Analytical and Clinical Performance Evaluation of the Elecsys HIV Combi PT Assay on the Cobas e 602 Analyzer for the Diagnosis of Human Immunodeficiency Virus

Denise L. Uettwiller-Geiger, PhD; Marvin Lessig, DO; Jie An, PhD; Tara Barsch; Susan Smith; Sharan Walker; Alexander Riedel, PhD; Yi Hao, MSc; Amin A. Mohammad, PhD

Disclosures

Am J Clin Pathol. 2019;151(4):377-385. 

In This Article

Discussion

Diagnostic assays for use in HIV screening must be highly sensitive and capable of detecting all subtypes of HIV. The ability to detect infection early in the disease course is also necessary to facilitate prompt treatment and prevent further transmission. The Elecsys HIV combi PT assay has been designed with a pretreatment step to enhance early detection and increase the assay sensitivity and specificity. In the current study, we demonstrate robust clinical and analytical performance of the Elecsys HIV combi PT assay under routine laboratory conditions, as well as good precision, and the assay reliably differentiated between HIV-positive and HIV-negative samples with high sensitivity and specificity relative to the final diagnosis. Importantly, the assay was well within regulatory authority criteria that require commercially available assays to detect both antigen and antibodies with a sensitivity for detection of p24 antigen of 2 IU/mL or less. Seroconversion detection sensitivity of the Elecsys HIV combi PT assay was similar to the FDA-approved reference assay, and no interference was observed from other viral disease states/medical conditions or commonly used drugs. These findings supported the FDA approval (June 2017) of the Elecsys HIV combi PT assay for diagnosing HIV-1 and/or HIV-2 infection (including acute or primary HIV-1 infection) in individuals 2 years or older and in pregnant women.

The current evaluation of the Elecsys HIV combi PT assay included almost 10,000 samples, the majority of which were US clinical samples, but non-US cohorts were also included. In this population, overall sensitivity was 100% and specificity was 99.94%, which is consistent with previous studies of the Elecsys HIV combi PT assay conducted in different geographical regions.[7,8,13] A study conducted in 12 centers across Europe, Australia, and Thailand showed an overall specificity of 99.81% in routine samples and 99.88% in blood donor samples,[7] while studies in Asia and South Korea have shown overall specificities of 99.86% and 99.50%, respectively.[8,13] Together, these studies demonstrate consistently high sensitivity and specificity for the Elecsys HIV combi PT assay and therefore confirm its applicability across a broad range of geographical regions.

The predominance of different HIV subtypes in different regions is a product of the rapid evolution of HIV, which has led to considerable genetic diversity. This diversity is a known challenge for HIV assays, with previous studies reporting difficulties detecting certain subtypes, such as group O.[14,15] Our study included cohorts from HIV-2 endemic regions, as well as samples with HIV-1 group O and M subtypes. The Elecsys HIV combi PT assay successfully detected known HIV-positive samples with high sensitivity regardless of HIV group or subtype and across different patient populations.

The Elecsys HIV combi PT assay showed excellent clinical performance and detection of seroconversion in comparison with the reference ARCHITECT HIV Ag/Ab combo assay. Furthermore, the high sensitivity observed in confirmed HIV-1–positive samples (100%) is equivalent or superior to the sensitivities previously determined for other commercially available assays, including the ARCHITECT HIV Ag/Ab combo (99.94%), BioPlex 2200 (Bio-Rad; 100%), and Centaur HIV Ag/Ab Combo assays (Siemens Healthcare Diagnostics; 100%).[16–18] The Elecsys HIV combi PT assay's specificity (99.94%) is also equivalent or superior to other HIV assays (98%-100%).[7,16–22] The analytical sensitivity of the HIV combi PT assay (.84 IU/mL) in the present study is lower than previously reported (.90–1.05 IU/mL) and well within the sensitivity of 2 IU/mL or less specified by regulatory authorities. Furthermore, these data compare favorably with other fourth-generation assays (ARCHITECT HIV Ag/Ab combo, .94 IU/mL; Centaur HIV Ag/Ab combo, 1.89 IU/mL; AxSYM HIV Ag/Ab combo, 1.20 IU/mL)[7,8] and demonstrate the suitability of the Elecsys HIV combi PT assay for use in HIV screening.

Early diagnosis of HIV in pregnant women is important so that antiretroviral therapy can be initiated as soon as possible to reduce the risk of vertical transmission, and the CDC recommends that all women are screened for HIV upon entering prenatal care.[10] In samples from pregnant women, the Elecsys HIV combi PT assay demonstrated an overall specificity of 97.43%; in pregnant women at high risk for HIV infection, specificity and sensitivity were 89.90% and 100.00%, respectively. It should be noted that the high reactivity of non-US high-risk pregnant women samples was the major factor contributing to the lower specificity of the overall high-risk pregnant women cohort (specificity in the US cohort was 98.53%). A secondary analysis based on retesting with individual reagent components showed that only two of 10 samples were false positives, resulting in specificities of 97.80% and 95.65% in the overall and non-US cohorts, respectively. Our results suggest that the Elecsys HIV combi PT assay may improve accuracy of HIV diagnosis in pregnant women compared with the reference assay, as well as reduce emotional stress and unnecessary follow-up associated with false-positive results.[23]

This study was designed to avoid biases in evaluation of clinical and analytical performance by obtaining samples from different collection sites and commercial vendors, as well as selecting samples for study testing based on clear inclusion and exclusion criteria. Analytical performance testing was conducted according to CLSI guidelines, and effects of multiple lots of reagents were evaluated in different final-user environments. Some of the population subgroup sample sizes were relatively small (ie, subgroups for confirmed HIV-positive pregnant women; pregnant women at high risk for HIV; confirmed HIV-1–positive children/adolescents; HIV-1 group O, HIV-1 group M subtypes; and antigen specimens), reflecting the rarity of some HIV subtypes and the relatively low rate of HIV infection in pregnant women in the United States. As a result, the statistical power of some of the cohort-specific calculations of sensitivity and specificity was low.

In conclusion, our findings provide further evidence of the excellent clinical and analytical performance of the Elecsys HIV combi PT assay on the cobas e 602 analyzer for the detection of early HIV infection in high- and low-risk adults and children/adolescents, pregnant women, and HIV-1–positive individuals under routine laboratory conditions in the United States, and they supported the recent FDA approval.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....