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Background
With shorter window periods than serologic point-of-care (POC) tests and faster turnaround than laboratory-based nucleic acid tests (NAT), POC NATs could improve early detection of HIV. Furthermore, semiquantitative POC NAT may provide real-time monitoring for persons with HIV. There have been limited evaluations of POC NAT implementation in the United States.
Objective
This paper describes the protocols and procedures used to evaluate the acceptability and feasibility of POC NAT implementation and test performance in clinical and community settings in Seattle, Washington.
Methods
The Greater Access and Impact through POC NAT (GAIN) study was a Centers for Disease Control and Prevention–funded study that enrolled participants at a Ryan White–funded, hospital-based clinic (Madison Clinic) and a community site (Seattle’s LGBTQ+ Center [the Center]). Persons seeking HIV testing, nonoccupational postexposure prophylaxis, or pre-exposure prophylaxis (PrEP) enrolled at either site received the standard of care plus the SAMBA II HIV-1 Qualitative Whole Blood Test (SAMBA Qual) and pooled laboratory HIV NAT, and persons with HIV enrolled at the Center received standard-of-care sexually transmitted infection testing plus the SAMBA II HIV-1 Semiquantitative Whole Blood Test (SAMBA Semi-Q) and laboratory viral load testing. Persons with HIV from Madison Clinic were recruited into a randomized clinical trial (RCT) to compare the clinical standard of care with the addition of the SAMBA Semi-Q (backed up by Food and Drug Administration–approved laboratory NAT). All participants completed a demographic survey during their study visit and contributed prospective data via electronic medical records. Subsets of participants from each group were invited to complete a postvisit acceptability survey and participate in an individual interview. Patient flow was observed at Madison Clinic to assess the impact of POC testing on clinic visit timing.
Results
From January 2022 to December 2024, 733 participants completed 753 GAIN research visits. Of those, 491 visits were completed by 489 participants seeking HIV testing and/or PrEP at the Center, and 61 visits were completed by 43 participants seeking HIV testing, nonoccupational postexposure prophylaxis, and/or PrEP at Madison Clinic. Test result data will assess test performance, with analyses anticipated in 2027. Seven people with HIV were enrolled at the Center, and 194 people with HIV were enrolled in the Madison Clinic RCT. Data from patients with HIV at Madison Clinic will be used to conduct a survival analysis evaluating the impact of POC NAT on time to viral suppression and to assess test performance, with analyses anticipated in 2026. In-depth acceptability surveys were completed by 193 participants, and 41 interviews were conducted. These data will contribute to qualitative and mixed methods analyses, which are anticipated in 2026. Time-and-motion observations conducted in 2021 and 2023 included 47 patients; results are anticipated in 2026.
Conclusions
The GAIN study is an important evaluation of POC NAT implementation in the United States in community and clinical care settings for HIV diagnosis and viral load monitoring. Results will be reported in future publications.
HIV testing is the critical entry point for the status neutral continuum of care. HIV screening allows for early detection of new HIV infections and linkage of individuals to care and initiate treatment quickly, which can prevent further transmission [1-5]. Furthermore, HIV testing is an important entry point for pre-exposure prophylaxis (PrEP) and is an essential PrEP monitoring tool [6]. Laboratory-based HIV testing can be highly sensitive, but results can take days or weeks and are less likely to be returned to a patient compared to point-of-care (POC) tests [7-9]. In contrast, the POC tests currently approved by the Food and Drug Administration (FDA) provide results in minutes, but they have longer window periods and are therefore more likely to misdiagnose persons with acute HIV infection (AHI) [9-20]. POC nucleic acid tests (NATs) have shorter window periods and can provide a result in about 2 hours, which makes them a promising tool to help identify AHI and provide rapid HIV testing for patients receiving PrEP [21]. No POC NAT is currently FDA-approved, although several are approved for use outside of the United States for early infant and adult diagnosis and viral load monitoring [22-24,25,26]. One study has evaluated POC NAT for HIV testing in the United States, finding that the POC NAT had comparable results to standard-of-care laboratory tests, and staff found the test acceptable, while noting that test timing, cost, and other logistical barriers may remain to implementation in the United States [27]. Staff noted in that study that the POC NAT could provide particular benefit for patients who experience barriers to care and follow-up [27].
For people with HIV, viral load monitoring is a critical component of HIV care, yet laboratory-based viral load testing does not provide real-time feedback while a patient is in the clinic. One study in South Africa suggested that providing results of a near-POC NAT along with tailored counseling was associated with improved care outcomes at 12 months [28,29]. Other studies in Africa have also found that POC NAT allowed for more rapid result delivery, more rapid treatment adjustments, was motivating for patient adherence, and supported patient emotional well-being [30-34]. If implemented in the United States, POC NATs could provide a similar opportunity to provide immediate feedback on viral load levels and tailored adherence counseling [35]. No studies on the implementation of POC NAT for viral load monitoring currently exist in the United States, but formative qualitative work by this group found that providers thought POC NAT would be acceptable, although integration into clinic flow could be a challenge [36], given that most patients spend less time in clinic than the POC NAT turnaround time (TAT) [37].
In 2019, the Centers for Disease Control and Prevention awarded the University of Washington (UW) research funding to conduct the Greater Access and Impact through POC NAT (GAIN) study. The aims of the study are to (1) assess the feasibility of POC NAT implementation among HIV testing programs, (2) evaluate POC NAT sensitivity, specificity, and clinical outcomes, (3) evaluate the impact of a semiquantitative POC NAT on time to virologic suppression among people with HIV in a clinical setting and assess the feasibility of viral load testing in a community setting among people with HIV, and (4) to describe the feasibility of POC NAT implementation in a clinical setting and assess the acceptability of the POC NAT among participants and care providers. In this paper, we will describe the protocols designed to achieve each of these aims, describe participants enrolled, and the planned timelines for data analyses and publication of results.
MethodsDescription of the Protocol for the GAIN Study
The GAIN study consists of 4 study aims, enrolling study populations at 2 sites (Figure 1). Baseline data obtained from the preenrollment period among nonstudy participants at both sites provided a retrospective preimplementation dataset for comparison with the study participants. Aim 1 evaluated the implementation of the SAMBA II HIV-1 Qual (SAMBA Qual, Diagnostics for the Real World Ltd, Morgan Hill, California, United States) among HIV testing programs via a longitudinal, prospective study of persons without HIV seeking HIV testing, nonoccupational postexposure prophylaxis (nPEP), and PrEP care at Seattle’s LGBTQ+ Center (the Center) and Madison Clinic. Aim 2 evaluated the sensitivity, specificity, and clinical outcomes using the data collected as a part of Aim 1. Aim 3 evaluated the impact of the SAMBA II HIV-1 Semiquantitative (SAMBA Semi-Q, Diagnostics for the Real World Ltd, Morgan Hill, California, United States) on time to virologic suppression via a randomized controlled trial (RCT; NCT04880200), for people with HIV at Madison Clinic and assessed the acceptability of viral load testing outside of a clinical setting among any people with HIV seeking sexually transmitted infection (STI) testing at the Center. Aim 4 examined acceptability and feasibility of the POC NAT using surveys and in-depth interviews with participants and care providers. Finally, a systems engineering component of the study conducted time and motion observations of patient flow through Madison Clinic at one time point preimplementation and 2 time points postimplementation, informed study implementation, and provided information about the impact of POC testing on clinic flow.
Greater Access and Impact through Point-of-Care Nucleic Acid Test (GAIN) study procedures and total participant visits by aim. CASI (computer-assisted self-interview); EDTA (Ethylenediaminetetraacetic acid); FS (fingerstick); HIPAA (Health Insurance Portability and Accountability); NAT (nucleic acid test); PCP (primary care provider); nPEP (non-occupational postexposure prophylaxis); POC (point of care); PrEP (pre-exposure prophylaxis); ROI (release of information); STI (sexually transmitted infection)
Study Sites
The Center is a community-based organization located in Seattle, Washington, that was established in 1995 and was formerly known as Gay City. The Center’s PrEP program was started by Dr Stekler in 2013 and served as a safety net clinic to link patients to ongoing PrEP care [38].
Madison Clinic is the largest provider of HIV care in Washington State and also offers HIV testing, PEP, and PrEP services. It was established in 1985 and is Ryan White-funded. Madison Clinic also hosts the Moderate Needs Subclinic, or the Moderate Needs (MOD) Clinic. [39] This drop-in subclinic is modeled on the Max Clinic, aimed at engaging the hardest-to-reach people with HIV in need of services [40]. The GAIN study enrolled both patients at Madison Clinic and MOD Clinic. The RCT initially prioritized patients at the MOD Clinic in order to recruit people living with HIV who were more likely to have detectable viral loads but expanded in January 2024 to include additional providers and patients at Madison Clinic.
POC NAT Selection
During protocol development, the study team considered available POC NATs to identify which test or tests could be used by the GAIN study. Tests considered included the Alere q 1/2 DETECT qualitative [25] and Alere q NAT quantitative [26], the Cepheid Xpert HIV-1 Qualitative [23] and Cepheid Xpert HIV-1 Viral Load XC [41], and the DRW SAMBA Qual [42] and SAMBA Semi-Q [22]. Factors considered included specimen type, volume required, result type, limit of detection, and TAT. The DRW SAMBA tests were selected because they are truly POC, have no requirement for centrifuging (a requirement for the Cepheid Xpert HIV-q Viral Load), and can be performed on fingerstick blood specimens. The SAMBA tests take up to 2 hours to return a result.
