Improved Laboratory Diagnosis of Acute HIV Infection
By Stan Deresinski, MD, FACP, FIDSA, Clinical Professor of Medicine, Stanford University, Hospital Epidemiologist, Sequoia Hospital, Redwood City, CA, Editor of Infectious Disease Alert.
SYNOPSIS: In 2006, the CDC recommended routine, voluntary HIV testing for persons aged 13-64 in all health care settings, with elimination of separate informed consent5 and this recommendation has basically now been adopted by the U.S. Preventive Services Task Force. It is also critical that clinicians be alert to the diagnosis of acute HIV infection. CDC now recommends that current practice be changed to reflect the results of the studies reviewed here.
SOURCE: Centers for Disease Control and Prevention. Detection of Acute HIV Infection in Two Evaluations of a New HIV Diagnostic Testing Algorithm - United States, 2011-2013. MMWR 2013;62(24):489-94.
Early treatment of acute or recent HIV infection is associated with improved CD4 cell recovery,1 as well as additional potential clinical benefits such as a reversal of neuronal inflammation as observed by magnetic resonance spectroscopy.2 It is also now recognized as a prevention strategy since many transmissions occur during this period of high viral load, often in the absence of symptoms.3 Unfortunately, most cases of HIV infection are not diagnosed until the infection has become chronic, either because the initial infection was asymptomatic or, in some symptomatic cases, because seroconversion may not have been detected with standard antibody testing.
The current standard HIV diagnostic algorithm consists of performing an immunoassay (IA) which, if initially positive, is repeated. A reproducibly positive IA is followed by use of a supplemental confirmatory test, such as the Western blot (WB) or indirect immunofluorescence assay (IFA). In acute infection, however, currently used IA tests detect HIV infection earlier than supplemental tests. During that interval before the supplemental test becomes positive, a reactive IA in combination with a negative supplemental test may erroneously be interpreted in some patients as indicating an absence of HIV infection. In addition, approximately 60% of HIV-2 infections are misclassified as HIV-1 infection. A recent study in 26 recent seroconverters in the U.S. found that one or more IAs became positive 5-26 days before Western Blot positivity.4 There has, however, been progressive improvement in HIV testing: 1st and 2nd generation tests, which use viral lysate antigens and either synthetic peptide or recombinant antigens, respectively, and which detect only IgG antibodies, have been largely supplanted by more sensitive tests.
>Most laboratories currently use either 3rd generation IAs that detect both IgM and IgG antibodies as well as p24 antigen. The changing technology of HIV testing has led the CDC to evaluate a new HIV diagnostic algorithm utilizing newer tests. In an initial study, in which a sensitive 3rd or 4th generation immunoassay was followed by an HIV-1 and HIV-2 discriminatory test, with discordant results settled by a nucleic acid amplification test, significantly more infections were detected than were with use of the standard algorithm with older tests.5 Furthermore, a 4th generation test performed better than a 3rd generation test. In contrast, the alternative algorithms performed equally well in patients with chronic HIV infection.
CDC has now extended the study of the alternative algorithm, using a 4th generation IA and replacing the Western Blot with an HIV-1/HIV-2 antibody differentiation assay and uses detection of HIV RNA to resolve cases in which the IA is positive but the supplemental result is negative. In one study in an Arizona emergency department, screening of all adults 18 through 64 years of age identified 37 previously unidentified HIV infections; 12 (32.4%) were acute and would have been missed by current testing practices. Separately, in a multisite study, 56 acute HIV infections would similarly have been missed by current testing practices [See Figure 1].
In 2006, the CDC recommended routine, voluntary HIV testing for persons aged 13-64 in all health care settings, with elimination of separate informed consent5 and this recommendation has basically now been adopted by the U.S. Preventive Services Task Force. It is also critical that clinicians be alert to the diagnosis of acute HIV infection. CDC now recommends that current practice be changed to reflect the results of the studies reviewed here.
Figure 1. New HIV diagnostic testing algorithm evaluated - United States, 2011-2013
Abbreviation: HIV = human immunodeficiency virus.
* Additional testing required to rule out dual infection with HIV-1 and HIV-2.
Alternate Text: The figure above is a flowchart depicting the new human immunodeficiency virus (HIV) diagnostic algorithm, which replaces the Western blot test with an HIV-1/HIV-2 antibody differentiation assay as the supplemental test and includes an RNA test to resolve a reactive immunoassay with a negative supplemental test result.
Source: Centers for Disease Control & Prevention
1. Le T, et al. Enhanced CD4+ T-cell recovery with earlier HIV-1 antiretroviral therapy. N Engl J Med 2013;368:218-30.
2. Sailasuta N, et al; RV254/SEARCH 010 protocol teams. Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection. PLoS One 2012;7:e49272.
3. Owen SM. Testing for acute HIV infection: implications for treatment as prevention. Curr Opin HIV AIDS 2012;7:125-30.
4. Masciotra S, et al. Evaluation of an alternative HIV diagnostic algorithm using specimens from seroconversion panels and persons with established HIV infections. J Clin Virol 2011;52 Suppl 1:S17-22.
5. Centers for Disease Control and Prevention. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR 2006;55(RR-14):1-17.