Abbott ARCHITECT HIV Research Articles

Performance evaluation of the new Access HIV Ag/Ab combo assay on the DxI 9000 Access Immunoassay Analyzer

Fourth-generation HIV immunoassays have been developed to reduce the window period of detection during seroconversion period, allowing for the detection of early and established infections. The aim of this work was to evaluate a newly developed assay, Access HIV Ag/Ab combo on the novel high throughput DxI 9000 Access Immunoassay Analyzer (Beckman Coulter, Inc.). The assay allows for simultaneous qualitative detection and differentiation of HIV-1 p24 antigen and HIV-1/2 antibodies.Assay performance was compared to two gold standard assays, the Abbott Architect HIV Ag/Ab Combo and Roche Elecsys HIV Duo, and assessed in a multicenter study, using a wide panel of samples (n > 9000, clinical samples and viral lysates) representative of genetic diversity for both antibodies and antigens, early phases of infection, negative, and cross-reacting samples.The clinical sensitivity was 100 % for clinical samples as well as for viral lysates. Data on viral lysates and early detection on seroconversion panels showed a better result with the Access assay. Analytical sensitivity showed a limit of p24 detection determined around 0.2 IU/mL. The overall specificity was 99.91 %, and no interference was found using the potentially cross-reactive samples.In conclusion, the Access HIV Ag/Ab combo assay demonstrated its ability for accurate diagnosis of chronic as well as primary HIV infections on the DxI 9000 Analyzer, despite the high level of genetic diversity of these viruses.

A-245 Reagent Lot Variation—When should I be Concerned?

Abstract Background Reagent lot variation is often considered a major source of concern for infectious disease serology testing. Regular review of quality control testing data for specific assays confirms that, when using traditional statistical methods, such as using small datasets to establish mean/SD and then applying Westgard rules, reagent lot variation is the most common cause of variation observed. To investigate every incident is time consuming, costly and likely unnecessary in the majority of cases. But how do we create an alternative to monitoring QC data that accepts normal reagent lot variation yet highlight unacceptable variation? Applying the results from two assays using the same multimarker QC sample to traditional and an alternative QC monitoring method such as QConnect highlights when we should be concerned with lot variation and when the variation is normal. Methods QC testing data from 14 lots of the multimarker QC “Optitrol Blue” over a three year period tested on two assays—Abbott ARCHITECT Anti-HCV (n = 54 102) and Abbott ARCHITECT HIV AgAb Combo (n = 62 682) were reviewed for lot variation using traditional and alternative QC monitoring methods. Results Numerous examples of lot variation were identified from the two assays over the three-year period. Applying traditional QC methods resulted in frequent recalculation of mean/SD to accommodate the lot variation, effectively making the lot variation part of the routine, negating its importance, and making the clinical significance of reagent lot variation difficult to ascertain. Using an alternative QC monitoring method such as QConnect, which incorporated normal lot in calculations to create a constant acceptance range, removed the uncertainty and highlighted instances where variation was outside ‘normal’, triggering further investigation by using meaningful QC ranges. A clear example was observed where two similar looking Levey-Jennings charts (one for ARCHITECT HCV and one for ARCHITECT HIV) demonstrated reagent lot variation that was detected as an outlier whereas Traditional methods identified all reagent lots as being outliers. Conclusion In infectious disease serology testing, reagent lot variation is frequent, normal, and rarely a cause for concern. However, it is difficult to determine how much variation is acceptable when using traditional QC methods, because most lot changes are flagged as “rejections”. QC processes that incorporate normal reagent lot variation, derived from historical data, allows for rapid identification of unacceptable variation, saving money and time (particularly when all reagent lot variation identified as outliers need unnecessary investigation), while reducing risk of poor results.