Study Populations and RecruitmentGAIN Baseline Data
GAIN baseline datasets were obtained retrospectively to describe the preimplementation populations and outcomes at the Center and Madison Clinic from January 2019 through December 2021. The Center provided a deidentified dataset that linked clients via a dummy identification number across multiple datasets in Access, Google Forms, and InSync electronic medical record (EMR) software. All dates were uniformly time-shifted before transmission to the study team to further deidentify the dataset. Data variables included demographics, HIV and STI testing, and PrEP care.
In order to obtain the Madison Clinic EMR data, we hired the Institute of Translational Health Sciences (ITHS) to pull and deidentify the requested data from the Clinic’s medical record system. ITHS is a collaborative research hub that supports researchers, health care providers, and community organizations working to advance translational science [43]. The study team provided a list of desired variables and worked with ITHS to use these variables to identify visit types for the patients of interest in the time frame of January 2019 through December 2021. These patient types included HIV testing visits, PrEP visits, nPEP visits, patients newly diagnosed with HIV, and patients in HIV care with a detectable viral load. The data were deidentified by creating a dummy identification number, and dates were uniformly time-shifted by an amount unknown to the study team. Data variables included basic demographics, HIV and STI testing, estimated creatinine clearance, viral load testing, and prescribed medications.
Additional data on patients receiving PrEP at Madison Clinic was obtained from the PrEP patient-reported outcomes dataset, a computer-administered self-interview (CASI) on a web-based platform developed for the Center for AIDS Research Network of Integrated Clinical Systems and administered to consenting patients receiving PrEP at 6-month intervals [44]. This dataset included information on adherence and substance use.
GAIN Aims 1 and 2 Eligibility (Implement POC NAT Among HIV Testing Programs and Evaluate the Sensitivity, Specificity, and Clinical Outcomes)
Participants were recruited for Aims 1 and 2 if they were at least 18 years old, proficient in English, and seeking HIV testing or PrEP care at the Center or HIV testing, nPEP, or PrEP at Madison Clinic. Participants could not be enrolled if they were testing anonymously. Testing and nPEP participants could be seen only once unless they initiated PrEP. Participants on PrEP could reenroll in the study at any PrEP follow-up visits. We call this group “participants seeking HIV testing.”
GAIN Aim 3 Eligibility (Evaluate the Impact of a Semiquantitative POC NAT on Time to Virologic Suppression Among People Living With HIV in a Clinical Setting and Assess Acceptability of Viral Load Testing in a Community Setting Among People Living With HIV)
Participants were recruited for Aim 3 if they were at least 18 years old, proficient in English, living with HIV, and seeking STI testing at the Center or HIV care at the Madison Clinic or MOD Clinic. These patients were only eligible to participate in the study once.
GAIN Aim 4 Eligibility (Describe the Feasibility of POC NAT Implementation in a Clinical Setting and Quantify Acceptability and Feasibility of the POC NAT Among Participants and Care Providers)
Participants completing a GAIN study visit were eligible to participate in a postvisit online acceptability survey. Participants who completed this postvisit survey were eligible to participate in a follow-up in-depth interview with study staff. Repeat study participants were invited only once to the acceptability survey and interview. Procedures and recruitment for care provider interviews have previously been described [36].
Time and Motion Eligibility
Any Madison Clinic or MOD Clinic patient was eligible to be observed by study staff during their clinic visit to assess pre- and post-study implementation clinic flow.
Recruitment Strategies
Participants were screened and approached regarding participation by study staff or provider referral. Patients at Madison Clinic could be called via phone in advance by study staff after chart review for eligibility, and patients at both sites were approached in the waiting room about study participation. A “priority score” was also developed using demographic and behavioral questions from a Center intake form for use in prioritizing clients at the Center for PrEP care and the GAIN study. Development and implementation of this priority score will be described separately.
For participants seeking HIV testing from the Center, we prioritized clients with a reactive POC antibody HIV test, those with any symptoms of AHI, and those who scored high on the priority score. For participants seeking HIV at Madison Clinic, we prioritized enrollment of patients seeking HIV testing and those seeking nPEP. Our recruitment target for these groups was 700 clients from the Center and 150 patients at Madison Clinic.
We aimed to recruit all people with HIV seeking STI testing at the Center. For people with HIV at Madison Clinic, we prioritized patients with low adherence and/or detectable viremia. Study staff attempted to conduct the study visit for these participants before their regular clinic visit, to initiate the POC NAT as soon as possible and maximize the chance that the participant might still be in clinic to receive their result in person. Our recruitment target for these groups was 50 clients at the Center and 212 patients at Madison Clinic.
Participants were invited during their study visit to participate in the extra survey and interview immediately after the study visit or on a later date. Our recruitment target for survey participation was 50 participants seeking HIV testing at each site and 50 people with HIV at each site. Our recruitment target for interview participation was 20 total participants seeking testing (at either site) and 20 total participants with HIV (at either site).
Study ProceduresGAIN Participants Seeking HIV Testing at Both Sites and Participants With HIV at the Center
Enrollment began in January 2022 for patients seeking HIV testing and March 2022 for people with HIV to give study staff time to achieve proficiency in one set of study procedures before adding another group. Participants signed a bi-directional release of information allowing the study team to obtain follow-up data for the year following the study visit and document research test results in the patient EMR. Study staff then completed a linking survey on a secure server including patient identifiable information and the study record of the participant. Then the participant completed a brief study visit survey in REDCap (Research Electronic Data Capture; Vanderbilt University) with demographic questions linked only to the participant’s study record.
After completing study paperwork, study staff collected fingerstick whole blood for the POC NAT. For participants seeking HIV testing, we used the SAMBA Qual, which provides a negative or positive result. European Union–approved materials state that the SAMBA Qual can detect as low as 400 copies of virus as early as 10 days after exposure [42,45]. For participants with HIV, we used the SAMBA Semi-Q, which provides a result of greater or less than 1000 copies per milliliter of blood [22]. Both versions of the test return a result in approximately 2 hours, and neither test is FDA approved. In June 2023, after a series of false-positive test results, we added a second SAMBA Qual using venipuncture whole blood for the participants seeking HIV testing at the Center to provide an additional backup to the fingerstick test.
Study staff collected specimens for all research tests and, if possible, any clinically indicated laboratory tests. HIV testing participants completed standard-of-care HIV testing as part of their visit at both sites, which could include the INSTI HIV-1/HIV-2 Antibody Test (bioLytical Laboratories, Inc) on a fingerstick specimen and/or the laboratory-based HIV-1/HIV-2 Combo enzyme immunoassay (Bio-Rad Laboratories, Inc). Reactive samples were confirmed using the Geenius HIV-1/2 Supplemental Assay (Bio-Rad Laboratories) with reflex testing via the RealTime HIV-1 viral load assay (Abbott Laboratories; for participants seen before November 2023) or the Cobas HIV-1 viral load assay (Roche Diagnostics; for participants seen in November 2023 and after), as appropriate. Laboratory testing was done at the Public Health–Seattle & King County Laboratory and the UW Virology Laboratory.
Initially, a 10 mL serum tube was collected for research HIV testing participants; in June 2023, this changed for participants at the Center to a 4 mL EDTA tube and a 6 mL serum tube to allow for running the SAMBA Qual on venipuncture blood and the laboratory testing on the serum tube. If all screening tests were negative, research laboratory testing also included a laboratory NAT pooled into a single 10-member pool and tested using the RealTime HIV-1 viral load assay (Abbott Laboratories; for participants seen before November 2023) or the Cobas HIV-1 viral load assay (Roche Diagnostics; for participants seen in November 2023 and after). If any screening HIV test was positive, a quantitative HIV-1 RNA test was performed. HIV-positive research participants at the Center had a 10 mL EDTA tube drawn for a laboratory NAT. For all research participants, pooled NAT or individual NAT was performed as the laboratory gold standard for backup of the non-FDA approved SAMBA test [46].
Research and clinic procedures took approximately 1 hour, except for the POC NAT result, and participants were given the option to remain in the clinic to await these results. If the participant was still in the clinic when their POC NAT result was ready, study staff delivered the result to the participant in person. If the participant had left the clinic, they were only notified of their result via a phone call from study staff for unexpected results (ie, a positive SAMBA Qual or a SAMBA Semi-Q result greater than 1000 copies in someone who was expecting to be undetectable). Otherwise, the research results were noted in the EMR, along with clinic laboratory HIV test results. Laboratory results were usually available via the EMR in 5 to 10 business days. Results of the laboratory NAT obtained by the research team were communicated to participants only if test results were discordant. Study staff provided counseling and referrals as appropriate.
Participants at the Center received follow-up phone calls at 1, 3, and 6 months after their study visit in order to check whether they had initiated PrEP (if they tested HIV negative) or linked to HIV care, initiated antiretroviral therapy (ART), and whether they knew their viral load status (if they tested positive for HIV). Staff stopped calling participants at subsequent follow-up time points if they indicated they had initiated PrEP or linked to HIV care. Study staff also obtained follow-up data from Center participants’ EMRs by providing the Center with a list of participants’ medical record numbers, which Center staff used to provide participant follow-up data back to the study team.
