New Testing Strategy to Detect Early HIV-1 Infection for Use in Incidence Estimates and for Clinical and Prevention Purposes

Abstract

Context.-Differentiating individuals with early human immunodeficiency virus 1 (HIV-1) infection from those infected for longer periods is difficult but important for estimating HIV incidence and for purposes of clinical care and prevention.Objective.-To develop and validate a serologic testing algorithm in which HIV-1-positive persons with reactive test results on a sensitive HIV-1 enzyme immunoassay (EIA) but nonreactive results on a less sensitive (LS) EIA are identified as having early infection.Design.-Diagnostic test and testing strategy development, validation, and application. Specimens were tested with both a sensitive HIV-1 EIA (3A11 assay) and a less sensitive modification of the same EIA (3A11-LS assay).Settings and Participants.-For assay development: 104 persons seroconverting to HIV-1 comprising 38 plasma donors, 18 patients of a sexually transmitted disease clinic in Trinidad, and 48 participants in the San Francisco Men's Health Study (SFMHS); 268 men without the acquired immunodeficiency syndrome (AIDS) in the SFMHS who had been infected for at least 2.5 years; and 207 persons with clinical AIDS; for testing strategy validation: 488 men in the SFMHS from 1985 through 1990 and 1 275 449 repeat blood donors at 3 American Red Cross blood centers from 1993 through 1995; and for HIV-1 incidence estimates: 2 717 910 first-time blood donors. We retrospectively identified persons eligible for a study of early infection.Main Outcome Measure.-Ability to identify early HIV infection. Results.-Estimated mean time to being 3A11 reactive/3A11-LS nonreactive was 129 days (95% confidence interval [CI], 109-149 days). Our testing strategy accurately diagnosed 95% of persons with early infection; however, 0.4% (1/268) of men with established infection and 2% (5/207) of persons with late-stage AIDS were misdiagnosed as having early HIV-1 infection. Average yearly incidence estimates in SFMHS subjects were 1.5% per year vs observed average incidence of 1.4 per 100 person-years. Incidence in repeat blood donors using the sensitive/less sensitive assay testing strategy was 2.95 per 100 000 per year (95% CI, 1.14-6.53/ 100 000) vs observed incidence of 2.60 per 100 000 person-years (95% CI, 1.49-4.21/100 000). Overall incidence in first-time blood donors was 7.18 per 100 000 per year (95% CI, 4.51-11.20/100 000) and did not change statistically significantly between 1993 and 1996. Use of the sensitive/less sensitive testing strategy alone would have identified all 17 persons with antibodies to HIV-1 eligible for a study of early HIV-1 infection and would have increased enrollment.Conclusions.-The sensitive/less sensitive testing strategy provides accurate diagnosis of early HIV-1 infection, provides accurate estimates of HIV-1 incidence, can facilitate clinical studies of early HIV-1 infection, and provides information on HIV-1 infection duration for care planning.

Loss of T cell responses following long-term cryopreservation

“…Participants from SCOPE were selected based on a history of strong HIV-specific CD4 + T cell IFN-γ secretion (Emu et al, 2005), including those in three categories: (1) long-term nonprogressor (LTNP) who have been infected at least 10 years with a viral load <5000 RNA copies/ml without antiretroviral therapy, (2) "elite" controllers who have an undetectable viral load (<75 RNA copies/ml) without antiretroviral therapy, and (3) progressors who have higher viral loads (> 10,000 RNA copies/ml) and CD4 counts <500 cells/ml. Participants selected from the Options cohort were in primary HIV infection, determined by a negative HIV antibody or detuned antibody test (Janssen et al, 1998), a high viral load and a normal CD4 count, and were within 12-50 days from the onset of symptoms at their screening visit. STI subjects with a range of CD4 + T cell responses to Gag, Towne CMV vaccine recipients and healthy uninfected donors with a range of responses to CMV pp65 were selected.…”

Incidence of HIV among injection drug users entering drug treatment programs in four US cities

“…The development of new methods for basing incidence estimates on cross-sectional samples (without the need for follow-up) will allow much closer monitoring of incidence in high-risk populations, including IDUs. 30 …”

Longitudinal analysis of B cell repertoire and antibody gene rearrangements during early HIV infection

“…The same specimens were tested in the three A11 less sensitive (LS/detuned)-EIA protocol as described. 8,9 Results are interpreted based on the standardized OD (SOD) of test samples, which is derived by dividing the mean OD of test sample on the LS-EIA by the mean OD of the CDC supplied assay Calibrator (Cal). Total plasma IgG quantification was performed by single radial immunodiffusion assay using commercially available kits according to the manufacturer's recommended protocol (The Binding Site, San Diego, CA, USA).…”

“…Analysis was based on IgG heavy chain gene utilization and CDR3 length measurement (spectratyping), 7 and relationship with CD4/CD8 counts, viral load, and serologic responses. Individuals with acute or recent HIV-1 infection were eligible for this study if the initial evaluation indicated that they met one or more of the criteria for recent HIV-1 infection: (1) detectable HIV-1 RNA in blood plasma and a negative or indeterminate Western blot assay for anti-HIV-1 antibodies; (2) a positive enzyme-linked immunosorbent assay (ELISA) with Western blot confirmation within 12 months of a documented negative HIV-1 antibody test; or (3) a sensitive/less sensitive (S/LS) dual ELISA testing optical density ratio of less than 0.75 8,9 with a history compatible with recent HIV infection. 10 The dual enzyme immunoassay (EIA) testing strategy using a standard high sensitivity EIA and an LS EIA takes advantage of the progressive development of HIV antibody response during the initial phase of infection.…”