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Objective: Evidence on socioeconomic inequalities in infections with the novel coronavirus (SARS-CoV-2) is still limited as most of the available studies are ecological in nature and individual-level data is sparse. We therefore analysed individual-level data on socioeconomic differences in the prevalence and perceived dangerousness of SARS-CoV-2 infections in local populations. Data were obtained from a population-based seroepidemiological study of adult individuals in two early German SARS-CoV-2 hotspots (n = 3903). Infection was determined by IgG antibody ELISA, RT-PCR testing and self-reports on prior positive PCR tests. The perceived dangerousness of an infection and socioeconomic position (SEP) were assessed by self-reports. Logistic and linear regression were applied to examine associations of multiple SEP measures with infection status and perceptions of dangerousness., Results: We found no evidence of socioeconomic inequalities in SARS-CoV-2 infections by education, occupation, income and subjective social status. Participants with lower education and lower subjective social status perceived an infection as more dangerous than their better-off counterparts. In successfully contained local outbreaks of SARS-CoV-2 in Germany, infections may have been equally distributed across the socioeconomic spectrum. But residents in disadvantaged socioeconomic groups might have experienced a higher level of mental distress due to the higher perceived dangerousness of an infection., (© 2021. The Author(s).)

Background: The aim of this study was to develop a standardized method to reconstruct persons' individual viral load (VL) courses to determine viral suppression and duration of viremia for the HIV care continuum in Germany using longitudinal cohort data., Methods: We analyzed data from two large, multi-center German cohort studies under the direction of the Robert Koch Institute. We included data from 1999 to 2018 of all diagnosed people and of people who initiated antiretroviral treatment (ART). We developed a model generating virtual VL values and an individual VL course corresponding to real VL measurements with a maximum distance of 180 days, considering ART status and VL dynamics. If the distance between VL measurements was > 180 days, the time between was defined as gap time. Additionally, we considered blips, which we defined as a single detectable VL < 1000 copies/ml within 180 days., Results: A total of 22,120 people (164,691 person-years, PY) after ART initiation were included in the analyses. The proportion of people with viral suppression (VL < 50 copies/ml) increased from 34% in 1999 to 93% in 2018. The proportion of people with VL < 200 copies/ml increased from 47% in 1999 to 96% in 2018. The proportion of people with viremia > 1000 copies/ml decreased from 37% in 1999 to 3% in 2018. The proportion of people with gap time fluctuated and ranged between 18 and 28%. An analysis of the first VL after gap time showed that 90% showed viral suppression, 5% VL between 50- < 1000 copies/ml and 5% VL > 1000 copies/ml., Conclusion: We provide a method for estimating viral suppression and duration of viremia using longitudinal VL data. We observed a continuous and remarkable increase of viral suppression. Furthermore, a notable proportion of those with viremia showed low-level viremia and were therefore unlikely to transmit HIV. Individual health risks and HIV drug resistance among those with low-level viremia are problematic, and viral suppression remains the goal. In 2018, 93 and 96% of people after ART initiation showed VL < 50 copies/ml and VL < 200 copies/ml, respectively. Therefore, using the threshold of VL < 200 copies/ml, Germany reached the UNAIDS 95 target of viral suppression since 2017.

Background: Detailed knowledge of the evolutionary potential of polymorphic sites in a viral protein is important for understanding the development of drug resistance in the presence of an inhibitor. We therefore set out to analyse the molecular evolution of the HIV-1 subtype B integrase at the inter-patient level in Germany during a 20-year period prior to the first introduction of integrase strand inhibitors (INSTIs)., Methods: We determined 337 HIV-1 integrase subtype B sequences (amino acids 1-278) from stored plasma samples of antiretroviral treatment-naïve individuals newly diagnosed with HIV-1 between 1986 and 2006. Shannon entropy was calculated to determine the variability at each amino acid position. Time trends in the frequency of amino acid variants were identified by linear regression. Direct coupling analysis was applied to detect covarying sites., Results: Twenty-two time trends in the frequency of amino acid variants demonstrated either single amino acid exchanges or variation in the degree of polymorphy. Covariation was observed for 17 amino acid variants with a temporal trend. Some minor INSTI resistance mutations (T124A, V151I, K156 N, T206S, S230 N) and some INSTI-selected mutations (M50I, L101I, T122I, T124 N, T125A, M154I, G193E, V201I) were identified at overall frequencies >5%. Among these, the frequencies of L101I, T122I, and V201I increased over time, whereas the frequency of M154I decreased. Moreover, L101I, T122I, T124A, T125A, M154I, and V201I covaried with non-resistance-associated variants., Conclusions: Time-trending, covarying polymorphisms indicate that long-term evolutionary changes of the HIV-1 integrase involve defined clusters of possibly structurally or functionally associated sites independent of selective pressure through INSTIs at the inter-patient level. Linkage between polymorphic resistance- and non-resistance-associated sites can impact the selection of INSTI resistance mutations in complex ways. Identification of these sites can help in improving genotypic resistance assays, resistance prediction algorithms, and the development of new integrase inhibitors.

