Evolving strategies for diagnosing human immunodeficiency virus infection.

Since the first antibody tests for the diagnosis of human immunodeficiency virus (HIV) infection were approved by the Food and Drug Administration in 1985, many “new and improved” HIV screening and diagnostic tests have been developed, and a variety of testing algorithms have come into use. HIV antibody tests have evolved from first generation HIV-1(clade B) viral lysate-based, indirect antibody enzyme immunoassays (EIAs) to third generation antigen-sandwich immunoassays that use synthetic peptide and recombinant DNAderived antigens that represent the immunodominant epitopes from diverse HIV-1 and HIV-2 strains. These third generation enzyme immunoassays have substantially enhanced sensitivity to divergent viral variants and have shortened the infection-to-seroconversion window period by more than 3 weeks compared with first generation tests. Assays have also been developed that detect and quantitate viral antigen (p24) and nucleic acids (HIV RNA or DNA) in blood, and in body fluids and tissues. These assays have seen increasing application in blood and organ donor screening, as well as in clinical diagnosis, prognosis, and therapeutic monitoring; and clinicians now have access to a broad and potentially confusing array of test options, each with its own advantages and limitations. Developing testing algorithms and interpretive criteria appropriate to a particular group of patients— high-risk adults; blood, plasma and organ donors; recently exposed healthcare workers; pediatric patients— poses a challenge, especially as new tests appear with tantalizing claims of enhanced performance. In this issue, Mylonakis et al (1) put forth a comprehensive and practical overview of the various laboratory tests currently available for diagnosis and management of HIV infection. The authors first review the standard algorithm for diagnostic testing, which relies primarily on serology and varies slightly according to the patients being tested. For the majority of patients in primary care settings, serologic strategies using antibody detection enzyme immunoassays and Western blots remain the most rational and cost-effective approach for screening and diagnosis. However, as will be discussed later, the authors also present a second option for screening using a combination of immunoassays and nucleic acid technologies. This approach is increasingly used in donor screening and may prove to be a more accurate and equivalently cost-effective approach for the diagnosis of HIV infection in the clinical setting. The authors then review several recent additions to the conventional blood-based antibody tests, including noninvasive testing strategies that apply optimized serological assays for HIV antibody detection in oral fluids, urine, and vaginal secretions. Although these tests are not yet widely used in diagnostic settings, they provide important alternatives to the traditional blood sample and may have advantages in certain settings, such as patients with poor venous access, those who refuse phlebotomy, or serial screening of sexual partners or contacts of HIV-positive patients. Also included in the review is a discussion of so-called rapid assays that offer the opportunity for point-of-care testing, thus avoiding the anxiety and other problems associated with delayed reporting of HIV test results. Most rapid tests are variations of HIV antibody enzyme immunoassays that have been configured into simple flowthrough cartridges to yield color read-outs within minutes of application of a blood specimen. These tests are relatively inexpensive and stable, and performing them requires little to no specialized training or equipment. While the sensitivity and specificity of rapid tests are generally not as high as with conventional immunoassays and Western blot assays, they may be very useful for selected patients. One example is the postexposure setting, in which determination of the HIV antibody status of the source of an exposure can guide decisions about postexposure prophylaxis. The Centers for Disease Control is also evaluating the utility of testing algorithms using serial rapid tests and immediate notification and counseling in public health test settings (anonymous test sites and sexually transmitted disease clinics) where 25% to 30% of tested subjects do not return for their results (2). Rapid and non-blood– based tests may also be valuable for screening in developing countries, where HIV incidence and prevalence rates are high and where low cost, ease of use, and stability of reagents are pressing requirements (3). Another novel antibody testing strategy briefly mentioned by Mylonakis et al utilizes a less sensitive or “detuned” HIV enzyme immunoassay to discriminate persons with recent versus long-standing HIV infection (4). Samples identified as seropositive by standard testing algorithms are simply reflex tested using the less sensitive assay, and those Am J Med. 2000;109:595–597. From the Blood Centers of the Pacific, Irwin Center, Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California. Requests for reprints should be addressed to Michael P. Busch, MD, PhD, Blood Centers of the Pacific, Irwin Center, Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California.