An observed, prospective field study to evaluate the performance and acceptance of a blood-based HIV self-test in Canada

BackgroundSelf testing for HIV is a targeted intervention with the potential to increase the access, uptake and frequency of HIV testing and more effectively reach the undiagnosed, especially in priority populations. The objectives of this study were to (1) evaluate the INSTI HIV self-test performance compared with laboratory reference testing, (2) document if intended users can perform the steps to use the HIV self-test device, and (3) document if intended users can successfully interpret contrived positive, negative, and invalid results. Study was intended to be submitted to Health Canada for review for regulatory approval purposes.MethodsThe study used a cross-sectional design and recruited consenting adults who were representative of intended users of HIV self-testing from four community sites across Ontario, Québec, and Manitoba between August 2019 and March 2020. The results of the observed HIV self-test were compared with results of the Abbott Architect HIV Ag/Ab Combo test. Usability outcomes for critical (e.g., lancing finger, blood droplet into bottle, shaking bottle four times) and noncritical self-test procedure steps were also determined.ResultsOverall, 77% (n = 522) of participants were between 18 and 45 years of age, 61% (n = 410) were male, 71% (n = 480) had some college or more education, and 45% (n = 307) were employed; identity for race and ethnicity: Caucasian (44%; n = 296), African, Caribbean or Black (17%; n = 113), Indigenous [First Nations, Métis or Inuit] (14%; n = 95), Asian (16%; n = 106), Latin American (7%; n = 46). Primary performance analysis on 678 completed HIV self-tests revealed a positive percent agreement of 100% (5/5, 95% CI: 43.6–97.0%) and a negative percent agreement of 99.5% (614/617, 95% CI: 98.6–99.8%) with the comparator method. The overall percent agreement of results interpretation between participant and observer was 93.5% (n = 633). For the 708 participants who took part in the usability study, the average success rate for steps determined to be “critical” for successful completion of the test was 92.4%. 97% (n = 670) of participants found the instructions easy to follow, and 95% (n = 655) of participants indicated that they would use the test again. Of the 404 participants who interpreted the strong positive, weak positive, negative, and invalid contrived results, successful interpretation ranged from 90.6% (for weak positive, n = 366) to 99.3% (for negative, n = 401).ConclusionsThe addition of a regulatory-approved self-test into the Canadian HIV testing landscape could significantly increase HIV testing rates. Having a blood-based HIV self-test approved in Canada can offer an accurate, acceptable, and simple alternative to facility-based HIV testing, particularly when impacted by Coronavirus pandemic restrictions.

Early Diagnosis of HIV-1 and HIV-2 Using Cobas HIV-1/HIV-2 Qualitative Test: A Novel Qualitative Nucleic Acid Amplification Test for Plasma, Serum, and Dried Blood Spot Specimens.

Background:Nucleic acid amplification tests (NATs) minimize the time from HIV infection to diagnosis, reducing transmission during acute HIV. NATs are especially useful for diagnosing HIV in children younger than 18 months and discriminating between HIV-1 and HIV-2.Methods:We evaluated the performance of the cobas HIV-1/HIV-2 qualitative (cobas HIV-1/2 Qual) test for use on cobas 6800/8800 Systems. The results of adult plasma and serum samples and pediatric dried blood spots were compared with those of the recomLine HIV-1 & HIV-2 Immunoglobulin G serological test and COBAS AmpliPrep/COBAS TaqMan HIV-1 qualitative test, v2.0. Genotype inclusivity and limits of detection were determined, and sensitivity on seroconversion panels was compared with that in the Bio-Rad Geenius HIV 1/2 Confirmatory Assay, Abbott ARCHITECT HIV Ag/Ab Combo serological test, and cobas TaqScreen MPX, v2.0.Results:Concordance of cobas HIV-1/2 Qual test with the comparator serological test and COBAS AmpliPrep/COBAS TaqMan test was ≥99.6% with all sample types. Reactivity with all HIV genotypes was 100%. LOD in plasma samples was 14.8, 12.6, and 27.9 copies/mL for HIV-1 group M, HIV-1 group O, and HIV-2, respectively, with similar results for serum samples. LOD in dried blood spots was 255 copies/mL for HIV-1 and 984 copies/mL for HIV-2. HIV infection was detected 18.9 days and 8.5 days earlier than the confirmatory and serological assays, respectively, and at a similar time to the NAT.Conclusions:The cobas HIV-1/2 Qual test enables early and accurate diagnoses of HIV-1 and HIV-2 in adults and children across sample types. The assay could help avert transmission during acute HIV, simplify HIV diagnostic algorithms, and promote the survival of HIV-infected children.

Viral suppression is associated with HIV-antibody level and HIV-1 DNA detectability in early treated children at 2 years of age.