Background: Understanding the immune response to combination antiretroviral therapy (cART) is essential for a clear approach to tuberculosis (TB) preventive therapy. We investigated the immunological recovery in cART-treated HIV-infected patients developing TB compared to those who remained free of TB., Methods: We extracted data of HIV-infected patients from a multicenter cohort for the HIV clinical surveillance in Germany. No patients included in our study had TB at the beginning of the observation. Using a longitudinal mixed model, we assessed the differences in the mean change of biomarkers (CD4+ cell count, CD8+ cell count, CD4:CD8 ratio and viral load) since cART initiation in patients who remained free of TB vs. those developing TB. To detect the best-fit trajectories of the immunological biomarkers, we applied a multivariable fractional polynomials model., Results: We analyzed a total of 10,671 HIV-infected patients including 139 patients who developed TB during follow-up. The highest TB incidences were observed during the first two years since cART initiation (0.32 and 0.50 per 100 person-years). In an adjusted multivariable mixed model, we found that the average change in CD4+ cell count recovery was significantly greater by 33 cells/μl in patients who remained free of TB compared with those developing TB. After the initial three months of cART, 65.6% of patients who remaining free of TB achieved CD4+ count of ≥400 cells/μl, while only 11.3% of patients developing TB reached this immunological status after the three months of cART. We found no differences in the average change of CD8+ cell count, CD4:CD8 ratio or viral load between the two-patient groups., Conclusion: All HIV-infected patients responded to cART. However, patients developing TB showed reduced recovery in CD4+ cell count and this might partly explain the incident TB in HIV-infected patients receiving cART. These findings reinforce the importance of adjunctive TB preventive therapy for patients with reduced recovery in CD4+ cell count.

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.

Background: In Germany, local public health departments (LPHD) are required to offer low-threshold access to confidential counselling and testing for sexually transmitted infections (STI) for sex workers. We collected data from LPHD in Germany to estimate the number of performed STI tests and the proportion of positive STI tests among attending female sex workers (FSW) in order to formulate recommendations for improving STI testing and care for FSW in Germany., Methods: We recruited LPHD across Germany to collect aggregated data on attending FSW between January 2010 and March 2011. Baseline characteristics, the number of attending FSW, STI tests (HIV, Chlamydia trachomatis, Neisseria gonorrhoea, syphilis and Trichomonas vaginalis) and the number of positive results were provided by participating LPHD. We described the number of STI tests per FSW visit and the proportion of positive test results, including interquartile range (IQR). We tested whether baseline characteristics of LPHD were associated with the proportion of positive test results., Results: Overall, 28 LPHD from 14 of the 16 federal states reported 9284 FSW visits over the study period, with a median of 188 FSW visits (IQR 45-440) per LPHD. Overall, a median of 77.1% (IQR 60.7-88.0) of visiting FSW received a test for Neisseria gonorrhoea, followed by HIV (66.0%, IQR 47.9-86.8), Chlamydia trachomatis (65.4%, IQR 50.7-83.6) and syphilis (61.6, IQR 48.6-78.6). In total, 22,914 STI tests were performed. The proportion of positive tests was 3.1% (IQR 1.3-4.8), with the highest proportion of positive tests for Chlamydia trachomatis (6.8%, IQR 2.5-10.4), followed by Neisseria gonorrhoea (3.2%, IQR 0.0-5.3), Trichomonas vaginalis (3.0%, IQR 0.0-15.4), syphilis (1.1%, IQR 0.0-1.3) and HIV (0.2%, IQR 0.0-0.4). The proportion of positive tests varied between 0 and 13.9% between LPHD, with a higher variation of proportion of positive tests in LPHD with a smaller number of reported STI tests., Conclusions: Participating LPHD varied in terms of performed STI tests and FSW visits. The proportion of positive STI tests was low, but varied between LPHD. This variation likely reflects different testing strategies. Existing testing guidelines should be used by all LPHD to ensure high quality care for FSW.

