Distribution of HIV Self-tests by Men Who have Sex with Men (MSM) to Social Network Associates.

Internet-recruited gay, bisexual, and other men who have sex with men (MSM) were offered HIV self-tests (HIVSTs) after completing baseline, 3-, 6-, and 9-month follow-up surveys. The surveys asked about the use and distribution of these HIVSTs. Among 995 who reported on their distribution of HIVSTs, 667 (67.0%) distributed HIVSTs to their social network associates (SNAs), which resulted in 34 newly identified HIV infections among 2301 SNAs (1.5%). The main reasons participants reported not distributing HIVSTs included: wanting to use the HIVSTs themselves (74.9%); thinking that their SNAs would get angry or upset if offered HIVSTs (12.5%); or not knowing that they could give the HIVSTs away (11.3%). Self-testing programs can provide multiple HIVSTs and encourage the distribution of HIVST by MSM to their SNAs to increase awareness of HIV status among persons disproportionately affected by HIV.

RESUMEN: Hombres gais, bisexuales y otros hombres que indicaron tener contacto sexual con hombres (MSM, por sus siglas en inglés) fueron reclutados por el Internet y se les ofreció autopruebas del VIH (HIVST, por sus siglas en inglés) después de completar una encuestas inicial y encuestas de seguimiento a los 3, 6 y 9 meses. Las encuestas recogieron datos sobre el uso y distribución de estas autopruebas del VIH. De los 995 MSM que indicaron distribuir las autopruebas, 667 (67.0%) distribuyeron las autopruebas a personas en sus redes sociales (SNA, por sus siglas en inglés), resultando en 34 nuevas infecciones por el VIH identificadas entre 2,301 SNA (1.5%). Las razones principales por las que algunos participantes no distribuyeron las autopruebas del VIH incluyen: el deseo de utilizar las autopruebas del VIH para sí mismos (74.9%); pensar que las SNA se enfadarían o molestarían si se les ofreciesen autopruebas del VIH (12.5%); o no saber que podían distribuir las autopruebas del VIH (11.3%). Los programas que proporcionen múltiples autopruebas del VIH podrían alentar la distribución de las autopruebas por parte de los MSM a las SNA para aumentar el conocimento sobre el estado del VIH entre personas afectadas de manera desproporcionada por el VIH.

Routine HIV Test Results in 6 US Clinical Laboratories Using the Recommended Laboratory HIV Testing Algorithm With Geenius HIV 1/2 Supplemental Assay.

BACKGROUND: Geenius HIV 1/2 Supplemental Assay (Geenius; Bio-Rad Laboratories) is the only Food and Drug Administration-approved HIV-1/HIV-2 antibody differentiation test for the second step in the HIV laboratory testing algorithm. We characterized the occurrence of true HIV-1 and HIV-2 infections as well as false results in 6 US clinical laboratories using Geenius. METHODS: We examined routine HIV testing outcome data from the time the laboratories began using the algorithm with Geenius until September 30, 2017. We calculated the positive predictive value for Geenius HIV-1 and HIV-2 reactivity separately. RESULTS: Of 5,046,684 specimens tested, 41,791 had reactive antigen/antibody test results. Most specimens with reactive antigen/antibody results were HIV-1 antibody-positive established infections (n = 32,421), 1,865 of which also had indeterminate HIV-2 bands present. Ninety-three specimens were HIV-2 antibody positive or untypable for HIV-1/HIV-2 antibody. Acute HIV-1 infections were found in 528 specimens; 881 specimens lacked the nucleic acid test to determine the possibility of acute HIV-1 infection. False-positive antigen/antibody test results were present in 7505 specimens. Few specimens (n = 363) had false-positive antigen/antibody results with indeterminate Geenius and negative HIV-1 nucleic acid test results. The positive predictive values of Geenius reactivity were 99.4% for HIV-1 and 4.3% for HIV-2. CONCLUSIONS: Routine testing using the laboratory testing algorithm with Geenius resulted in most specimens resolving as HIV negative or HIV-1 positive. The occurrence of indeterminate HIV-2 bands with a Geenius final assay interpretation of HIV-1 positive was more common than true HIV-2 infections. Reporting indeterminate HIV-2 results in this situation may cause confusion with interpreting HIV infection status.