Madison Clinic participant follow-up data were captured through patient medical records obtained and transferred monthly to the study staff by ITHS via REDCap. The study team also obtained data on PrEP study participants from the PrEP patient-reported outcomes dataset.
GAIN Participants With HIV in the Madison Clinic RCT
Participants in the RCT signed a release of information and completed the linking survey and study visit survey as described above [36]. Then participants in this group were randomized by 1:1, variable-block-size randomization to either receive either the clinic standard of care or the standard of care plus the SAMBA Semi-Q and tailored counseling.
Beginning in April 2023, study staff also performed venipuncture for participants in both arms and drew a 10 mL EDTA tube for a study laboratory NAT and, if possible, for the convenience of the participant, any additional tubes for clinical purposes. This change was made to ensure that all persons had an FDA-approved NAT that could be used as the primary way to guide clinical decision-making.
For participants in both arms, study staff obtained follow-up data from ITHS to monitor patient outcomes for 1 year after the study visit. Viral loads were obtained from the standard-of-care group at the time of the study visit and through up to 1 year of follow-up so that time to virologic suppression could be compared between the 2 arms.
For participants randomized to the intervention arm, study staff also conducted a fingerstick and initiated the SAMBA Semi-Q. After the study procedures were completed, study staff connected the participant with their care team to complete their clinic visit. When the SAMBA Semi-Q result was ready, study staff delivered the result to the participant’s physician. When participants were still in the clinic, the physician delivered the result along with the brief adherence counseling intervention developed for the study in collaboration with clinic providers, the process for which has already been described (Multimedia Appendices 1 and 2) [36]. For participants who had left the clinic, the physician followed up with the patient either via phone or by EMR message, whichever was considered most appropriate. For each participant randomized to the POC NAT arm, the physician reported to the research study whether they discussed the POC NAT result with the participant in person, via phone, or not at all. SAMBA Semi-Q and research laboratory NAT results were manually entered into the EMR by the research team.
GAIN Acceptability Survey Participants
An additional acceptability survey was offered to a subgroup of participants beginning in May 2023. A small number of participants were not offered participation for a variety of reasons (eg, study staff forgot, the participant had a complicated visit, and it was logistically best to not offer an additional component). We delayed the offer of acceptability surveys until after the study had been enrolling for approximately 1 year.
At the study visit, study staff offered participants the optional extra survey. Participants who expressed willingness to take the extra survey were emailed a link to the REDCap CASI within 3 days of their study visit. For people with HIV at Madison Clinic, we also began offering the survey immediately after the study visit on a study tablet or laptop to increase access for participants with limited email or internet.
The CASI asked questions about the acceptability of the POC NAT and result delivery. Participants testing for HIV received a survey that included questions on PrEP use and sexual history, and a set of 12 discrete-choice questions about HIV testing preferences (Multimedia Appendix 3). People with HIV received questions on POC NAT acceptability, ART use, viral load testing and cutoff levels, and undetectable = untransmittable (Multimedia Appendix 4). People with HIV at Madison Clinic also received questions about their provider and the delivery of the adherence counseling intervention (Multimedia Appendix 5). Because of the sensitive nature of some of the questions, the survey instructions recommended that participants take the survey in a private setting. The CASI was designed to take about 10 minutes, and participants were sent a US $10 gift card via email or received US $10 cash following survey completion.
GAIN Participant Interviews
From June through November 2023, all participants who completed the postvisit acceptability survey were invited to complete a semistructured interview with study staff either in person, via phone, or via Zoom (Zoom Video Communications, Inc.). Participants were contacted via email, and study staff attempted to schedule interviews within 1 month of the participant’s study visit to maximize recall. The conversations were audio-recorded and transcribed by HIPAA (Health Insurance Portability and Accountability Act)–compliant Global Marketing Resources (GMR) Transcription. Once the transcripts were reviewed for accuracy and any identifying information was removed, the original recordings were deleted.
The topics covered in the interviews included more detailed, open-ended questions about the acceptability of the POC NAT and result delivery and, for participants who tested HIV-negative, a discussion of their HIV testing preferences (Multimedia Appendix 6). People with HIV were asked about viral load monitoring and their care preferences, viral load cutoff levels, and undetectable = untransmittable, and the adherence intervention conversation with their provider (Multimedia Appendices 7 and 8).
When thematic saturation appeared to have been reached for participants who tested HIV-negative, recruitment continued until February 2024 only for participants who tested HIV-negative who were persons of color or transgender, in order to increase the diversity of the sample. These interviews continued with people with HIV through the duration of the study.
GAIN Provider Interviews
We also interviewed providers at Madison Clinic to obtain input on the acceptability and feasibility of POC NAT use in the clinical setting from the provider perspective. In a first round of preimplementation key informant interviews with providers at Madison Clinic, we explored perspectives on the possible utility of POC NAT and integration into clinic flow. We also solicited provider input on the development of an ultra-brief adherence counseling intervention using motivational interviewing and problem-solving counseling techniques, the results of which have been described elsewhere [36]. Brief, postimplementation interviews were conducted with providers who successfully delivered a POC NAT result to a participant to gain insight into the process of test result delivery and adherence counseling. More formal interviews are planned at the completion of the project to solicit feedback on the utility of the SAMBA Semi-Q.
GAIN Time and Motion Observations
Time-and-motion studies were conducted at three times: February-July 2021 before study enrollment began to inform study implementation, March-April 2023 for a post-COVID pandemic repeat assessment (during a regulatory study pause in enrollment), and November 2023 to October 2024 during study enrollment to assess the impact of the POC NAT on clinic flow [37]. Patients were observed by study staff from the time they arrived in the waiting room until they departed the clinic, with staff noting the type of visit and the time of each subsequent segment of the patient visit (eg, front desk check-in, waiting room time, and time the patient spent with each provider type). The final time-and-motion dataset conducted during study enrollment also noted participant time spent on research procedures. That final dataset evaluating the impact of POC NAT implementation will be reported elsewhere.
Data Collection and Statistical Analysis
GAIN study data sources are shown in Table 1. We present demographic data for client visits in the baseline dataset and GAIN participants in Tables 2-4 as descriptive statistics. When data from the study visit survey were missing, we filled in missing values whenever possible with EMR data. Demographic data are presented at the participant level and include gender, race, insurance, and PrEP and ART status. Planned statistical analyses are described with anticipated timelines for completion.
Data sources for the Greater Access and Impact through Point-of-Care Nucleic Acid Test study.
Dataset
Source
Participants
Data included
Baseline data from Seattle’s LGBTQ+a Center
Seattle’s LGBTQ+ Center InSync EMRb, Google Forms intake
Preimplementation, nonstudy participants
Demographics, HIV POCc and laboratory test results, PrEPd prescriptions
Baseline data from Madison Clinic
Madison Clinic Epic EMR, PrEP PROe
Preimplementation, nonstudy participants
Demographics, HIV POC and laboratory test results, PrEP visits, viral load results, and ARfT medications
Linking survey
REDCapg, study staff completed at the study visit
All participants
Patient EMR, Study ID, name, date of birth, and contact information
Study visit survey
REDCap, participant completed at the study visit
All participants
Patient demographics, substance use, and ART use
Test results
REDCap, study staff completed at the study visit and after the study visit
All participants
POC and laboratory HIV test results
Follow-up phone calls
REDCap, study staff completed after the study visit
All participants at Seattle’s LGBTQ+ Center
PrEP initiation, ART use, viral load results, and connection to HIV care
Follow-up acceptability survey
REDCap, participant completed after the study visit
Subset of all participants
POC NATh perspectives, PrEP preferences, and viral load testing preferences
Follow-up in-depth interview
Qualitative interview conducted after the study visit
Subset of participants completing the acceptability survey
POC NAT perspectives, PrEP preferences, and viral load testing preferences
Prospective data from Seattle’s LGBTQ+ Center
Seattle’s LGBTQ+ Center InSync EMR, Google Forms intake
All participants at Seattle’s LGBTQ+ Center
Demographics, HIV POC and laboratory test results, and PrEP prescriptions
Prospective data from Madison Clinic
Madison Clinic Epic EMR, PrEP PRO
All participants at Madison Clinic
Demographics, HIV POC and laboratory test results, PrEP visits, viral load results, and ART medications
Time and motion data
Observational data on patient flow through Madison Clinic collected by study staff
Nonparticipants, Madison participants with HIV
Timing of clinic and study visit components
aLGBTQ+: lesbian, gay, bisexual, transgender, queer, and others.
bEMR: electronic medical record.
cPOC: point-of-care.
dPrEP: pre-exposure prophylaxis.
ePRO: patient-reported outcomes.
fART: antiretroviral therapy
gREDCap: Research Electronic Data Capture
hNAT: nucleic acid test.
Characteristics of baseline visits by clients at Seattle’s LGBTQ+a Center (January 2019-December 2021) and participants in the GAINb study who were seeking HIV and STIc testing and PrEPd (January 2022-August 2024).