Background: People who inject drugs (PWID) are at increased risk of acquiring and transmitting HIV and Hepatitis C (HCV) due to sharing injection paraphernalia and unprotected sex. To generate seroprevalence data on HIV and HCV among PWID and related data on risk behaviour, a multicentre sero- and behavioural survey using respondent driven sampling (RDS) was conducted in eight German cities between 2011 and 2014. We also evaluated the feasibility and effectiveness of RDS for recruiting PWID in the study cities., Methods: Eligible for participation were people who had injected drugs within the last 12 months, were 16 years or older, and who consumed in one of the study cities. Participants were recruited, using low-threshold drop-in facilities as study sites. Initial seeds were selected to represent various sub-groups of people who inject drugs (PWID). Participants completed a face-to-face interview with a structured questionnaire about socio-demographics, sexual and injecting risk behaviours, as well as the utilisation of health services. Capillary blood samples were collected as dried blood spots and were anonymously tested for serological and molecular markers of HIV and HCV. The results are shown as range of proportions (min. and max. values (%)) in the respective study cities. For evaluation of the sampling method we applied criteria from the STROBE guidelines., Results: Overall, 2,077 PWID were recruited. The range of age medians was 29-41 years, 18.5-35.3 % of participants were female, and 9.2-30.6 % were foreign born. Median time span since first injection were 10-18 years. Injecting during the last 30 days was reported by 76.0-88.4 % of participants. Sharing needle/syringes (last 30 days) ranged between 4.7 and 22.3 %, while sharing unsterile paraphernalia (spoon, filter, water, last 30 days) was reported by 33.0-43.8 %. A majority of participants (72.8-85.8 %) reported incarceration at least once, and 17.8-39.8 % had injected while incarcerated. Between 30.8 and 66.2 % were currently in opioid substitution therapy. Unweighted HIV seroprevalence ranged from 0-9.1 %, HCV from 42.3-75.0 %, and HCV-RNA from 23.1-54.0 %. The implementation of RDS as a recruiting method in cooperation with low-threshold drop in facilities was well accepted by both staff and PWID. We reached our targeted sample size in seven of eight cities., Conclusions: In the recruited sample of mostly current injectors with a long duration of injecting drug use, seroprevalence for HIV and HCV varied greatly between the city samples. HCV was endemic among participants in all city samples. Our results demonstrate the necessity of intensified prevention strategies for blood-borne infections among PWID in Germany.

Background: Migrants from sub-Saharan Africa (MisSA) are a relevant sub-group for HIV-transmission in Germany. A total of 10-15 % of all newly diagnosed cases are MisSA, and approximately one third acquired HIV in Germany. There is limited information on knowledge, attitudes, behaviors and practices (KABP) regarding sexual health in African communities residing in Germany., Methods: From October-December 2013 we conducted a cross-sectional survey on KABP regarding HIV, viral hepatitis (HEP), and sexually transmitted infections (STI) among MisSA in Hamburg as a community-based participatory research project to identify knowledge gaps, sexual risk behavior regarding HIV/HEP/STI, HIV/STI-testing history and attitudes toward people living with HIV (PLWH). Trained peer researchers recruited participants through outreach. Questionnaires in German, English or French were either administered face-to-face or self-completed. Questions on knowledge about HIV/HEP/STI presented true statements; participants were asked if they knew the information before. To detect differences in sub-groups, unadjusted odds ratios (OR) were calculated, and a multivariate analysis for knowledge on HIV/HEP/STI was performed., Results: The final sample included 569 participants of whom 57 % were men. Most participants originated from Western and Central sub-Saharan Africa. Median time living in Germany was 6 years. Overall, 28 % had a university degree and 54 % reported a good level of German language. Over 80 % knew the risks for HIV transmission. A total of 44 % of respondents wrongly assumed that an HIV-diagnosis might lead to deportation and 64 % were not aware of the free and anonymous local HIV/STI-testing service. The proportion of participants with knowledge of presented facts on HEP varied from 40-58 %. The respective proportion on STI was 28-68 % and better among women compared to men (44 % vs. 54 %; OR = 1.45; 95 % CI 1.22-1.74). Men reported more often casual sex partners than women (43 % vs. 23 %; OR = 2.6; 95 % CI 1.7-4.0), and more frequently a previous STI (58 % vs. 39 %; OR = 2.1; 95 % CI 1.1-4.1). Overall, 16 % of women reported a history of sexual violence. The majority of respondents (75 %) reported that they would treat PLWH like any other person., Conclusion: Study participants demonstrated good knowledge on HIV-transmission but knowledge gaps regarding HIV/STI-testing services, HEP and STI. This calls for targeted interventions providing more information about these topics in African communities in Hamburg and possibly also elsewhere.