Prospective Evaluation of HIV Testing Technologies in a Clinical Setting: Protocol for Project DETECT.

BACKGROUND: HIV testing guidelines provided by the Centers for Disease Control and Prevention (CDC) are continually changing to reflect advancements in new testing technology. Evaluation of existing and new point-of-care (POC) HIV tests is crucial to inform testing guidelines and provide information to clinicians and other HIV test providers. Characterizing the performance of POC HIV tests using unprocessed specimens can provide estimates for the window period of detection, or the time from HIV acquisition to test positivity, which allows clinicians and other HIV providers to select the appropriate POC HIV tests for persons who may be recently infected with HIV. OBJECTIVE: This paper describes the protocols and procedures used to evaluate the performance of the newest POC tests and determine their sensitivity during early HIV infection. METHODS: Project DETECT is a CDC-funded study that is evaluating POC HIV test performance. Part 1 is a cross-sectional, retrospective study comparing behavioral characteristics and HIV prevalence of the overall population of the Public Health-Seattle & King County (PHSKC) Sexually Transmitted Disease (STD) Clinic to Project DETECT participants enrolled in part 2. Part 2 is a cross-sectional, prospective study evaluating POC HIV tests in real time using unprocessed whole blood and oral fluid specimens. A POC nucleic acid test (NAT) was added to the panel of HIV tests in June 2018. Part 3 is a longitudinal, prospective study evaluating seroconversion sensitivity of POC HIV tests through serial follow-up testing. For comparison, HIV-1 RNA and HIV-1/HIV-2 antigen/antibody tests are also performed for participants enrolled in part 2 or 3. A behavioral survey that collects information about demographics, history of HIV testing, STD history, symptoms of acute HIV infection, substance use, sexual behaviors in the aggregate and with recent partners, and use of pre-exposure prophylaxis and antiretroviral therapy is completed at each part 2 or 3 visit. RESULTS: Between September 2015 and March 2019, there were 14,990 Project DETECT-eligible visits (part 1) to the PHSKC STD Clinic resulting in 1819 part 2 Project DETECT study visits. The longitudinal study within Project DETECT (part 3) enrolled 27 participants with discordant POC test results from their part 2 visit, and 10 (37%) were followed until they had fully seroconverted with concordant positive POC test results. Behavioral survey data and HIV test results, sensitivity, and specificity will be presented elsewhere. CONCLUSIONS: Studies such as Project DETECT are critical for evaluating POC HIV test devices as well as describing characteristics of persons at risk for HIV acquisition in the United States. HIV tests in development, including POC NATs, will provide new opportunities for HIV testing programs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/16332.

Could HIV-1 RNA Testing be an Option as the Second Step in the HIV Diagnostic Algorithm?

