Dataset Information

Assessment of recent HIV-1 infection by a line immunoassay for HIV-1/2 confirmation.

ABSTRACT:

Background

Knowledge of the number of recent HIV infections is important for epidemiologic surveillance. Over the past decade approaches have been developed to estimate this number by testing HIV-seropositive specimens with assays that discriminate the lower concentration and avidity of HIV antibodies in early infection. We have investigated whether this "recency" information can also be gained from an HIV confirmatory assay.

Methods and findings

The ability of a line immunoassay (INNO-LIA HIV I/II Score, Innogenetics) to distinguish recent from older HIV-1 infection was evaluated in comparison with the Calypte HIV-1 BED Incidence enzyme immunoassay (BED-EIA). Both tests were conducted prospectively in all HIV infections newly diagnosed in Switzerland from July 2005 to June 2006. Clinical and laboratory information indicative of recent or older infection was obtained from physicians at the time of HIV diagnosis and used as the reference standard. BED-EIA and various recency algorithms utilizing the antibody reaction to INNO-LIA's five HIV-1 antigen bands were evaluated by logistic regression analysis. A total of 765 HIV-1 infections, 748 (97.8%) with complete test results, were newly diagnosed during the study. A negative or indeterminate HIV antibody assay at diagnosis, symptoms of primary HIV infection, or a negative HIV test during the past 12 mo classified 195 infections (26.1%) as recent (< or = 12 mo). Symptoms of CDC stages B or C classified 161 infections as older (21.5%), and 392 patients with no symptoms remained unclassified. BED-EIA ruled 65% of the 195 recent infections as recent and 80% of the 161 older infections as older. Two INNO-LIA algorithms showed 50% and 40% sensitivity combined with 95% and 99% specificity, respectively. Estimation of recent infection in the entire study population, based on actual results of the three tests and adjusted for a test's sensitivity and specificity, yielded 37% for BED-EIA compared to 35% and 33% for the two INNO-LIA algorithms. Window-based estimation with BED-EIA yielded 41% (95% confidence interval 36%-46%).

Conclusions

Recency information can be extracted from INNO-LIA-based confirmatory testing at no additional costs. This method should improve epidemiologic surveillance in countries that routinely use INNO-LIA for HIV confirmation.

SUBMITTER: Schupbach J

PROVIDER: S-EPMC2100138 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundSerologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have previously demonstrated that a patient's antibody reaction pattern in a confirmatory line immunoassay (INNO-LIA™ HIV I/II Score) provides information on the duration of infection, which is unaffected by clinical, immunological and viral variables. In this report we have set out to determine the diagnostic performance of Inno-Lia algorithms for identifying incident infections in patients with known duration of infection and evaluated the algorithms in annual cohorts of HIV notifications.MethodsDiagnostic sensitivity was determined in 527 treatment-naive patients infected for up to 12 months. Specificity was determined in 740 patients infected for longer than 12 months. Plasma was tested by Inno-Lia and classified as either incident (< = 12 m) or older infection by 26 different algorithms. Incident infection rates (IIR) were calculated based on diagnostic sensitivity and specificity of each algorithm and the rule that the total of incident results is the sum of true-incident and false-incident results, which can be calculated by means of the pre-determined sensitivity and specificity.ResultsThe 10 best algorithms had a mean raw sensitivity of 59.4% and a mean specificity of 95.1%. Adjustment for overrepresentation of patients in the first quarter year of infection further reduced the sensitivity. In the preferred model, the mean adjusted sensitivity was 37.4%. Application of the 10 best algorithms to four annual cohorts of HIV-1 notifications totalling 2'595 patients yielded a mean IIR of 0.35 in 2005/6 (baseline) and of 0.45, 0.42 and 0.35 in 2008, 2009 and 2010, respectively. The increase between baseline and 2008 and the ensuing decreases were highly significant. Other adjustment models yielded different absolute IIR, although the relative changes between the cohorts were identical for all models.ConclusionsThe method can be used for comparing IIR in annual cohorts of HIV notifications. The use of several different algorithms in combination, each with its own sensitivity and specificity to detect incident infection, is advisable as this reduces the impact of individual imperfections stemming primarily from relatively low sensitivities and sampling bias.

Project description:BackgroundHIV surveillance requires monitoring of new HIV diagnoses and differentiation of incident and older infections. In 2008, Switzerland implemented a system for monitoring incident HIV infections based on the results of a line immunoassay (Inno-Lia) mandatorily conducted for HIV confirmation and type differentiation (HIV-1, HIV-2) of all newly diagnosed patients. Based on this system, we assessed the proportion of incident HIV infection among newly diagnosed cases in Switzerland during 2008-2013.Methods and resultsInno-Lia antibody reaction patterns recorded in anonymous HIV notifications to the federal health authority were classified by 10 published algorithms into incident (up to 12 months) or older infections. Utilizing these data, annual incident infection estimates were obtained in two ways, (i) based on the diagnostic performance of the algorithms and utilizing the relationship 'incident = true incident + false incident', (ii) based on the window-periods of the algorithms and utilizing the relationship 'Prevalence = Incidence x Duration'. From 2008-2013, 3'851 HIV notifications were received. Adult HIV-1 infections amounted to 3'809 cases, and 3'636 of them (95.5%) contained Inno-Lia data. Incident infection totals calculated were similar for the performance- and window-based methods, amounting on average to 1'755 (95% confidence interval, 1588-1923) and 1'790 cases (95% CI, 1679-1900), respectively. More than half of these were among men who had sex with men. Both methods showed a continuous decline of annual incident infections 2008-2013, totaling -59.5% and -50.2%, respectively. The decline of incident infections continued even in 2012, when a 15% increase in HIV notifications had been observed. This increase was entirely due to older infections. Overall declines 2008-2013 were of similar extent among the major transmission groups.ConclusionsInno-Lia based incident HIV-1 infection surveillance proved useful and reliable. It represents a free, additional public health benefit of the use of this relatively costly test for HIV confirmation and type differentiation.