Early infant HIV diagnosis and antiretroviral therapy (ART) initiation are now implemented shortly after birth. Maintaining and monitoring ART adherence is difficult and requires frequent visits. We, therefore, investigated whether HIV antibodies and HIV-1 DNA levels are markers of cumulative viremia. We conducted a cross sectional investigation at 2 years of age of HIV antibodies and HIV-1 DNA levels in a well characterized cohort of 31 children who started ART shortly after birth. HIV antibodies were measured by a combination of the Abbott ARCHITECT HIV Ag/Ab Combo and Geenius HIV 1/2 supplemental assays; and total HIV-1 DNA quantified using a sensitive quantitative PCR (qPCR) assay targeting the HIV-1 integrase gene. Infant post-exposure prophylaxis consisted of zidovudine (AZT) and nevirapine (NPV) (or NVP only, in one child) within 1 day of birth, transitioning, after positive diagnosis, to three-drug ART, at a median [interquartile range (IQR)] of 7 (4-9.5) days. Twelve of 31 children had well suppressed HIV plasma viral loads (HIVVL) and the remainder periods of viremia (HIVVL > 100 copies/ml after 3 months of ART), classified as non-suppressed. At 24 months of age: 11 of 12 (92%) of well suppressed children had undetectable HIV-1 antibodies versus 3 of 19 (16%) non-suppressed children (P < 0.001) and 7 of 12 (58%) well suppressed children had undetectable HIV-1 DNA versus 3 of 19 (16%) non-suppressed children (P = 0.02). Considering low assay costs and the high proportion of well suppressed children with undetected antibody levels at 2 years, HIV antibody levels may be a valuable marker of cumulative adherence in children who start treatment shortly after birth and could prompt adherence and viral load investigation.

A high prevalence of potential HIV elite controllers identified over 30 years in Democratic Republic of Congo

BackgroundIn-depth analysis of the HIV pandemic at its epicenter in the Congo basin has been hampered by 40 years of political unrest and lack of functional public health infrastructure. In recent surveillance studies (2017-18), we found that the prevalence of HIV in Kinshasa, Democratic Republic of Congo (11%) far exceeded previous estimates.Methods10,457 participants were screened in Kinshasa with rapid tests from 2017-2019. Individuals confirmed as reactive by the Abbott ARCHITECT HIV Ag/Ab Combo assay (n=1968) were measured by the Abbott RealTime HIV-1 viral load assay. Follow up characterization of samples was performed with alternate manufacturer viral load assays, qPCR for additional blood borne viruses, unbiased next generation sequencing, and HIV Western blotting.FindingsOur data suggested the existence of a significant cohort (n=429) of HIV antibody positive/viral load negative individuals. We systematically eliminated collection site bias, sample integrity, and viral genetic diversity as alternative explanations for undetectable viral loads. Mass spectroscopy unexpectedly detected the presence of 3TC antiviral medication in approximately 60% of those tested (209/354), and negative Western blot results indicated false positive serology in 12% (49/404). From the remaining Western blot positives (n=53) and indeterminates (n=31) with reactive Combo and rapid test results, we estimate 2.7-4.3% of infections in DRC to be potential elite controllers. We also analyzed samples from the DRC collected in 1987 and 2001-03, when antiretroviral drugs were not available, and found similarly elevated trends.InterpretationViral suppression to undetectable viral loads without therapy occurs infrequently in HIV-1 infected patients around the world. Mining of global data suggests a unique ability to control HIV infection arose early in central Africa and occurs in <1% of founder populations. Identification of this group of elite controllers presents a unique opportunity to study potentially novel genetic mechanisms of viral suppression.FundingAbbott Laboratories funded surveillance in DRC and subsequent research efforts. Additional funding was received from a MIZZOU Award from the University of Missouri. Research was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH.

HIV serology false positivity among expatriates from Africa: a screening dilemma.