Characteristic
Baseline client visits (Jan 2019-Dec 2021)
GAINb study participant visits
HIV and STIc testing visits
PrEPd visits
Total visits
Visits by participants seeking HIV testing and PrEP (Jan 2022- Aug 2024)
Visits by participants with HIV seeking STI testing (Mar 2022-Aug 2024)
Total, n (%)
6906 (96.2)
272 (3.8)
7178 (100)
489 (100)
7 (100)
Age (years), median (IQR)
30 (26-38)
28 (24-33)
30 (26-37)
30 (25-35)
57 (41-61)
Gender, n (%)
Cisgender man
5487 (79.5)
216 (79.4)
5703 (79.5)
333 (68.1)
7 (100)
Cisgender woman
430 (6.2)
0 (0.0)
430 (6.0)
35 (7.2)
0 (0)
Transgender man
99 (1.4)
2 (0.7)
101 (1.4)
13 (2.7)
0 (0)
Transgender woman
190 (2.8)
13 (4.8)
203 (2.8)
17 (3.5)
0 (0)
Nonbinary or genderqueer (AMABe)
307 (4.4)
14 (5.1)
321 (4.5)
51 (10.4)
0 (0)
Nonbinary or genderqueer (AFAB)f
206 (3.0)
1 (0.4)
207 (2.9)
30 (6.1)
0 (0)
Nonbinary or genderqueer (another gender or intersex at birth, missing sex at birth)
18 (0.3)
0 (0.0)
18 (0.3)
6 (1.2)
0 (0)
Missing
169 (2.4)
26 (9.6)
195 (2.7)
4 (0.8)
0 (0)
Race or ethnicity, n (%)
American Indian or Alaska Native
40 (0.6)
2 (0.7)
42 (0.6)
1 (0.2)
0 (0)
Asian
1015 (14.7)
26 (9.6)
1041 (14.5)
69 (14.1)
0 (0)
Black or African American
628 (9.1)
34 (12.5)
662 (9.2)
28 (5.7)
0 (0)
Native Hawaiian or Other Pacific Islander
75 (1.1)
10 (3.7)
85 (1.2)
2 (0.4)
1 (14.3)
White
3375 (48.9)
77 (28.3)
3452 (48.1)
278 (56.9)
5 (71.4)
Latinxg
1194 (17.3)
77 (28.3)
1271 (17.7)
72 (14.7)
1 (14.3)
Multiracialh
451 (6.5)
16 (5.9)
467 (6.5)
36 (7.4)
0 (0)
Middle Eastern or South Asian
37 (0.5)
2 (0.7)
39 (0.5)
NDi
ND
Missing or no response
91 (1.3)
28 (10.3)
119 (1.7)
3 (0.6)
0 (0)
Insurance, n (%)
Public insurance
391 (5.7)
27 (9.9)
418 (5.8)
87 (17.8)
2 (28.6)
Private insurance
1663 (24.1)
46 (16.9)
1709 (23.8)
250 (51.1)
5 (71.4)
Unspecified type
2648 (38.3)
0 (0.0)
2648 (36.9)
11 (2.2)
0 (0)
No insurance
2138 (31.0)
47 (17.3)
2185 (30.4)
121 (24.7)
0 (0)
Not sure or missing
66 (1.0)
152 (55.9)
218 (3.0)
20 (4.3)
0 (0)
Substance use, n (%)
IDUj (past year)k
224 (3.4)
12 (11.1)
236 (3.5)
NDi
ND
IDU (past 3 mo)
ND
ND
ND
4 (0.8)
0 (0)
Meth (past 3 mo)l
65 (2.1)
6 (5.2)
71 (2.2)
13 (2.7)
0 (0)
HIV status and PrEP or ARTm use, n (%)
HIV negative
5937 (86.0)
N/An
N/A
489 (100)
0 (0.0)
Currently on PrEP
929 (15.6)
N/A
N/A
123 (25.5)
N/A
HIV positive
175 (2.5)
N/A
N/A
0 (0)
7 (100)
Currently on ART
55 (31.4)
N/A
N/A
N/A
6 (85.7)
Not currently on ART
15 (8.6)
N/A
N/A
N/A
1 (14.3)
ART status unknown or missing
105 (60.0)
N/A
N/A
N/A
0 (0)
HIV status unknown or missing
794 (11.5)
N/A
N/A
0 (0)
0 (0)
aLGBTQ+: lesbian, gay, bisexual, transgender, queer, and others.
bGAIN: Greater Access and Impact through Point-of-Care Nucleic Acid Test.
cSTI: sexually transmitted infection.
dPrEP: pre-exposure prophylaxis.
eAMAB: assigned male at birth
fAFAB: assigned female at birth.
gParticipants who selected Latinx and any other race were categorized as Latinx.
hParticipants who selected any 2 or more races but not Latinx were categorized as multiracial.
iND: no data available; data that was not collected for the group listed.
jIDU:
kAsked of 6575 test participants and 108 PrEP participants.
lAsked of 3107 test participants and 108 PrEP participants.
mART: antiretroviral therapy
nN/A: not applicable; variable does not apply to the group listed.
Characteristics of baseline visits from patients at Madison Clinic (Jan 2019-Dec 2021) and participants in the GAINa study seeking HIV and STIb testing, nPEPc, or PrEPd (January 2022-August 2024).
GAINa study participant visits (Jan 2022-Aug 2024)
nPEP visits
HIV testing visits
PrEP visits
Total visits
HIV and STI testing, nPEP, and PrEP visits
Total, n (%)
117 (13.8)
328 (38.8)
400 (47.3)
845 (100)
43 (100)
Age (years), median (IQR)
31 (26-39)
32 (27-42)
33 (27-44.5)
33 (27-43)
35 (31-44)
Gender, n (%)
Cisgender man
117 (100)
177 (54)
348 (87)
642 (76)
37 (86)
Cisgender woman
0 (0)
150 (45.7)
51 (12.8)
201 (23.8)
1 (2.3)
Transgender man
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
Transgender woman
0 (0)
0 (0)
0 (0)
0 (0)
2 (4.7)
Nonbinary or genderqueer (AMABe)
0 (0)
0 (0)
0 (0)
0 (0)
1 (2.3)
Nonbinary or genderqueer (AFABf)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
Nonbinary (unknown sex at birth)
0 (0.0)
1 (0.3)
1 (0.3)
2 (0.2)
0 (0.0)
Another gender identity
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
2 (4.7)
Missing
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
Race or ethnicity, n (%)
American Indian or Alaska Native
1 (0.9)
3 (0.9)
10 (2.5)
14 (1.7)
0 (0.0)
Asian
20 (17.1)
33 (10.1)
36 (9.0)
89 (10.5)
2 (4.7)
Black or African American
12 (10.3)
44 (13.4)
25 (6.3)
81 (9.6)
2 (4.7)
Hispanic or Latinxg
20 (17.1)
13 (4.0)
40 (10.0)
73 (8.6)
11 (25.6)
Native Hawaiian or Other Pacific Islander
1 (0.9)
1 (0.3)
2 (0.5)
4 (0.5)
1 (2.3)
White
51 (43.6)
178 (54.3)
198 (49.5)
427 (50.5)
27 (62.8)
Multiracialh
1 (0.9)
7 (2.1)
11 (2.8)
19 (2.2)
0 (0.0)
Missing or no response
11 (9.4)
49 (14.9)
78 (19.5)
138 (16.3)
0 (0.0)
Insurance, n (%)
Public insurance
39 (33.3)
94 (28.7)
121 (30.3)
329 (38.9)
19 (44.2)
Private insurance
55 (47.0)
125 (38.1)
149 (37.3)
254 (30.1)
16 (37.2)
Another insurance
5 (4.3)
62 (18.9)
75 (18.8)
142 (16.8)
0 (0.0)
Missing
18 (15.4)
47 (14.3)
55 (13.8)
120 (14.2)
9 (20.9)
PrEP use (reported by participant), n (%)
Never
NDi
ND
ND
ND
7 (16.3)
Previously
ND
ND
ND
ND
6 (14.0)
Currently
ND
ND
ND
ND
30 (69.8)
Missing
ND
ND
ND
ND
0 (0.0)
Reason for visit (reported by study staff), n (%)
HIV testing
ND
ND
ND
ND
6 (14.0)
PEP
ND
ND
ND
ND
6 (14.0)
PrEP start
ND
ND
ND
ND
5 (11.6)
PrEP persistence
ND
ND
ND
ND
26 (60.5)
aGAIN: Greater Access and Impact through Point-of-Care Nucleic Acid Test.
bSTI: sexually transmitted infection.
cnPEP: nonoccupational postexposure prophylaxis.
dPrEP: pre-exposure prophylaxis.
eAMAB: assigned male at birth.
fAFAB: assigned female at birth
gParticipants who selected Latinx and any other race were categorized as Latinx.
hParticipants who selected any 2 or more races but not Latinx were categorized as multiracial.
iND: no data available; data that wasn’t collected for this variable for this group
Characteristics of baseline visits by patients at Madison Clinic (Jan 2019-Dec 2021) and GAINa study participants living with HIV (Jan 2022-Aug 2024).
