Rapid HIV-1/2 antibody-based tests performed at POC are becoming the global standard for HIV testing, particularly in the developing world. The efficacy and acceptability of rapid, POC HIV antibody tests have been confirmed by over a decade of studies which show that rapid HIV testing increases the number of people that truly know their infection status compared to non-rapid HIV testing strategies[2
]. In addition, cost-analyses have shown that rapid POC testing is cheaper per test result delivered when compared to standard blood testing[6
]. HIV diagnosis is typically accomplished through the sequential use of a two separate rapid HIV-1/2 antibody tests[7
]. In resource-limited settings (RLS), concordant serological reactivity on two appropriately selected rapid tests is highly predictive of infection and frequently considered sufficient for presumptive diagnosis of HIV infection. In more developed countries, confirmation of antibody positive rapid samples are accomplished by use of an independent HIV test method, such as the detection of HIV nucleic acids or specific HIV antigen reactivity patterns using Western blots or line immuno-assays.
Despite these advantages, rapid HIV antibody, as well as non-rapid serologic, tests do have certain limitations. They can yield false-negative results for acute HIV infection (prior to, or early following seroconversion), and false-positive results in uninfected HIV vaccine participants and infants with passive maternal antibodies derived from HIV-seropositive mothers. In addition, the current rapid antibody testing strategies may yield false-positive interpretations unless relatively costly confirmation and/or follow-up testing are conducted.
Combination antigen-antibody tests have been introduced to make ‘near-to-patient’ testing possible[9
]. These so-called 4th generation enzyme or chemiluminescent immunoassays (EIAs; ChIAs) are engineered for dual detection of p24 antigen and immunodominant HIV antibodies. These antigen-antibody tests are widely available in Europe, Australia, and recently in Latin America[10
] and can detect a subset of acute infections without the need for specimen pooling, which is normally done to increase efficiency and reduce costs of (Nucleic Acid Amplification Tests) NAATs[13
]. While somewhat more expensive than antibody tests, these new 4th
generation assays have the advantage of a single test that can be performed on a wide array of available equipment, making them adaptable to most ‘1st tier’ laboratory settings in the developing world. However, some of these tests have formats that only work with a given dedicated instrument, and thus implementation might be more costly than traditional EIAs that do not require such equipment. Unfortunately, 4th generation HIV EIAs/ChIAs assays are not yet FDA-approved for use in the US, and only a few Ag/Ab assays are available in rapid POC formats outside the US. However, novel rapid-format 4th
generation technologies are being developed to capture more window phase infections in areas with limited resources. These types of tests have shown encouraging early results in terms of detection and discrimination of acute and chronic HIV infections (Inverness Medical: Determine®
HIV-1/2 Ag/Ab Combo)[14
]. Nevertheless, the accuracy of this test will be compromised for HIV-vaccine participants and babies born to HIV-infected mothers because of vaccine-induced or maternal antibodies.
High-quality, sophisticated diagnostic tests targeting HIV-1 DNA or RNA, definitive markers of active HIV-1 infection, are widely available in the developed world. However, these types of tests are currently neither affordable nor likely accessible in RLS due to lack of financial resources, absence of trained personnel and minimal laboratory facilities. Furthermore, the majority of currently available molecular diagnostic assays require expensive equipment that is often dedicated to a specific manufacturer’s platform. These assays are technologically complex and require physical resources such as clean water, air conditioning, cold storage, efficient transport under low temperature, and an uninterrupted electricity supply, all of which are often not available in RLS.
Gen-Probe’s (APTIMA®) HIV-1 RNA qualitative assay[15
] is the only molecular assay that is FDA approved for diagnosis of acute infections and as a confirmatory test for diagnosing HIV-1 in samples that test reactive for HIV-1 antibodies[16
]. Other commercially available molecular assays were developed as quantitative viral load assays for therapeutic monitoring, and are currently only available in expensive, high-throughput formats (see Stevens in this supplement). The use of RNA testing of dried blood spots (DBS), often as a complement to rapid serological assays, has enabled these molecular technologies to reach more remote settings, especially for the detection of HIV-1 nucleic acid in infants[17
]. However, DBS test results do not return to the point of initial collection for patient notification for weeks to months. Therefore, DBS molecular testing is neither efficient nor effective since it does not provide the benefits of same-day treatment decisions and fails to address the substantial proportion of tested individuals who are lost to follow up.