Accelerating Human Immunodeficiency Virus Self-Testing in the United States: A Call to Action

Abstract

Human immunodeficiency virus (HIV) self-testing has emerged as a tool to increase the proportion of people to know their status. Since the first HIV self-test was approved in 2012 by the US Food and Drug Administration (FDA), global access to HIV self-tests has been bolstered by public-private partnerships to ensure equitable access in low- and middle-income countries. However, no company has applied for FDA clearance in a decade. We highlight the potential benefits to reclassifying HIV self-tests from class III to class II.

Human immunodeficiency virus (HIV) self-testing is used to increase the proportion of people knowing their status. No company has applied for FDA clearance in a decade. We highlight potential benefits of reclassifying HIV self-tests from class III to class II.

(See the Viewpoints by Wood and Stekler on pages 1681–4.)

In the United States, human immunodeficiency virus (HIV) remains undiagnosed in an estimated 13% of HIV-infected people [1]. The Centers for Disease Control and Prevention (CDC) has recommended that all adolescents and adults be screened for HIV at least once and that some populations be screened at least annually [2]. Despite the availability of HIV testing through healthcare providers and community-based services, some populations still experience significant barriers to HIV testing. Consequently, the average time from acquisition of HIV to diagnosis is 3 years in the United States, resulting in continued transmission and adverse health outcomes [3].

Access to high-quality HIV testing is the first step in the HIV care continuum. In 1996, to facilitate access to HIV testing, an HIV self-collection kit, using dried blood spots that were mailed to a laboratory for testing, was approved by the US Food and Drug Administration (FDA). Although this product is no longer available for purchase, other HIV self-collection kits that provide results in 2–5 days are available on the internet but are not currently FDA approved. In contrast, HIV self-testing provides results in approximately 20 minutes, allows persons to obtain results privately, confidentially, and accurately, and has the potential to increase access to HIV testing by overcoming some barriers associated with accessing existing services. The approval of the first over-the-counter HIV self-test in July 2012 facilitated access to HIV testing by allowing consumers to buy tests directly from pharmacies and via the internet. A decade later, the OraQuick In-Home HIV Test (OraSure Technologies) remains the only HIV self-test to have received FDA approval and has a retail price of about $40, which has limited uptake [4].

The World Health Organization (WHO) recommends including HIV self-testing as part of a country's national HIV prevention program and has approved (prequalified) 6 HIV self-tests since 2016; 5 use fingerstick whole blood, and 1 uses oral fluid. The WHO prequalification program assesses available evidence to ensure that in vitro devices meet acceptable quality and performance standards and works with national regulatory authorities and partner organizations to facilitate large-scale procurement to improve access to diagnostics. In 2019, WHO concluded that harms associated with HIV self-testing were rare and comparable to those of other HIV testing services [5]. By 2020, 88 countries had policies that allowed HIV self-testing, and another 31 countries had policies in development. Numerous countries, nongovernmental organizations, and the WHO have made a concerted effort to expand access to HIV self-tests, especially in low- and middle-income countries (LMICs). With the commitment to HIV self-test purchasing through procurement agreements, companies have dropped the public sector cost of a HIV self-test to $1 per unit for LMICs in 2022 [6].

Why have so few tests received FDA clearance in the United States? The FDA classifies in vitro diagnostic devices by the level of risk and the controls necessary for assurance of safety and effectiveness of the device. Most vitro diagnostic devices are classified as class II. Class III devices are classified as products that “usually sustain or support life, are implanted, or present a potential unreasonable risk of illness or injury” [7]. Glucose monitors and pregnancy tests are class II devices, while implantable pacemakers and cochlear implants are class III. In 1985, the first FDA-approved HIV test was classified as a class III device because it was used to screen the nation's blood supply. However, on 15 June 2022, the FDA reclassified select HIV serological diagnostic and supplemental tests and HIV nucleic acid diagnostic and supplemental tests to class II. HIV self-tests remain class III devices [7].