Characteristics
Baseline visits by patients at Madison Clinic (Jan 2019-Dec 2021)
GAINa study visits (Jan 2022-Aug 2024)
Patients with first reactive HIV result
Patients with detectableHIV viral load
Total patients
Participants with HIV
Total, n (%)
146 (22.2)
511 (77.8)
657 (100)
194 (100)
Age (years), median (IQR)
34 (28‐47)
43 (32‐52)
41 (31‐51)
44.5 (35-57)
Gender, n (%)
Cisgender man
117 (80.1)
406 (79.5)
523 (79.6)
144 (74.2)
Cisgender woman
29 (19.9)
104 (20.4)
133 (20.2)
19 (9.8)
Transgender man
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
Transgender woman
0 (0.0)
0 (0.0)
0 (0.0)
10 (5.2)
Nonbinary or genderqueer (AMAB)b
0 (0.0)
0 (0.0)
0 (0.0)
15 (7.7)
Nonbinary or genderqueer (AFAB)c
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
Nonbinary or genderqueer (unknown sex at birth)
0 (0.0)
1 (0.2)
1 (0.2)
0 (0.0)
Another gender identity
0 (0.0)
0 (0.0)
0 (0.0)
6 (3.1)
Missing
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
Race or ethnicity, n (%)
American Indian or Alaska Native
0 (0)
14 (2.7)
14 (2.1)
3 (1.6)
Asian
10 (6.8)
20 (3.9)
30 (4.6)
4 (2.1)
Black or African American
43 (29.5)
152 (29.7)
195 (29.7)
53 (27.3)
Hispanic or Latinxd
12 (8.2)
21 (4.1)
33 (5.0)
27 (13.9)
Native Hawaiian or Other Pacific Islander
1 (0.7)
8 (1.6)
9 (1.4)
5 (2.6)
White
56 (38.4)
239 (46.8)
295 (44.9)
84 (43.3)
Multiraciale
4 (2.7)
4 (0.8)
8 (1.2)
17 (8.8)
Missing or no response
20 (13.7)
20 (3.9)
40 (6.1)
1 (0.5)
Insurance, n (%)
Public insurance
55 (37.7)
325 (63.6)
380 (29.8)
162 (83.5)
Private insurance
61 (41.8)
135 (26.4)
196 (57.8)
28 (14.4)
Another insurance
12 (8.2)
17 (3.3)
29 (4.4)
1 (0.5)
Missing
18 (12.3)
34 (6.7)
52 (7.9)
3 (1.6)
ARTf use, n (%)
Never
NDg
ND
ND
38 (19.6)
Previously
ND
ND
ND
19 (29.4)
Currently
ND
ND
ND
134 (69.1)
missing
ND
ND
ND
3 (1.6)
Laboratory viral load, n (%)h
Detectable (≥40 copies)
N/Ai
N/A
N/A
63 (32.5)
Undetectable (<40 copies)
N/A
N/A
N/A
113 (58.2)
Laboratory viral load not done
N/A
N/A
N/A
18 (9.3)j
Randomization arm, n (%)
Standard of care
N/A
N/A
N/A
97 (50)
Point-of-care NATk
N/A
N/A
N/A
97 (50)
aGAIN: Greater Access and Impact through Point-of-Care Nucleic Acid Test.
bAMAB: assigned male at birth.
cAFAB: assigned female at birth.
dParticipants who selected Latinx and any other race were categorized as Latinx.
eParticipants who selected any 2 or more races but not Latinx were categorized as multiracial.
fART: antiretroviral therapy
gND: no data available; data that was not collected for the group listed.
hFilled in with clinic electronic medical record if available within 15 days of visit date when study VL not available.
iN/A: not applicable; variable does not apply to the group listed
jLaboratory viral load test was not done for participants enrolled before October 2022 (n=7) and for participants from whom no blood could be drawn due to hard stick (n=8). When available, viral load values were obtained from the clinic electronic medical record.
kNAT: nucleic acid test.
Ethical Considerations
The study received ethical approval from the UW Human Subjects Division (STUDY 00010387). A waiver of informed consent was granted by the UW Human Subjects Division for baseline data collection and time and motion procedures, as no identifiers were obtained. Study staff performed consent procedures and obtained informed written consent for study participants in Aims 1‐4. To protect participant data, participants from Aims 1‐4 were assigned a study ID, and their study data was stored in connection with that ID. A separate linking survey connected their study ID to their medical record number, which was used to obtain prospective data. A Human Subjects Division–approved Data Safety and Monitoring Plan was used to ensure protective measures to safeguard participant information, including appropriate levels of training for staff, limited data access, secure digital and physical storage places, and data transmission. Madison Clinic participants initially received a US $20 cash incentive and a US $5 meal voucher. Participants at the Center initially did not receive an incentive, but this was amended in April 2023 to provide a US $25 online gift card for consistency between sites. To help boost enrollment, the participation incentive was increased to US $40 in cash and a US $5 meal voucher for participants at Madison Clinic in August 2023. Participants who completed the additional acceptability survey were provided a US $10 electronic gift card upon survey completion. Participants who participated in the interview were provided a US $40 electronic gift card. In August 2024, we began offering incentives in cash as participants noted lack of email access as a barrier for survey and interview participation.
Results
During the baseline data period of January 2019 to December 2021 at the Center, 6906 unique clients were seen for 8492 HIV and STI testing visits, and 272 clients had 612 PrEP visits (Table 2). Most clients (n=5703, 79.5%) were cisgender men. Almost half were White (n=3452, 48.1%). Nearly one-third (n=2185, 30.4%) reported no insurance. Among testing visit clients, about 86% (n=5937) were HIV negative (though HIV status was missing or unknown for 11.5% [n=794]), of whom, 15.6% (n=929) reported being on PrEP. About 2.5% (n=175) of testing visit patients were living with HIV, and about one-third of those clients reported that they were on ART (n=55, 31.4%), though data were missing for most clients (n=105, 60%).
At Madison Clinic during the same baseline period (Table 3), there were 117 unique patients seen for nPEP, 328 unique patients seen for HIV testing visits, and 400 unique patients seen for PrEP visits. There were 146 patients who tested positive for HIV for the first time and 511 patients with HIV whose viral load was detectable (>40 copies/mL) at some point during that time (Table 4). Among patients seen, 48.1% were White (n=722), 18.4% were Black or African American (n=276), 7.9% were Asian (n=119), and 7.1% were Hispanic or Latinx (n=106). Most (77.6%) were male (n=1065), 22.2% were female (n=334), and only 0.2% were transgender or nonbinary (n=3).
During study enrollment from January 2022 to December 2024, 733 unique people completed 753 GAIN study research visits (Tables 2-4). Of those visits, 491 visits were completed by 489 participants seeking HIV testing and/or PrEP at the Center. Most of those participants were seeking HIV testing (96%), were cisgender men (333/489, 68.1%), were White (278/489, 56.9%), with a median age of 30 (IQR 25‐35) years. About one-quarter (123/489, 25.2%) were currently on PrEP. Seven people with HIV seeking STI testing were enrolled from the Center. These participants were all cisgender men, most were White (n=7, 71.4%), with a median age of 57 (IQR 41‐61) years. Of those participants, 1 was not taking ART but had previously, the other 6 were currently taking ART.
At Madison Clinic, 61 visits were completed by 43 participants seeking HIV testing, nPEP, and/or PrEP. The majority of participants were there for a PrEP persistence visit (n=26, 60.5%). Most of these participants were cisgender men (n=37, 86%) and White (n=27, 62.8%), with a median age of 35 (IQR 31‐44) years, and most (n=30, 69.8%) were on PrEP. At Madison Clinic and MOD Clinic, 194 people with HIV seeking care were enrolled during the same time period. These participants were mostly cisgender men (n=144, 74.2%); 43.3% (n=84) were White, 27.3% (n=53) were Black or African American, and their median age was 44.5 (IQR 35‐57) years. Among Madison and MOD Clinic participants with HIV, 69.1% (n=134) were currently taking ART and 32.5% (n=63) had a detectable viral load (>40 copies/mL) at the time of their study visit. Differences in the populations of participants at the Center and Madison Clinic reflect the different populations seen at the 2 sites.
As part of Aim 4 study activities (Table 5), during a recruitment period that included 228 study visits completed by participants seeking HIV and STI testing at the Center, staff invited 198 to take the postvisit acceptability survey, of whom 133 (67.2%) participants completed. During 6 study visits by PWH at the Center, staff sent participants 4 survey invitations, and 3 participants completed them (75% completion). Among 25 Madison Clinic participant visits for HIV and STI testing, nPEP, and PrEP, 10 of 21 invited participants completed the survey (47.6% completion). During 161 study visits for PWH at Madison and MOD Clinics, 47 of 77 (61%) invited participants completed the survey. Of those who completed the additional surveys, 21 participants seeking HIV and STI testing, nPEP, or PrEP from both sites and 20 people with HIV from both sites also participated in an in-depth interview. Only participants who completed the survey were invited to participate in interviews, and participation rates were at or below 50% for all groups. However, we stopped inviting eligible participants who were seeking HIV and STI testing, nPEP, or PrEP to the interview after we achieved saturation of themes.
Acceptability survey and interview completions for participants in the GAINa study from Seattle’s LGBTQ+b Center and Madison Clinic.
