In 2021, the majority of new HIV infections in the United States occurred in sexual minority men [1]. The US federal government targeted resources toward the goal of reducing new HIV infections by 75% by the year 2025 through the “Ending the HIV Epidemic” initiative [2] and highlights the prevention of new infections as a key component of the plan. While pre-exposure prophylaxis (PrEP) has been proven to reduce new HIV diagnoses at the population level [3,4], it remains an underused intervention. Preliminary evidence suggests that only 36% of people in the United States with an indication for PrEP received a prescription in 2022, up only slightly from 30% in 2021 [5]. Though PrEP coverage among sexual minority men at greatest risk for HIV in Seattle-King County, Washington approached 65% in 2021 [6], PrEP use remains low among younger people and some sexual minority men of color [4,6]. As part of its Ending the HIV Epidemic initiative, Public Health-Seattle and King County (PHSKC) aims to achieve ≥70% PrEP coverage among sexual minority men and transgender persons, with equal use among all racial and ethnic groups.

Structural barriers such as lack of access to PrEP medical providers and the burden of quarterly clinical monitoring visits have stymied PrEP scale-up in the United States for years [7-9]. PrEP retention (defined as maintaining all aspects of PrEP care, including attending follow-up visits and obtaining monitoring tests every 3 months according to US guidelines [10]) represents a substantial gap in the PrEP care continuum [11,12]. Studies on national PrEP retention rates suggest only 56% of individuals who initiate PrEP remain on PrEP for at least 1 year, and only 41% persist through year 2 [13]. Younger age, Black race, and unstable or lower income are each associated with discontinuations and being lost to follow-up [14]. We have observed similar levels of PrEP retention in the PHSKC Sexual Health Clinic (SHC), with 40% of PrEP users discontinuing the intervention at least once within 12 months [15]. The COVID-19 pandemic created dramatic reductions in sexual health service capacity [16] that only further exacerbated and continues to impact existing structural barriers that lead to lower PrEP access and higher numbers of discontinuations [17-19]. Among sexual minority men newly diagnosed with HIV in King County, previous PrEP use and discontinuations are common and underscore the urgent need to develop and implement novel targeted strategies to minimize barriers and provide individuals with more options to stay on PrEP [20].

Home-based PrEP (HB-PrEP), whereby an individual self-collects PrEP monitoring specimens at home, mails them into a laboratory for testing, and follows up with a provider remotely to renew PrEP prescriptions, has the potential to decrease PrEP access barriers and increase PrEP continuation rates. Studies confirm that patients are comfortable self-collecting bacterial sexually transmitted infection (STI) screening specimens [21] and that HB-PrEP monitoring is acceptable and often preferable to in-person care [11,22,23]. Configuring PrEP programs to users’ needs can optimize both uptake and delivery [24]. Particularly for young sexual minority men, programs that are convenient, discreet, and provide them with agency over PrEP use and monitoring may reduce the stigma associated with PrEP use, and increase PrEP uptake and retention [11,23]. Furthermore, HB-PrEP may decongest high-volume clinical sites and create additional capacity to grow PrEP programs.

Several direct-to-consumer companies [25] and fewer research or clinic-based PrEP programs provide PrEP services completely from home [22,23,26]. However, opportunities to adequately screen for newly acquired syphilis and HIV in the home setting are often limited. Given that STI incidence is high among people on PrEP, [27] the US Centers for Disease Control and Prevention guidelines recommend PrEP users be screened for STI quarterly, specifically for syphilis and HIV using assays with narrow windows from infection to test positivity [12]. Syphilis is highly associated with HIV acquisition in PrEP users; [28] thus, it is important that PrEP monitoring include tests that can distinguish new from old syphilis, such as with the quantitative rapid plasma reagin (RPR). Approximately 40% of PHSKC PrEP users have a history of syphilis, of which 25% are serofast (have a persistently positive RPR despite treatment in the past) and require a quantitative RPR for syphilis screening [29]. Although previous HB-PrEP studies used procedures that allowed PrEP users to collect all specimens (gonorrhea and chlamydia [GC and CT] swabs and blood samples) from home [22,26], nearly all require fingerstick specimens to perform a less accurate rapid HIV antibody test and collected insufficient blood volume to perform RPR titers, limiting the ability to determine whether titers were stable or indicative of newly acquired syphilis. We previously conducted a pilot study [29] that showed the acceptability and feasibility of using a novel blood self-collection device (formerly Tasso OnDemand, second-generation larger volume device Tasso+) [30] to obtain samples suitable for HIV antigen and antibody and quantitative RPR testing. However, whether these devices could be used successfully within a dedicated program for serial PrEP monitoring remains unknown.