BACKGROUND: There is benefit to early HIV-1 diagnosis and treatment, but there is no Food and Drug Administration-approved quantitative assay with a diagnostic claim. We compared the performance of the Hologic Aptima HIV-1 Quant (APT-Quant) and Aptima HIV-1 Qual (APT-Qual) assays for diagnostic use and the performance of a diagnostic algorithm consisting of Bio-Rad BioPlex 2200 HIV Ag-Ab assay (BPC) followed by APT-Quant (2-test) compared with BPC followed by Geenius HIV-1/2 supplemental assay (Geenius) with reflex to APT-Qual (3-test). METHODS: Five hundred twenty-four plasma, which included 419 longitudinal specimens from HIV-1 seroconverters (78 were after initiating antiretroviral therapy [ART]) and 105 from ART-naive persons with established HIV-1 infections, were used to evaluate APT-Quant performance for diagnostic use. Specimens from 200 HIV-negative persons were used to measure specificity. For the algorithm comparison, BPC-reactive specimens were evaluated with the 2-test or 3-test algorithm. McNemar's test was used to compare performance. RESULTS: The APT-Quant detected more samples early in infection compared with APT-Qual. The APT-Quant specificity was 99.8%. Before ART initiation, the algorithms performed similarly among samples from different stages of infection. After ART initiation, the 3-test algorithm performed significantly better (P = 0.0233). CONCLUSIONS: The APT-Quant has excellent performance for diagnostic use. The 2-test algorithm works well in ART-naive samples, but its performance decreases after the IgG response is elicited and with ART-induced suppressed viremia. Providing confirmation and viral load assay with 1 test result could be advantageous for patient care. However, additional factors and challenges associated with the implementation of this 2-test algorithm, such as cost, specimen type, and collection need further evaluation.

Trends in HIV-2 Diagnoses and Use of the HIV-1/HIV-2 Differentiation Test - United States, 2010-2017.

Since 2014, the recommended laboratory testing algorithm for diagnosing human immunodeficiency virus (HIV) infection has included a supplemental HIV-1/HIV-2 differentiation test to confirm infection type on the basis of the presence of type-specific antibodies (1). Correctly identifying HIV-1 and HIV-2 infections is vital because their epidemiology and clinical management differ. To describe the percentage of diagnoses for which an HIV-1/HIV-2 differentiation test result was reported and to categorize HIV type based on laboratory test results, 2010-2017 data from CDC's National HIV Surveillance System (NHSS) were analyzed. During 2010-2017, a substantial increase in the number of HIV-1/HIV-2 differentiation test results were reported to NHSS, consistent with implementation of the HIV laboratory-based testing algorithm recommended in 2014. However, >99.9% of all HIV infections identified in the United States were categorized as HIV-1, and the number of HIV-2 diagnoses (mono-infection or dual-infection) remained extremely low (<0.03% of all HIV infections). In addition, the overall number of false positive HIV-2 test results produced by the HIV-1/HIV-2 differentiation increased. The diagnostic value of a confirmatory antibody differentiation test in a setting with sensitive and specific screening tests and few HIV-2 infections might be limited. Evaluation and consideration of other HIV tests approved by the Food and Drug Administration (FDA) that might increase efficiencies in the CDC and Association of Public Health Laboratories-recommended HIV testing algorithm are warranted.

Performance of an Alternative Laboratory-Based HIV Diagnostic Testing Algorithm Using HIV-1 RNA Viral Load.

BACKGROUND: Since 2014, the recommended algorithm for laboratory diagnosis of HIV infection in the United States has consisted of an HIV-1/2 antigen/antibody (Ag/Ab) test followed by an HIV-1/2 antibody (Ab) differentiation test and, if necessary, a diagnostic HIV-1 nucleic acid test to resolve discordant or indeterminate results. METHODS: Using stored specimens from persons seeking HIV testing who had not received a previous diagnosis or treatment, we compared the performance of a 3-step alternative algorithm consisting of an Ag/Ab test followed by a quantitative HIV-1 RNA viral load assay and, if viral load is not detected, an Ab differentiation test, to that of the recommended algorithm. We calculated the sensitivity and specificity of 5 Ag/Ab tests and the proportion of specimens correctly classified by the alternative algorithm compared with the recommended algorithm. Results were examined separately for specimens classified as early infection, established infection, and false-reactive screening. RESULTS: Sensitivity and specificity were similar among all Ag/Ab tests. Viral load quantification correctly classified all specimens from early infection, all false-reactive screening specimens, and the majority of specimens from established infection. CONCLUSIONS: Although cost, regulatory barriers, test availability, and the ability to differentiate early from established infection must be considered, this alternative algorithm can potentially decrease the total number of tests performed and reduce turnaround time, thereby streamlining HIV diagnosis and initiation of treatment.

