Acute human immunodeficiency virus (HIV) infection (AHI) can be defined as the time from HIV acquisition until seroconversion. Incident HIV infection is less well defined but comprises the time from the acquisition of HIV (acute infection) through seroconversion (early or primary HIV infection) and the following months until infection has been well established, as characterized by a stable HIV viral load (viral load set point) and evolution of antibodies with increased concentration and affinity for HIV antigens. During AHI, a viral latent pool reservoir develops, the immune system suffers irreparable damage, and the infected (often unsuspecting) host may be most contagious. It has proved very difficult to find individuals with AHI either in longitudinal cohorts of subjects at high risk for acquiring the virus or through cross-sectional screening, and the opportunity for diagnosis is generally missed during this phase. We review the technical strategies for identifying individuals with acute or incident HIV infection. We conclude that further technical advances are essential to allow more widespread detection of patients with AHI and to affect HIV treatment outcomes and transmission prevention.

The Detection of Acute HIV Infection

2. Specimens with a reactive antigen/antibody combination immunoassay result (or repeatedly reactive, if repeat testing is recommended by the manufacturer or required by regulatory authorities) should be tested with an FDA-approved antibody immunoassay that differentiates HIV-1 antibodies from HIV-2 antibodies. Reactive results on the initial antigen/antibody combination immunoassay and the HIV1/HIV-2 antibody differentiation immunoassay should be interpreted as positive for HIV-1 antibodies, HIV-2 antibodies, or HIV antibodies, undifferentiated.

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Laboratory testing for the diagnosis of HIV infection : updated recommendations

Purpose of Review
Acute HIV infection (AHI), the earliest period after HIV acquisition, is only a few weeks in duration. In this brief period, the concentration of HIV in blood and genital secretions is extremely high, increasing the probability of HIV transmission. Although a substantial role of AHI in the sexual transmission of HIV is biologically plausible, the significance of AHI in the epidemiological spread of HIV remains uncertain.

Role of acute and early HIV infection in the sexual transmission of HIV.

Summary Background The focus on prevention strategies aimed at curbing the HIV epidemic is growing, and therefore screening for HIV has again taken centre stage. Our aim was to establish whether a convenient, non-invasive, HIV test that uses oral fluid was accurate by comparison with the same test with blood-based specimens. Methods We did a systematic review and meta-analysis to compare the diagnostic accuracy of a rapid HIV-antibody-based point-of-care test (Oraquick advance rapid HIV-1/2, OraSure Technologies Inc, PA, USA) when used with oral versus blood-based specimens in adults. We searched five databases of published work and databases of five key HIV conferences. Studies we deemed eligible were those focused on adults at risk of HIV; we excluded studies in children, in co-infected populations, with self-reported inferior reference standards, and with incomplete reporting of key data items. We assessed the diagnostic accuracy of testing with oral and blood-based specimens with bivariate regression analysis. We computed positive predictive values (PPVs) in high-prevalence and low-prevalence settings with Bayesian methods. Findings In a direct head-to-head comparison of studies, we identified a pooled sensitivity about 2% lower in oral (98·03%, 95% CI 95·85–99·08) than in blood-based specimens (99·68%, 97·31–99·96), but similar specificity (oral 99·74%, 99·47–99·88; blood 99·91%, 99·84–99·95). Negative likelihood ratios were small and similar (oral 0·019, 0.009–0·040; blood 0·003, 0·001–0·034), but positive likelihood ratios differed (oral 383·37, 183·87–799·31; blood 1105·16, 633·14–2004·37). Although in high-prevalence settings PPVs were similar (oral 98·65%, 95% credible interval 85·71–99·94; blood 98·50, 93·10–99·79), in low-prevalence settings PPVs were lower for oral (88·55%, 77·31–95·87) than blood (97·65%, 95·48–99·09) specimens. Interpretation Although Oraquick had a high PPV in high-prevelence settings in oral specimens, the slightly lower sensitivity and PPV in low-prevalence settings in oral specimens should be carefully reviewed when planning worldwide expanded initiatives with this popular test. Funding Canadian Institutes for Health Research (CIHR KRS 102067).

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Head-to-head comparison of accuracy of a rapid point-of-care HIV test with oral versus whole-blood specimens: a systematic review and meta-analysis.