Through a hybrid [31] randomized controlled trial (RCT), we aim to simultaneously evaluate the effectiveness of HB-PrEP as a strategy for improving PrEP retention and its implementation into an urban SHC’s existing PrEP program.

The specific aims of our study are to: (1) evaluate the impact of HB-PrEP on PrEP retention rates among groups assigned to either home-based monitoring or routine care and (2) assess the program’s reach and define the factors that influence HB-PrEP implementation.

The HOT4PrEP (Home Option Testing for PrEP) project is a series of interrelated studies designed to implement and evaluate an HB-PrEP monitoring system that includes the option for biological specimen self-collection at home and remote clinical follow-up in Seattle-King County, Washington. A detailed description of Tasso device use and results of preimplementation acceptability and feasibility analyses are published elsewhere [29]. The current phase of the HOT4PrEP project is an explanatory sequential mixed methods study consisting of 2 components, that are (1) a hybrid RCT wherein we evaluate HB-PrEP as an implementation strategy and its effect on PrEP retention over time along with other secondary outcomes, and (2) semistructured interviews with study participants and clinic staff to explore individual and system-level barriers and facilitators to HB-PrEP implementation.

For the first study component, we will enroll 458 participants from the PHSKC SHC and randomly assign participants 1:1 to either continue the PrEP standard of care ([SOC], control group) or to have an HB-PrEP monitoring option (intervention). Participants in both arms will complete serial web-based surveys and receive PrEP follow-up through telehealth or at the clinic (Textbox 1). At the time of trial conception, monitoring intervals were initially set at every 3 months; however, these changed to every 4 months in March 2023 following the SHC PrEP program’s shift to reduce the total number of required annual visits. HB-PrEP participants receive mailed sampling kits containing instructions and materials to collect extragenital (pharyngeal and rectal) GC and CT swabs and 2 devices to self-collect capillary blood from the upper arm into microtainer tubes. Participants mail kits through United Parcel Service to the PHSKC laboratory for creatinine, quantitative syphilis serologies, and fourth-generation HIV antigen/antibody testing. Secondary outcomes include reach (number of kits requested and used per participant), user satisfaction with the assigned PrEP monitoring program, STI incidence, and time from resulting of abnormal laboratory values to participant notification. Participation in this first RCT component is not incentivized.

For the second component of the study, we will use quantitative data from surveys to inform semistructured interview guides. In-depth interviews will take place with study participants, staff, and administrative personnel to determine factors associated with the program’s implementation.

The PHSKC SHC provides direct medical services related to sexual health and STI to over 6500 patients each year and is the largest single diagnosing site for HIV infection in the Pacific Northwest region of the US. Of all patients seen annually in the SHC, approximately 41% identify as sexual minority men and 42% as racial or ethnic minorities. Disease and research intervention specialists (DRIS), who are nonclinical public health staff trained in HIV and STI prevention and to provide partner services, currently serve as PrEP navigators and conduct all PrEP initiation and nonclinical monitoring visits in the SHC [32]. They will continue to fulfill this role during the study, augmenting their current work to manage HB-PrEP, and along with the lead research coordinator will help with eligibility screening, recruitment, and retention efforts.

The study is considered human subjects research. All study procedures were reviewed and approved by the University of Washington institutional review board (IRB; STUDY00013871) and considered not to pose any more than minimal risk to study participants. Informed consent forms describing all study procedures, potential risks, compensation (if applicable), and contact information for the IRB and study staff were available in English and Spanish. Participation in the first study component (home-based monitoring vs SOC with web-based surveys) is not compensated. Patients and staff who participate in interviews for the qualitative study component will receive US $25 compensation.

All study staff are required to uphold strict confidentiality in accordance with the HIPAA. Only the information necessary to conduct the clinical trial or coordinate clinical care with providers will be viewed or used by authorized study staff. Home kits are in nonlabeled, plain boxes with no external information to identify study participants. Identifiable data is kept on an approved and password-locked database and only linked with indirect identifiers. Contributions in qualitative interviews will be deidentified and only general information used to derive themes for analysis.

The HOT4PrEP trial is a hybrid implementation study that randomizes new or current HIV PrEP patients at the Sexual Health Clinic in Seattle, Washington, to have the option of home-based monitoring with self-collection of samples for HIV, syphilis, gonorrhea, chlamydia and creatinine and telehealth follow-up versus standard care including in-clinic visits and monitoring. The primary outcome is PrEP retention at 20 months.

Enrollment for the trial began in March 2022 and continued through May 2022 when all research was halted in the SHC to focus on the emerging mpox outbreak. Study enrollment then resumed in December 2022 and is ongoing.

