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      Surveillance of recent HIV infections among newly diagnosed HIV cases in Germany between 2008 and 2014

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          Abstract

          Background

          The HIV surveillance system in Germany is based on mandatory, anonymous notification of newly diagnosed HIV cases by laboratories. Because the time between HIV infection and the diagnosis of HIV varies widely between persons, it is difficult to determine the number of cases of recent HIV infection among newly diagnosed cases of HIV. In Germany, the BED-capture-enzyme immunoassay (BED-CEIA) has been used to distinguish between recent and long-standing HIV infection. The aim of this analysis is to report the proportion of cases of recent HIV infection among newly diagnosed cases in Germany between 2008 and 2014 and to identify factors associated with recent infections.

          Methods

          A sample of voluntary laboratories among all HIV diagnostic laboratories was recruited. Residual blood from HIV diagnostic tests was spotted on filter paper as dried serum or dried plasma spots and was sent along with the notification form of the HIV cases. The BED-CEIA test was performed. A case was defined as recent HIV infection with a BED-CEIA test result of less than 0.8 normalized optical density, with the exclusion of CDC stage C. The proportion of recent newly diagnosed HIV infections among different groups (such as transmission groups, gender or age groups) was calculated. We used logistic regression to identify factors associated with recent HIV infection and to identify subpopulations with high proportions of recent HIV infections.

          Results

          Approximately 10,257 newly diagnosed cases were tested for recency using the BED-CEIA. In total, 3084 (30.4%) of those were recently infected with HIV. The highest proportion of recent HIV infections was found among men who had sex with men (MSM) (35%) and persons between 18 and 25 years of age (43.0%). Logistic regression revealed that female German intravenous drug users with a recent HIV infection had a higher chance of being detected than German MSM (OR 2.27).

          Conclusions

          Surveillance of recent HIV infection is a useful additional tool to monitor the HIV epidemic in Germany. We could observe ongoing HIV transmission in Germany in general and in different subgroups, and we could identify factors associated with recent HIV infection in Germany.

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          Most cited references26

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          Quantitative detection of increasing HIV type 1 antibodies after seroconversion: a simple assay for detecting recent HIV infection and estimating incidence.

          We have devised a simple enzyme immunoassay (EIA) that detects increasing levels of anti-HIV IgG after seroconversion and can be used for detecting recent HIV-1 infection. Use of a branched peptide that included gp41 immunodominant sequences from HIV-1 subtypes B, E, and D allowed similar detection of HIV-specific antibodies among various subtypes. Because of the competitive nature of the capture EIA, a gradual increase in the proportion of HIV-1-specific IgG in total IgG was observed for 2 years after seroconversion. This was in contrast to results obtained with the conventional EIA using the same antigen in solid phase, which plateaus soon after seroconversion. The assay was used to test 622 longitudinal specimens from 139 incident infections in the United States (subtype B) and in Thailand (subtypes B and E). The assay was also performed with an additional 8 M urea incubation step to assess the contribution of high-avidity antibodies. Normalized optical density (OD-n) was calculated (ODspecimen/ODcalibrator), using a calibrator specimen. An incremental analysis indicated that a cutoff of 1.0 OD-n and a seroconversion period of 160 days offered the best combination of sensitivity and specificity for classifying incident or long-term infections. The urea step increased the seroconversion period to 180 days with similar sensitivity and specificity. Separate analysis of B and E subtype specimens yielded the same optimal OD-n threshold and similar seroconversion periods. The assay was further validated in African specimens (subtypes A, C, and D) where the observed incidence was within 10% of the expected incidence. This assay should be useful for detecting recent HIV-1 infection and for estimating incidence among diverse HIV-1 subtypes worldwide.
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            New testing strategy to detect early HIV-1 infection for use in incidence estimates and for clinical and prevention purposes.

            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. 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. 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). 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 1275449 repeat blood donors at 3 American Red Cross blood centers from 1993 through 1995; and for HIV-1 incidence estimates: 2717910 first-time blood donors. We retrospectively identified persons eligible for a study of early infection. Ability to identify early HIV infection. Estimated mean time from being 3A11 reactive/3A11-LS nonreactive to being 3A11 reactive/3A11-LS reactive was 129 days (95% confidence interval [CI], 109-149 days) [corrected]. 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 100000 per year (95% CI, 1.14-6.53/100000) vs observed incidence of 2.60 per 100000 person-years (95% CI, 1.49-4.21/100000). Overall incidence in first-time blood donors was 7.18 per 100000 per year (95% CI, 4.51-11.20/100000) 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. 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.
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              Accuracy of serological assays for detection of recent infection with HIV and estimation of population incidence: a systematic review.

              We systematically reviewed the accuracy of serological tests for recent infections with HIV that have become widely used for measuring population patterns incidence of HIV. Across 13 different assays, sensitivity to detect recent infections ranged from 42-100% (median 89%). Specificity for detecting established infections was between 49.5% and 100% (median 86.8%) and was higher for infections of durations longer than 1 year (median 98%, range 31.5-100.0). For four different assays, comparisons were made between assay-derived population incidence estimates and a reference incidence estimate. The median percentage difference between the assay-derived incidence and reference incidence was 26.0%. Serological assays have reasonable sensitivity for the detection of recent infection with HIV, but are vulnerable to misclassifying established infections as recent-potentially leading to biases in incidence estimates. This conclusion is highly qualified by the apparent absence of a standardised approach to assay evaluation. There is an urgent need for an internationally agreed framework for evaluating and comparing these tests.
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                Author and article information

                Contributors
                HofmannA@rki.de
                HauserA@rki.de
                ZimmermannR@rki.de
                Santos-HoevenerC@rki.de
                JBaetzing-Feigenbaum@zi.de
                stephan.wildner@sgs.com
                KuechererC@t-online.de
                BannertN@rki.de
                HamoudaO@rki.de
                BremerV@rki.de
                Gunsenheimer-BartmeyerB@rki.de
                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                11 July 2017
                11 July 2017
                2017
                : 17
                : 484
                Affiliations
                [1 ]ISNI 0000 0001 0940 3744, GRID grid.13652.33, Department for Infectious Disease Epidemiology, Unit 34 HIV/AIDS, STI and Blood-Borne Infections, , Robert Koch-Institute, ; Seestr.10, 13353 Berlin, Germany
                [2 ]ISNI 0000 0001 2218 4662, GRID grid.6363.0, , Charité, Universitätsmedizin, ; Berlin, Germany
                [3 ]ISNI 0000 0001 0940 3744, GRID grid.13652.33, Department of Infectious Diseases, Unit 18 HIV and Other Retroviruses, , Robert Koch-Institute, ; Nordufer 20, 13353 Berlin, Germany
                [4 ]Central Research Institute of Ambulatory Health Care in Germany (Zi), Berlin, Germany
                [5 ]SGS Belgium NV, Generaal De Wittelaan 19, B-2800 Mechelen, Belgium
                [6 ]ISNI 0000 0001 0940 3744, GRID grid.13652.33, Department for Infectious Disease Epidemiology, , Robert Koch-Institute, ; Seestr.10, 13353 Berlin, Germany
                Article
                2585
                10.1186/s12879-017-2585-4
                5504740
                28693564
                8680b3da-0c93-40bf-8fe6-7d4f2716548d
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 26 January 2017
                : 3 July 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003107, Bundesministerium für Gesundheit;
                Award ID: IIA5-2007-2507AUK382
                Award ID: IIA5-2010-2510AUK377
                Funded by: Robert Koch Institut
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Infectious disease & Microbiology
                surveillance,hiv,recent hiv infection,test for recency of infection,bed-ceia,germany

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