Overall, 17.6% (319/1814) of the samples from women more than 2 years after seroconversion had BED-CEIA values <0.8 OD-n; in contrast, only 3.0% (55/1814) had avidity assays <40% and only 3.9% (70/1814) had avidity values <90% in this time frame.
The following factors were associated with false-recent misclassification using the BED-CEIA in univariate analysis (Table 3 and Table S1, Supplemental Digital Content, http://links.lww.com/QAI/A472): CD4 cell count < 200 cells per microliter (P < 0.05); missing CD4 data (P < 0.05); viral load < 400 copies per milliliter (P < 0.01); and on ART < 1 year (P < 0.01). In a multivariate model, false-recent misclassification was associated with missing CD4 cell count data (P < 0.05) and on ART < 1 year (P < 0.01) and on ART > 1 year (P < 0.01). In a multivariate model, false-recent misclassification using the avidity assay was associated with the duration of infection (48–72 months, P < 0.01) and HIV subtype (P < 0.05). We compared results obtained using the BED-CEIA and avidity assays. False-recent misclassification with the BED-CEIA was seen in 17.3% (305/1759) samples that had avidity assay results >40% and in 25.5% (14/55) samples with avidity assay results <40%; this difference was not statistically significant.
Previous studies in other cohorts have demonstrated that individuals with long-standing subtype D HIV infection often have low levels of anti-HIV antibodies detected with serologic HIV incidence assays.14,18 This type of false-recent misclassification lowers the precision of these assays for HIV incidence estimation in populations where subtype D is prevalent. This report investigated the biologic basis for false-recent misclassification in adults with subtype D infection by evaluating antibody maturation and antibody regression in a cohort of women with subtypes A and D infection. We found that differences in the performance of the BED-CEIA and avidity assays in these 2 subtypes reflect a weaker initial antibody response to HIV infection in those with subtype D infection. We did not see a significant difference in antibody regression (decline in BED-CEIA and avidity assay results) in these 2 subtypes. For both the subtypes, antibody regression was associated with the initiation of ART and duration of treatment.
In a previous study of individuals from the Rakai Community Cohort Study (RCCS), we observed more frequent false-recent misclassification among women with subtype D compared with women with subtype A; this association was not observed for men with these subtypes.18 In this report, we extended that study by showing that 9% women with subtype D infection did not attain a mature antibody response even after many years of infection; this failure of antibody maturation was uncommon in women with subtype A infection. This study also extends our previous study of the RCCS, because the GS cohort analyzed in this report included women who initiated ART during the study follow-up. In the GS cohort, women with subtype D were less likely to attain BED-CEIA values above the assay cutoff; this indicates that they maintained low levels of HIV-specific IgG in their serum, even years after seroconversion.22 BED-CEIA values also declined over time in more women with subtype D than in those with subtype A; this effect, which we refer to as antibody regression, was associated with ART use.
The findings in this report support the use of multiassay algorithms (MAAs) for cross-sectional HIV incidence estimation.22 The performance of MAAs is likely to be improved when they include 2 serologic assays that measure different features of the immune response to HIV infection; in this study, false-recent misclassification by the BED-CEIA and avidity assay was not associated.22 In this report, low CD4 cell count and duration of time on ART were associated with misclassification by the BED-CEIA. Use of ART for more than 1 year doubled the frequency of false-recent misclassification by the BED-CEIA; the duration of ART was also associated with false-recent misclassification by the BED-CEIA in previous studies.14,32 Inclusion of nonserologic biomarkers in MAAs, such as CD4 cell count and HIV viral load, may further reduce the frequency of false-recent misclassification.14 For both the subtypes A and D, the performance of the avidity assay was superior to that of the BED-CEIA.
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