Developing a next level integrated genomic surveillance: Advances in the molecular epidemiology of HIV in Germany.

Advances in the molecular epidemiological studies of the Human Immunodeficiency Virus (HIV) at the Robert Koch Institute (RKI) by laboratory and bioinformatic automation should allow the processing of larger numbers of samples and more comprehensive and faster data analysis in order to provide a higher resolution of the current HIV infection situation in near real-time and a better understanding of the dynamic of the German HIV epidemic. The early detection of the emergence and transmission of new HIV variants is important for the adaption of diagnostics and treatment guidelines. Likewise, the molecular epidemiological detection and characterization of spatially limited HIV outbreaks or rapidly growing sub-epidemics is of great importance in order to interrupt the transmission pathways by regionally adapting prevention strategies. These aims are becoming even more important in the context of the SARS-CoV2 pandemic and the Ukrainian refugee movement, which both have effects on the German HIV epidemic that should be monitored to identify starting points for targeted public health measures in a timely manner. To this end, a next level integrated genomic surveillance of HIV is to be established.

Human Immunodeficiency Virus Continuum of Care in 11 European Union Countries at the End of 2016 Overall and by Key Population: Have We Made Progress?

BACKGROUND: High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. METHODS: A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. RESULTS: We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. CONCLUSIONS: The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control.

Characterization of a hepatitis C virus genotype 1 divergent isolate from an HIV-1 coinfected individual in Germany assigned to a new subtype 1o.

BACKGROUND: HCV exhibits a high genetic diversity and is classified into 7 genotypes which are further divided into 86 confirmed subtypes. However, there are multiple isolates with unassigned subtypes. We aimed to amplify and characterize the full-length genome sequence of an HCV genotype 1 (HCV-1) divergent isolate (DE/17-0414) in Germany. METHODS: The HCV infection was detected in an HIV-1-positive German female within an HCV/HIV-coinfection study using a commercially available antigen-antibody HCV ELISA kit and confirmed by an in-house quantitative real-time RT-PCR assay. Preliminary genotyping was done by sequencing and phylogenetic analysis on partial NS5B region. The full-length genome sequence was determined by consensus RT-PCR assays. Resistance-associated substitutions (RASs) were analyzed using the web-based tool Geno2pheno[HCV]. RESULTS: Partial NS5B region of the isolate DE/17-0414 showed more than 95% identity to 73-08460349-1 l and HCV_Fr_003 from France and QC316 from Canada. Full-length genome analysis of the DE/17-0414 strain showed 91.8% identity to QC316 but less than 79.6% to other HCV-1 strains. Phylogenetic analyses demonstrated that DE/17-0414, 73-08460349-1 l, HCV_Fr_003, and QC316 formed a separate subcluster within HCV-1. DE/17-0414 had a distinct 3 amino acids insertion at the N-terminal of hypervariable region 1 (HVR1) within viral envelope glycoprotein 2 (E2) and several potential antiviral RASs among the NS3 and NS5A genes. CONCLUSIONS: We identified and analyzed an HCV-1 divergent isolate derived from an HIV-1 coinfected individual in Germany, which will be assigned to a new HCV-subtype 1o. Our understanding of the origin and transmission dynamics of this new subtype 1o requires further assessments from patients worldwide.

Cost-effectiveness and budget effect of pre-exposure prophylaxis for HIV-1 prevention in Germany from 2018 to 2058.

BackgroundPre-exposure prophylaxis (PrEP) is a highly effective HIV prevention strategy for men-who-have-sex-with-men (MSM). The high cost of PrEP has until recently been a primary barrier to its use. In 2017, generic PrEP became available, reducing the costs by 90%.AimOur objective was to assess cost-effectiveness and costs of introducing PrEP in Germany.MethodsWe calibrated a deterministic mathematical model to the human immunodeficiency virus (HIV) epidemic among MSM in Germany. PrEP was targeted to 30% of high-risk MSM. It was assumed that PrEP reduces the risk of HIV infection by 85%. Costs were calculated from a healthcare payer perspective using a 40-year time horizon starting in 2018.ResultsPrEP can avert 21,000 infections (interquartile range (IQR): 16,000-27,000) in the short run (after 2 years scale-up and 10 years full implementation). HIV care is predicted to cost EUR 36.2 billion (IQR: 32.4-40.4 billion) over the coming 40 years. PrEP can increase costs by at most EUR 150 million within the first decade after introduction. Ten years after introduction, PrEP can become cost-saving, accumulating to savings of HIV-related costs of EUR 5.1 billion (IQR: 3.5-6.9 billion) after 40 years. In a sensitivity analysis, PrEP remained cost-saving even at a 70% price reduction of antiretroviral drug treatment and a lower effectiveness of PrEP.ConclusionIntroduction of PrEP in Germany is predicted to result in substantial health benefits because of reductions in HIV infections. Short-term financial investments in providing PrEP will result in substantial cost-savings in the long term.