Characteristic
Seattle’s LGBTQ+ Center
Madison Clinic
Total, n (%)
Participants seeking HIV and STIc testing, n (%)
Participants with HIV, n (%)
Participants seeking HIV and STI testing, nPEPd, and PrEPe, n (%)
Participants with HIV, n (%)
Total study visitsf
228 (47)
6 (86)
25 (58)
161 (83)
420 (57)
Survey invitations sentg
198 (86.8)
4 (66.7)
21 (84)
77 (47.8)
300 (71.4)
Surveys completed
133 (67.2)
3 (75)
10 (47.6)
47 (61)
193 (64.3)
Interviews completed
16 (12)h
1 (33.3)
5 (50)
19 (40.4)
41 (21.2)
aGAIN: Greater Access and Impact through Point-of-Care Nucleic Acid Test.
bLGBTQ+: lesbian, gay, bisexual, transgender, queer, and others.
cSTI: sexually transmitted infection.
dnPEP: nonoccupational postexposure prophylaxis.
ePrEP: pre-exposure prophylaxis.
fIncludes study visits during which participation in the acceptability survey was being offered
gIncludes participants who were offered, agreed, and were eligible to be sent the acceptability survey at their study visit.
hStudy staff stopped offering enrollment to all participants after thematic saturation was attained; therefore, not all eligible participants were invited.
Time-and-motion observations were made in 2021 for 25 total patients at Madison Clinic, 13 of whom were from the MOD Clinic (Table 6). We found that the median clinic visit time was 73 (IQR 54‐92) minutes. An additional set of time-and-motion observations, made in 2023 during a pause in study enrollment, included 22 total patients at Madison Clinic (10 of whom were from the MOD Clinic) and revealed a median clinic visit time of 64 (IQR 45‐88) minutes. This demonstrated that most patient visits were shorter than the amount of time the POC NAT used for the study would take to return a result (120 min). This finding led the study team to develop a protocol prioritizing recruitment of participants before their regular clinic visit to initiate the SAMBA test as soon as possible.
Total time observed in clinic (minutes), including waiting room time, during 1 observation period preenrollment (2021) and 1 period while enrollment was paused (2023).
Year and statistics
MODa Clinic
Madison Clinic
Total
2021, n
13
12
25
Range
46-301
19-155
19-301
Mean (SD)
93.5 (66.9)
66.8 (36.2)
80.7 (55.0)
Median (IQR)
74 (55-97)
64 (42-85)
73 (54-92)
2023, n
10
12
22
Range
32‐185
45‐95
32‐185
Mean (SD)
75.2 (43.6)
65.3 (17.2)
69.8 (31.6)
Median (IQR)
68 (61-74)
61 (51-80)
64 (45-88)
aMOD: Moderate Needs.
Test results data from Aim 1 participants at both the Center and Madison Clinic will contribute to a performance assessment of the SAMBA Qual, anticipated in 2027. For this analysis, we will calculate the overall specificity and sensitivity of the SAMBA II Qual whole blood test across all tested samples and at HIV-1 RNA thresholds of detectable (>40), 200, 400, 1000, 2000, and 3000 copies/mL. SAMBA performance will be compared to laboratory RNA test results. We hypothesize that the sensitivity and specificity of the SAMBA II Qual will be similar to those of laboratory-based pooled NAT.
Test results and longitudinal follow-up from Aim 3 participants at Madison Clinic will contribute to a survival analysis of time to undetectable viral load, as well as a performance assessment of the SAMBA Semi-Q, anticipated in 2026. We will report the limit of detection using the plasma HIV RNA level as the gold standard, and the agreement (kappa) between SAMBA and plasma HIV RNA levels, dichotomized at 1000 copies/mL and within the range of 1000 copies/mL ± 0.3 log.
For the survival analysis, we will report the time to an undetectable viral load by study arm. We calculated a sample size of 106 per arm, assuming a baseline of 40% of participants with an undetectable viral load, to detect a 20% increase in the proportion of participants with an undetectable viral among people with HIV at Madison Clinic, assuming a 20% loss to follow-up. We hypothesize that the SAMBA Semi-Q will have high agreement with the laboratory-based RNA testing, and that time to virologic suppression will be shorter among participants randomized to the POC NAT-tailored intervention compared with standard of care.
Data from Aim 4 will contribute to a paper on the acceptability of POC NAT among persons testing for HIV, anticipated in 2026 (Table 7). Another paper will address the acceptability of POC NAT among people with HIV using both qualitative data from interviews and participant survey responses, anticipated in 2026. Another paper using data collected as part of Aim 4 activities will explore HIV testing preferences using both the acceptability survey and interview data. We will use a convergent parallel mixed methods design for integration of qualitative and quantitative data. For the interview sample size, we planned to conduct 20 interviews each among the HIV testing group and people with HIV, or until saturation of themes. For surveys, a sample size of 100 HIV testing participants and 100 people with HIV was determined based on feasibility, the literature, and consultation with a choice-modeling expert. We hypothesize that more than 80% of participants surveyed will report a positive experience with POC NAT and that SAMBA implementation will be acceptable in community- and clinic-based settings. However, we hypothesize that the 2-hour TAT will be a limitation to the feasible implementation of POC NAT and that the semiquantitative nature of the test and the limit of detection of 1000 copies/mL may cause some hesitation in the use of the SAMBA Semi-Q.
Planned publication topics, analyses, and timelines.
Anticipated publication topics
Contributing aims and sites
Planned analysis
Target sample size
Attained sample size
Anticipated publication date
Performance of SAMBA Qual for HIV Testing
Aim 1, Seattle’s LGBTQ+ Center and Madison Clinic
Laboratory and POCa NATb concordance
850 study visits
550 study visits
2027
Impact of POC NAT on time to undetectable viral load and SAMBA Semi-Q performance
Aim 3, Madison Clinic
Survival analysis, laboratory, and POC NAT concordance
212 study visits with up to 1-year longitudinal follow-up
194 study visits
2026
Acceptability of POC NAT among persons testing for HIV
Aim 4 interviews, Seattle’s LGBTQ+ Center and Madison Clinic
Qualitative
20 or until saturation of themes
21 interviews
2026
HIV testing preferences
Aim 4 interviews and surveys, Seattle’s LGBTQ+ Center and Madison Clinic
Qualitative, discrete choice analysis
20 or until saturation of themes, 100 surveys
21 interviews, 143 surveys
2026
Acceptability of POC NAT among patients with HIV
Aim 4 interviews and surveys, Madison Clinic and Seattle’s LGBTQ+ Center
Qualitative and descriptive statistics
20 or until saturation of themes,100 surveys
20 interviews,50 surveys
2026
Time and motion
Patients at Madison Clinic and MOD Clinic
Rank-sum tests and flow analysis
10 visits per clinic per observation period
47 patient visits
2026
aPOC: point-of-care.
bNAT: nucleic acid test.
Data collected as part of the time-and-motion component of the study will be the subject of a paper anticipated in 2026. We calculated a sample size of 20 participants during each observation period, assuming a mean visit duration without SAMBA of 66 minutes, an SD of 29, α=.05, 80% power, and that 50% of participants would be randomized to receive SAMBA Semi-Q testing. We hypothesize that the average clinic visit will be less than the 2-hour TAT of the POC NAT and that the impact of study procedures on clinic flow will be minimal.
DiscussionPrincipal Findings
The GAIN study was designed to assess the acceptability and feasibility of implementing POC NAT in community and clinical settings. This paper describes the protocol, the populations recruited into the study, and planned analyses. During 3 years of enrollment, the GAIN study conducted 552 visits with HIV testing participants at the 2 study sites. Enrollment of persons seeking HIV testing occurred predominantly at the Center due to the focus of its HIV/STI testing programs. During the same period, the study enrolled 201 people with HIV from both sites. Conversely, recruitment of people with HIV was predominantly from Madison Clinic. Recruitment for the qualitative components of Aim 4 included 193 total poststudy visit surveys and 41 in-depth interviews. At the Center, we found that transgender, nonbinary, and genderqueer people represented a greater proportion of our study population (23.9% of Aim 1 participants) compared with the baseline visits at the Center (11.9%). This may reflect changing demographics of clients at the Center due to shifting priorities of the organization combined with the prioritization of study recruitment among clients at highest likelihood of having HIV [47,48]. Among participants seeking HIV testing at the Center, 25.2% said they were currently on PrEP, which is significantly higher than in the baseline group of participants seeking HIV testing, of whom 15.6% reported being on PrEP. This could also be due to the study focus on recruiting clients who were high priority for PrEP, and could also be influenced by baseline data missingness, as 11.5% of the Center baseline participants did not have a recorded HIV status or PrEP status.
In the baseline population at the Center, 2.5% of clients were people with HIV. Based on that rate, we would expect approximately 50 clients with HIV to visit the Center annually. The GAIN study enrolled only 7 clients with HIV at the Center during the nearly 3 years of enrollment. This low enrollment could be due to some participants not identifying themselves as living with HIV when completing the Center’s intake form, preventing study staff from identifying all eligible clients for recruitment. Future studies may wish to further examine how POC NAT could be used among people with HIV seeking STI testing in a community setting.
At Madison Clinic, the GAIN study enrolled fewer HIV-negative cisgender women (2.3%) than were observed in the Madison Clinic baseline dataset among patients seeking HIV testing (45.7% women) and PrEP (12.8% women). We saw a much higher number of participants identifying as transgender, genderqueer, or persons with another gender identity (11.6%) than were identified in our baseline dataset (0.2% among those seeking HIV testing, nPEP, and PrEP). This is because the study data collection instruments had greater capacity for capturing these gender identities than the EMR, which supplied the baseline data. The GAIN study also enrolled far more patients receiving PrEP (69.8%) than patients seeking HIV testing or nPEP. Future studies could focus more on the utility of the POC NAT among broader clinical patient populations.