HIV prevalence in Oman is low (<5 %); however, 45 % of the population are expatriates, including a portion originating from countries with high HIV prevalence (>5 %). HIV screening is performed at regional public health laboratories as part of a medical fitness programme for residency applicants. We conducted a retrospective evaluation of indeterminate serology results from 11 females of African origin, aged 21–43 years. Serology testing for HIV was conducted according to the national Oman algorithm: fourth-generation immunoassays (Bio-Rad GS HIV Combo Ag/Ab EIA, Siemens Enzygnost HIV Integral 4, Abbott ARCHITECT HIV Ag/Ab Combo, Roche Elecsys HIV Combi PT, bioMérieux VIDAS HIV DUO QUICK), confirmatory assays (Geenius HIV 1/2 Confirmatory, INNO-LIA HIV I/II Score) and PCR testing. Confirmatory testing to resolve indeterminate results was conducted with available samples for five patients using a combination of immunoassays, confirmatory assays, PCR/PERT and pro-viral DNA levels, at three external laboratories; Roche Diagnostics (Germany), Swiss National Laboratory (Switzerland) and Barts Health NHS Trust (UK). Nineteen serum, 15 plasma and two whole-blood samples were analysed. Nine of ten patients analysed on Bio-Rad and Siemens immunoassays were highly reactive; seven were highly reactive on the Abbott assay. Eight of nine patients tested with the Roche assay were negative. Three of four patients tested on the bioMérieux assay were negative. Five patients underwent confirmatory testing at external laboratories; all were negative by HIV-RNA or pro-viral DNA testing. In conclusion, HIV-RNA and pro-viral DNA testing is recommended for HIV screening of individuals from high-prevalence regions coming to low-prevalence regions.

Data on the relationship of signal-to-cutoff ratio of two HIV antigen/antibody combination assays to subsequent confirmation of HIV-1 infection in a low-prevalence population.

HIV-1/2 antigen/antibody (Ag/Ab) immunoassays that detect HIV-1 and HIV-2 antibodies and HIV-1 p24 antigen are commonly used in the diagnosis of HIV-1/HIV-2 infections in human plasma/serum. Samples from patients with positive screening results require confirmation by antibody differentiation and/or HIV PCR assays. HIV screening assays are commonly reported as positive or negative based on a signal-to-cutoff (S/CO) threshold. For some HIV screening assays, the strength of the S/CO value correlates with likelihood that confirmatory testing will be positive. The data in this article provide results from two HIV Ag/Ab combination assays (Abbott Architect HIV Ag/Ab Combo Assay, a 4th generation combination assay; Bio-Rad Bioplex 2200 HIV Ag-Ab Assay, a 5th generation assay). The data include 23,331 HIV screening results, S/CO ratios, antibody differentiation or Western blot results (for samples with positive HIV screens), HIV-1 PCR results (if performed), patient location at time of testing, age, and sex. Distribution of S/CO ratios for the Bio-Rad HIV screening assay data and the distribution of S/CO values for samples with positive screening results were analyzed.

Precision and diagnostic accuracy verification of VITROS HIV combo assay

Background/Objective: NACO has laid down three structured algorithms (I, II, III) for HIV screen, surveillance and diagnosis. It is the responsibility of the laboratories to select, verify and evaluate the methods fitting into the algorithm of HIV testing. The present study has attempted to evaluate VITROS® HIV combo assay through comparison with Abbott Architect HIV combo assay. Method: The study evaluated VITROS® HIV combo assay through precision verification and diagnostic accuracy assessment by adopting CLSI guidelines. Precision verification of the VITROS HIV combo assay is done based on CLSI EP15A3 and diagnostic accuracy verification based on CLSI EP12A2. Result: Precision verification showed a repeatability CV% (CVR) -2.35% and within lab CV% (CVWL)-3.77%. This was compared against the manufacturer’s claims (σR-3%, σWL-4.8%) and found to be within acceptable limits. Diagnostic accuracy verification showed that difference in paired sensitivity between VITROS® HIV combo assay and Abbott Architect HIV combo assay was zero and difference in paired specificities was 0.3%. This difference was proved to be statistically insignificant based on 95% confidence interval for the paired sensitivities and specificities. Conclusion: The study showed an acceptable performance of VITROS HIV combo assay in terms of precision and diagnostic accuracy.