Background: This study aimed to determine the number of people living with HIV receiving antiretroviral therapy (ART) between 2006 and 2013 in Germany by using the available numbers of antiretroviral drug prescriptions and treatment data from the ClinSurv HIV cohort (CSH)., Methods: The CSH is a multi-centre, open, long-term observational cohort study with an average number of 10.400 patients in the study period 2006-2013. ART has been documented on average for 86% of those CSH patients and medication history is well documented in the CSH., Results: The proportion of CSH patients receiving TCMs increased continuously over time (from 85% to 93%; 2006-2013). In contrast, treatment interruptions declined remarkably (from 11% to 2%; 2006-2013). The total number of HIV-infected people with ART experience in Germany increased from 31,500 (95% CI 31,000-32,000) individuals to 54,000 (95% CI 53,000-55,500) over the observation period (including 16.3% without SHI and persons who had interrupted ART). An average increase of approximately 2,900 persons receiving ART was observed annually in Germany., Conclusions: A substantial increase in the number of people receiving ART was observed from 2006 to 2013 in Germany.

Background: People who inject drugs are at high risk for hepatitis B, hepatitis C and HIV. HTLV was reported by neighboring countries to be prevalent in this population, but the situation for Germany is unclear. To generate seroprevalence and related behavioural data and to enhance prevention efforts against these infections for drug users in Germany, a multicentre sero- and behavioural survey was initiated. People who inject drugs are not well reached by services for testing and counselling for blood-borne infections in Germany. An interventional part of the study is intended to prove feasibility and acceptance of testing and counselling in low-threshold drop-in settings., Methods/design: Between May 2011 and March 2015, eligible participants (persons having injected drugs within the last 12 months, aged 16 years+, and living in the study city) are recruited by respondent driven sampling, using low-threshold drop-in facilities as study-sites in eight German cities with large drug scenes. Calculated sample size is 2,033 participants. Capillary blood samples collected as dried blood spots are anonymously tested for serological and molecular markers of hepatitis B and C, HIV, and HTLV I and II. A detailed face-to-face-interview about hepatitis- and HIV-related knowledge, former testing, imprisonment, sexual and injecting risk behaviour is conducted with participants. Staff is trained to offer pre- and post-test-counselling of blood-borne infections and HIV rapid testing to participants., Discussion: We chose respondent driven sampling for recruitment of participants to improve representativeness of results. Persons, who are not reached by the facility where the study is conducted, are aimed to be included by recruitment through their personal social network of injecting drug users. To reduce differential biases in the questions on knowledge of transmission and prevention of infections, we present true statements on hepatitis B, C and HIV, their possible routes of transmission and measures of prevention to participants. Participants are told that the statements are true and are asked to answer if they knew this fact already or if it is new to them. In case of knowledge gaps they are offered free targeted counselling as well as free HIV rapid testing and post-test counselling of HIV and hepatitis test results.

Background: One out of ten newly diagnosed patients in Europe was infected with a virus carrying a drug resistant mutation. We analysed the patterns over time for transmitted drug resistance mutations (TDRM) using data from the European Spread program., Methods: Clinical, epidemiological and virological data from 4317 patients newly diagnosed with HIV-1 infection between 2002 and 2007 were analysed. Patients were enrolled using a pre-defined sampling strategy., Results: The overall prevalence of TDRM in this period was 8.9% (95% CI: 8.1-9.8). Interestingly, significant changes over time in TDRM caused by the different drug classes were found. Whereas nucleoside resistance mutations remained constant at 5%, a significant decline in protease inhibitors resistance mutations was observed, from 3.9% in 2002 to 1.6% in 2007 (p = 0.001). In contrast, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) doubled from 2.0% in 2002 to 4.1% in 2007 (p = 0.004) with 58% of viral strains carrying a K103N mutation. Phylogenetic analysis showed that these temporal changes could not be explained by large clusters of TDRM., Conclusion: During the years 2002 to 2007 transmitted resistance to NNRTI has doubled to 4% in Europe. The frequent use of NNRTI in first-line regimens and the clinical impact of NNRTI mutations warrants continued monitoring.

