Introduction

The persistent burden of HIV (39 million worldwide [1] and 1.2 million in the U.S. [2]), particularly among marginalized populations, along with suboptimal testing rates, highlights the need to expand and innovate HIV testing efforts. HIV disproportionately affects sub-populations in the U.S., including people who inject drugs (PWID) [3]. Despite some success in reducing transmission among PWID through syringe service programs, the expanding injection drug epidemic and effects of COVID-related reduction in healthcare access have led to HIV outbreaks among PWID, who are already marginalized from the mainstream HIV care continuum [4,5]. The higher prevalence of HIV compounded with a range of social, economic, and demographic factors (e.g., stigma, education, income, rurality) can further increase risk for transmission, affect access to testing and care services, and potentially lead to worse outcomes and quality of life after HIV diagnosis in these high-risk populations [6].

HIV testing allows PLWHIV to make informed decisions about behaviors associated with HIV transmission, and once an individual receives a positive result they can then engage in HIV treatment and reduce viral load to untransmissible levels. Yet, almost 40% of new HIV infections in the U.S. are transmitted from people who did not know they were infected, and 13% (158,500) of people don’t know their status [7]. While those who reported at least one high-risk behavior for HIV (e.g., injecting drugs, unprotected sex) had higher rates of testing than those who did not (65.2% compared to 44.2% in 2016), 34.8% still had never been tested, and 65.8% had not been tested in the past 12 months [8].

The highest risk of HIV transmission occurs in the acute HIV infection (AHI) phase, the first stage of infection that occurs in the first 2–4 weeks [9], yet current rapid tests fail to detect HIV in this stage. Existing tests that are most used to screen for HIV are rapid antibody or antibody/antigen tests that can produce results within 1–30 minutes from fingerstick blood or oral fluid. These tests require a waiting period of up to 90 days after exposure as they cannot detect the virus at the AHI stage when individuals are most likely to spread HIV to others. Novel rapid AHI tests, designed to detect infection earlier and closer to the time of exposure, could transform testing by identifying individuals who are most infectious and linking them to care sooner. Such tests are particularly relevant for high-risk populations, including people who inject drugs, who often face barriers to accessing traditional healthcare.

The FDA previously approved two point-of-care antigen/antibody tests designed to shorten the diagnostic window to less than one month [10]. Field tests of the Ag/Ab assays demonstrated improved detection of AHI compared to Ab only tests, however with highly variable performance ranging from detection of 28–64% of AHI infections [11–13]. While laboratory-based nucleic acid tests can detect HIV infection earlier (10–33 days after exposure), these require intravenous blood draw, expensive equipment, time-consuming protocols, cold-chain reagent storage and trained personnel. As such, researchers are working to further advance rapid HIV testing to detect viral RNA during the acute phase and at the point-of-care (POC) [14–19]. Dr. Linnes and colleagues are developing a POC AHI test capable of detecting the equivalent of <1000 HIV virions/mL from a finger prick blood sample within 60 minutes. This test, called MicroRAAD, is a fully integrated, handheld, sample-to-answer device that uses reverse-transcription loop mediated isothermal amplification (RT-LAMP) to amplify HIV-1 RNA and provides a colorimetric readout for the amplification products via a lateral flow immunoassay. This platform can currently detect the virus within 90 minutes [15], and is being further developed with the goal of achieving results within 60 minutes. One of the most novel aspects of this device is achieving detection through whole blood sampling by automatically performing the multistep processes of isolating the virus from the sample, amplifying the RNA, and then transferring RT-LAMP products to the detection zone; making this a straightforward molecular testing platform for AHI. The test is designed to empower those at high-risk for HIV to detect and monitor their HIV status earlier following potential exposures.

This new testing paradigm has the potential to transform the HIV care continuum by making critical AHI detection possible at sites ranging from substance abuse treatment facilities to syringe services, addressing access barriers in areas of high HIV risk. However, without ensuring that a diagnostic POC technology is linking patients into the existing care continuum, even the most exquisitely sensitive POC devices will fail to make a difference in clinical outcomes. The success of this, and all technology platforms, will depend on the extent of adoption by, and delivery to, end-users. According to human-centered design frameworks, this requires examination of context-specific needs early and throughout the design process with end-users and experts who have lived experience or engage with the priority communities of an innovation [20].

