False-positive HIV Research Articles

HIV false positive screening serology due to sample contamination reduced by a dedicated sample and platform in a high prevalence environment.

Automated testing of HIV serology on clinical chemistry analysers has become common. High sample throughput, high HIV prevalence and instrument design could all contribute to sample cross-contamination by microscopic droplet carry-over from seropositive samples to seronegative samples resulting in false positive low-reactive results. Following installation of an automated shared platform at our public health laboratory, we noted an increase in low reactive and false positive results. Subsequently, we investigated HIV serology screening test results for a period of 21 months. Of 485 initially low positive or equivocal samples 411 (85%) tested negative when retested using an independently collected sample. As creatinine is commonly requested with HIV screening, we used it as a proxy for concomitant clinical chemistry testing, indicating that a sample had likely been tested on a shared high-throughput instrument. The contamination risk was stratified between samples passing the clinical chemistry module first versus samples bypassing it. The odds ratio for a false positive HIV serology result was 4.1 (95% CI: 1.69-9.97) when creatinine level was determined first, versus not, on the same sample, suggesting contamination on the chemistry analyser. We subsequently issued a notice to obtain dedicated samples for HIV serology and added a suffix to the specimen identifier which restricted testing to a dedicated instrument. Low positive and false positive rates were determined before and after these interventions. Based on measured rates in low positive samples we estimate that before the intervention, of 44 117 HIV screening serology samples, 753 (1.71%) were false positive, declining to 48 of 7 072 samples (0.68%) post-intervention (p<0.01). Our findings showed that automated high throughput shared diagnostic platforms are at risk of generating false-positive HIV test results, due to sample contamination and that measures are required to address this. Restricting HIV serology samples to a dedicated platform resolved this problem.

False reactive HIV rapid antibody test in pregnancy

Background: Universal screening of HIV infection in pregnant women is recommended by CDC as well as Indonesia Ministry of Health to prevent mother-to-child HIV transmission. Algorithm of HIV testing in pregnant women in Indonesia is similar to that in Integrated Counseling and Testing Centre (ICTC) which refes to WHO HIV Testing Strategy III. Pregnancy has been observed to be associated with false positive HIV testing that can cause serious emotional distress and unnecessary follow-up. Case Description: A 21 y old pregnant woman was referred to a tertiary hospital with premature rupture of the membranes. Before C-section, preoperative laboratory test panels were ordered, including for HIV to which she consented. A rapid HIV test (A1) was performed and tested reactive for antibodies against HIV. The second (A2) and third (A3) rapid tests were then performed and yielded non-reactive results, concluding the final result as negative. Reassessment of the patients showed no risk factors for HIV infection. This was the third case of reactive A1 with non-reactive A2 and A3 within the last year in the hospital. After confirmatory tests, which came back non-reactive and negative for fourth-generation HIV test and Western Blot, respectively, the A1 test was considered as false positive. Discussion: Based on several reports, there are alloantibodies in pregnancy, transfusions, transplantations, and autoimmune diseases that account for the increased false positive rate. Positive HIV antibody test results can occur in the absence of infection due to cross-reactivity between viral proteins and tested specimens, but such cross-reactivity is less common using current peptide-based EIAs which contain fewer antigens than previous viral lysate-based EIAs. However, clinicians should be aware that when HIV prevalence is low, as is often the case among pregnant women, a reactive EIA result is more likely to be false positive. Conclusion: Counselling and HIV test should be integrated in antenatal care. Diagnostic procedure of HIV test in pregnant women refers to WHO Testing Strategy III. Because the positive predictive value of HIV test in obstetric population is low, positive screening results should be handled carefully and appropriate confirmatory testing should always be pursued.

HIV-positive deceased donor-to-HIV-positive recipient kidney transplantation: The HOPE must go on.

Nowadays, HIV infection is a chronic disease, this is due to the efficacy of antiretroviral therapy (ART) in the control of viral replication. The prevalence of chronic kidney disease (CKD) among those well-controlled HIV positive (HIV+) patients is higher than in the general population and kidney transplantation has been established as the best therapeutic option for HIV+ patients with end-stage renal disease. However, this population has lower access to transplantation.

