Impact of the 2014 CDC HIV testing guidelines on detection of acute HIV infections.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) issued updated guidelines for HIV testing in 2014. These guidelines recommend screening using an HIV-1/2 antigen/antibody (Ag/Ab) test and create the ability to identify algorithm-defined acute HIV infections (AHI). The guidelines also recommend laboratory confirmation of preliminary positive point of care (POC) rapid HIV test results and specimens from high-risk individuals who test POC rapid negative. The Florida Public Health Laboratory (FPHL) switched from an antibody-only algorithm to the CDC recommended algorithm April 16, 2012. OBJECTIVES: To analyze the FPHL HIV testing data and evaluate the impact of the CDC recommended algorithm on the identification of AHI, time to result and inconclusive HIV reports. STUDY DESIGN: FPHL HIV test data, for the period January 1, 2010 through December 31, 2019, was reviewed to determine the number of AHI cases identified, the number of indeterminate HIV results and the time from specimen receipt to result for tests in the antibody-only and CDC recommended algorithms. In addition, POC rapid results were compared to laboratory-based results for AHI cases for which rapid test results were available. RESULTS: There was no difference in time to result between the antibody-only and CDC recommended algorithms for HIV negative specimens. The time to result for HIV-1 positive specimens decreased from an average of 5 days with the antibody-only algorithm to an average of 1 day with the CDC recommended algorithm. The average number of indeterminate results per month decreased from 6.25 per month with the antibody-only algorithm to an average of 2.5 per month using the CDC recommended algorithm. Despite HIV seropositivity decreasing by 0.5% during the study period (2012 = 3.1% [3,892/124,394]: 2019 = 2.6% [2,456/95,525]), AHI cases increased annually from a total of 4 in 2012 to over 50 in 2019 and cases were identified in 30 of 67 Florida counties. The increase in identification of AHIs is credited to educational efforts with healthcare providers to encourage further testing on individuals with risk factors for HIV and a recent POC HIV-1/2 rapid negative test result. CONCLUSIONS: Data indicates that performing HIV testing according to the CDC recommended algorithm decreased time to result for HIV positive results, reduced the number of indeterminate results and identified algorithm-defined AHI. In addition, laboratory-based testing is warranted for high-risk individuals who test negative by POC rapid testing.

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.

Comparative performance of the Geenius™ HIV-1/HIV-2 supplemental test in Florida's public health testing population.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) published updated guidelines in 2014 for the laboratory diagnosis of HIV in the United States, which recommend use of a supplemental immunoassay (IA) that differentiates HIV-1 from HIV-2 after a repeatedly reactive HIV-1/2 antigen/antibody "Combo" screening test. In October 2014, Bio-Rad Laboratories introduced the FDA-cleared Geenius HIV-1/HIV-2 Supplemental assay and in July 2016, it replaced the Multispot HIV-1/HIV-2 differentiation rapid test as the second test in the HIV diagnostic algorithm. OBJECTIVE: To compare performance of the new FDA-cleared Bio-Rad Geenius HIV-1/HIV-2 Supplemental assay and the Bio-Rad Multispot HIV-1/HIV-2 differentiation assay for use as the primary supplemental test in the 2014 CDC/APHL HIV Diagnostic Algorithm. STUDY DESIGN: Two sets of specimens were used to assess the performance of Geenius; 340 select retrospective specimens, obtained through routine clinical submissions from individuals seeking HIV serostatus determinations and 10 known HIV-2 antibody reactive specimens provided by Bio-Rad Laboratories. Panels were created and characterized solely by in-house laboratory results. The panels consisted of: algorithm-defined "established HIV-1 infections" (n=250), "acute HIV-1 infections" (n=20), "early HIV-1 infections" (n=10) and "false positive Combo specimens" (n=60). RESULTS: CONCLUSIONS: The Geenius assay provides significant advantages over Multispot as an appropriate replacement for the primary supplemental test in the HIV Diagnostic Algorithm. In this retrospective study, Geenius was highly concordant with Multispot, reclassified some acute and early algorithm-defined HIV-1 positive specimens and demonstrated a potential decrease in the number HIV-1 RNA nucleic acid amplification tests needed to complete the diagnostic algorithm.

Performance of the new HIV-1/2 diagnostic algorithm in Florida's public health testing population: a review of the first five months of utilization.