Reclassification of point-of-care and laboratory HIV tests from class III to class II is expected to substantially lower the regulatory and administrative burden for medical device companies and decrease the time for devices to reach the market. All class III vitro diagnostic devices need to undergo a premarket approval (PMA) application. PMA application fees cost approximately $310 000, and the company must also conduct clinical trials to prove the device is safe and effective in its intended population [8]. The review time for PMA applications is set at 180 days for FDA review. Meanwhile, class II devices use 510(k) applications, costing approximately $10 000, and have a FDA review time of 90 days [8]. The average cost to bring a medical device to the market through a PMA is $94 million, compared with $31 million through the 510(k) process [9]. If the FDA determines that a class II device is as safe and effective as a preexisting device on the market, the device is cleared by the FDA.

Although there is a preexisting FDA-approved oral fluid HIV self-testing device on the market, and 5 additional WHO-prequalified devices (using capillary fingerstick blood), the FDA specifically excluded HIV self-tests from the reclassification to class II. The FDA continues to express concern that there is a higher risk with self-testing for HIV than for other infectious and noninfectious conditions [8]. Risks include the possibility of receiving a false-negative result and thus not seeking care, adverse physical or psychological events associated with a positive result, and the stigma associated with HIV infection as an incurable disease. However, a counterargument is the risk associated with individuals with risk factors for HIV infection never testing because they do not have access to affordable HIV self-tests and are unable or unwilling to use existing testing services. Studies of HIV self-testing have shown that increasing access to self-tests effectively increases testing; 16%–36% of study participants reported never testing previously [10–12]. A randomized clinical trial showed that self-tests increased the number of new HIV cases diagnosed, with no increased in sexual risk behaviors other than serosorting, with a secondary analysis showing limited incidences of pressure and no reported physical harm [11, 13].

When integrated into public health programs as a comprehensive service model, HIV self-testing is an important component of HIV epidemic control. Self-testing can help individuals avoid stigma and also may address health disparities that are driving the US HIV epidemic. A randomized trial demonstrated that online distribution of HIV self-tests to gay, bisexual and other men who have sex with men provided accurate diagnosis [11] and was cost saving [14]. In addition, the CDC and collaborators distributed 100 000 HIV self-tests in the United States over 8 months through internet orders during the coronavirus disease 2019 (COVID-19) pandemic, and the CDC has committed to distributing a million HIV self-tests over the next 5 years [12, 15]. Globally, procurement agreements via the US President's Emergency Plan for AIDS Relief, Unitaid, and the Global Fund to Fight AIDS, Tuberculosis and Malaria have acquired more than 7.5 million self-tests in 2021, with a projected demand of 25 million by 2025 in LMICs [16].

No company has applied for FDA approval for an HIV self-test in the past decade. Barriers associated with obtaining the necessary FDA approval should be reduced, and reclassification of HIV self-tests would be an important step. This may encourage more companies to seek FDA clearance, increase market competition, and thereby drive down cost.

Early in the COVID-19 pandemic, the pricing of COVID-19 antigen tests was a barrier to testing. However, the United States government began distributing free tests by mail as an epidemic control method, serving both individuals and public health control. An estimated 158 000 people have undiagnosed HIV infection in the United States, with tens of thousands of new infections each year. To end the HIV epidemic, we need to develop and use innovative tools. Self-testing is safe and effective, and its potential has not yet been fully realized.

Notes

Disclaimer. The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. Research reported in this publication was supported by the National Institute of Biomedical Imaging And Bioengineering of the National Institutes of Health under Award Number U54EB007958 and Fogarty International Center of the National Institutes of Health under Award Number D43TW009771. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Financial support. This work was salary support from the National Institute of Health [NIBIB U54EB007958 (YCM, SM), NIAID UM1AI068613(YCM), and Fogarty International Center 5D43TW009771 (YCM)] and the US Centers for Disease Control U01PS005204 (YCM).