The Ending the HIV Epidemic initiative in the U.S. aims to reduce new incidences of HIV by 90% by 2030 and to “diagnose all people living with HIV as early as possible” [21]. Marion County, Indiana represents one of the 48 priority counties that account for more than half of all new HIV diagnoses in the U.S [22]. This study sought to engage key stakeholders from organizations across Indiana who conduct HIV testing (direct users) with PWID and other high-risk populations, and clients of syringe services or HIV testing services (indirect users), to inform the development and implementation of the novel rapid AHI test. The objectives of this study were to 1) understand context-specific experiences with and barriers to HIV testing in Indiana; 2) assess the acceptability of this novel AHI test (that can detect the acute phase of HIV but takes longer to produce results than current HIV rapid tests) in this context, and 3) identify the target end-user and related implementation considerations for the test.

Methods

Results

A total of 19 interviews were conducted (n = 14 staff, direct users of HIV tests and n = 5 clients, indirect users of HIV tests). Of the 14 staff interviewed, five were directors or managers of Testing and Outreach units in their organization, while the remaining 10 directly conducted HIV and/or sexually transmitted infection (STI) testing. Most of the people who performed HIV testing also provided or coordinated counseling and outreach services, and two identified as a Peer Recovery Specialist or CHW. Years of experience in these or similar roles ranged from less than 1 year to over 20 years with an average of 6.3 years. Of the five clients interviewed, two identified as male, two as female, and one unreported. Most identified as White (4) and one person as Hispanic. Two clients were experiencing homelessness, four were unemployed (no income reported), and education levels ranged from high school to completion of a master’s degree. Almost all had used intravenous drugs (4). Those who injected drugs reported sharing needles never (2), rarely (1), and half the time (1). The number of sexual partners in the past year ranged from 1-3. All clients knew their current partner’s HIV status and reported low condom use (3 never used condoms and 2 rarely used them).

The staff interviewed represented 10 organizations that provide HIV testing services across six counties throughout Indiana (Allen, Marion, Monroe, Scott, Tippecanoe, Vanderburgh), including county health departments, syringe service programs, and healthcare clinics. Some organizations were part of larger networks and partnerships, serving up to 45 counties and partnering with up to 75 other HIV/AIDS organizations. Most organizations also provided education and outreach on HIV and STIs, ranging from positing flyers in public spaces to actively going out to the community with testing kits, as well as healthcare navigation, and medical and non-medical case management (e.g., housing assistance). About half of the organizations also provided HIV treatment and PrEP services. While few organizations were specifically focused on PWID and had a syringe service or harm reduction program, all organizations had experience working with high-risk populations and many targeted specific efforts to further reach populations in their area at high-risk for HIV or who have low utilization of HIV testing services.

Experiences and Barriers to HIV Testing

Fig 1 summarizes the Indiana HIV testing experience as described by interviewees. From the organization perspective, a client may seek testing once because of a known or suspected exposure whereas others test regularly, from every 3 months to yearly, likely because of risky behaviors. Clients shared that choosing to get tested depended on their individual risk assessment such as drug use and sexual activity. Those who viewed their risk as high (e.g., due to injection drugs) tended to test more regularly and frequently. Clients reported accessing testing at treatment and recovery centers (e.g., needle exchange programs), HIV testing organizations, and/or doctor’s offices and were last tested anywhere from 1-3 months prior to their interview, either by a rapid test or lab-based blood test. All staff reported using rapid HIV testing as the initial test for clients. INSTI® HIV-1/HIV-2 Antibody Test by bioLytical Laboratories Inc. [28] and Determine™ HIV-1/2 Ag/Ab by Abbott [29] were specifically mentioned as initial rapid tests that detect HIV from a finger prick of blood and yield results in one-minute and 20 minutes, respectively. OraQuick ADVANCE® [30], another rapid test that detects HIV antibodies, from oral fluid and yields results in 20 minutes, is used by staff as a second rapid test to confirm only positive INSTI results. Clients who test positive using a rapid test would then take a lab-based test that can take up to a week for results. The positive lab result officially confirms the HIV case so that the organization can report it to the Indiana State Health Department, per state law.

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Fig 1. HIV Testing Experience Pathway.

https://doi.org/10.1371/journal.pgph.0005366.g001

Clients who test positive are connected with a case manager to link directly to care within their organization, often starting them on treatment same day. Organizations who do not offer treatment services refer clients to other partner organizations. Many also noted that providing education before, during, and after testing is considered crucial for both positive and negative tests.

