Increasing hepatitis B vaccination coverage and decreasing hepatitis B co-infection prevalence among people with HIV-1 in Germany, 1996-2019. Results from a cohort study primarily in men who have sex with men.

OBJECTIVES: Viral hepatitis co-infection among people living with HIV is known to accelerate the progression of liver disease and AIDS. An increased prevalence and incidence of hepatitis B virus (HBV) infection among people living with HIV demands continuous monitoring to adapt targeted prevention strategies to reach the global goals of eliminating viral hepatitis as a public health threat. METHODS: We determined the prevalence and incidence of HBV for the years 1996-2019 from yearly blood sample testing and questionnaire reports among people living with HIV belonging to a nationwide, multicentre observational, prospective cohort study. RESULTS: Among this study population of 3479 participants, the majority (87%) indicated that being men who have sex with men (MSM) was their likely HIV transmission route; 51% were recruited from Berlin. HBV prevalence for acute/chronic and resolved infections decreased from 4.1% and 45% in 1996-1999 to 1.3% and 16% in 2019, respectively. Simultaneously, participants with a serological status indicating HBV vaccination increased from 25% in 1996-1999 to 69% in 2019. Among vaccinated participants with relevant information (n = 1135), 38% received their first HBV vaccination after HIV infection. The HBV incidence rate in 565 eligible participants decreased from 6.9/100 person-years in 2004-2007 to 0.45/100 person-years in 2015. CONCLUSION: Increasing vaccination coverage because of a general HBV vaccination recommendation and catch-up vaccination efforts among risk groups decreased HBV infection prevalence over time among this study population of people living with HIV, primarily MSM and from Berlin. Despite this success, the prevalence and incidence of HBV remains higher than in the general population in Germany. This emphasizes the need for continued HBV prevention by promoting HBV vaccination and HBV screening at regular intervals based on the individual risk behaviour.

Areas with high HIV prevalence: A spatial analysis of nationwide claims data in Germany.

OBJECTIVE: We aimed to identify spatial clusters of high HIV prevalence in Germany. METHODS: Using nationwide outpatient claims data comprising information of about 88% of the total German population (N = 72 041 683), we examined spatial variations and spatial clusters of high HIV prevalence at the district level (N = 401). People with HIV were identified using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10 codes) B20, B22, and B24 (HIV disease) documented as 'confirmed'. RESULTS: Among 72 041 683 people with statutory health insurance in Germany in 2021, 72 636 had diagnosed HIV, which corresponds to a prevalence of 101 per 100 000 individuals (0.10%). Of these, 56 895 were males (78%). At a district level, the HIV prevalence varied by a factor of 32 between 13 in a rural district in Bavaria and 417 per 100 000 individuals in the German capital, Berlin. The spatial autocorrelation coefficient was 0.24 (p < 0.0001, Global Moran's I). Several high-prevalence spatial clusters of different sizes were identified, mostly located in western Germany. The largest cluster comprised eight districts in the southern part of Hesse, including the city of Frankfurt and the city of Mainz in Rhineland-Palatinate. The second cluster consisted of four districts in North Rhine-Westphalia, including the cities of Cologne and Düsseldorf. Two districts in southern Germany (Mannheim and Ludwigshafen) formed the third cluster. Only urban districts were observed in spatial clusters of high HIV prevalence. CONCLUSIONS: The current study identified for the first time spatial clusters with high HIV prevalence in Germany. This understanding is of particular importance when planning the general and specialized medical care of patients with HIV and to support preventive measures.

Clinical outcome of HIV-infected patients with discordant virological and immunological response to antiretroviral therapy.

BACKGROUND: A subgroup of human immunodeficiency virus type 1 (HIV-1)-infected patients with severe immunodeficiency show persistently low CD4+ cell counts despite sustained viral suppression. It is unclear whether this immuno-virological discordance translates into an increased risk for clinical events. METHODS: Data analysis from a large multicenter cohort incorporating 14,433 HIV-1-infected patients in Germany. Treatment-naive patients beginning antiretroviral therapy (ART) with CD4+ cell counts <200 cells/µL who achieved complete and sustained viral suppression <50 copies/mL (n = 1318) were stratified according to the duration of immuno-virological discordance (failure to achieve a CD4+ cell count ≥200 cells/µL). Groups were compared by descriptive and Poisson statistics. The time-varying discordance status was analyzed in a multivariable Cox model. RESULTS: During a total of 5038 person years of follow-up, 42 new AIDS events occurred. The incidence rate of new AIDS events was highest in the initial 6 months of complete viral suppression (immuno-virological discordance group, 55.06; 95% confidence interval [CI], 30.82-90.82; and immune responder group, 24.54; 95% CI, 10.59-48.35) and decreased significantly by 65% per year in patients with immuno-virological discordance (incidence risk ratio, 0.35; 95% CI, 0.14-0.92; P = .03). Immuno-virological discordance and prior AIDS diagnosis were independently associated with new AIDS events (hazard ratio, 3.10; 95% CI, 1.09-8.82; P = .03). CONCLUSION: Compared with immune responders, patients with immuno-virological discordance seem to remain at increased risk for AIDS. Absolute risk is greatly reduced after the first 6 months of complete viral suppression.

Cohort profile: the German ClinSurv HIV project--a multicentre open clinical cohort study supplementing national HIV surveillance.