A prospective multicenter pilot study of HIV-positive deceased donor to HIV-positive recipient kidney transplantation: HOPE in action.

HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D-/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D- (22 recipients from D- with false positive HIV tests). Median follow-up was 1.7years. There were no deaths nor differences in 1-year graft survival (91% D+ vs 92% D-, P=.9), 1-year mean estimated glomerular filtration rate (63mL/min D+ vs 57mL/min D-, P=.31), HIV breakthrough (4% D+ vs 6% D-, P>.99), infectious hospitalizations (28% vs 26%, P=.85), or opportunistic infections (16% vs 12%, P=.72). One-year rejection was higher for D+ recipients (50% vs 29%, HR: 1.83, 95% CI 0.84-3.95, P=.13) but did not reach statistical significance; rejection was lower with lymphocyte-depleting induction (21% vs 44%, HR: 0.33, 95% CI 0.21-0.87, P=.03). In this multicenter pilot study directly comparing HIV D+/R+ with HIV D-/R+ KT, overall transplant and HIV outcomes were excellent; a trend toward higher rejection with D+ raises concerns that merit further investigation.

HIV and organ transplantation.

This review summarizes the advances that have occurred over the past 2 years in organ transplantation in the setting of HIV. Although HIV+ organ transplantation is both safe and effective, recent studies show that HIV+ patients continue to experience barriers to transplantation. In the United States, the HOPE Act is not only expected to increase the donor pool for HIV+ transplant candidates, but to also allow for the use of donors with false-positive HIV+ tests, which had previously been banned under the US National Organ Transplant Act. More effective HCV treatment, increased experience with heart and lung transplantation and the potential for increased organ availability with the inclusion of HIV+ organ donors have provided for significant advances in the care of these patients. There continues to be progress in the field of organ transplantation in persons living with HIV. Future efforts should continue aiming to limit barriers to transplantation and improving the understanding of immunologic derangements seen in transplant recipients with HIV infection.

HIV diagnostic algorithm requires confirmatory testing for initial indeterminate or positive screens in the first week of life.

Risk for nondiagnostic and false-positive HIV testing has not been quantified for neonates. From April 2015 to July 2018, we screened HIV-exposed infants in Botswana less than 96 h from birth by qualitative DNA PCR. Repeat blood draws for DNA and RNA PCR testing occurred for initial positive and indeterminate results to establish final diagnosis. We compared screening DNA PCR cycle threshold values with final HIV status of the child. Of 10 622 HIV-exposed infants, 10 549 (99.3%) had no HIV DNA detected (negative), 42 (0.4%) had HIV DNA detected (positive), and 31 (0.3%) tested indeterminate at first HIV screen. Repeat testing identified 2 (5.0%) of 40 positive screens (2 declined additional testing) as false positives and confirmed 2 (6.5%) of 31 indeterminate screens as infected. Median cycle threshold value at screening was 28.1 (IQR 19.8--34.8) for children with final positive status, and 35.5 (IQR 32.8--41.4) for indeterminates who were ultimately negative. Six (15%) of 40 infants with final positive status had cycle threshold value greater than 33 at first screen, whereas 3 (9.7%) of 31 indeterminates with final negative status had cycle threshold value 33 or less at first screen. This threshold resulted in a negative predictive value of 82% and a positive predictive value of 92% for a single screen. Although a DNA PCR cycle threshold value of 33 was predictive of the final HIV status in newborns, overlap occurred for true positives, false positives, and initial indeterminates. Testing additional samples should be standard practice for positive and indeterminate HIV DNA PCR tests in the first week of life.

The use of the GeeniusTM HIV-1/2 Rapid confirmatory test for the enrolment of patients and blood donors in the WHO Universal Test and Treat Strategy in Cameroon, Africa.