I-106 Early treatment initiation in children with vertical HIV infection influences HIV specific immune responses

Background: Despite successes in prevention of mother to child HIV transmission (MTCT), issues related to early diagnosis, ART initiation and adherence play a role in the disease course of HIV infected children. Early ART initiation in HIV infected infants leads to reduced size of HIV reservoirs and curtails clinical progression but role of the immune system in this process is not well understood. With early initiation of ART, HIV infected infants preserve their CD4+ T cells and in some instances remain seronegative for HIV due to limited exposure of B cells to HIV antigen. We are performing immunologic assessments in the HIV Exposed Pediatric Patients (HEPP) Project and discuss a group of children from Rome, Italy. The goal of the present study is to evaluate HIV-specific immunity of vertically HIV infected children in relation to timing of ART initiation. Methods: The study group consists of older vertically infected HIV+ children and adolescents who initiated ART at different ages after birth and have maintained durable viral control (plasma HIV-RNA &lt;50 cp/mL). Immunologic studies were performed in 27 children (at ages 2.1–15.7 yrs) of whom 22 had started ART early, at age &lt;6 mo [early treated (ET)] and 5 who started ART later, at age &gt;2 yrs [late treated (LT)] with ET experiencing longer duration of ART (P &lt; 0.05) at the time of study. ET children were also evaluated by HIV serology (Abbott Architect HIV Ag/Ab Combo Assay) to establish if they were seropositive (SP) or seronegative (SN) to HIV. Flow cytometry was performed using BD LSRFortessa for T cells and BD FACS Aria II for B cells. HIV-gag specific CD4+ and CD8+ T cells were investigated by flow cytometry in cryopreserved PBMC for the induction of intracellular cytokines (IL-2, IFN-g, TNF, IL-21) in CD40L+ CD4+ T cells and intracellular cytokines (IL-2, IFN-g, TNF) as well as Perforin, Granzyme B and CD107a in CD69+ CD8+ T cells following 12 hours stimulation with HIV gag PTE peptides. In addition, Env-specific CD4+ T cells were evaluated following 12 hours stimulation of PBMC with Env peptides. IgD+ and IgM+ B cell subsets were determined in gp140+ B cells. Moreover, env-specific and non-specific B cells were sorted to perform transcriptomic analysis with Fluidigm (Biomark). Differences between groups were determined by unpaired or Mann-Whitney t tests if the data were normally distributed or not, respectively. Results: In this group of HIV+ children, frequencies of HIV gag-specific CD4+ T cells and CD8+ T cells were similar between ET and LT but differed qualitatively. Gag stimulated CD4+ T cells of ET exhibited higher proportions of IL-21 and IFNg with enrichment of polyfunctional T cells defined by the simultaneous presence of 3 or more cytokines. Gag stimulated CD8+ T cells of ET exhibited higher frequencies of cytotoxic cells (CD107a+Perf+GrzB+). In ET, serologic evaluation of HIV Ab revealed 6/22 (27.3%) to be SN. The gp140-specific CD4+ T cell frequencies were similar in SN and SP but intracellular IL-21 expression was higher in SP. Frequencies of gp140+ CD19+ B cells were similar between SN and SP, but HIV-specific CD27+ memory B cells were predominantly IgM+ in SN while in SP, the gp140+CD27+ memory B cells were enriched in IgD-cells. Gene expression signatures in gp140+IgM+ cells revealed upregulation of genes involved in both plasma cell differentiation (PRDM1) and GC reaction (BCL6) only in SP after in-vitro stimulation. Conclusions: Time of ART initiation after birth has a long-term impact on the quality of the host HIV-specific immune responses in vertically infected HIV+ children with durable virus suppression. Earlier ART initiation is associated with preserved HIV gag-specific CD4+ and CD8+ T cells. Moreover, even in those who become seronegative for HIV, the HIV Env-specific CD4+ T cells and B cells persist, the latter demonstrating a blunted differentiation with enrichment of IgM+ B cells. ET children with consistent viral control are prime candidates for therapeutic approaches aimed at permanent remission of HIV. These studies are supported by ViiV Health Care grant to EPIICAL and NIH grant AI127347 to SP.