Performance evaluation of four point-of-care HIV tests using unprocessed specimens.

BACKGROUND: The performance of recently approved point-of-care (POC) HIV tests should be assessed using unprocessed specimens. OBJECTIVE: To evaluate the sensitivity and specificity of four POC HIV tests using whole blood (WB) and two using oral fluid (OF) among persons recruited from health clinics in Seattle, Washington, during September 2015-September 2017. STUDY DESIGN: Participants were tested with the POC tests, additional plasma and serum were collected for laboratory testing, and participant- reported use of antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP) was recorded. Participants testing negative on all tests could reenroll every 90 days. Specimens from persons previously diagnosed with HIV infection as well as from those who were newly diagnosed during the study were included in the sensitivity estimate. Sensitivity and specificity were calculated based on HIV status determined by laboratory testing. RESULTS: Of 1,256 visits, 179 were from persons with HIV infection; 120 of these were taking ART. Among 1,077 visits from participants not diagnosed with HIV, PrEP use was reported at 155 (14.4%) visits. Sensitivity was similar among POC WB tests (95.53%-97.21%; p>0.05). Among participants on ART, sensitivity was lower for the same test performed on OF compared to WB (p<0.003). Specificity was high for all tests (99.44%- 100.00%); we did not detect specificity differences with PrEP use. CONCLUSIONS: These POC tests displayed relatively high sensitivity and specificity using unprocessed specimens, suggesting their effectiveness in identifying HIV infections whenever laboratory-based testing is not feasible. Nonetheless, clients with recent risk should retest to rule out the possibility of a false-negative result.

Three Years of Shared Service HIV Nucleic Acid Testing for Public Health Laboratories: Worthwhile for HIV-1 but Not for HIV-2.

BACKGROUND: In 2016, HIV-2 nucleic acid testing (NAT) was added to a shared service program that conducts HIV-1 NAT for public health laboratories performing the recommended algorithm for diagnosing HIV. Here, we evaluate the usefulness of HIV-2 NAT in this program as compared with HIV-1 NAT. METHODS: Specimens eligible for HIV-1 NAT were reactive on an HIV-1/2 antibody or antigen/antibody initial test and nonreactive or indeterminate on a supplemental antibody test or were reactive for HIV-1 antigen-only on an HIV-1/2 antigen/antibody initial test. Specimens eligible for HIV-2 NAT were reactive on an initial test, HIV-2 indeterminate or HIV indeterminate on a supplemental antibody test and had no detectable HIV-1 RNA or were reactive for HIV-2 antibody on an HIV-1/2 antigen/antibody test, and this reactivity was not confirmed with a supplemental antibody assay. All specimens were tested in a reference laboratory using APTIMA HIV-1 qualitative RNA and/or a validated qualitative HIV-2 RNA real-time PCR assay. RESULTS: During 2016 to 2019, HIV-1 RNA was detected in 234 (14%) of 1731 specimens tested. HIV-2 RNA was not detected in 52 specimens tested. Median time from specimen collection to reporting of HIV-1 and HIV-2 NAT results by year ranged from 9 to 10 days and from 22 to 27 days, respectively. Two specimens with HIV-2 indeterminate results on a supplemental antibody test had detectable HIV-1 RNA. CONCLUSIONS: A shared service model for HIV-1 NAT is both feasible and beneficial for public health laboratories. However, because no HIV-2 infections were detected, our data suggest that this program should reconsider the usefulness of HIV-2 NAT testing.

Men Who Have Sex with Men (MSM) Who Have Not Previously Tested for HIV: Results from the MSM Testing Initiative, United States (2012-2015).