While most clients found HIV testing to be accessible, staff mentioned key access barriers including lack of awareness of where or how to access testing, concerns about cost, and transportation, specifically for high-risk populations such as PWID, people experiencing homelessness, or people who are incarcerated. Stigma was viewed as one of the most significant barriers to testing, for clients, in terms of drug use, fear of results, and worrying about other people learning their HIV status. From the staff perspective, stigma as a testing barrier is related to societal attitudes and beliefs about drug use and sex, and something they actively try to improve through education and counseling, “I think stigma is a huge reason, obviously, that people stay away from getting tested. They don’t want to feel dirty. They don’t want to be judged for their sexual activities” (James, HIV/STI Tester). Stigma was also associated with lack of knowledge about HIV and resulting misconceptions about HIV risk, or fear of getting tested because others might find out: “they’re afraid, in a small town, that somebody might find out that they’re being tested or what if they are positive, then what are they going to do? People are just afraid, a lot of times to find out (Bonnie, HIV Tester/Counselor).

Target End-users

Possible target end-users discussed for this test were: 1) client (i.e., self-testing), and 2) testing by a CHW or peer recovery specialist (i.e., CHW/peer-based testing). Table 1 outlines the benefits and limitations of each end-user as perceived by participants.

Overall, there was a greater preference for CHW/peer-based testing over self-testing, however clients were more comfortable and open to self-testing than staff. Despite staff hesitancy, most recognized that self-testing has “its place” and could serve as “a good tool for people to have”, or at the very least can be a last resort to reaching others who wouldn’t otherwise get tested. Participants suggested that conducting the HIV rapid test could be done by anyone who is adequately trained, including on follow-up and linkage to care, “training doesn’t necessarily mean they have to be a doctor or a nurse. It just means that they should be prepared to give the results, whatever the results may be…and if it were to turn out positive, then somebody who knows how to get connected to care” (Terrence, client). These skills are some of the benefits mentioned for CHW/peer-based testing in Table 1.

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Table 1. Benefits and Concerns regarding different target end-users of the rapid AHI test.

https://doi.org/10.1371/journal.pgph.0005366.t001

Additionally, organizations preferred CHW/peer-based testing, especially for high-risk or hard-to-reach communities like PWID,

“either peer-led or community health testing… I think would definitely benefit [PWID] … we’re able to test quite a few injection drug users just because we’re going to where they’re at, and we have an education component … nobody wants to be tested in the beginning, but then as the educator is halfway through the education, 6 of the 10 now want to be tested.” (Kennedy, Director of Outreach Services)

Discussion

This study aimed to understand context-specific challenges to HIV testing in Indiana, assess the acceptability of a novel AHI test in this context, and identify the target end-user and related implementation considerations for the technology. The required waiting period (up to 90 days post-exposure) of existing rapid tests is a significant barrier to preventing transmission and facilitating access to care in these populations. To that end, the need to detect HIV earlier among high-risk groups was expressed by many participants, and a novel AHI rapid test that would allow for this, despite taking up to an hour to produce results, was deemed highly acceptable. These findings both support and inform the continued development of this novel device.

This work can inform the development and implementation of broader emerging AHI tests. Portable RNA tests for POC AHI detection have recently been developed but not yet implemented [32–35]. Additionally, alternative antigen-antibody 4^th generation POC tests have been developed to detect AHI at the POC [36], however, both field and multi-laboratory trials have shown that the antigen detecting capabilities of these tests were unsuccessful [37,38]. With additional incubation or sample preparation steps [39] these 4^th generation tests may be better able to detect AHI. Our findings demonstrate that these additional steps may be worthwhile despite the added time to result, as our participants found this tradeoff to be acceptable if it meant earlier AHI detection.

While the FDA has approved qualitative laboratory-based HIV RNA tests for diagnosis, current CDC testing algorithms only recommend using laboratory RNA tests after HIV antigen/antibody testing for confirmation or genotyping, or if the first tests are indeterminant [40]. RNA-based AHI tests are more expensive than antibody/antigen counterparts [41]. Babigumira et al compared found that offering POC RNA-based testing to outpatients who present with symptoms of AHI would be a cost-effective strategy [42]. Similar analyses for screening of high-risk individuals in lower-burden countries would also be important to understand potential costs for implementation effectiveness in the US.