OBJECTIVE: The Centers for Disease Control and Prevention and the Association of Public Health Laboratories have proposed a new HIV-1/2 Diagnostic Algorithm: a fourth-generation HIV-1/2 Ag/Ab immunoassay (IA) followed, when repeatedly reactive, by an HIV-1/HIV-2 antibody differentiation test, and if that is non-reactive, HIV-1 nucleic acid amplification testing (NAT). The objective of the study was to evaluate performance of the new algorithm after five months of utilization in our high volume, high HIV-1 seroprevalence public health population. METHODS: Algorithm sensitivity and specificity was evaluated on 51,953 prospective serum or plasma specimens from individuals self-referring for HIV serostatus determination. Specimens were tested on the day of receipt or maintained at 4°C until the next testing opportunity. If the initial HIV-1/2 Ag/Ab IA (Abbott Combo) was nonreactive, a negative lab interpretation report would follow. If the initial IA was reactive, repeat screening in duplicate was immediately performed. Repeatedly reactive specimens were tested with an HIV-1/HIV-2 differentiation assay (Multispot [MS] HIV-1/HIV-2 Rapid Test) on the same or next workday. If the Abbott Combo-MS assays were discordant, HIV-1 NAT (APTIMA(®) HIV-1 RNA) was performed. In addition to the algorithm performance, we also evaluated the laboratory "specimen receipt to reporting" turnaround time (TAT). RESULTS: The sensitivity and specificity of the new HIV Diagnostic Algorithm with serum and plasma specimens over the initial 5 month period was 100% (922/922) and 99.99% (51,030/51,031), respectively. Two algorithm-defined acute HIV-1 infections (AHI) were detected. In addition only 3 of the 992 MS secondary tests performed were interpreted as HIV-1 Indeterminate (HIV-1 recombinant gp41 reactivity only). Of these, 2 were HIV-1 NAT reactive, defined in-house as an early HIV infection (EHI) and one was HIV-1 NAT nonreactive, indicating a false positive initial screening result. Laboratory TAT for reporting concordant reactive Abbott Combo-MS results in ≤ 2 workdays was 96%, compared to 22% for reporting concordant reactive 3rd generation IA-Western blot results. CONCLUSIONS: In our public health testing population, results from the new HIV Diagnostic Algorithm exceeded those of the 3rd generation IA-WB algorithm with respect to HIV-1 sensitivity. The identification of two algorithm-defined AHIs provided the opportunity to inform these individuals of their HIV status and link them to medical care earlier than the scheduled posttest counseling appointment.

HIV single staging algorithm: integration and maximization of resources by reducing time between HIV diagnosis and treatment.

BACKGROUND: Early HIV diagnosis, linkage and engagement into care are vital to improved personal health outcomes. The initiation of antiretroviral therapy, with retention in care and drug adherence leads to viral load suppression, a significant decrease in HIV transmission rates and ultimately a reduction in HIV incidence rates. In the U.S only 51% of those diagnosed with HIV infection are retained in care and 28% have a suppressed viral load. Reducing the time and number of visits from HIV diagnosis to entry into care, has the potential to engage and treat an increased number of infected individuals. OBJECTIVE: (1) Evaluate the feasibility of conducting HIV-1 supplemental testing concurrently with baseline clinical management testing; (2) to evaluate whether all tests could be completed and reported prior to the traditional posttest counseling appointment; (3) to monitor the return activity for posttest and medical provider appointments. METHODS: Baseline CD4 and HIV-1 viral load tests were performed concurrently with an HIV-1/2 antibody immunoassay (IA) and HIV-1 Western blot (WB) on 105 individuals with preliminary positive rapid test results. Participating study-sites were located in high-risk, high-morbidity locations: a county jail, a county mobile unit and a county hospital emergency department. Based on the individual's self-reporting statement of "No" to a previous HIV diagnosis and the POC preliminary positive rapid test result, blood specimens were processed via the Single Staging Algorithm. Study site data and medical record review established time intervals between the rapid test and subsequent visits. RESULTS: Of the 105 individuals with HIV-1 preliminary positive rapid test results, 102 were confirmed positive with HIV-1 WB (plus 3rd generation IA repeatedly reactive) and one was confirmed by an HIV-1 WB indeterminate (gp160), HIV-1 Nucleic Acid Amplification Test (NAAT) reactive (an algorithm-defined early infection). The concordance between POC preliminary positive rapid tests and the confirmatory test of the single staging algorithm was 98%. Ninety-six (91%) HIV-1 baseline viral load test results and 82 (78%) CD4/CD8 absolute counts were performed and made available to the provider prior to posttest counseling. The average number of visits for posttest counseling at 14 days was 44.7% (range 37.9-56.5%) with an additional 31.1% (range 22.7-37.9%) returning within 30 days. The average number of clients that returned for the medical provider appointment was 55.4%. CONCLUSION: A high percentage of HIV-1 clinical management baseline results (78-91%) and 100% confirmatory diagnostic results were completed and reported prior to the traditional posttest counseling appointment. Additional data and analysis is needed to determine the impact of the Single Staging Algorithm on medical provider appointments if the posttest appointment is more than 30 days after the preliminary HIV diagnosis.