Among Madison Clinic patients with HIV, we also enrolled more patients who identified as transgender, genderqueer, or persons with another gender identity (16%) than the patients seen at Madison Clinic during baseline (0.2% among those with a first reactive HIV result and patients with a detectable viral load). Again, this is likely due to constraints of the EMR that was the source of the baseline data. We also saw fewer cisgender women (9.8%) than were seen during the baseline data period (20.4%). The GAIN study aimed to prioritize the enrollment of participants with detectable viral loads to assess the impact of POC NAT on time to viral suppression, and 32.5% of people with HIV enrolled at Madison Clinic had detectable viral loads at their study visit (however, for 9.3% of participants, viral load data were missing). In 2024, about 10% of patients at Madison Clinic had a detectable viral load (>200 copies/mL), so the study was able to oversample this population (data not published). There is a high percentage of patients in the region who have achieved viral suppression in King County; the 2022 HIV Epidemiology Report and Community Profile estimated that 85% of people living with HIV in the region were virally suppressed [49]. Having a sample with a sufficient number of participants with a detectable viral load will strengthen the planned time-to-event analyses for participants achieving an undetectable VL. We also hypothesized that a POC NAT result would likely have a greater impact on patient visits where real-time counseling can be provided for the adherence counseling intervention component.
At both sites, the baseline data were affected by COVID-19 pandemic-related changes to patient flow. In order to address this, we expanded the baseline dataset to include 2021 as well as 2020, when clinic procedures were better adjusted to the impact of the pandemic. The study also experienced other challenges due to the pandemic, including delays in laboratory testing due to overloaded laboratory staff, shifts to the provision of PrEP services via telemedicine, and clinical and laboratory supply shortages. The study also experienced delays due to the initial Office of Management and Budget approval process, which extended more than 2 years beyond the local Institutional Review Board approval process.
The GAIN study is among the first studies to evaluate the implementation of a POC NAT in the United States for screening among participants who were HIV-negative (including patients receiving PrEP) and POC viral load monitoring among PWH. The study team is aware of only 1 other such study in the United States, which assessed a different POC NAT platform for performance in comparison to laboratory NAT for HIV testing and staff acceptability [27]. Participating staff found the test acceptable, and agreement with laboratory NAT was high; however, the authors noted that workflow challenges remained to be resolved, particularly with regards to returning results to participants with the 90-minute TAT. Staff speculated that this would be longer than most patients would want to wait; however, the study did not attempt to return results to participants. The GAIN study will report on efforts to return results to participants. Future studies could focus on the logistics of delivery of POC NAT results. As this technology develops and availability increases in the United States, this protocol can serve as a model for future studies.
Limitations
The GAIN study has limitations that should be noted. Baseline data and prospective data collected from Madison Clinic and Center datasets could be incomplete because data were deidentified when transferred to the study team and might not perfectly reflect the participants recruited into the study. However, the study team worked closely with data managers from both sites to achieve as complete a dataset as possible. For study visits and follow-up interviews, only participants who spoke English were enrolled, excluding individuals with limited English proficiency. Poststudy survey and interview contact occurred primarily via email, which led to lower uptake and likely excluded participants without access to email. We modified our process in 2024 to allow these activities to be completed in person immediately after the study visit and provided cash reimbursement, which enabled some inclusion of participants without internet access. Though the original proposed protocol called for a comparison of multiple POC NATs, because of challenges with suppliers, the study team was not able to procure any other POC NATs for comparison. Future studies of POC NATs could assess other testing platforms.
Additional analyses based on the GAIN study protocol described here are planned and in progress. Future reports will include papers on the acceptability of the POC NAT among participants seeking HIV testing and people with HIV based on survey and interview results, an assessment of participant HIV testing preferences based on survey and interview results, an assessment of the impact of POC NAT on time to viral suppression, evaluations of the performance of POC NAT in comparison with laboratory NAT, and a final set of Madison Clinic time-and-motion data. Additional POC NAT implementation studies in US settings are needed to assess the acceptability and feasibility of this technology.
The authors would like to thank the study participants for their contribution. We express gratitude to Seattle’s LGBTQ+ Center, Madison Clinic, and the Public Health–Seattle & King County Laboratory for their partnership in the project. We also thank study, Center, and Clinic staff, including Eyael Getachew, Deepa Rao, Dana Atkins, Sarah McDougal, Ryan Sha, Raaka Kumbhakar, Jehan Budak, Elle Brooks, Josh Freese, Jifu Lai, Dilpreet Kochhar, Chief Odood, Francis Slaughter, Yahaira Arenas, Garfield Hillson, and Luis Enrique Herrera Perales. We thank the Centers for Disease Control and Prevention staff Kevin Delaney, Jeffrey A Johnson, Jeffrey Wiener, Mary Tanner, Kirk Henny, Tameka Hayes, Damian Denson, and Cari Courtenay-Quirk for their contributions to the study. We also thank Public Health–Seattle & King County Laboratory staff Candice Le and Paul Swenson. We thank the Institute of Translational Health Sciences, which supports REDCap (Vanderbilt University), the survey software platform used by the study. Institute of Translational Health Sciences is supported by the National Institutes of Health, National Center for Advancing Translational Sciences, under award number UL1TR002319. We also thank the PrEP patient-reported outcomes team for providing additional data on study participants. Generative artificial intelligence was not used in any portion of this paper generation.
Funding
The Greater Access and Impact through Point-of-Care Nucleic Acid Test study was funded by the Centers for Disease Control and Prevention, National Center for HIV, Viral Hepatitis, STD, and Tuberculosis Prevention (award U01PS005196). Approximately 275 tests were donated in-kind by Diagnostics for the Real World for quality control purposes.
Data Availability
The datasets generated during this study are available from the corresponding author on reasonable request.
LAN contributed to data curation, formal analysis, investigation, project administration, visualization, and writing of the original draft. LRV contributed to data curation, formal analysis, investigation, software, project administration, and writing through review and editing. AC-H contributed to investigation and writing through review and editing. MM contributed to investigation and writing through review and editing. CC contributed to investigation and writing through review and editing. MD contributed to data curation and writing through review and editing. AW contributed to methodology and writing through review and editing. SF contributed to investigation and writing through review and editing. SD contributed to supervision and writing through review and editing. SET contributed to writing through review and editing. KWH contributed to conceptualization, supervision, and writing through review and editing. JDS contributed to conceptualization, funding acquisition, methodology, supervision, and writing through review and editing.
None declared.