The Human Immunodeficiency Virus Continuum of Care in European Union Countries in 2013: Data and Challenges.

BACKGROUND.: The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a "90-90-90" target to curb the human immunodeficiency virus (HIV) epidemic by 2020, but methods used to assess whether countries have reached this target are not standardized, hindering comparisons. METHODS.: Through a collaboration formed by the European Centre for Disease Prevention and Control (ECDC) with European HIV cohorts and surveillance agencies, we constructed a standardized, 4-stage continuum of HIV care for 11 European Union countries for 2013. Stages were defined as (1) number of people living with HIV in the country by end of 2013; (2) proportion of stage 1 ever diagnosed; (3) proportion of stage 2 that ever initiated ART; and (4) proportion of stage 3 who became virally suppressed (≤200 copies/mL). Case surveillance data were used primarily to derive stages 1 (using back-calculation models) and 2, and cohort data for stages 3 and 4. RESULTS.: In 2013, 674500 people in the 11 countries were estimated to be living with HIV, ranging from 5500 to 153400 in each country. Overall HIV prevalence was 0.22% (range, 0.09%-0.36%). Overall proportions of each previous stage were 84% diagnosed, 84% on ART, and 85% virally suppressed (60% of people living with HIV). Two countries achieved ≥90% for all stages, and more than half had reached ≥90% for at least 1 stage. CONCLUSIONS.: European Union countries are nearing the 90-90-90 target. Reducing the proportion undiagnosed remains the greatest barrier to achieving this target, suggesting that further efforts are needed to improve HIV testing rates. Standardizing methods to derive comparable continuums of care remains a challenge.

HIV-prevalence in tuberculosis patients in Germany, 2002-2009: an estimation based on HIV and tuberculosis surveillance data.

Tuberculosis (TB) and HIV comorbidity is a major challenge in TB prevention and control but difficult to assess in Germany as in other countries, where data confidentiality precludes notifying the HIV status of TB patients. We aimed to estimate the HIV-prevalence in TB patients in Germany, 2002-2009, and to characterize the HIV/TB patients demographically. Data from the long-term observational open multicentre cohort ClinSurv HIV were used to identify incident TB in HIV-positive individuals. We assessed the cohort's coverage for the nationwide HIV-positive population by contrasting ClinSurv HIV patients under antiretroviral therapy (ART) with national HIV patient numbers derived from ART prescriptions (data by Insight Health; available for 2006-2009). The HIV-prevalence in TB patients was calculated as the number of HIV/TB cases projected for Germany over all culture-positive TB notifications. From 2002 to 2009, 298 of 15,531 HIV-positive patients enrolled in the ClinSurv HIV cohort were diagnosed with TB. A 21% cohort coverage was determined. The annual estimates of the HIV-prevalence in TB patients were on average 4.5% and ranged from 3.5% (95%CI 2.3-5.1%) in 2007 to 6.6% (95%CI 5.0-8.5%) in 2005. The most recent estimate for 2009 was 4.0% (95%CI 2.6-5.9%). The 298 HIV/TB patients were characterized by a male-to-female ratio of 2.1, by a median age of 38 years at TB diagnosis, and by 59% of the patients having a foreign origin, mainly from Subsahara Africa. We provide, to our knowledge, the first estimate of the HIV-prevalence in TB patients for Germany by joint evaluation of anonymous HIV and TB surveillance data sources. The identified level of HIV in TB patients approximates available surveillance data from neighbouring countries and indicates a non-negligible HIV/TB burden in Germany. Our estimation approach is valuable for epidemiological monitoring of HIV/TB within the current legal frameworks.