The healthcare landscape is changing due to technological developments in Human Immunodeficiency Virus (HIV) testing combined with large-scale public health campaigns aimed at identifying people who are unknowingly carrying the virus or not engaged in care. These efforts allow clinicians to begin treatment sooner and ultimately improve patient outcomes.
According to the U.S. Department of Health & Human Services, of the more than 1.1 million people living in the United States with HIV infection, about 1 in 6 are unaware of being infected.
"Individuals who live in remote places and are perfectly healthy may not think they need to see a doctor, and therefore, don't get tested," explained Belinda Yen-Lieberman, PhD, SV(ASCP), medical director of virology at the Cleveland Clinic, member of the American Society for Clinical Pathology. "This population is dangerous. How can we capture these individuals who are HIV positive and don't know?"
Over the past few years, major advancements in HIV testing have occurred on multiple levels from shifts in public health guidelines and health policy to innovations at the basic science level, according to Carolyn Chu, MD, MSc, medical director of the Ryan/Chelsea-Clinton Community Health Center in New York City.
Ramping Up Screening Efforts
Many professional organizations and federal agencies have recently begun to stress the importance of HIV testing in order to facilitate early diagnosis and treatment, Chu told ADVANCE.
"In order to maximally benefit from antiretroviral therapy, people living with HIV/AIDS need to first become fully and successfully engaged in medical care," Chu said. "Before antiretroviral therapy initiation and engagement in care can occur, individuals must be aware of their HIV status -- and this can only be accomplished through HIV testing and follow-up."
In April 2013, in a move supporting 2006 guidelines produced by the CDC, the U.S. Preventive Services Task Force changed their recommendation for universal HIV screening for everyone aged 15 to 65 to a grade "A."
According to Chu, this recommendation helped open the door for hospitals and healthcare centers to intensify their HIV screening efforts, as testing subsequently became a preventive service that many health insurance programs were required to reimburse (thereby eliminating out-of-pocket costs for patients).
"The recommendation also underscores a shift away from testing only those perceived to be at high risk, a practice subject to variations in clinical interpretation, and furthermore may help reduce stigma surrounding HIV testing," Chu observed.
Advances in HIV Testing
In 2010, the U.S. Food and Drug Administration approved the first "fourth-generation" HIV Ag/Ab combo assay. Compared with third-generation assays, fourth-generation assays have the ability to detect HIV infection earlier due to inclusion of the HIV p24 antigen. This reduces the "window period" by an estimated 7 days (range 0-20) and can subsequently identify up to 90% of acutely-infected individuals who would have been missed using third-generation tests, reported Chu.
The most common HIV test, the immunoassay, tests for the antibodies the body makes against HIV. The immunoassay is performed on blood or oral fluid in a laboratory. A rapid test is an immunoassay used for screening that can produce results in 20 minutes or less. According to Chu, the rapid tests effectively eliminate wait time for turnaround between the testing location and off-site laboratory.
If an immunoassay result is positive, then follow-up diagnostic testing is performed. Follow-up tests include: an antibody differentiation test, which distinguishes HIV-1 from HIV-2; an HIV-1 nucleic acid test, which looks for virus directly; and the Western blot or indirect immunofluorescence assay, which detect antibodies.
With the fourth generation test, Yen explained, the same sample is gathered from the patient but the test is designed to screen for the HIV p24 Ag and the antibody at the same time which produces more accurate results. "The new versions of HIV tests have changed the way we approach HIV diagnosis. We can capture more HIV infected people now," she said.
Because acutely-infected individuals tend to be highly infectious due to high levels of HIV virus, identifying people sooner gives healthcare workers more opportunity to counsel patients at a very important time from a public health perspective, Chu explained.
"This test will be very important because it reaches all grassroots effort," Yen said. "HIV testing should be part of all routine checkups and physicians need to make sure partners are checked as well."
Antiretroviral therapy regimens are now simpler, more potent and less toxic than before. Additionally, Chu explained, novel research within the last five years indicates that HIV "pre-exposure prophylaxis" medications are an effective vehicle to prevent HIV acquisition.
"These advances effectively confirm that HIV is now both treatable and preventable, and HIV testing should therefore be a part of routine care," Chu said.
Next Generation Testing
The Enzygnost HIV Integral 4 Assay is a combination assay that provides qualitative determination of HIV-1 antigen as well as antibodies specific for all relevant HIV subtypes including HIV-1, HIV-1 group O, and HIV-2. The HIV Integral 4 assay employs proven ELISA technology and runs on microtiter plates.
"An extraordinary low detection limit for p24 antigen was materialized which so far, has only been achieved for HIV-antigen-only tests," said Stefan Wolf, CEO of the hemostasis, hematology and specialty business unit of Siemens Healthcare Diagnostics.
The test, which is not approved in the United Sates, is subject to guidelines from the European Union that call for certain sensitivity criteria and increased screening for HIV infection. "Sensitive testing technologies are central to this move," Wolf said. "Use of a combination test that detects both antigens and antibodies to HIV provides an improvement in earlier detection compared to antibody-only assays."
According to Wolf, the high specificity and sensitivity of the Enzygnost HIV Integral 4 Assay allow earlier identification of HIV infection so clinicians can begin treatment sooner and ultimately improve patient care.
On the Horizon
On a global scale, multi-national programs such as USAID and UNITAID are supporting investigations involving micro-fluid lab on a chip (or lab on a disk/lab on a DVD) platforms, according to Chu. "These cost-effective platforms have significant potential as diagnostic and evaluative devices for resource-limited areas, by using miniature portable chips or DVDs with minimal processing requirements to help automate complicated assays normally performed in a laboratory setting," she said.
Patient samples are loaded into micro-channels that can then be scanned by equipment such as DVD readers. In addition to identifying people who are HIV-infected, this type of technology could also potentially be used by workers in the field to measure CD4 or HIV viral load levels, Chu relayed.
"With revised recommendations for universal screening from bodies such as the CDC, providers and outreach programs may perceive fewer barriers to testing and thus more widely implement it into everyday practice," Chu said.
Chu believes that with widespread and regular HIV testing, infected individuals can be identified early in the course of illness and start transitioning across the various stages of engagement in care.
Rebecca Knutsen is on staff at ADVANCE. Contact: email@example.com.