Heterophilic interference in specimens yielding false-reactive results on the Abbott 4th generation ARCHITECT HIV Ag/Ab Combo assay

BackgroundFalse-reactivity in HIV-negative specimens has been detected in HIV fourth-generation antigen/antibody or ‘combo’ assays which are able to detect both anti-HIV-1/HIV-2 antibodies and HIV-1 antigen. ObjectivesWe sought to characterize these specimens and determine the effect of heterophilic interference. Study designSpecimens previously testing as false-reactive on the Abbott ARCHITECT HIV Ag/Ab combo assay and re-tested on a different (Siemens ADVIA Centaur HIV Ag/Ab) assay. A subset of these specimens were also pre-treated with heterophilic blocking agents and re-tested on the Abbott assay. ResultsHere we report that 95% (252/264) of clinical specimens that were repeatedly reactive on the Abbott ARCHITECT HIV Ag/Ab combo assay (S/Co range, 0.94–678) were negative when re-tested on a different fourth generation HIV combo assay (Siemens ADVIA Centaur HIV Ag/Ab). All 264 samples were subsequently confirmed to be HIV negative. On a small subset (57) of specimens with available volume, pre-treatment with two different reagents (HBT; Heterophilic Blocking Tube, NABT; Non-Specific Blocking Tube) designed to block heterophilic antibody interference either eliminated (HBT) or reduced (NABT) the false reactivity when re-tested on the ARCHITECT HIV Ag/Ab combo assay. ConclusionsOur results suggest that the Abbott ARCHITECT HIV Ag/Ab combo assay can be prone to heterophilic antibody interference.

Infection Staging and Incidence Surveillance Applications of High Dynamic Range Diagnostic Immuno-Assay Platforms

Custom HIV staging assays, including the Sedia HIV-1 Limiting Antigen (LAg) Avidity EIA and avidity modifications of the Ortho VITROS anti-HIV-1+2 and Abbott ARCHITECT HIV Ag/Ab Combo assays, are used to identify "recent" infections in clinical settings and for cross-sectional HIV incidence estimation. However, the high dynamic range of chemiluminescent platforms allows differentiating recent and long-standing infection on signal intensity, and this raises the prospect of using unmodified diagnostic assays for infection timing and surveillance applications. We tested a panel of 2500 well-characterized specimens with estimable duration of HIV infection with the 3 assays and the unmodified ARCHITECT. Regression models were used to estimate mean durations of recent infection (MDRIs), context-specific false-recent rates (FRRs) and correlation between diagnostic signal intensity and LAg measurements. Hypothetical epidemiological scenarios were constructed to evaluate utility in surveillance applications. Over a range of MDRIs (reflecting recency discrimination thresholds), a diluted ARCHITECT-based RITA produced lower FRRs than the VITROS platform (FRR ≈ 0.5% and 1.5%, respectively at MDRI ≈ 200 days), and the unmodified diagnostic ARCHITECT produces incidence estimates with comparable precision to LAg (relative SE ≈ 17.5% and 15%, respectively at MDRI ≈ 200 days). ARCHITECT S/CO measurements were highly correlated with LAg optical density measurements (r = 0.80), and values below 200 are strongly predictive of LAg recency and duration of infection less than 1 year. Low quantitative measurements from the unmodified ARCHITECT obviate the need for additional recency testing, and its use is feasible in clinical staging and incidence surveillance applications.

Performance comparison of the 4th generation Bio-Rad Laboratories GS HIV Combo Ag/Ab EIA on the EVOLIS™ automated system versus Abbott ARCHITECT HIV Ag/Ab Combo, Ortho Anti-HIV 1 + 2 EIA on Vitros ECi and Siemens HIV-1/O/2 enhanced on Advia Centaur