Background. Since 2002, the US Food and Drug Administration has approved 6 rapid human immuno-deﬁciency virus (HIV) tests for use in the United States. To date, there has been no direct comparison of theperformance of all 6 tests.Methods. Persons known to be HIV-infected and persons who sought HIV testing at 2 clinical sites in LosAngeles, California, were recruited for evaluation of 6 rapid HIV tests with whole blood, oral ﬂuid, serum, andplasmaspecimens.Sensitivityandspeciﬁcityoftherapidtestswerecomparedwithvirallysateandimmunoglobulin(Ig) M–sensitive peptide HIV enzyme immunoassays (EIAs).Results. A total of 6282 specimens were tested. Sensitivity was .95% and speciﬁcity was .99% for all rapidtests.ComparedwiththeIgM-sensitiveEIA,rapidtestsgavefalse-negativeresultswithanadditional2–5specimens.All rapid tests had statistically equivalent performance characteristics, based on overlapping conﬁdence intervals forsensitivity and speciﬁcity, compared with either conventional EIA.Conclusions. All 6 rapid tests have high sensitivity and speciﬁcity, compared with that of conventional EIAs. Becauseperformance was similar for all tests and specimen types, other characteristics, such as convenience, time to result,shelflife,andcostwilllikelybedeterminingfactorsforselectionofarapidHIVscreeningtestforaspeciﬁcapplication.In 1998, when the Centers for Disease Control andPrevention (CDC) encouraged the use of rapid humanimmunodeﬁciency virus (HIV) tests to increase the re-ceipt of results among persons tested for HIV [1], onlytheSingleUseDiagnosticSystemforHIV-1(SUDS)wascommercially available in the United States [2]. Since2002, the US Food and Drug Administration (FDA) hasapproved 6 rapid HIV tests [3] that have become in-tegral to initiatives designed to promote more wide-spread HIV testing [4–10].Rapid HIV antibody tests provide results in ,30min [3]. FDA-approved rapid HIV tests (Table 1)employ either immunochromatography (lateralﬂow) or immunoconcentration (ﬂow-through) tech-niques [11] and contain antigens that correspond toenvelope regions of HIV-1 (gp41, gp120, or both).Some tests also have an HIV type 2 (HIV-2) envelope(gp36) antigen. However, recent studies have docu-mented that rapid HIV tests have lower sensitivity,especially during early infection, than that of someconventional assays [12–14]. False-negative test re-sults have also been observed in individuals with ad-vanced disease [15] and in some persons who arereceiving effective antiretroviral therapy (ART) [16,17]. Because test manufacturers do not explicitlyidentify which reference tests were used to calculatesensitivity and speciﬁcity (Table 1), this study wasundertakentocomparecontemporaryrapidHIVtestsand conventional enzyme immunoassays (EIAs) whenperformed on specimens fromthesamepersons.METHODSThe two-phase ﬁeld study was conducted at the Los An-geles Gay and Lesbian Center (LAGLC), an HIV testing

Evaluation of the Performance Characteristics of 6 Rapid HIV Antibody Tests

Background The yield of nucleic acid amplification testing (NAAT) after routine screening for human immunodeficiency virus (HIV) antibody to detect acute HIV infection (AHI) may vary with different HIV-antibody assays. Methods From April 24, 2006, through March 28, 2008, patients underwent routine HIV-antibody screening using a first-generation assay at 14 county sexually transmitted disease (STD) clinics and 1 community clinic serving homosexual patients in Los Angeles; using a second-generation rapid test at 3 municipal STD clinics in New York; and using a third-generation assay at 80 public health clinics in Florida. To identify AHI, seronegative specimens were pooled for NAAT, followed by individual NAAT of specimens with positive findings. All AHI samples screened by first- and second-generation assays also underwent third-generation testing. Results We screened 37 012 persons using NAAT after first-generation testing; 35 AHIs were identified, increasing HIV case detection by 8.2%. After a second-generation rapid test, 6547 persons underwent NAAT; 7 AHIs were identified, increasing HIV case detection by 24.1%. After third-generation testing, 54 948 persons underwent NAAT; 12 AHI cases were identified, increasing HIV case detection by 1.4%. Overall, pooled NAAT after negative third-generation test results detected 26 AHI cases, increasing HIV case detection by 2.2%. Most of the AHI cases from Los Angeles (26 of 35 [74%]) were identified at the community clinic where NAAT after third-generation testing increased HIV case detection by 11.9%. Conclusions Pooled NAAT after third-generation testing increases HIV case detection, especially in venues of high HIV seropositivity. Therefore, targeted AHI screening using pooled NAAT after third-generation testing may be most effective, warranting a cost-benefit analysis.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/481525/ioi90117_66_74.pdf

Detecting Acute Human Immunodeficiency Virus Infection Using 3 Different Screening Immunoassays and Nucleic Acid Amplification Testing for Human Immunodeficiency Virus RNA, 2006-2008

Pat Simmons

Papers

Detecting Acute Human Immunodeficiency Virus Infection Using 3 Different Screening Immunoassays and Nucleic Acid Amplification Testing for Human Immunodeficiency Virus RNA, 2006-2008