Project description:IntroductionThe need for detection of new and recent HIV infections is essential for surveillance and assessing interventions in controlling the epidemic. HIV recency assays are one way of providing reliable incidence estimates by determining recent versus non-recent infection. The objective of this study was to review the current body of knowledge of the limiting antigen avidity enzyme immunoassay to expand supported applications through an assessment of what is known and the gaps.MethodsA search for peer-reviewed literature in PubMed, Embase, and Web of Science Core Collection was conducted using the search term "human immunodeficiency virus and avidity". Non-peer reviewed published reports from the Population-based HIV Impact Assessment Project were also included. These were limited to literature published in English between January 2010 and August 2021.ResultsThis search resulted in 2080 publications and 14 reports, with 137 peer-reviewed studies and 14 non-peer reviewed reports that met the inclusion criteria, yielding a total of 151 studies for the final review. There were similar findings among studies that compared the performances of assay manufacturers and sample types. Studies that evaluated various assay algorithms and thresholds were heterogeneous, illustrating the need for context-specific test characteristics for classifying recent infections. Most studies estimated subtype-specific test characteristics for HIV subtypes A, B, C, and D. This was further illustrated when looking only at studies that compared HIV incidence estimates from recency assay algorithms and longitudinal cohorts.ConclusionsThese findings suggest that the current body of knowledge provides important information that contributes towards distinguishing recent and non-recent infection and incidence estimation. However, there are knowledge gaps with respect to factors that influence the test characteristics (e.g., HIV-1 subtype, population characteristics, assay algorithms and thresholds). Further studies are needed to estimate and establish context-specific test characteristics that consider these influencing factors to improve and expand the use of this assay for detection of recent HIV infection.

Project description:BackgroundTests for recent infections (TRIs) are important for HIV surveillance. We have shown that a patient's antibody pattern in a confirmatory line immunoassay (Inno-Lia) also yields information on time since infection. We have published algorithms which, with a certain sensitivity and specificity, distinguish between incident (< = 12 months) and older infection. In order to use these algorithms like other TRIs, i.e., based on their windows, we now determined their window periods.MethodsWe classified Inno-Lia results of 527 treatment-naïve patients with HIV-1 infection < = 12 months according to incidence by 25 algorithms. The time after which all infections were ruled older, i.e. the algorithm's window, was determined by linear regression of the proportion ruled incident in dependence of time since infection. Window-based incident infection rates (IIR) were determined utilizing the relationship 'Prevalence = Incidence x Duration' in four annual cohorts of HIV-1 notifications. Results were compared to performance-based IIR also derived from Inno-Lia results, but utilizing the relationship 'incident = true incident + false incident' and also to the IIR derived from the BED incidence assay.ResultsWindow periods varied between 45.8 and 130.1 days and correlated well with the algorithms' diagnostic sensitivity (R(2) = 0.962; P<0.0001). Among the 25 algorithms, the mean window-based IIR among the 748 notifications of 2005/06 was 0.457 compared to 0.453 obtained for performance-based IIR with a model not correcting for selection bias. Evaluation of BED results using a window of 153 days yielded an IIR of 0.669. Window-based IIR and performance-based IIR increased by 22.4% and respectively 30.6% in 2008, while 2009 and 2010 showed a return to baseline for both methods.ConclusionsIIR estimations by window- and performance-based evaluations of Inno-Lia algorithm results were similar and can be used together to assess IIR changes between annual HIV notification cohorts.

Project description:BackgroundDiffusion tensor imaging has been widely used to measure HIV effects on white matter microarchitecture. While many authors have reported reduced fractional anisotropy and increased mean diffusivity in HIV, quantitative inconsistencies across studies are numerous.PurposeOur aim was to evaluate the consistency across studies of HIV effects on DTI measures and then examine the DTI reliability in a longitudinal seropositive cohort.Data sourcesPublished studies and investigators.Study selectionThe meta-analysis included 16 cross-sectional studies reporting fractional anisotropy and 12 studies reporting mean diffusivity in the corpus callosum.Data analysisRandom-effects meta-analysis was used to estimate study standardized mean differences and heterogeneity. DTI longitudinal reliability was estimated in seropositive participants studied before and 3 and 6 months after beginning treatment.Data synthesisMeta-analysis revealed lower fractional anisotropy (standardized mean difference, -0.43; P < .001) and higher mean diffusivity (standardized mean difference, 0.44; P < .003) in seropositive participants. Nevertheless, between-study heterogeneity accounted for 58% and 66% of the observed variance (P < .01). In contrast, the longitudinal cohort fractional anisotropy was higher and mean diffusivity was lower in seropositive participants (both, P < .001), and fractional anisotropy and mean diffusivity measures were very stable during 6 months, with intraclass correlation coefficients all >0.96.LimitationsMany studies pooled participants with varying treatments, ages, and disease durations.ConclusionsHIV effects on WM microstructure had substantial variations that could result from acquisition, processing, or cohort-selection differences. When acquisition parameters and processing were carefully controlled, the resulting DTI measures did not show high temporal variation. HIV effects on WM microstructure may be age-dependent. The high longitudinal reliability of DTI WM microstructure measures makes them promising disease-activity markers.