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

Emily H. Adhikari, Devin Macias, Donna Gaffney, Sarah White, Vanessa L. Rogers, Donald D. McIntire, Scott W. Roberts

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: 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. Objective: 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. Study Design: 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 among women 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. Results: 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). Conclusion: 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.

Original languageEnglish (US)
JournalAmerican Journal of Obstetrics and Gynecology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Pregnancy Tests
HIV
RNA
HIV Infections
Pregnant Women
Zidovudine
Population
County Hospitals
Pregnancy
HIV Antibodies
Population Characteristics
Centers for Disease Control and Prevention (U.S.)
Breast Feeding
Viral Load
Hispanic Americans
Reflex
HIV-1
Confidence Intervals

Keywords

  • false positive HIV tests in pregnancy
  • fourth-generation HIV screening

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

@article{e496a7e681a64153978ee2bcd25b883c,
title = "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",
abstract = "Background: 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. Objective: 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. Study Design: 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 among women 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. Results: 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). Conclusion: 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.",
keywords = "false positive HIV tests in pregnancy, fourth-generation HIV screening",
author = "Adhikari, {Emily H.} and Devin Macias and Donna Gaffney and Sarah White and Rogers, {Vanessa L.} and McIntire, {Donald D.} and Roberts, {Scott W.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.ajog.2018.06.008",
language = "English (US)",
journal = "American Journal of Obstetrics and Gynecology",
issn = "0002-9378",
publisher = "Mosby Inc.",

}

TY - JOUR

T1 - 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

AU - Adhikari, Emily H.

AU - Macias, Devin

AU - Gaffney, Donna

AU - White, Sarah

AU - Rogers, Vanessa L.

AU - McIntire, Donald D.

AU - Roberts, Scott W.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: 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. Objective: 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. Study Design: 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 among women 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. Results: 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). Conclusion: 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.

AB - Background: 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. Objective: 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. Study Design: 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 among women 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. Results: 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). Conclusion: 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.

KW - false positive HIV tests in pregnancy

KW - fourth-generation HIV screening

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DO - 10.1016/j.ajog.2018.06.008

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JO - American Journal of Obstetrics and Gynecology

JF - American Journal of Obstetrics and Gynecology

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