In the WHO Universal test and treat strategy, false-positive HIV blood donors and patients may be unnecessarily put under antiretroviral treatment and false-negative subjects may be lost to follow-up. This study assessed the false positivity rate of the Cameroonian national HIV screening testing algorithm and the benefit of a confirmation test in the enrolment of patients and donors in the HIV care programme. We included initial HIV reactive blood donors and patients in a cross-sectional study conducted in two Cameroonian hospitals. Samples were retested according to the Cameroon national algorithm for HIV diagnosis. A positive or discordant sample was retested with the Geenius Bio-Rad HIV 1&2 (Bio-Rad, Marnes-la-Coquette, France) for confirmation. The Geenius HIV-1-positive results with 'poor' profiles were retested for RNA as well as the Geenius indeterminate results. Of the 356 participants, 190/225 (84·4%) patients and 76/131 (58%) blood donors were declared positive with the national algorithm; 257 participants (96·6%) were confirmed HIV-1-positive. The study revealed that about 34/1000 blood donors and patients are false-positive and unnecessarily put on treatment; 89/1000 blood donors and patients declared discordant could have been included immediately in the HIV care programme if confirmatory testing was performed. The second test of the algorithm had a false-negative rate of 3%. Eleven samples (3·1%) were Geenius poor positive and NAT negative. The universal test and treat strategy may identify and refer more individuals to HIV care if a third rapid confirmatory test is performed for discordant cases.

Testing for HIV infection in the emergency departments of 2 hospitals in the Southeastern United States.

BackgroundIn 2006, the Centers for Disease Control and Prevention (CDC) recommended non‐targeted, opt‐out HIV screening in all healthcare settings, including emergency departments (EDs). Multiple HIV testing programs have been implemented in EDs across the United States with varying designs and testing platforms. We report findings from a free, non‐targeted, rapid HIV testing program in 2 EDs in the Southeastern United States.MethodsFrom 2008 to 2012, adults ≥18 years of age were offered free rapid HIV testing using an oral swab test (OraQuick ADVANCE Rapid HIV‐1/2 antibody test) in the EDs of a large academic medical center and an affiliated community hospital in Durham, North Carolina.ResultsIn total, 5443 ED patients were offered HIV testing. The overall acceptance rate was 66.9% (3639/5443). Younger persons were significantly more likely to accept testing (78.2% for 18–29 years old vs 67.1% for ≥30 years old; P < 0.001) as were Black participants (72.6% Black vs 66.5% White; P < 0.001). Acceptance rates improved significantly after opt‐out oral consent replaced written consent (71.3% vs 63.1%; P < 0.001). Seven new HIV diagnoses were confirmed during the testing program, resulting in a seropositivity rate of 0.19% (7/3639). There were 8 false–positive rapid oral HIV tests (positive predictive value = 46.7%).ConclusionsAlthough the number of new HIV diagnoses was low, implementation of this rapid, non‐targeted ED screening program was feasible with high acceptance rates, particularly after introducing the opt‐out oral consent approach.

SUN-524 Patient with Pseudohypoparathyroidism Type 1B, Graves Disease, and False Positive HIV Screen- a Rare Presentation

Background: Pseudohypoparathyroidism 1B (PHP1B) is a disorder that can lead to thyroid stimulating hormone (TSH) resistance and hypothyroidism, although it is rarely associated with thyrotoxicosis.Clinical Case: A 25-year-old female with a history of PHP1B, seizures due to hypocalcemia, and family history of PHP1B in her three sisters and brother presented to our emergency room with a fever of 1030F and generalized malaise. Two months prior, she was seen at an outside hospital with palpitations and bulging of the left eye. There, she was diagnosed with hyperthyroidism, started on methimazole, and asked to continue levetiracetam and calcitriol upon discharge.On our exam, she had tachycardia of 120 beats per minute, left eye proptosis, positive Chvostek sign, and a large goiter with bruit. Reflexes were 3+.Laboratory evaluation revealed corrected serum calcium of 6.1 (8.5-10.5 mg/dL), TSH < 0.01 (0.34-5.60 mU/L), free T4 2.81 (0.60-1.60 ng/dL), free T3 13.0 (2.4-4.2 ng/dL), and iPTH 131 (12-88 pg/mL). ELISA testing for screening of HIV was positive. She was treated with IV calcium gluconate, methimazole, propranolol, and hydrocortisone. Her home doses of calcitriol and calcium were resumed. She was referred for total thyroidectomy as an outpatient once she became euthyroid. The confirmatory Western blot test for HIV was negative. It was determined that presence of thyroid stimulating immunoglobulin resulted in the false positive ELISA test.Discussion: Hyperthyroidism with Graves disease seen in PHP has only very rarely been reported. (1) It has been postulated that abnormal electrolytes and elevated parathyroid hormone from PHP may lead to stimulation of the thyroid gland and perpetuate Graves disease symptoms. (2) Furthermore, the presentation of thyrotoxicosis despite TSH resistance in PHP indicates that there may be other mechanisms for TSH receptor antibodies to take effect in these patients which have not yet been determined. (3) Lastly, autoimmune diseases, including Graves disease, can cause a false-positive HIV ELISA as seen in our patient.Conclusion: Although rare, thyrotoxicosis may present in patients with PHP1B. Additionally, it should be kept in mind that autoimmune diseases such as Graves disease can cause a false positive HIV ELISA, and follow-up Western blot testing should therefore be performed.