AbbreviationsAHI
acute HIV infection
ART
antiretroviral therapy
CASI
computer-administered self-interview
EMR
electronic medical record
FDA
US Food and Drug Administration
GAIN
Greater Access and Impact through Point-of-Care Nucleic Acid Test
GMR
Global Marketing Resources
ITHS
Institute of Translational Health Sciences
MOD
moderate needs
NAT
nucleic acid test
nPEP
nonoccupational postexposure prophylaxis
POC
point-of-care
PrEP
preexposure prophylaxis
RCT
randomized controlled trial
STI
sexually transmitted infection
TAT
turnaround time
UW
University of Washington
ReferencesMalhotraUBerreyMMHuangYEffect of combination antiretroviral therapy on T-cell immunity in acute human immunodeficiency virus type 1 infectionJ Infect Dis200001181112113110.1086/31520210608758RosenbergESAltfeldMPoonSHImmune control of HIV-1 after early treatment of acute infectionNature20000928407680352352610.1038/3503510311029005SmithDBerreyMMRobertsonMVirological and immunological effects of combination antiretroviral therapy with zidovudine, lamivudine, and indinavir during primary human immunodeficiency virus type 1 infectionJ Infect Dis200009182395095410.1086/31575310950796WawerMJGrayRHSewankamboNKRates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, UgandaJ Infect Dis200505119191403140910.1086/42941115809897YerlySVoraSRizzardiPAcute HIV infection: impact on the spread of HIV and transmission of drug resistanceAIDS2001112315172287229210.1097/00002030-200111230-0001011698702KelleyCFKahleESieglerAApplying a PrEP continuum of care for men who have sex with men in Atlanta, GeorgiaClin Infect Dis2015111561101590159710.1093/cid/civ66426270691HutchinsonABBransonBMKimAFarnhamPGA meta-analysis of the effectiveness of alternative HIV counseling and testing methods to increase knowledge of HIV statusAIDS200608120121597160410.1097/01.aids.0000238405.93249.1616868440SpielbergFBransonBMGoldbaumGMChoosing HIV counseling and testing strategies for outreach settings: a randomized trialJ Acquir Immune Defic Syndr200503138334835515735456SteklerJDSwensonPDCoombsRWHIV testing in a high-incidence population: is antibody testing alone good enough?Clin Infect Dis200908149344445310.1086/60004319538088SteklerJDWoodRWSwensonPDGoldenMNegative rapid HIV antibody testing during early HIV infectionAnn Intern Med20070717147214714810.7326/0003-4819-147-2-200707170-0002217638724SteklerJDUreGO’NealJDPerformance of Determine Combo and other point-of-care HIV tests among Seattle MSMJ Clin Virol2016037681310.1016/j.jcv.2015.12.01126774543SteklerJDO’NealJDLaneARelative accuracy of serum, whole blood, and oral fluid HIV tests among Seattle men who have sex with menJ Clin Virol20131258 Suppl 10 1e1192210.1016/j.jcv.2013.09.01824342471KuunEBrashawMHeynsADSensitivity and specificity of standard and rapid HIV-antibody tests evaluated by seroconversion and non-seroconversion low-titre panelsVox Sang1997721111510.1046/j.1423-0410.1997.00011.x9031494SamdalHHGutigardBGLabayDWiikSISkaugKSkarAGComparison of the sensitivity of four rapid assays for the detection of antibodies to HIV-1/HIV-2 during seroconversionClin Diagn Virol19961071556110.1016/s0928-0197(96)00244-99077430BeelaertGVercauterenGFransenKComparative evaluation of eight commercial enzyme linked immunosorbent assays and 14 simple assays for detection of antibodies to HIVJ Virol Methods200209105219720610.1016/s0166-0934(02)00102-712270653OwenSMYangCSpiraTAlternative algorithms for human immunodeficiency virus infection diagnosis using tests that are licensed in the United StatesJ Clin Microbiol2008054651588159510.1128/JCM.02196-0718322061SteklerJDTapiaKMaenzaJNo time to delay! Fiebig stages and referral in acute HIV infection: Seattle primary infection program experienceAIDS Res Hum Retroviruses20180834865766610.1089/AID.2017.027629756456MasciotraSLuoWYoungpairojASPerformance of the Alere Determine™ HIV-1/2 Ag/Ab Combo Rapid Test with specimens from HIV-1 seroconverters from the US and HIV-2 infected individuals from Ivory CoastJ Clin Virol20131258 Suppl 1Suppl 1e54810.1016/j.jcv.2013.07.00223911678BrauerMDe VilliersJCMayaphiSHEvaluation of the Determine™ fourth generation HIV rapid assayJ Virol Methods201304189118018310.1016/j.jviromet.2013.01.01723391823DuongYTMavengereYPatelHPoor performance of the determine HIV-1/2 Ag/Ab combo fourth-generation rapid test for detection of acute infections in a national household survey in SwazilandJ Clin Microbiol20141052103743374810.1128/JCM.01989-1425122853AgutuCANgetsaCJPriceMASystematic review of the performance and clinical utility of point of care HIV-1 RNA testing for diagnosis and carePLOS One20190627146e021836910.1371/journal.pone.021836931246963SAMBA II HIV-1 semi-quantitative whole blood testDiagnostics for the Real World2026-04-21https://www.drw-ltd.com/solutions/tests/item/samba-ii-hiv-1-semi-q-whole-blood-test/Xpert ® HIV-1 qual XC a molecular point-of-care test that delivers results in around 90 minutes20182026-04-21Cepheidhttps://www.cepheid.com/en-CZ/tests/blood-virology-womens-health-sexual-health/xpert-hiv-1-qual.htmlLaboratory and point-of-care diagnostic testing for sexually transmitted infections, including HIVWorld Health Organization2026-04-21https://www.who.int/publications/i/item/9789240077089m-PIMA™ HIV-1/2 DetectAbbott Point of Care2026-04-21https://www.globalpointofcare.abbott/ww/en/product-details/alere-q-hiv-12-detect.htmlAlere q AnalyserAbbott Point of Care2026-04-21https://www.globalpointofcare.abbott/ww/en/product-details/alere-q-analyser.htmlMooreKJrTourneauNLAlvarezJFeasibility and staff acceptability of implementing Xpert HIV-1 viral load point-of-care testing: a pilot study in San FranciscoBMC Infect Dis20250162512610.1186/s12879-024-10384-239762731DrainPKDorwardJVioletteLRPoint-of-care HIV viral load testing combined with task shifting to improve treatment outcomes (STREAM): findings from an open-label, non-inferiority, randomised controlled trialLancet HIV20200474e229e23710.1016/S2352-3018(19)30402-332105625DorwardJDrainPKGarrettNPoint-of-care viral load testing and differentiated HIV careLancet HIV20180151e8e910.1016/S2352-3018(17)30211-429290227MsimangoLGibbsAShoziHAcceptability of point-of-care viral load testing to facilitate differentiated care: a qualitative assessment of people living with HIV and nurses in South AfricaBMC Health Serv Res20201125201108110.1186/s12913-020-05940-w33239012BoekeCEJosephJAtemCEvaluation of near point-of-care viral load implementation in public health facilities across seven countries in sub-Saharan AfricaJ Int AIDS Soc202101241e2566310.1002/jia2.2566333455081NicholasSPouletEWoltersLPoint-of-care viral load monitoring: outcomes from a decentralized HIV programme in MalawiJ Int AIDS Soc201908228e2538710.1002/jia2.2538731441242QianSRWHassanSAScallonAJ“After viral load testing, I get my results so I get to know which path my life is taking me”: qualitative insights on routine centralized and point-of-care viral load testing in western Kenya from the Opt4Kids and Opt4Mamas studiesBMC Health Serv Res20221217221154010.1186/s12913-022-08593-z36528677NakyanziANaddungaFBulterysMA“It Soothes Your Heart”: a multimethod study exploring acceptability of point-of-care viral load testing among Ugandan pregnant and postpartum women living with HIVDiagnostics (Basel)202312281417210.3390/diagnostics1401007238201381ManabeYCHamillMMPalamountainKMThe critical importance of clinical use case to inform point-of-care technology development: a case study of HIV nucleic acid assays in the United StatesClin Infect Dis2026029821e93e9910.1093/cid/ciaf51041128485AtkinsDLVioletteLNeimannLProvider perspectives on the use of motivational interviewing and problem-solving counseling paired with the point-of-care nucleic acid test for HIV carePLoS One20220622176e027030210.1371/journal.pone.027030235731794Lisa A. NiemannMSWLauren R. VioletteMPHAndy Cornelius-HudsonBAPatient Flow Assessed In Preparation For Point-Of-Care HIV Nucleic Acid Testing (POC NAT) Implementation At A Large HIV Clinic In Seattle2022SteklerJDMcMahanVBallingerLHIV pre-exposure prophylaxis prescribing through telehealthJ Acquir Immune Defic Syndr20180415775e40e4210.1097/QAI.000000000000162129280768KumbhakarRGBudakJZTaoYThe impact of a walk-in human immunodeficiency virus care model for people who are incompletely engaged in care: The Moderate Needs (MOD) ClinicOpen Forum Infect Dis20221212101ofac67010.1093/ofid/ofac67036628059DombrowskiJCRamchandaniMDhanireddySHarringtonRDMooreAGoldenMRThe Max Clinic: medical care designed to engage the hardest-to-reach persons living with HIV in Seattle and King County, WashingtonAIDS Patient Care STDS20180432414915610.1089/apc.2017.031329630852EhretRHarbKBreuerSObermeierMPerformance assessment of the new Xpert® HIV-1 viral load XC assay for quantification of HIV-1 viral loadsJ Clin Virol20220414910512710.1016/j.jcv.2022.10512735305378SAMBA II HIV-1 Qualitative Whole Blood TestDiagnostics for the Real World2026-04-21https://www.drw-ltd.com/solutions/tests/item/samba-ii-hiv-1-qualitative-whole-blood-test/AboutITHS2026-01-24https://www.iths.org/about/CraneHMLoberWWebsterERoutine collection of patient-reported outcomes in an HIV clinic setting: the first 100 patientsCurr HIV Res2007015110911810.2174/15701620777931636917266562VioletteLRCornelius-HudsonASnidarichMEvaluation of SAMBA II: A qualitative and semiquantitative HIV point-of-care nucleic acid testJ Acquir Immune Defic Syndr2022041589553754510.1097/QAI.000000000000290234974473SteklerJSwensonPDWoodRWHandsfieldHHGoldenMRTargeted screening for primary HIV infection through pooled HIV-RNA testing in men who have sex with menAIDS2005081219121323132510.1097/01.aids.0000180105.73264.8116052089HabartaNWangGMulatuMSLarishNHIV testing by transgender status at centers for disease control and prevention-funded sites in the United States, Puerto Rico, and US Virgin Islands, 2009-2011Am J Public Health20150910591917192510.2105/AJPH.2015.30265926180964PitasiMAKeraniRPKohnRChlamydia, gonorrhea, and human immunodeficiency virus infection among transgender women and transgender men attending clinics that provide sexually transmitted disease services in six US cities: results from the sexually transmitted disease surveillance networkSex Transm Dis20190246211211710.1097/OLQ.000000000000091730278030HIV/AIDS dataKing County, Washington2025-12-22https://kingcounty.gov/en/dept/dph/health-safety/disease-illness/hiv-sti-hcv/data-reports/annual-reports
GAIN study presentation for providers: brief counseling skills to improve ART adherence, motivational interviewing, and problem-solving therapy.
“A taste of MI” exercise.
GAIN study patient acceptability computer-administered self-interview for HIV testing participants.
GAIN study patient acceptability computer-administered self-interview for persons with HIV at the Center.
GAIN study patient acceptability computer-administered self-interview for persons with HIV at Madison Clinic.
GAIN study interview guide for HIV testing participants.
GAIN study interview guide for persons with HIV at the Center.
GAIN study interview guide for persons with HIV at Madison Clinic.