Background: Data on knowledge, attitudes, behaviour and practices (KABP) of persons with recent HIV infection compared to controls with negative HIV test result provide information on current risk patterns and can help to re-focus HIV prevention strategies., Methods: From March 2008 through May 2010, persons newly diagnosed with HIV (cases) and HIV-negative controls were recruited by physicians in Germany. To distinguish recent (< 5 months) from longstanding (> 5 months) infection, dried blood spots from people newly diagnosed with HIV were tested with the BED IgG-capture ELISA. Cases and controls completed a KABP-questionnaire. We compared cases with recent infection and controls among men having sex with men (MSM) regarding reported risk behaviour in the previous 6 months. To detect differences, unadjusted Odds Ratios (OR) were calculated and multivariate analysis was performed., Results: Cases and controls did not differ in terms of knowledge on transmission risks, HIV testing frequency, partnership status, or regarding the frequency of any unprotected sex with partners known to be HIV-positive or assumed to be HIV-negative. Cases more often reported a shorter duration of partnership (< 6 months) with a primary partner than controls (OR = 3.9; p = 0.003) and indicated lower rates of condom use outside of primary relationships, with acquaintances (OR = 2.5; p = 0.01), and with persons met online (OR = 4.5; p = 0.04). Unprotected sex with persons of unknown HIV-serostatus was more often indicated by cases than controls (OR = 3.0; p = 0.003). Having a conversation about HIV serostatus before having sex was associated with a lower risk of infection (OR = 0.2; p = 0.01). In multivariate analysis "being always safe" (always using a condom when having sex in different situations outside of a relationship) and talking about serostatus before sex (OR = 0.23; p = 0.004; OR = 0.14; p = 0.014) were negatively associated with HIV- infection., Conclusions: There were no significant differences regarding knowledge about HIV-transmission risks among cases and controls. Differences in risk behaviour were observed regarding unprotected sex with partners of unknown HIV-serostatus and duration of primary partnership at the time of diagnosis, suggesting some HIV-transmissions occurring in newly formed partnerships. The practice of discussing serostatus with prospective sex partners before engaging in sex seems to be protective for HIV-transmission.

Background: Tuberculosis (TB) still presents a leading cause of morbidity and mortality among people living with HIV/AIDS (PLWHA), including those on antiretroviral therapy. In this study, we aimed to determine the long-term incidence density rate (IDR) of TB and risk factors among PLWHA in relation to combination antiretroviral therapy (cART)-status., Methods: Data of PLWHA enrolled from 2001 through 2011 in the German ClinSurv HIV Cohort were investigated using survival analysis and Cox regression., Results: TB was diagnosed in 233/11,693 PLWHA either at enrollment (N = 62) or during follow-up (N = 171). The TB IDR during follow-up was 0.37 cases per 100 person-years (PY) overall [95% CI, 0.32-0.43], and was higher among patients who never started cART and among patients originating from Sub-Saharan Africa (1.23 and 1.20 per 100PY, respectively). In two multivariable analyses, both patients (I) who never started cART and (II) those on cART shared the same risk factors for TB, namely: originating from Sub-Saharan Africa compared to Germany (I, hazard ratio (HR); [95% CI]) 4.05; [1.87-8.78] and II, HR 5.15 [2.76-9.60], CD4+ cell count <200 cells/μl (I, HR 8.22 [4.36-15.51] and II, HR 1.90 [1.14-3.15]) and viral load >5 log10 copies/ml (I, HR 2.51 [1.33-4.75] and II, HR 1.77 [1.11-2.82]). Gender, age or HIV-transmission risk group were not independently associated with TB., Conclusion: In the German ClinSurv HIV cohort, patients originating from Sub-Saharan Africa, with low CD4+ cell count or high viral load at enrollment were at increased risk of TB even after cART initiation. As patients might be latently infected with Mycobacterium tuberculosis complex, early screening for latent TB infection and implementing isoniazid preventive therapy in line with available recommendations is crucial.

Background: International travel plays a role in the spread of HIV-1 across Europe. It is, however, not known whether international travel is more important for spread of the epidemic as compared to endogenous infections within single countries. In this study, phylogenetic associations among HIV of newly diagnosed patients were determined across Europe., Results: Data came from the SPREAD programme which collects samples of newly diagnosed patients that are representative for national HIV epidemics. 4260 pol sequences from 25 European countries and Israel collected in 2002-2007 were included.We identified 457 clusters including 1330 persons (31.2% of all patients). The cluster size ranged between 2 and 28. A number of 987 patients (74.2%) were part of a cluster that consisted only of patients originating from the same country. In addition, 135 patients (10.2%) were in a cluster including only individuals from neighboring countries. Finally, 208 patients (15.6%) clustered with individuals from countries without a common border. Clustering with patients from the same country was less prevalent in patients being infected with B subtype (P-value <0.0001), in men who have sex with men (P-value <0.0001), and in recently infected patients (P-value =0.045)., Conclusions: Our findings indicate that the transmission of HIV-1 in Europe is predominantly occurring between patients from the same country. This could have implications for HIV-1 transmission prevention programmes. Because infections through travelling between countries is not frequently observed it is important to have good surveillance of the national HIV-1 epidemics.