BackgroundA multisite study was conducted to evaluate the performance of the Bio-Rad 4th generation GS HIV Combo Ag/Ab EIA versus Abbott 4th generation ARCHITECT HIV Ag/Ab Combo. The performance of two 3rd generation EIAs, Ortho Diagnostics Anti-HIV 1+2 EIA and Siemens HIV 1/O/2 was also evaluated. ObjectiveStudy objective was comparison of analytical HIV-1 p24 antigen detection, sensitivity in HIV-1 seroconversion panels, specificity in blood donors and two HIV false reactive panels. Study designAnalytical sensitivity was evaluated with International HIV-1 p24 antigen standards, the AFFSAPS (pg/mL) and WHO 90/636 (IU/mL) standards; sensitivity in acute infection was compared on 55 seroconversion samples, and specificity was evaluated on 1000 negative blood donors and two false reactive panels. ResultsGS HIV Combo Ag/Ab demonstrated better analytical HIV antigen sensitivity compared to ARCHITECT HIV Ag/Ab Combo: 0.41IU/mL versus 1.2IU/mL (WHO) and 12.7pg/mL versus 20.1pg/mL (AFSSAPS); GS HIV Combo Ag/Ab EIA also demonstrated slightly better specificity compared to ARCHITECT HIV Ag/Ab Combo (100% versus 99.7%). The 4th generation HIV Combo tests detected seroconversion 7–11 days earlier than the 3rd generation HIV antibody only EIAs. ConclusionBoth 4th generation immunoassays demonstrated excellent performance in sensitivity, with the reduction of the serological window period (7–11 days earlier detection than the 3rd generation HIV tests). However, GS HIV Combo Ag/Ab demonstrated improved HIV antigen analytical sensitivity and slightly better specificity when compared to ARCHITECT HIV Ag/Ab Combo assay, with higher positive predictive values (PPV) for low prevalence populations.

Identification of early HIV infections using the fourth generation Abbott ARCHITECT HIV Ag/Ab Combo chemiluminescent microparticle immunoassay (CIA) in San Diego County

BackgroundHIV screening assays have gone through several generations of development in an effort to narrow the “window period” of detection. Utilizing a fourth generation HIV screening assay has the potential to detect earlier HIV infection, thus reducing HIV-1 transmission. ObjectiveTo identify acute infections to decrease HIV transmission in San Diego County. Study designSerum specimens were collected from clients seen by multiple submitters in San Diego County. All acceptable specimens were screened using the 4th Gen Combo Assay. Initially reactive specimens were repeated in duplicate and if repeatedly reactive, were confirmed by HIV-1 Immunofluorescent Antibody Assay (IFA).IFA negative/inconclusive specimens were sent for HIV-1 NAT and HIV-2 antibody testing to referral laboratories. BioRad Multispot HIV-1/HIV-2 Rapid Test was also performed on a subset of specimens. ResultsOf 14,559 specimens received in 20 months, 14,517 specimens were tested. Of the 14,517 specimens that were tested, a total of 279 (1.9%) specimens were CIA repeatedly reactive and 240 of the 279 confirmed by HIV-1 IFA. Thirty-nine gave IFA negative/inconclusive result and 30 were further tested for HIV-1 NAT and 36 for HIV-2 antibody. Thirteen specimens were considered false positives by CIA and 17 specimens were classified as acute infections. Eleven of 39 IFA negative/inconclusive specimens were further tested by Multispot. Five of the 11 were positive by Multispot. ConclusionThe fourth generation Abbott ARCHITECT HIV Ag/Ab Combo Assay identified 17 patients who may have been missed by the prior HIV-1 screening assay used at San Diego County Public Health Laboratory.

O15.4 Field Performance of the Alere Determine HIV Combo Assay in a Large Australian Multi-Centre Study in a Sexual Health Clinic Setting

BackgroundRapid HIV testing has been available to gay and other men who have sex with men (MSM) overseas for many years. Alere’s Determine HIV Combo ‘fourth generation’ rapid test containing...

Valutazione di un test per la determinazione simultanea degli anticorpi e antigene p24 dell’HIV

A fourth generation immunoassay for the detection of antibodies to HIV-1 and HIV-2 and of HIV antigen p24 (Abbott Architect HIV Ag/Ab Combo) has been evaluated in comparison with two Ab-only third generation assays on 894 routine specimens and on preselected repository specimens.The Combo assay showed a better specificity (99.88% vs. 99.43-99.83%) and an analytical sensitivity for p24 of 22 pg/mL on a BBI commercial panel. The Architect assays gave a negative result on 22/24 repository false positive specimens from 18 subjects and, conversely, was positive on all the 39 repository specimens from 24 HIV-positive patients. On six patients with acute HIV infection the Architect assay gave an earlier positivity than the antibody-only assays (EIA and WB) on three cases, all viremic and positive for HIV p24.The performance characteristics of the new HIV Combo assay guarantee an advanced clinical sensitivity and a high specificity.