89.6%), increased privacy, convenience, and autonomy, and helped circumvent social and healthcare provider stigma.(37). Our prior work found that peer-delivery of HIV self-tests was acceptable to 90% of MSM in Uganda.(38,39). All newly diagnosed participants with HIV infection were linked successfully to receive confirmatory testing at a friendly health facility and linked to treatment using a peer-assisted linkage model.(38). Thus, HIVST and syphilis self-testing linked with partner services may empower MSM and expand testing uptake and coverage.(1).

1.5. Integrating assisted partner notification with peer-led self-testing approaches could accelerate prevention uptake among MSM Assisted partner notification is an evidence-based strategy in which a trained provider encourages persons with an HIV/STI diagnosis to disclose their status to their sexual partners. Assisted partner notification is recommended by WHO, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), and the Uganda Ministry of Health and offers testing services to sexual partners of index cases with their consent(40,41). Assisted partner notification is acceptable and feasible(42-45) and increases testing uptake among sexual partners(42,45,46), enables early diagnosis, and linkage to care and other prevention services, motivates behavior change in index cases and partners, and may reduce STI and HIV burden(42-45). A pilot partner services program in rural Uganda that enrolled 464 people with HIV (PWH) and tested their recent sexual partners found that 32% (61/193) of sexual partners who were traced and tested had HIV(46). A mathematical modeling study in South Africa found that assisted partner notification could enable the identification of new HIV diagnoses among MSM(47). Similarly, a combination of assisted partner notification, HIVST, and community worker outreach was acceptable and feasible in Kenya(48) and increased uptake of HIV testing and linkage to care and PrEP among MSM and their sexual partners(48,49). A systematic review of 26 trials found that assisted partner notification identified more undiagnosed syphilis cases than passive notification(50). Thus, partner services could efficiently identify MSM with undiagnosed HIV and syphilis and help reach the first UNAIDS 95 target and global syphilis elimination goals.

1.6. Cost-effectiveness analysis is critical in designing a scalable prevention strategy HIVST and syphilis self-testing was highly acceptable to MSM in 10 studies(37,51-60). Peer-delivered combination prevention campaigns have identified undiagnosed HIV infections, linked people with HIV to care and those without HIV to other prevention strategies such as pre-exposure prophylaxis (PrEP)(61,62). However, in many regions like Uganda, where HIV prevalence has experienced substantial declines and is concentrated in key populations (KP)(63)Standard HIV testing approaches are inefficient.(7), incurring higher costs and yielding fewer HIV and syphilis infections detected per number of KP tested(7,64). However, targeted testing for MSM and assisted partner notification is cost-saving (median of $20 per life-year saved) compared with the secondary distribution of self-tests to partners of pregnant women (median of $130 per life-year saved)(47). Peer approaches can improve efficiency and contain costs by testing MSM at high risk of HIV and syphilis. Therefore, cost-effectiveness analyses evaluating peer-delivered combination approaches linked with partner services are needed to inform guidelines and interventions that can be scaled up.

1.1. Background and rationale Joint delivery of peer-delivered HIV/syphilis self-tests with assisted partner notification is an empowering, innovative approach that could substantially increase testing among MSM in Uganda and help achieve global HIV 95:95:95 targets (95% of people who know their status on treatment and 95% of people on treatment with suppressed viral loads). However, no studies to our knowledge have evaluated the effectiveness of peer-delivered HIV/syphilis self-tests and assisted partner notification services for MSM in any setting. The proposed work is uniquely positioned to improve prevention uptake for MSM, a high-risk, marginalized, and underserved population. This pilot study will be among the first to measure the benefits and cost-effectiveness of using a peer-delivered combination prevention strategy among MSM to scale up HIV, syphilis self-testing, and assisted partner notification strategies and will inform program costs.

1.7. Preliminary data This approach builds from our pilot study of MSM peer-driven distribution of HIVST to sexual networks.(54,65,66) (Table 1). Our work found that peer-delivery of HIVST was acceptable to 90% of MSM in our population tested in Uganda(54). All undiagnosed MSM with HIV received confirmatory testing, were linked to care, and started on treatment. Overall, peer delivery of HIVST resulted in higher HIV positivity yield (4.9 vs. 1.4%) and could avert more HIV infections per quarter compared with facility-based testing(66).

1.8. Study setting This study will be conducted in Kampala and Wakiso districts as study recruitment districts. In these districts, through a PEPFAR grant. IDI manages a network of 200 key population peers across Kampala and Wakiso districts to improve HIV outcomes (identification, linkage, retention, and viral suppression) along the care cascade. Peers are assigned to high-volume key population facilities, drop-in centers and community venues. Peer capacity building occurs through tailored HIV-related training, mentorships, and site support supervision. Peers also support the demand for the creation and distribution of HIVST kits to their social network members. Peer distributors receive three-day training focused on self-test kit use, the importance of HIV-positive result confirmation, inventory management of test kits including storage and documentation, HIV counseling, and linkage to care. Telephone numbers for both peers and key populations that received HIVST kits are recorded with consent for follow-up purposes. All HIVST kits are recorded in the national HIV self-test kit distribution log. Recipients who don't report results within two days are followed up through a phone call by a trained health worker. Recipients who reported HIV-positive results are offered confirmatory testing at the nearest health facility of their choice. T