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

Results

Clinical Sensitivity

Reactivity in different study cohorts using the Elecsys HIV combi PT assay and reference assay is shown in Table 2 . Overall sensitivity of the Elecsys HIV combi PT assay in all confirmed HIV-1–positive individuals (United States and outside the United States; n = 1,460, including adults, children/adolescents, and HIV-positive pregnant women) was 100.00% (95% CI, 99.75%-100.00%). Among individuals at high risk for HIV (n = 758, including adults [United States], children/adolescents [United States], and pregnant women [United States and outside the United States]), 51 and 41 were repeatedly reactive using the Elecsys HIV combi PT assay and reference assay, respectively, and 38 were confirmed positive by Western blot. Overall sensitivity of the Elecsys HIV combi PT assay in the HIV-2 endemic area cohort was 99.64% (276/277; 95% CI, 98.01%-99.99%); sensitivity of the Elecsys HIV combi PT assay in confirmed HIV-2–positive individuals (n = 211) was 100.00% (95% CI, 98.27%-100.00%).

All samples from confirmed HIV-1–positive children/adolescents (United States and outside the United States; n = 50) were repeatedly reactive using both the Elecsys HIV combi PT assay and reference assay. Of 134 samples from children/adolescents at high risk for HIV (United States), one was repeatedly reactive using both the Elecsys HIV combi PT assay and reference assay, as well as confirmed positive by Western blot (Table 2; Supplementary Table 6).

All 60 samples from HIV-positive pregnant women (United States and outside the United States) were repeatedly reactive using the Elecsys HIV combi PT assay and reference assay. Nine of the 10 reactive samples from high-risk pregnant women that were not confirmed as HIV positive originated from outside the United States. In high-risk pregnant women (United States), specificity was 98.53% (67/68; 95% CI, 92.08%-99.96%) and sensitivity was 100.00% (10/10; 95% CI, 69.15%-100.00%). In high-risk pregnant women (outside the United States), specificity was 68.75% (22/32; 95% CI, 49.99%-83.88%), and sensitivity was 100.00% (15/15; 95% CI, 78.20%-100.00%). Secondary analysis (against HIV-1, HIV-2, and p24 antigen individually) in high-risk pregnant women samples (United States, n = 1; outside the United States, n = 9) that were reactive on the Elecsys HIV combi PT assay but had a final diagnosis of HIV negative demonstrated that 8 of 10 samples were true positives. Recalculation of specificity and sensitivity yielded a specificity of 97.80% (89/91; 95% CI, 92.29%-99.73%) and sensitivity of 100.00% (34/34; 95% CI, 89.72%-100.00%) in the overall high-risk pregnant women cohort (United States and outside the United States), as well as a specificity of 95.65% (22/23; 95% CI, 78.05%-99.89%) and sensitivity of 100.00% (24/24; 95% CI, 85.75%-100.00%) in the non-US cohort.

Sensitivity of the Elecsys HIV combi PT assay for samples reactive for HIV-1 p24 antigen, antibody negative, and Western blot negative/indeterminate was 96.30% (95% CI, 81.03%-99.91%). All HIV-1 group M samples were reactive using the Elecsys HIV combi PT assay and reference assay (Supplementary Table 7). Sensitivity of the Elecsys HIV combi PT assay in the HIV-1 group O cohort (from Cameroon) was 100.00% (42/42; 95% CI, 91.59%-100.00%).

Clinical Specificity

Overall specificity of the Elecsys HIV combi PT assay in individuals at low risk for HIV (United States; n = 6,843, including adults, children/adolescents, and confirmed HIV-negative pregnant women) was 99.94% (6,754/6,758; 95% CI, 99.85%-99.98%). In low-risk adults (excluding pregnant women), specificity was 99.97% (5,963/5,965; 95% CI, 99.88%-100.00%; Table 2).

Analytical Performance

Repeatability (within-run precision) and intermediate precision (within-laboratory precision) for eight human serum pools (HSPs) and five levels of controls are shown in Table 3 . Analysis of the HSPs on the Elecsys HIV combi PT assay produced mean COIs and CVs that were consistent with PreciControl controls. Reproducibility measurements evaluating between-run, between-day, between-lot, and between-site variations were also similar between HSPs and PreciControl controls. All precision and reproducibility tests with positive samples exhibited acceptable performance.

Seroconversion Detection Sensitivity

Twenty commercial seroconversion panels consisting of 140 bleeds were compared between the Elecsys HIV combi PT assay on the cobas e 602 analyzer and the Certificate of Analysis results from the reference assay where available (or compared with the reference assay result from clinical testing if not available). Equivalent performance was initially observed in 138 of 140 samples, but equivalent results were observed in all 140 samples after retesting in duplicate. All 20 panels demonstrated seroconversion from nonreactive to reactive.

Analytical Sensitivity/Specificity

Analytical sensitivity of the Elecsys HIV combi PT assay in an internal study (0.84 ± 0.11 IU/mL) was within the expected range (≤2 IU/mL). A total of 293 samples from individuals with other viral diseases/medical conditions and confirmed HIV-negative pregnant women were tested for cross-reactivity with the Elecsys HIV combi PT assay; no interference was observed from any of the agents tested.

Potential Interfering Analytes, Endogenous Substances, and Therapeutic Drugs

The Elecsys HIV combi PT assay demonstrated an overall specificity of 100.00% (10/10; 95% CI, 69.15%-100.00%) for each virus tested (for hepatitis C, specificity was 100.00% [9/9; 95% CI, 66.37%-100.00%]). No false-positive results (neat samples) and no false-negative results (spiked samples) were observed.

No interference was observed with biotin up to 49 ng/mL, bilirubin up to 60 mg/dL, hemoglobin up to 500 mg/dL, intralipid up to 1,500 mg/dL, human serum albumin up to 10 g/dL, or rheumatoid factors up to 1,500 IU/mL.

No interference was observed with each of the 18 therapeutic drugs at the concentrations examined (Supplementary Table 2).

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