Background: Understanding HIV-1 subtype distribution and epidemiology can assist preventive measures and clinical decisions. Sequence variation may affect antiviral drug resistance development, disease progression, evolutionary rates and transmission routes., Results: We investigated the subtype distribution of HIV-1 in Europe and Israel in a representative sample of patients diagnosed between 2002 and 2005 and related it to the demographic data available. 2793 PRO-RT sequences were subtyped either with the REGA Subtyping tool or by a manual procedure that included phylogenetic tree and recombination analysis. The most prevalent subtypes/CRFs in our dataset were subtype B (66.1%), followed by sub-subtype A1 (6.9%), subtype C (6.8%) and CRF02&#95;AG (4.7%). Substantial differences in the proportion of new diagnoses with distinct subtypes were found between European countries: the lowest proportion of subtype B was found in Israel (27.9%) and Portugal (39.2%), while the highest was observed in Poland (96.2%) and Slovenia (93.6%). Other subtypes were significantly more diagnosed in immigrant populations. Subtype B was significantly more diagnosed in men than in women and in MSM > IDUs > heterosexuals. Furthermore, the subtype distribution according to continent of origin of the patients suggests they acquired their infection there or in Europe from compatriots., Conclusions: The association of subtype with demographic parameters suggests highly compartmentalized epidemics, determined by social and behavioural characteristics of the patients.

Background: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and virulence in absence of therapy and major resistance mutations. We previously designed a modeling technique that quantifies genotypic footprints of in vivo treatment selective pressure, including both drug resistance mutations and polymorphic compensatory mutations, through the quantitative description of a fitness landscape from virus genetic sequences., Results: Genotypic correlates of viral load and CD4 cell count were evaluated in subtype B sequences from recently diagnosed treatment-naive patients enrolled in the SPREAD programme. The association of surveillance drug resistance mutations, reported compensatory mutations and fitness estimated from drug selective pressure fitness landscapes with baseline viral load and CD4 cell count was evaluated using regression techniques. Protease genotypic variability estimated to increase fitness during treatment was associated with higher viral load and lower CD4 cell counts also in treatment-naive patients, which could primarily be attributed to well-known compensatory mutations at highly polymorphic positions. By contrast, treatment-related mutations in reverse transcriptase could not explain viral load or CD4 cell count variability., Conclusions: These results suggest that polymorphic compensatory mutations in protease, reported to be selected during treatment, may improve the replicative capacity of HIV-1 even in absence of drug selective pressure or major resistance mutations. The presence of this polymorphic variation may either reflect a history of drug selective pressure, i.e. transmission from a treated patient, or merely be a result of diversity in wild-type virus. Our findings suggest that transmitted drug resistance has the potential to contribute to faster disease progression in the newly infected host and to shape the HIV-1 epidemic at a population level.

Background: With ageing of the HIV-infected population, long-term exposure to treatment, varying adherence, emerging resistance and complications to therapies, effectiveness of Highly Active Antiretroviral Therapy (HAART) needs to be monitored continuously at the population level. The German HIV-1 Seroconverter Cohort is a multi-centre, open, long-term observational cohort including patients with a known or reliably estimated date of HIV-infection i.e. last negative and first positive HIV antibody test within a maximum three-year interval or laboratory evidence of seroconversion. Our study aims to investigate survival improvements and changes in AIDS risk over calendar periods in the German HIV-1 Seroconverter Cohort., Methods: Retrospective (for the pre-1997 period) and prospective (since 1997) data from the German HIV-1 Seroconverter Cohort were used. Time from seroconversion to first AIDS-defining event over calendar periods was analysed by using Cox models adjusting for age at seroconversion, sex, transmission groups and short HIV test interval. Kaplan-Meier methods were used to determine expected survival (remaining AIDS-free) by calendar period., Results: 2162 seroconverters with 8976 person-years of observation were included in our analysis (up to 31.12.2010). A total of 196 first AIDS defining events were reported. Two periods i.e. 19972000 and 2007-2010 were statistically associated with a reduction in the risk of AIDS, accounting for an overall reduction of 80%. Compared to1997-2000, hazard ratios were 2.6 (95%CI, 1.6-4.8; p=0.000) in pre-1997 and 0.5 (95%CI, 0.3-0.8; p=0.007) in 20072010. Independent risk factor for AIDS progression was age at seroconversion (HR, 1.3 per 10 year-increase; p=0.001)., Conclusion: HAART effectiveness has improved in the German HIV-1-Seroconverter Cohort. The risk to develop AIDS decreased significantly in 19972000 and in 20072010. However, elderly may require particular monitoring in view of their faster progression to AIDS.