Utilization of PHS Increased Risk for Transmission of Infectious Disease Donor Organs in Lung Transplantation: One Center's 7-year Experience

Over the past several years 37 to 41% of all deceased donor organs in Region 1 were designated as Public Health Service increased risk for infectious disease transmission compared to 25-27% nationally. Limited by the number of standard donors our Center sought to develop guidelines for utilizing these donors and implement a system for follow-up testing for disease transmission. We reviewed our single-center 7-year experience utilizing PHS donor organs in our lung transplant program. Our Center developed a protocol based on the PHS Guidelines to guide the lung transplant program in the management of recipients. Transplant recipients of PHS donor organs had blood testing (serology and viral load) for HIV, HBV and HCV performed on the day of transplant; 1-3 months and 6-12 months after transplant. A QAPI project was implemented to ensure medical record documentation and follow-up testing was conducted. From 2013 to October 2019 there were 66 lung transplants performed from PHS donor organs. A retrospective analysis revealed one false positive HIV antibody test; and 15 recipients (23%) converted their HBV core antibody from negative to positive at the 1-3 month time frame after surgery. Of the 15, 11 converted back to HBV core antibody negative within a year after transplant; 2 patients did not have testing performed/expired; and 2 patients were still within the first year after surgery and remained HBV core antibody positive. Although the etiology of the conversion remains unclear it was attributed to the administration of cytomegalovirus immune globulin in the recipients. Of note, 8 of the 66 PHS organs (12%) were also HCV positive and were transplanted under an IRB protocol. The recipients of HCV NAT positive donor organs were started on direct acting anti-viral agents. All of these patients remained HCV viral load negative after transplant. In addition to these donors, there was one HCV antibody/NAT positive donor organ that did not meet PHS criteria that was tracked and the recipient was HCV viral load negative after transplant. Our Center experience suggests that there is limited risk to using PHS donor organs in lung transplantation. Special considerations may be warranted in tracking recipients of HCV positive donor organs that may not meet PHS donor organ criteria.

Use of an Indeterminate Range in HIV Early Infant Diagnosis: A Systematic Review and Meta-Analysis.

Expanded access to HIV antiretrovirals has dramatically reduced mother-to-child transmission of HIV. However, there is increasing concern around false-positive HIV test results in perinatally HIV-exposed infants but few insights into the use of indeterminate range to improve infant HIV diagnosis. A systematic review and meta-analysis was conducted to evaluate the use of an indeterminate range for HIV early infant diagnosis. Published and unpublished studies from 2000 to 2018 were included. Study quality was evaluated using GRADE and QUADAS-2 criteria. A random-effects model compared various indeterminate ranges for identifying true and false positives. The review identified 32 studies with data from over 1.3 million infants across 14 countries published from 2000 to 2018. Indeterminate results accounted for 16.5% of initial non-negative test results, and 76% of indeterminate results were negative on repeat testing. Most results were from Roche tests. In the random-effects model, an indeterminate range using a polymerase chain reaction cycle threshold value of ≥33 captured over 93% of false positives while classifying fewer than 9% of true positives as indeterminate. Without the use of an indeterminate range, over 10% of infants could be incorrectly diagnosed as HIV positive if their initial test results are not confirmed. Use of an indeterminate range appears to lead to substantial improvements in the accuracy of early infant diagnosis testing and supports current recommendations to confirm all initial positive tests.