The Centers for Disease Control and Prevention recommends annual HIV tests for men who have sex with men (MSM), yet some have never tested. We analyzed data from the MSM Testing Initiative. Of 68,185 HIV tests, 8% were with MSM who never previously tested ("first-time testers"). Among tests with first-time testers, 70.7% were with MSM from racial or ethnic minorities; 66.5% were with MSM younger than 30 years. Tests with MSM who reported female partners only during the past year (compared to male partners only) or were recruited for at-home testing (compared to venue-based recruitment) were 4 times (prevalence ratio [PR] 3.62, 95% CI 3.15-4.15) and 5 times as likely (PR 4.69, 95% CI 4.22-5.21) to be associated with first-time testing. At-home testing and focusing on MSM who have sex with women may be effective methods for reaching MSM who are first-time testers.

Performance of the Alere Determine™ HIV-1/2 Ag/Ab Combo Rapid Test with algorithm-defined acute HIV-1 infection specimens.

BACKGROUND: The capacity of HIV Antigen/Antibody (Ag/Ab) immunoassays (IA) to detect HIV-1 p24 antigen has resulted in improved detection of HIV-1 infections in comparison to Ab-only screening assays. Since its introduction in the US, studies have shown that the Determine HIV-1/2 Ag/Ab Combo assay (Determine Ag/Ab) detects HIV infection earlier than laboratory-based IgM/IgG-sensitive IAs, but its sensitivity for HIV-1 p24 Ag detection is reduced compared to laboratory-based Ag/Ab assays. However, further evaluation is needed to assess its capacity to detect acute HIV-1 infection. OBJECTIVE: To assess the performance of Determine Ag/Ab in serum from acute HIV-1 infections. STUDY DESIGN: Select serum specimens that screened reactive on a laboratory-based Ag/Ab IA or IgM/IgG Ab-only IA, with a negative or indeterminate supplemental antibody test and detectable HIV-1 RNA were retrospectively tested with Determine Ag/Ab. Results were compared with those of the primary screening immunoassay to evaluate concordance within this set of algorithm-defined acute infections. RESULTS: Of 159 algorithm-defined acute HIV-1 specimens, Determine Ag/Ab was reactive for 105 resulting in 66.0% concordance. Of 125 that were initially detected by a laboratory-based Ag/Ab IA, 81 (64.8%) were reactive by Determine Ag/Ab. A total of 34 acute specimens were initially detected by a laboratory-based IgM/IgG Ab-only IA and 24 (70.6%) of those were reactive by Determine Ag/Ab. CONCLUSIONS: Due to their enhanced sensitivity, laboratory-based Ag/Ab IAs continue to be preferred over the Determine Ag/Ab as the screening method used by laboratories conducting HIV diagnostic testing on serum and plasma specimens.

How well are U.S. primary care providers assessing whether their male patients have male sex partners?

Identifying patients at-risk for HIV infection, such as men who have sex with men (MSM), is an important step in providing HIV testing and prevention interventions. It is unknown how primary care providers (PCPs) assess MSM status and related HIV-risk factors. We analyzed data from a panel-derived web-based survey for healthcare providers conducted in 2014 to describe how PCPs in the U.S. determined their patients' MSM status. We calculated adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) to describe PCP characteristics associated with systematically determining MSM status (i.e., PCP used "a patient-completed questionnaire" or "routine verbal review of sex history"). Among the 1008 PCPs, 56% determined MSM status by routine verbal review of sexual history; 41% by patient disclosure; 39% by questions driven by symptoms/history; 23% by using a patient-completed questionnaire, and 9% didn't determine MSM status. PCPs who systematically determined MSM status (n=665; 66%) were more likely to be female (aPR=1.16, CI=1.06-1.26), to be affiliated with a teaching hospital (aPR=1.15, CI=1.06-1.25), to routinely screen all patients aged 13-64 for HIV (aPR=1.29, CI=1.18-1.41), and to estimate that 6% or more of their male patients are MSM (aPR=1.14, CI=1.01-1.30). The majority of PCPs assessed MSM status and HIV risk factors through routine verbal reviews of sexual history. Implementing a systematic approach to identify MSM status and assess risk may allow PCPs to identify more patients needing frequent HIV testing and other preventive services, while mitigating socio-cultural barriers to obtaining such information.