Background: Sexual transmitted infections (STIs) have increased in Germany and other countries in Europe since the mid-nineties. To obtain a better picture of diagnostic methods used in STI testing institutions in Germany, we performed a nationwide survey amongst STI specialists in order to evaluate the quality of STI reports and provide recommendations to harmonize and possibly improve STI diagnostics in Germany., Methods: We asked sentinel physicians and randomly chosen gynaecologists, urologists and dermato-venerologists, about the diagnostic methods used in 2005 to diagnose HIV, chlamydia (CT), gonorrhoea (GO) and syphilis (SY) in a national cross-sectional survey in order to recognize potential problems and provide recommendations., Results: A total of 739/2287 (32%) physicians participated. Of all participants, 80% offered tests for HIV, 84% for CT, 83% for GO and 83% for SY. Of all participants who performed HIV testing, 90% requested an antibody test, 3% a rapid test and 1% a nucleic acid amplification test (NAAT). For CT testing, NAAT was used in 33% and rapid tests in 34% of participants. GO resistance testing was performed by 31% of the participants. SY testing was performed in 98% by serology., Conclusions: Diagnostic methods for STI vary highly among the participants. Diagnostic guidelines should be reviewed and harmonised to ensure consistent use of the optimal STI diagnostic methods.

Objectives: There is only little data on immune reconstitution in antiretroviral naive AIDS-patients with toxoplasmosis. The observation of several cases with reduced increase of CD4-cells upon start of antiretroviral treatment (ART) prompted us to investigate the topic using the ClinSurv cohort., Methods: 17 German HIV treatment centers contribute to ClinSurv, a multicentre observational cohort under the auspices of the Robert Koch Institute. We retrospectively selected all antiretroviral-naive patients with toxoplasmic encephalitis (TE) and - as comparator group - with pneumocystosis (PCP) between January 1999 and December 2005., Results: A total of 257 patients were included in the analysis, 61 with TE and 196 with PCP. Demographic baseline data showed differences with regard to gender, transmission group, and baseline CD4 superset+ counts (60.9 vs. 44.7/microl, p = 0.022). After ART-initiation the increase in CD4 superset+ lymphocytes was lower in the TE- versus the PCP-group in the first, second and fourth three-month-period (74.4 vs. 120.3/microl, p = 0.006; 96.6 vs. 136.2/microl, p = 0.021; 156.5 vs. 211.5/microl, p = 0.013). Viral load (VL) was higher in the PCP-group at baseline (4.46 log subset10cop/ml vs. 5.00 log subset10cop/ml, p = 0.008), while virological success of ART was equal., Conclusions: Our data show for the first time that the average CD4 superset+ T-cell increase of patients with toxoplasmosis is impaired compared to PCP-patients. Most clinicians would not be prepared to discontinue follow-up TE-therapy unless CD4 superset+ counts of 200/microl are reached. Explanation for our finding might be the myelosuppressive side effect of pyrimethamine, possible interactions of toxoplasmosis therapy with ART, or an unknown direct biological influence of toxoplasmosis on immune restoration.

Background: Measurement of prevalence and incidence of infections in a hard to reach population like men who have sex with men (MSM) is hampered by its unknown size and regional distribution. Population-based surveys have recently been used to estimate the total number of MSM, but these surveys are usually not large enough to measure regional differences in the proportion of MSM in the population. We explored the use of the proportional regional distribution of participants of large internet-based surveys among MSM from Germany to estimate the regional distribution of MSM in Germany., Methods: We compared participants from two separate MSM behavioural surveys with each other and with the distribution of user profiles of the largest contact and dating website for gay and other MSM in Germany in terms of the representativeness of the regional distribution. In addition, we compared the regional distribution of reportedly HIV positive survey participants with the regional distribution of HIV notifications within the national surveillance system that can be attributed to transmission through homosexual contacts., Results: Regional distribution of survey participants was almost identical in both surveys, despite little overlap between survey participants. Slight discrepancies between surveys and user profiles could be observed. Proportional regional distribution of survey participants with HIV diagnosis resembled national surveillance data., Conclusion: Considering the difficulties to obtain representative data by other sampling methods for "hidden" populations like MSM, internet-based surveys may provide an easy and low cost tool to estimate the regional population distribution -- at least in Western post-industrialized countries. Some uncertainties remain about the exact place of residence of MSM in larger cities or catchment areas of these cities. Slightly different results from different datasets may be due to unequal popularity of MSM websites in different regions. The total population size of the MSM population can be estimated based on e.g. data from representative national population surveys. Both estimates can then be combined to calculate the absolute size of regional MSM populations.

