title: Poor performance of the determine HIV-1/2 Ag/Ab combo fourth-generation rapid test for detection of acute infections in a National Household Survey in Swaziland.
abstract: Fourth-generation HIV rapid tests (RTs) claim to detect both p24 antigen (Ag) and HIV antibodies (Ab) for early identification of acute infections, important for targeting prevention and reducing HIV transmission. In a nationally representative household survey in Swaziland, 18,172 adults, age 18 to 49 years, received home-based HIV rapid testing in 2010 and 2011. Of the 18,172 individuals, 5,822 (32.0%) were Ab positive (Ab(+)) by the Determine HIV-1/2 Ab/Ab combo test, and 5,789 (99.4%) of those were confirmed to be reactive in the Uni-Gold test. Determine combo identified 12 individuals as having acute infections (Ag(+)/Ab negative [Ab(-)]); however, none had detectable HIV-1 RNA and 8 of 12 remained HIV negative at their 6-week follow-up visit (4 were lost to follow-up). All RT-nonreactive samples were pooled and tested by nucleic acid amplification testing (NAAT) to identify acute infections. NAAT identified 13 (0.1%) of the 12,338 HIV antibody-negative specimens as HIV RNA positive, with RNA levels ranging from 300 to >10,000,000 copies/ml. However, none of them were Ag(+) by Determine combo. Follow-up testing of 12 of the 13 NAAT-positive individuals at 6 months demonstrated 12 seroconversions (1 individual was lost to follow-up). Therefore, the Determine combo test had a sensitivity of 0% (95% confidence interval, 0 to 28) and positive predictive value of 0% for the detection of acute infections. The ability of the 4th-generation Determine combo to detect antigen was very poor in Swaziland. Thus, the Determine combo test does not add any value to the current testing algorithm; rather, it adds additional costs and complexity to HIV diagnosis. The detection of acute HIV infections may need to rely on other testing strategies.
authors.affiliation: Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Yen T
authors.initials: YT
authors.lastname: Duong
authors.affiliation: ICAP, Mailman School of Public Health, Columbia University, New York, New York, USA.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Mavengere
authors.affiliation: Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Hetal
authors.initials: H
authors.lastname: Patel
authors.affiliation: Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Carole
authors.initials: C
authors.lastname: Moore
authors.affiliation: ICAP, Mailman School of Public Health, Columbia University, New York, New York, USA.
authors.forename: Julius
authors.initials: J
authors.lastname: Manjengwa
authors.affiliation: Ministry of Health, Mbabane, Swaziland.
authors.forename: Dumile
authors.initials: D
authors.lastname: Sibandze
authors.affiliation: Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Rasberry
authors.affiliation: ICAP, Mailman School of Public Health, Columbia University, New York, New York, USA.
authors.forename: Charmaine
authors.initials: C
authors.lastname: Mlambo
authors.affiliation: Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutchison Cancer Research Center, Seattle, Washington, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutchison Cancer Research Center, Seattle, Washington, USA.
authors.forename: Lynda
authors.initials: L
authors.lastname: Emel
authors.affiliation: Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Naomi
authors.initials: N
authors.lastname: Bock
authors.affiliation: Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Moore
authors.affiliation: Ministry of Health, Mbabane, Swaziland.
authors.forename: Rejoice
authors.initials: R
authors.lastname: Nkambule
authors.affiliation: ICAP, Mailman School of Public Health, Columbia University, New York, New York, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Justman
authors.affiliation: Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Reed
authors.affiliation: Centers for Disease Control and Prevention, Mbabane, Swaziland.
authors.forename: George
authors.initials: G
authors.lastname: Bicego
authors.affiliation: Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Ellenberger
authors.affiliation: Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Nkengasong
authors.affiliation: Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, USA bparekh@cdc.gov.
authors.forename: Bharat S
authors.initials: BS
authors.lastname: Parekh
mesh_terms: D000293:Adolescent; D000328:Adult; D003430:Cross-Sectional Studies; D013541:Eswatini; D005191:Family Characteristics; D005260:Female; D015483:HIV Antibodies / Q000097:blood*; D015488:HIV Antigens / Q000097:blood*; D015658:HIV Infections / Q000175:diagnosis*; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D013997:Time Factors; D055815:Young Adult
chemical_list: D015483:HIV Antibodies; D015488:HIV Antigens