Comparison of Methods to Detect Recent HIV Type 1 Infection in Cross-Sectionally Collected Specimens from a Cohort of Female Sex Workers in the Dominican Republic

Abstract

Interest in estimating HIV-1 incidence using specimens obtained as part of cross-sectional surveys has led to the development of new methods to detect recent HIV-1 infection through the testing of a single anti-HIV-positive specimen. These assays are based on quantitative and qualitative differences in anti-HIV-1 antibodies between recent and long-standing infections. An ongoing vaccine preparedness study enrolled female sex workers in the Dominican Republic. Specimens from women found to be HIV positive at baseline were tested for recent HIV-1 infection using the detuned assay, avidity index, and BED-CEIA assay. An unweighted kappa statistic in pairwise comparisons was used to estimate the correlation of recent HIV-1 infection detection by the three methods. Nineteen (3.9%) of 482 women were positive for HIV-1 infection. The incidence of HIV infection was 1.4% [95% confidence interval (CI): 0.2, 5.3], 0.9%(95% CI: 0.1, 4.4), and 1.0%(95% CI: 0.1, 4.4) using detuned assay, avidity index, and BED-CEIA techniques, respectively. The overall agreement between both detuned assay and avidity index and detuned assay and BED-CEIA was 94%(kappa = 0.8, 95% CI; 0.3, 1.0). The correlation was highest between BED-CEIA and avidity index methods (100%; kappa = 1.0). All three methods performed similarly in detecting recent HIV-1 infection in this region dominated by clade B HIV-1 infection. Although incidence estimates were slightly higher using the detuned assay method, they were not significantly different. These assays may be of value in both clinical research and practice. The utility of individual assays for recent infection detection will depend upon operating characteristics, HIV-1 subtype limitations, and selection of appropriate assay cutoff values.

Significantly Diminished Long-Term Specificity of the BED Capture Enzyme Immunoassay Among Patients With HIV-1 With Very Low CD4 Counts and Those on Antiretroviral Therapy

“…1 But such protocols and the use of clinical information to improve assay performance are unlikely to be feasible in resource-constrained setting. The essential problem in using the BED method to estimate HIV incidence thus continues to lie in the lack of unequivocal identification of persons with long-term HIV infections.…”

“…[1][2][3][4][5][6][7][8] Although some success has been achieved, obstacles still remain to widespread use of these methods, especially in the developing world, where such methods and technologies are most urgently required. 1,9 The most reliable way of measuring HIV incidence is following up HIV-uninfected but susceptible cohorts, measuring new infections over specified time periods. This, however, is subject to a number of biases, is expensive, and involves following up large numbers of people over long periods of time.…”

Estimates of HIV-1 incidence based on serological methods: a brief methodological review

“…However, low CD4 counts and viral load, as well as antiretroviral treatment, had no effect in the AI 32 . Comparative studies of the avidity assay with detuned or BED-CEIA showed similar performances for the three assays to identify recent infections in a region where subtype B predominates 35 . More recently, evaluating known seroconversion rates of HIV-seropositive samples from Uganda, where subtypes D and A predominate, the mean AI found for patients with recent infection was 0.55±0.21, while AI of 0.93±0.14 was detected for those from long-term infections 36 .…”

Current and future assays for identifying recent HIV infections at the population level

“…Since currently there is no agreement which RITA assay is accurate and robust enough for the intended use, and no single test fulfills the required characteristics, the use of a combination of 2 or more assays has been suggested [34,51]. It was also proposed to apply algorithms including clinical status and information such as T CD4 + cell count, and/or HIV RNA testing, and/or determination of antiretroviral use for the purpose of achieving the most accurate detection of recent HIV infection [3,5,38].…”