From March 2022 to May 2023, a total of 161 PrEP patients were screened to enroll the first 100 participants into the intervention arm (49/100, 49%) or standard care arm (51/100, 51%). In total, 2 PrEP patients (1.2%) were deemed ineligible to enroll, 55 (34%) declined to participate, and staff were not able to discuss enrollment with 4 (2.5%) patients. Common reasons for declining to participate included preferring to come into the clinic or having an aversion to seeing blood during the self-collection process.

Table 1 describes demographics and other baseline characteristics participants self-reported upon enrollment. The baseline survey completion rate was 96% for both trial arms. Median age was 34 (IQR 28-39, range 19-67) years. Of the participants who elected to provide sex and gender information, all were assigned male sex at birth (47/47, 100%). Most identified as cisgender men (41/47, 87%), gay (42/47, 89%), and their race and ethnicity as non-Hispanic White (n=36, 38%) or Asian (n=23, 24%). Most participants reported an annual income of US $30,000 or more (75%) and at least some college education (91%).

All participants in the intervention arm were contacted before their 4-month follow-up visit to ask if they would prefer to come into clinic or receive home kits. Of the 49 participants contacted, 33 (67%) opted to collect samples at home and follow up through telehealth, 14 (29%) opted to come in person to the clinic, and 2 (4%) canceled their appointments. Of those who opted for home sample collection and telehealth follow up, 27 (82%) returned test kits with samples for HIV and STI testing, 5 (15%) came in person to the clinic for their visit, and 1 (3%) canceled their appointment.

Preliminary data from the first 100 participants of this hybrid RCT suggest that thus far, the implementation strategy of HB-PrEP monitoring, consisting of self-collected GC and CT swabs, blood specimens obtained using the Tasso device, and telehealth follow-up, is acceptable to users and feasible to incorporate into a busy PrEP clinic. Though results are preliminary, reach appears to be high among participants randomized to the intervention arm. Two-thirds of participants who were offered the option of HB-PrEP chose to use it, and of those who received kits, 27 (82%) successfully returned kits containing samples sufficient to complete their requisite PrEP monitoring laboratory tests.

Our initial pilot study undertaken during the COVID-19 pandemic (2020-2021) found that 98 (80%) of surveyed patients in our clinic preferred home-based services over coming into the clinic. Some studies conducted in the prepandemic era [22,23,40] and another completed more recently among men who have sex with men in a Dutch sexual health center [41] came to similar conclusions about the preference for home-based sampling. However, at least 1 other study conducted in a real-world pharmacy-based PrEP program found that less than half of participants used home kits when offered them [26]. Factors affecting a participants’ decision to do home sampling over coming to the clinic may be variable and depend on one’s self-efficacy and assessments of potential risks (eg, breach of privacy) versus benefits (eg, increased convenience and saved time) [26]. While our preliminary results of home kit uptake are promising, it remains to be seen if stated preference or intention to self-collect samples at home will equate to consistent use over time. Survey data and interviews of participants will aim to identify reasons motivating choice over time.

Our trial faces a few challenges and limitations. Interpretation of preliminary results remains limited given that enrollment in the randomized portion of the trial is ongoing. Study staff are recruiting for the qualitative component of the study, and analyses of preliminary PrEP retention rates at 4 and 8 months and secondary outcomes are also underway. While the initial cohort is diverse from a racial and ethnic standpoint, other demographics and characteristics may not represent groups of PrEP patients in other settings. Our clinic is large, serves an urban population, and is fairly well-resourced; thus, results may not be generalizable to smaller clinics in less populous or less well-resourced areas. We will not be able to verify that returned samples came from the enrolled participant, but we do not anticipate this to be a significant problem since abnormal or positive test results will require an in-person clinic visit for confirmatory retesting and treatment. Finally, the first component of our RCT is not incentivized which may be associated with decreasing engagement over time with study procedures (eg, survey completion). However, this trial was designed to be pragmatic with study procedures that could be reproducible for similar clinics where routine PrEP care is not incentivized in the real world. Despite these challenges, we feel the study seeks to answer important questions and will yield useful information about the utility, barriers, and facilitators of this implementation strategy for expanding PrEP access locally and beyond.

While not every person may choose to use a home-based option for every PrEP follow-up visit, HB-PrEP holds promise as a strategy to decrease barriers for staying on PrEP, increase patient autonomy and accessibility, and expand the capacity of clinics to initiate and maintain a greater number of people on PrEP. In turn, if successful even for a proportion of users, HB-PrEP has the potential to contribute to larger efforts to end the HIV epidemic by increasing PrEP uptake and retention. Our results will provide important information about the feasibility and value of implementing HB-PrEP into growing programs seeking to strike a balance between expanding PrEP access, maintaining capacity for in-person services, and facilitating patient choice and convenience.