Pilot Evaluation of the Ability of Men Who Have Sex with Men to Self-Administer Rapid HIV Tests, Prepare Dried Blood Spot Cards, and Interpret Test Results, Atlanta, Georgia, 2013.

In the United States, an estimated 67% of new HIV diagnoses are among men who have sex with men (MSM), however 25% of HIV-positive MSM in the 2014 National HIV Behavioral Surveillance Survey were unaware of their infection. HIV self-testing (HIVST) with rapid diagnostic tests (RDTs) may facilitate access to HIV testing. We evaluated the ability of 22 MSM to conduct two HIV RDTs (OraQuick ® In-Home HIV Test and a home-use prototype of Sure Check ® HIV 1/2 Assay), interpret sample images of test results, and collect a dried blood spot (DBS) specimen. While some participants did not follow every direction, most participants were able to conduct HIVST and correctly interpret their results. Interpretation of panels of RDT images was especially difficult when the "control" line was missing, and 27% of DBS cards produced were rated as of bad quality. Modifications to the DBS instructions were necessary prior to evaluating the performance of these tests in real-world settings.

Highlights from the 2016 HIV diagnostics conference: The new landscape of HIV testing in laboratories, public health programs and clinical practice.

The 2016 HIV Diagnostics Conference, held in Atlanta, Georgia, was attended by public health officials, laboratorians, HIV testing program managers, surveillance coordinators and industry representatives. The conference addressed test performance data, the implementation of new testing algorithms, quality assurance, and the application of new tests in a variety of settings. With regard to the recommended Centers for Disease Control and Prevention/Association of Public Health Laboratories HIV laboratory testing algorithm, the conference featured performance data, implementation challenges such as a lack of test options for the second and third steps, as well as data needs for new tests that may be used as part of the algorithm. There are delays when nucleic acid testing is needed with the algorithm. Novel tests such as point of care nucleic acid tests are needed on the U.S. market to readily identify acute infection. Multiplex tests are being developed which allow for the simultaneous detection of multiple pathogens. CDC staff highlighted new guidance for testing in non-clinical settings. Innovative approaches to linking testing and care in some settings have led to identification of early infections, improved receipt of test results and expedited initiation of therapy. Work continues to optimize testing so that infections are accurately identified as early as possible and time to treatment is minimized to improve health outcomes and prevent transmission.

Acute infections, cost and time to reporting of HIV test results in three U.S. State Public Health Laboratories.

OBJECTIVE: In three U.S. State Public Health Laboratories (PHLs) using a fourth-generation immunoassay (IA), an HIV-1/HIV-2 differentiation antibody IA and a nucleic acid test (NAT), we characterized the yield and time to reporting of acute infections, and cost per positive specimen. METHODS: Routine HIV testing data were collected from July 1, 2012-June 30, 2013 for Massachusetts and Maryland PHLs, and from November 27, 2012-June 30, 2013 for Michigan PHL. Massachusetts and Michigan used fourth-generation and differentiation IAs with NAT conducted by a referral laboratory. In Maryland, fourth-generation IA repeatedly reactive specimens were followed by a Western blot (WB), and those with negative or indeterminate results were tested with a differentiation IA and HIV-1 NAT, and if positive by NAT, confirmed by a different HIV-1 NAT. Specimens from WB-positive persons at risk for HIV-2 were tested with a differentiation IA and, if positive, with an HIV-2 WB and/or differential HIV-1/HIV-2 proviral DNA polymerase chain reaction. RESULTS: Among 7914 specimens from Massachusetts PHL, 6069 from Michigan PHL, and 36,266 from Maryland PHL, 0.10%, 0.02% and 0.05% acute infections were identified, respectively. Massachusetts and Maryland PHLs each had 1 HIV-2 positive specimen. The median time from specimen receipt to laboratory reporting of results for acute infections at Massachusetts, Michigan and Maryland PHLs was 8, 11, and 7 days respectively. The laboratory cost per HIV positive specimen was $336 (Massachusetts), $263 (Michigan) and $210 (Maryland). CONCLUSIONS: Acute and established infections were found by PHLs using fourth-generation IA in conjunction with antibody tests and NAT. Time to reporting of acute HIV test results to clients was suboptimal, and needs to be streamlined to expedite treatment and interrupt transmission.

