title: Specificity of four laboratory approaches for cross-sectional HIV incidence determination: analysis of samples from adults with known nonrecent HIV infection from five African countries.
abstract: Assays to determine cross-sectional HIV incidence misclassify some individuals with nonrecent HIV infection as recently infected, overestimating HIV incidence. We analyzed factors associated with false-recent misclassification in five African countries. Samples from 2197 adults from Botswana, Kenya, South Africa, Tanzania, and Uganda who were HIV infected > 12 months were tested using the (1) BED capture enzyme immunoassay (BED), (2) avidity assay, (3) BED and avidity assays with higher assay cutoffs (BED+ avidity screen), and (4) multiassay algorithm (MAA) that includes the BED+ avidity screen, CD4 cell count, and HIV viral load. Logistic regression identified factors associated with misclassification. False-recent misclassification rates and 95% confidence intervals were BED alone: 7.6% (6.6, 8.8); avidity assay alone: 3.5% (2.7, 4.3); BED+ avidity screen: 2.2% (1.7, 2.9); and MAA: 1.2% (0.8, 1.8). The misclassification rate for the MAA was significantly lower than the rates for the other three methods (each p < 0.05). Misclassification rates were lower when the analysis was limited to subtype C-endemic countries, with the lowest rate obtained for the MAA [0.8% (0.2, 1.9)]. Factors associated with misclassification were for BED alone: country of origin, antiretroviral treatment (ART), viral load, and CD4 cell count; for avidity assay alone: country of origin; for BED+ avidity screen: country of origin and ART. No factors were associated with misclassification using the MAA. In a multivariate model, these associations remained significant with one exception: the association of ART with misclassification was completely attenuated. A MAA that included CD4 cell count and viral load had lower false-recent misclassification than the BED or avidity assays (alone or in combination). Studies are underway to compare the sensitivity of these methods for detection of recent HIV infection.
authors.affiliation: Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. olaeyen1@jhmi.edu
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
authors.forename: Ron
authors.initials: R
authors.lastname: Brookmeyer
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Mullis
authors.forename: Deborah
authors.initials: D
authors.lastname: Donnell
authors.forename: Jairam
authors.initials: J
authors.lastname: Lingappa
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
authors.forename: Mary S
authors.initials: MS
authors.lastname: Campbell
authors.forename: Max
authors.initials: M
authors.lastname: Essex
authors.forename: Guy
authors.initials: G
authors.lastname: de Bruyn
authors.forename: Carey
authors.initials: C
authors.lastname: Farquhar
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.forename: Susan H
authors.initials: SH
authors.lastname: Eshleman
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000453:epidemiology* / Q000276:immunology*; D000328:Adult; D000465:Algorithms; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001902:Botswana / Q000453:epidemiology; D018791:CD4 Lymphocyte Count; D005260:Female; D015483:HIV Antibodies / Q000097:blood*; D006679:HIV Seropositivity / Q000188:drug therapy / Q000453:epidemiology* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D007630:Kenya / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D012680:Sensitivity and Specificity; D013019:South Africa / Q000453:epidemiology; D013636:Tanzania / Q000453:epidemiology; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D015483:HIV Antibodies