BACKGROUND: New forms of HIV/AIDS therapy require new surveillance instruments to meet shifting public health demands. The Clinical Surveillance of HIV Disease (ClinSurv HIV) project was established in 1999 as a collaboration between major HIV treatment centres in Germany and the Robert Koch Institute (RKI). The project contributes to national HIV surveillance and focuses on the changing epidemiology of HIV/AIDS after the introduction of new therapies in 1995. METHODS: ClinSurv HIV is designed as an open multicentre observational cohort study of HIV-infected patients. Anonymized data on diagnoses, treatment and laboratory parameters are collected in a standardized format. Data are currently sampled biannually via 11 centres specializing in HIV diagnosis and care within the legal framework of the German Protection against Infection Act [Infektionsschutzgesetz (IfSG)]. RESULTS: A total of 14874 patients were enrolled in the study by 30 June 2009. Of these, 10221 patients (68.7%) were enrolled after 1 January 1999 and 6006 patients (40.4%) were known to have been diagnosed as positive for HIV before 1999. Evaluation indicators, such as the number of newly enrolled patients per half-year period, loss to follow-up, completeness of data per case, availability of data per possible clinical contact, and internal quality control parameters, show a very stable evolution in the cohort, which although open, can be observed. Comparison with the national HIV surveillance data suggests a high degree of representativeness according to major demographic variables. CONCLUSION: Bearing in mind the obvious strengths and weaknesses discussed, the German ClinSurv HIV cohort provides a broad range of research opportunities in the field of HIV/AIDS both within Germany and in international collaborative research.

Impaired CD4-cell immune reconstitution upon HIV therapy in patients with toxoplasmic encephalitis compared to patients with pneumocystis pneumonia as AIDS indicating disease.

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.

HIV incidence increasing in MSM in Germany: factors influencing infection dynamics.

After an initial peak in the mid-1980s, HIV incidence in men who have sex with men (MSM) declined in most western industrialised countries and then levelled off during the 1990s. Since the late 1990s, increasing numbers of newly diagnosed HIV infections in MSM have been observed in the majority of countries with large and visible MSM communities. Based on a review of national and international behavioural surveillance studies of MSM and national HIV surveillance data, we propose a model for the HIV epidemic in MSM in Germany. The model includes aspects such as individuals' increasing numbers of sexual partners and increasing frequency of unprotected anal intercourse, conditional condom use based on real or perceived HIV status of sexual partners (HIV "serosorting") and sexual role assignments (insertive versus receptive based on HIV status (HIV "seropositioning"), selection of partners and formation of sexual networks through seeking sexual partners on the internet, the introduction of HAART and changing HAART treatment strategies. All these aspects have been shown or are suspected to increase or decrease HIV transmission risk in MSM. We conclude that increasing HIV incidence in MSM in recent years has been fuelled by a spread of HIV in high-risk sexual networks with an increasing proportion of infections transmitted during highly infective early HIV infection, acquired mostly from casual sexual partners.

HIV incidence increasing in MSM in Germany: factors influencing infection dynamics.

After an initial peak in the mid-1980s, HIV incidence in men who have sex with men (MSM) declined in most western industrialised countries and then levelled off during the 1990s. Since the late 1990s, increasing numbers of newly diagnosed HIV infections in MSM have been observed in the majority of countries with large and visible MSM communities. Based on a review of national and international behavioural surveillance studies of MSM and national HIV surveillance data, we propose a model for the HIV epidemic in MSM in Germany. The model includes aspects such as individuals' increasing numbers of sexual partners and increasing frequency of unprotected anal intercourse, conditional condom use based on real or perceived HIV status of sexual partners (HIV 'serosorting') and sexual role assignments (insertive versus receptive based on HIV status (HIV 'seropositioning'), selection of partners and formation of sexual networks through seeking sexual partners on the internet, the introduction of HAART and changing HAART treatment strategies. All these aspects have been shown or are suspected to increase or decrease HIV transmission risk in MSM. We conclude that increasing HIV incidence in MSM in recent years has been fuelled by a spread of HIV in high-risk sexual networks with an increasing proportion of infections transmitted during highly infective early HIV infection, acquired mostly from casual sexual partners.

[Epidemiology of HIV infections in Germany]. / Verlauf der HIV-Epidemie in Deutschland.

The course of the HIV epidemic in Germany can be modelled by back calculation until the beginning of the nineties. The recent course of the epidemic can only be derived from surveillance data of newly diagnosed HIV infections in conjunction with other data sources. Based on these surveillance data HIV incidence in Germany can be estimated to have been stable with 2000 to 2500 new infections per year since the early nineties, after having peaked in the early eighties. The most affected group are men who have sex with men followed by persons infected by heterosexual contact and migrants from high prevalence countries. The number of intravenous drug users has declined over the years and is now in fourth place. There are indications that increased risk behaviour and rising numbers of other sexually transmitted infections together with a change towards later initiation of antiretroviral therapy has led to an increase in new HIV infections in Germany in recent years. An improvement of the epidemiological surveillance for "indicator" STIs in combination with the assessment of risk behaviours in high risk groups would be desirable steps towards a second generation surveillance in Germany.

Relation between the HIV and the re-emerging syphilis epidemic among MSM in Germany: an analysis based on anonymous surveillance data.

In 2003, for the first time since the introduction of highly active antiretroviral therapy (HAART), the number of newly diagnosed HIV infections in Germany increased considerably compared to the previous year. The increase was largely restricted to men who have sex with men (MSM) from larger cities. In this group the number of newly diagnosed HIV infections increased about 30% compared to 2002. Since the late 1990s syphilis infections among MSM also increased in Germany, concentrated in larger cities.