Acute Infections, Cost per Infection and Turnaround Time in Three United States Hospital Laboratories Using Fourth-Generation Antigen-Antibody Human Immunodeficiency Virus Immunoassays.

Background. To improve clinical and public health outcomes through early human immunodeficiency virus (HIV) detection, fourth-generation antigen/antibody immunoassay (4IA) and supplemental testing results must be returned rapidly. Methods. We examined HIV testing data at Harborview Medical Center (HMC), Massachusetts General Hospital (MGH), and the Medical University of South Carolina (MUSC), which used 4IA and supplemental antibody and nucleic acid tests (NATs). At MGH and MUSC, HIV-1 Western blot (WB) and HIV-2 testing were conducted at a reference laboratory. We compared time from specimen collection to laboratory result for established (positive WB) and acute infections (reactive 4IA, negative/indeterminate WB, detectable NAT), and we calculated testing cost per positive-test result. Results. From 3731 (MUSC) to 19 774 (MGH) tests were conducted; 0.01% (MGH) to 0.05% (HMC) were acute infections. Each laboratory had reactive 4IA, WB-negative, or indeterminate specimens without NAT (ie, potential acute infections). Time to result was 1.5 (HMC) to 5.2 days (MGH) for acute and 1.0 (HMC) to 5.2 days (MGH) for established infections. Costs were $1054 (MGH) to $1521 (MUSC). Conclusions. Conducting supplemental testing in-house lowered turnaround times, which may be further reduced with rapid HIV-1/HIV-2 differentiation tests. Hospitals may benefit from quantitative NATs not requiring physician orders, so all potential acute infections receive NAT.

Nucleic acid testing by public health referral laboratories for public health laboratories using the U.S. HIV diagnostic testing algorithm.

BACKGROUND: Many public health laboratories adopting the U.S. HIV laboratory testing algorithm do not have a nucleic acid test (NAT), which is needed when the third- or fourth-generation HIV screening immunoassay is reactive and the antibody-based supplemental test is non-reactive or indeterminate. OBJECTIVES: Among public health laboratories utilizing public health referral laboratories for NAT conducted as part of the algorithm, we evaluated the percentage of screening immunoassays needing NAT, the number of specimens not meeting APTIMA (NAT) specifications, time to APTIMA result, the proportion of acute infections (i.e., reactive APTIMA) among total infections, and screening immunoassay specificity. STUDY DESIGN: From August 2012 to April 2013, 22 laboratories enrolled to receive free APTIMA (NAT) at New York or Florida public health referral laboratories. Data were analyzed for testing conducted until June 2013. RESULTS: Submitting laboratories conducted a median of 4778 screening immunoassays; 0-1.3% (median 0.2%) needed NAT. Of 140 specimens received, 9 (6.4%) did not meet NAT specifications. The median time from specimen collection to reporting the 11 reactive NAT results was ten days, including six days from receipt in the submitting laboratory to shipment to the referral laboratory. Acute infections ranged from 0 to 12.5% (median 0%) of total infections. Third- and fourth-generation immunoassays met package insert specificity values. CONCLUSIONS: Public health referral laboratories provide a feasible option for conducting NAT. Reducing the time from specimen collection to submission of specimens for NAT is an important step toward maximizing the public health impact of identifying acute infections.

Evaluation of supplemental testing with the Multispot HIV-1/HIV-2 Rapid Test and APTIMA HIV-1 RNA Qualitative Assay to resolve specimens with indeterminate or negative HIV-1 Western blots.