To inform further design of this novel test, different testing modalities were discussed with participants to gauge preferences for the target end-user (self-testing vs CHW/peer-led testing) and related implementation considerations. While participants expressed important benefits and concerns for both end-user groups, the majority felt that CHW/peer-led testing would better meet the needs of high-risk populations, particularly regarding the need for counseling and navigation to care. These findings support a growing body of literature on the acceptability of both HIV community-based/peer-led and self-testing more broadly [43–49]. Several reviews have found that while interest in self-testing is high among vulnerable groups because of convenience, privacy, and user desire to keep track of their status [50,51] many are concerned about the reliability and accuracy of tests and linkage to care and counseling [44–46]. These are many of the same concerns that existed when HIV antibody self-tests were first instituted [52]. Clear and simple instructions for self-tests, including next steps for a positive result, are important implementation considerations. With these in mind, it has been well documented that self-testers can reliably and accurately conduct rapid HIV testing compared to trained healthcare providers [53]. Future work will prioritize usability testing of the resulting rapid AHI test for both CHW/peers and clients to ensure ease of use.

This study also contributes to literature on model approaches for appropriate technology development that meaningfully consider and incorporate contextual investigation early in the design process of novel health technologies [20]. The utilization of human-centered design frameworks and engagement of diverse stakeholders to inform the acceptability and preferences of HIV testing interventions are key strategies to understand and promote their successful implementation, uptake and adoption [54,55]. Relatedly, a key limitation of this study is that recruitment relied on flyers posted at HIV service organizations, which likely biased the client sample toward individuals already engaged in HIV testing or care. As a result, the perspectives of medically underserved or less connected populations may not be fully captured. Future research should adopt proactive recruitment strategies, such as outreach in non-clinical community settings, to reach individuals not currently accessing testing or care. Given the sensitivity of the topic and the vulnerability of this population, our study relied on community partnerships with established client relationships. As such, our sample size of clients was relatively small and thematic saturation was not reached among this participant group. Recruitment was constrained by the ethical need to rely on passive, low-burden strategies during the COVID-19 pandemic. These constraints limited sample size but were necessary to ensure participant safety and confidentiality. Nonetheless, our findings provide important context-specific insights for technology development and offer significant support for future research around AHI diagnostics.

The staff we interviewed represented 10 organizations spanning six counties in Indiana, including health departments, syringe service programs, and healthcare clinics. While this diversity captures a range of service models and settings, it may not fully represent all geographic areas of the state or other organizational perspectives. Our study did not include perspectives from broader stakeholders such as policy makers or payers, who could provide important insights into regulatory and funding considerations. Future work must reach broader stakeholders including local health departments and insurance companies to understand implementation considerations related to reporting and reimbursement. Because the study was conducted in Indiana, findings may not generalize to regions with different HIV prevalence rates, healthcare infrastructure, or sociopolitical environments. Further studies in diverse geographic and epidemiologic contexts are needed to validate and expand these findings.

Given the positive response towards the goal of detecting AHI with POC technology, our findings have informed key next steps in accuracy, simplicity to use, and cost considerations. To increase accuracy, the limit of detection is being improved with new RNA assay designs. Further, the manufacturing costs are being reduced with streamlined device design that uses fewer parts and requires fewer steps for assembly. Lastly, an internal amplification control ensuring test validity and easily interpretable results will be adapted to the AHI detection.

A detailed target product profile (TPP) describing HIV test sensitivity, specificity, cost, failure rates, time-to-result, and operating conditions for at-home HIV testing was previously developed in 2014 [56]. However, this was focused on post seroconversion detection of HIV. While newer TPPs for recent HIV infection have been developed, these focus on epidemiologic surveillance [57], a new TPP with detailed specifications for POC AHI testing is warranted. Awareness of this need has long been known and the MicroRAAD device was originally based off of initial targets for NIH-funded development of technologies for AHI self-testing (PAR-17–471, https://grants.nih.gov/grants/guide/pa-files/PAR-17-471.html). These desired characteristics included acceptability among end-users, rapid test results within 1-hour, detection of 1000 virus particles per mL, specificity for circulating HIV clades, ease-of-use within an integrated sample-to-answer system, simple presentation and interpretation of results, refrigeration-independent storage, minimal electricity dependence, and cost effectiveness for end-users. The early-stage contextual investigation and acceptability study presented herein, combined with responsive technology design iteration and usability testing among the intended users, brings together best practices of human- and equity-centered design.

Supporting information