1299. Cluster of False-Positive “Fifth-Generation” HIV Test Results During Implementation of a Routine HIV Screening Program in an Emergency Department

BackgroundIn November 2014, the University of Illinois Hospital (UI Health) introduced an electronic medical record (EMR)-driven HIV screening program in the emergency department (ED). In October 2016, our hospital laboratory introduced “Fifth-generation” HIV testing using the Bio-Rad BioPlex 2200 HIV Antigen/Antibody diagnostic assay. Fifth-generation HIV testing has the advantage of separately detecting and reporting HIV antibody and HIV-1 p24 antigen. Although the literature and manufacturer report high sensitivity and specificity of this test, we encountered higher than expected rates of false-positive tests during the introduction of this test.MethodsWe retrospectively reviewed the results of our ED HIV screening program from October 2016 to March 2019 to describe the outcomes of HIV testing, determine the rates of false-positive HIV tests and determine if false-positive rates were temporally clustered. We also investigated various potential causes of higher than expected false positives including pre-analytical and analytical error. We defined a false-positive test as a repeatedly reactive initial HIV antigen and/or HIV-1 antibody result with a subsequent negative or indeterminate HIV-1/2 antibody differentiation immunoassay and negative HIV-1 nucleic amplification test.ResultsDuring the review period, out of a total of 17,385 HIV tests which were performed, 85 tests were confirmed positive and 27 were false positives. This represents an HIV prevalence of 0.5%. Eighteen of the 27 false positives occurred during an 8 month period between October 2016 and April 2017 (see Figure 1). During our investigation of potential causes of the false-positive tests, we discovered that a reagent lot for the test was changed in June 2017 which resulted in a significant decrease in the false-positive rate (0.33% to 0.07%).ConclusionWe provide data which suggests that a reagent lot may have been the cause of higher than expected false-positive tests for HIV testing. Monitoring of testing outcomes during implementation of a routine HIV testing program can help identify potential root causes of false-positive tests. Disclosures All authors: No reported disclosures.

Evolving complexities of infant HIV diagnosis within Prevention of Mother-to-Child Transmission programs.

Early diagnosis of HIV infection among infants and children is critical as prompt initiation of antiretroviral therapy prevents morbidity and death. Yet despite advances in the accuracy and availability of infant HIV diagnostic testing, there are increasing challenges with making an early definitive diagnosis. These challenges relate primarily to advances in prevention of mother-to-child transmission (PMTCT) of HIV. Although PMTCT programs have proven to be highly effective in reducing infant HIV infection, infants who are HIV-infected may achieve virological suppression and loss of detectability of HIV nucleic acid prior to diagnosis because of antiretroviral drug exposure. Hence, false-negative and indeterminate HIV polymerase chain reaction (PCR) results can occur, especially among high-risk infants given multi-drug prophylactic regimens. However, the infant HIV diagnostic landscape is also complicated by the inevitable decline in the positive predictive value of early infant diagnosis (EID) assays. As PMTCT programs successfully reduce the mother-to-child transmission rate, the proportion of false-positive EID results will increase. Consequently, false-negative and false-positive HIV PCR results are increasingly likely despite highly accurate diagnostic assays. The problem is compounded by the seemingly intractable prevalence of maternal HIV within some settings, resulting in a considerable absolute burden of HIV-infected infants despite a low mother-to-child transmission rate.

Dried blood spot and mini-tube blood sample collection kits for postal HIV testing services: a comparative review of successes in a real-world setting

ObjectivesThis is a comparative review between using dried blood spot (DBS) and mini-tube (MT) HIV sampling kits as part of an online sexually transmitted infection (STI) postal testing service. England...

Clinical Application Evaluation of a Fourth-Generation HIV Antigen Antibody Combination Screening Assay.

Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) are infectious diseases with high mortality. Early diagnosis is crucial. Combining HIV antibody and p24 antigen, the Elecsys HIV combi PT assay is a fourth generation HIV screening assay. The sensitivity and specificity of this assay was examined. A total of 111,556 samples was conducted from January 1, 2016, to June 30, 2018 in Zhongshan Hospital of Yat-Sen University. We conducted a fourth-generation HIV test of retrospective HIV screening samples and assessed the reliability of using signal-to-cutoff (S/CO) ratios to distinguish false positive HIV antibody reactions and analyzed false positives. A total of 122 specimens were confirmed as HIV-1 infected by western blot (WB) and HIV nucleic acid assays. The median S/CO ratio for HIV false positive specimens was 3.27, while for the HIV-infected specimen it was 391.7. Receiver operating characteristic (ROC) analysis showed that the best diagnostic point for HIV was 22.85 S/CO. The sensitivity, specificity, and Youden index were 100%, 97.8%, and 0.978, respectively. The highest false positive rate of 26.4% was found in patients with malignant tumors and blood diseases. The results of this study show that the fourth-generation Elecsys HIV combination PT test can identify early HIV infected and can be a useful adjunct to help clinicians to manage the disease by viral load testing and starting an appropriate therapy. Our research data provides a reference for subsequent research and HIV testing in the region.

HIV self-test performance among female sex workers in Kampala, Uganda: a cross-sectional study

ObjectiveTo evaluate HIV self-testing performance and results interpretation among female sex workers (FSWs) in Kampala, Uganda, who performed unassisted HIV self-testing.MethodsIn October 2016, 104 participants used an oral HIV self-test...

Brief Report: The Amsterdam Symptom and Risk-Based Score Predicts for Acute HIV Infection in Men Who Have Sex With Men in San Diego.

Dijkstra et al recently described a risk- and symptom-based score moderately predictive for HIV seroconversion in the preceding 6-12 months in men who have sex with men (MSM) in Amsterdam. Our objective was to determine whether this "Amsterdam Score" could also predict for acute HIV infection (AHI) in MSM. This study is a case-control analysis of a prospectively enrolled cohort of MSM who voluntarily presented for HIV testing in San Diego. The study sample was composed of MSM who screened HIV antibody-negative and then either tested positive with AHI [HIV nucleic acid test (NAT)-positive] or tested HIV NAT-negative. The Amsterdam Score was calculated for each participant in the study sample. Score performance was assessed using receiver operating characteristic curves and their area under the curve (AUC). An optimal cutoff was determined using the Youden index. Seven hundred fifty-seven MSM (110 AHI and 647 HIV NAT-negative) were included in the analysis. AHI and HIV-negative cases were similar in age [median 32 years (interquartile range 26-42) vs 33 (27-45), respectively, P = 0.082]. The Amsterdam Score yielded a receiver operating characteristic curve with an AUC of 0.88 (95% confidence interval: 0.84 to 0.91). An optimal cutoff of ≥1.6 was 78.2% sensitive and 81.0% specific. The risk- and symptom-based Amsterdam Score was highly predictive (AUC of 0.88) of AHI in MSM in San Diego. The Amsterdam Score could be used to target NAT utilization in resource-poor settings among MSM who test HIV antibody-negative, although the potential cost-savings must be balanced with the risk of missing AHI diagnoses.

Repeated False-Positive HIV Test Results in a Patient Taking HIV Pre-Exposure Prophylaxis.

Regular HIV testing is required to ensure the safety of HIV pre-exposure prophylaxis (PrEP). We describe and discuss a series of false-positive HIV test results from an individual receiving PrEP. The expansion of PrEP will likely result in greater numbers of false-positive test results that may pose challenges for interpretation.

Organs from deceased donors with false-positive HIV screening tests: An unexpected benefit of the HOPE act.

Organs from deceased donors with suspected false-positive HIV screening tests were generally discarded due to the chance that the test was truly positive. However, the HIV Organ Policy Equity (HOPE) Act now facilitates use of such organs for transplantation to HIV-infected (HIV+) individuals. In the HOPE in Action trial, donors without a known HIV infection who unexpectedly tested positive for anti-HIV antibody (Ab) or HIV nucleic acid test (NAT) were classified as suspected false-positive donors. Between March 2016 and March 2018, 10 suspected false-positive donors had organs recovered for transplant for 21 HIV+recipients (14 single-kidney, 1 double-kidney, 5 liver, 1 simultaneous liver-kidney). Median donor age was 24years; cause of death was trauma (n = 5), stroke (n =4), and anoxia (n = 1); three donors were labeled Public Health Service increased infectious risk. Median kidney donor profile index was 30.5 (IQR 22-58). Eight donors were HIV Ab+/NAT-; two were HIV Ab-/NAT+. All 10 suspected false-positive donors were confirmed to be HIV-noninfected. Given the false-positive rates of approved assays used to screen>20000 deceased donors annually, we estimate 50-100 HIV false-positive donors per year. Organ transplantation from suspected HIV false-positive donors is an unexpected benefit of the HOPE Act that provides another novel organ source.