BACKGROUND: The use of Western blot (WB) as a supplemental test after reactive sensitive initial assays can lead to inconclusive or misclassified HIV test results, delaying diagnosis. OBJECTIVE: To determine the proportion of specimens reactive by immunoassay (IA) but indeterminate or negative by WB that could be resolved by alternative supplemental tests recommended under a new HIV diagnostic testing algorithm. STUDY DESIGN: Remnant HIV diagnostic specimens that were reactive on 3rd generation HIV-1/2 IA and either negative or indeterminate by HIV-1 WB from 11 health departments were tested with the Bio-Rad Multispot HIV-1/HIV-2 Rapid Test (Multispot) and the Gen-Probe APTIMA HIV-1 RNA Qualitative Assay (APTIMA). RESULTS: According to the new testing algorithm, 512 (89.8%) specimens were HIV-negative, 55 (9.6%) were HIV-1 positive (including 19 [3.3%] that were acute HIV-1 and 9 [1.6%] that were positive for HIV-1 by Multispot but APTIMA-negative), 2 (0.4%) were HIV-2 positive, and 1 (0.2%) was HIV-positive, type undifferentiated. 47 (21.4%) of the 220 WB-indeterminate and 8 (2.3%) of the 350 WB-negative specimens were HIV-1 positive. CONCLUSION: Applying the new HIV diagnostic algorithm retrospectively to WB-negative and indeterminate specimens, the HIV infection status could be established for nearly all of the specimens. IA-reactive HIV-infected persons with WB-negative results had been previously misclassified as uninfected, and HIV diagnosis was delayed for those with WB-indeterminate specimens. These findings underscore the limitations of the WB to confirm HIV infection after reactive results from contemporary 3rd or 4th generation IAs that can detect HIV antibodies several weeks sooner than the WB.

Costs and outcomes of laboratory diagnostic algorithms for the detection of HIV.

BACKGROUND: An alternative HIV testing algorithm, designed to improve the detection of acute and early infections and differentiate between HIV-1 and HIV-2 antibodies, has been developed by the Centers for Disease Control and Prevention and the Association of Public Health Laboratories. While it promises greater sensitivity, it also raises concerns about costs. OBJECTIVE: We sought to compare the most commonly used algorithm which was developed in 1989, a third-generation (3G) immunoassay (IA) and Western blot confirmatory test, to a newer algorithm. The new algorithm includes either a 3G or a fourth-generation (4G) initial IA, followed by confirmatory testing with a HIV-1/HIV-2 differentiation IA and, if needed, a nucleic acid amplification test (NAT). STUDY DESIGN: We conducted an analysis of HIV testing costs from the perspective of the laboratory, and classified costs according to IA testing volume. We developed a decision analytic model, populated with cost data from 17 laboratories and published assay performance data, to compare the cost-effectiveness of the testing algorithms for a cohort of 30,000 specimens with a 1% HIV prevalence and 0.1% acute HIV infection prevalence. RESULTS: Costs were lower in high-volume laboratories regardless of testing algorithm. For specimens confirmed positive for HIV antibody, the alternative algorithm (IA, Multispot) was less costly than the current algorithm (IA, WB); however, there was wide variation in reported testing costs. For our cohort, the alternative algorithm initiated with a 3G IA and 4G IA identified 15 and 25 more HIV infections, respectively, than the 1989 algorithm. In medium-volume laboratories, the 1989 algorithm was more costly and less effective than the alternative algorithm with a 3G IA; in high-volume laboratories, the alternative algorithm with 3G IA costs $162 more per infection detected. The alternative algorithm with 4G instead of 3G incurred an additional cost of $14,400 and $4865 in medium- and high-volume labs, respectively. DISCUSSION: HIV testing costs varied with IA testing volumes. The additional cost of 4G over 3G IA might be justified by the additional cases of HIV detected and transmissions averted due to earlier detection. CONCLUSION: The alternative HIV testing algorithm compares favorably to the 1989 algorithm in terms of cost and effectiveness.