Background: Measuring prevalence and incidence of sexually transmitted infections in hard to reach populations like men who have sex with men (MSM) is hampered by unknown size and regional distribution of this population. Community sample- and study-based measurements are often fraught with participation biases and do not allow generalization of the results for other regions or the whole population group of MSM., Methods: We used the proportional regional distribution of participants of large internet-based surveys among MSM from Germany together with a general population survey-derived estimate of the MSM population to estimate regional population sizes. Based on transmission group category from surveillance data and regional MSM population size we calculated regional population-specific incidence rates of newly diagnosed HIV infection and syphilis. For HIV prevalence we compared estimates of prevalent HIV infections in MSM from a surveillance data-based model with a mixed model in which we used the proportional regional distribution of HIV positive participants from surveys and the estimated total number of prevalent HIV infections from the surveillance based model., Results: Assuming a similar regional distribution of survey participants and the MSM population as a whole, the regional proportion of MSM in the general population can be estimated. Regional incidence calculated with the estimated MSM population as denominator and national surveillance data as numerator results in regional peak incidence rates of 7-8 per 1,000 MSM for newly diagnosed HIV infection and syphilis. The gradient between metropolitan and rural areas narrows considerably compared with calculations which use the total (male) population as denominator. Regional HIV prevalence estimates are comparable in the two models., Conclusion: Considering the difficulties to obtain regionally representative data by other sampling methods for MSM, in Western post-industrialized countries internet-based surveys may provide an easy and low cost tool to estimate regional population distributions. With national surveillance data, which categorize transmission groups, regional population-specific incidence rates for reportable sexually transmitted infections can be estimated. HIV prevalence estimates for regional MSM populations show differences related to the level of urbanization, MSM concentration, and starting points of the HIV epidemic in western and eastern Germany.

Background: The prevalence and the origin of HIV-1 subtype B, the most prevalent circulating clade among the long-term residents in Europe, have been studied extensively. However the spatial diffusion of the epidemic from the perspective of the virus has not previously been traced., Results: In the current study we inferred the migration history of HIV-1 subtype B by way of a phylogeography of viral sequences sampled from 16 European countries and Israel. Migration events were inferred from viral phylogenies by character reconstruction using parsimony. With regard to the spatial dispersal of the HIV subtype B sequences across viral phylogenies, in most of the countries in Europe the epidemic was introduced by multiple sources and subsequently spread within local networks. Poland provides an exception where most of the infections were the result of a single point introduction. According to the significant migratory pathways, we show that there are considerable differences across Europe. Specifically, Greece, Portugal, Serbia and Spain, provide sources shedding HIV-1; Austria, Belgium and Luxembourg, on the other hand, are migratory targets, while for Denmark, Germany, Italy, Israel, Norway, the Netherlands, Sweden, Switzerland and the UK we inferred significant bidirectional migration. For Poland no significant migratory pathways were inferred., Conclusion: Subtype B phylogeographies provide a new insight about the geographical distribution of viral lineages, as well as the significant pathways of virus dispersal across Europe, suggesting that intervention strategies should also address tourists, travellers and migrants.

Background: In Germany, vaccination against hepatitis B is recommended for infants, children and adolescents since 1995 and for specific target groups since 1982. Little is known about knowledge about viral hepatitis and attitudes toward hepatitis B vaccination-factors likely to influence vaccine uptake., Methods: In order to estimate vaccination coverage in adult target groups and in the overall adult population and to assess knowledge and attitudes, we conducted a nationwide cross-sectional telephone survey among 412 persons in November 2004. We defined participants as being vaccinated if they reported at least one previous vaccination against hepatitis B., Results: Vaccination coverage (vc) standardised for age, sex and residence was 29.6% in the general population and 58.2% in target groups for hepatitis B vaccination. Particular gaps in vaccine coverage were detected among health care workers (vc: 69.5%) and chronically ill persons (vc: 22.0%). Knowledge on risk factors and transmission was far below expectations, whereas the acceptance of vaccination in the majority of the population (79.0%) was good., Conclusion: We conclude that educational measures could lead to a higher vaccination uptake in adult target groups.