Diagnostic accuracy of fourth-generation ARCHITECT HIV Ag/Ab Combo assay and utility of signal-to-cutoff ratio to predict false-positive HIV tests in pregnancy

False-positive HIV screening tests in pregnancy may lead to unnecessary interventions in labor. In 2014, the Centers for Disease Control and Prevention released a new algorithm for HIV diagnosis using a fourth-generation screening test, which detects antibodies to HIV as well as p24 antigen and has a shorter window period compared with prior generations. A reactive screen requires a differentiation assay, and supplemental qualitative RNA testing is necessary for nonreactive differentiation assay. One screening test, the ARCHITECT Ag/Ab Combo assay, is described to have 100% sensitivity and >99% specificity in nonpregnant populations; however, its clinical performance in pregnancy has not been well described. The objective of the study was to determine the performance of the ARCHITECT assay among pregnant women at a large county hospital and to assess whether the relative signal-to-cutoff ratio can be used to differentiate between false-positive vs confirmed HIV infections in women with a nonreactive differentiation assay. This is a retrospective review of fourth-generation HIV testing in pregnant women at Parkland Hospital between June 1, 2015, and Jan. 31, 2017. We identified gravidas screened using the ARCHITECT Ag/Ab Combo assay (index test), with reflex to differentiation assay. Women with reactive ARCHITECT and nonreactive differentiation assay were evaluated with a qualitative RNA assay (reference standard). We calculated sensitivity, specificity, predictive value, and false-positive rate of the ARCHITECT screening assay in our population and described characteristics of women with false-positive HIV testing vs confirmed infection. Among women with a nonreactive differentiation assay, we compared interventions amongwomen with and without a qualitative RNA assay result available at delivery and examined relative signal-to-cutoff ratios of the ARCHITECT assay in women with false-positive vs confirmed HIV infection. A total of 21,163 pregnant women were screened using the ARCHITECT assay, and 190 tested positive. Of these, 33 of 190 (17%) women had false-positive HIV screening tests (28 deliveries available for analysis), and 157 of 190 (83%) had confirmed HIV-1 infection (140 available for analysis). Diagnostic accuracy of the ARCHITECT HIV Ag/Ab Combo assay in our prenatal population (with 95% confidence interval) was as follows: sensitivity, 100% (97.7-100%); specificity, 99.8% (99.8-99.9%); positive likelihood ratio, 636 (453-895); negative likelihood ratio, 0.0 (NA); positive predictive value, 83% (77-88%); and false positive rate, 0.16% (0.11-0.22%), with a prevalence of 7 per 1000. Women with false-positive HIV testing were younger and more likely of Hispanic ethnicity. A qualitative RNA assay (reference standard) was performed prenatally in 24 (86%) and quantitative viral load in 22 (92%). Interventions occurred more frequently in women without a qualitative RNA assay result available at delivery, including intrapartum zidovudine (75% vs 4%, P= .002), breastfeeding delay (75% vs 8%, P= .001), and neonatal zidovudine initiation (75% vs 4%, P= .002). The ARCHITECT signal-to-cutoff ratio was significantly lower for women with false-positive HIV tests compared with those with established HIV infection (1.89 [1.27, 2.73] vs 533.65 [391.12, 737.22], respectively, P < .001). While the performance of the fourth-generation ARCHITECT HIV Ag/Ab Combo assay among pregnant women is comparable with that reported in nonpregnant populations, clinical implications of using a screening test with a positive predictive value of 83% in pregnancy are significant. When the qualitative RNA assay result is unavailable, absence of risk factors in combination with an ARCHITECT HIV Ag/Ab assay S/Co ratio <5 and nonreactive differentiation assay provide sufficient evidence to support deferral of unnecessary intrapartum interventions while awaiting qualitative RNA results.