The Robert Koch Institute (RKI): main building in Berlin. more
Germany’s Public Health institute RKI monitors the population’s health and wellbeing. more
The Robert Koch Institute is the German government's central institution for the identification, surveillance and prevention of infectious diseases in the Portfolio of the German Ministry of Health. more
Heads: Dr. Kirsten Hanke & Dr. Karolin Meixenberger
In spring 2023, the Molecular Surveillance of HIV (MolSurv-HIV) was renamed Integrated Genomic Surveillance of HIV (IGS-HIV). The integrated genomic surveillance of newly diagnosed HIV sees itself as an important part of the national program for monitoring the German HIV epidemic. Within the framework of the IGS-HIV, HIV sequences are obtained in order to analyze the current course of HIV infection from a molecular and epidemiological point of view.
The main study objectives are included
For this purpose, the sample material from the incidence surveillance of new HIV diagnoses [more] is used, which means that serum or plasma from around 60% of all new HIV diagnoses is currently available for analysis. In an automated process, the viral RNA is isolated and several HIV genome regions are amplified using RT-PCR. A total of four amplicons are generated, comprising three enzymes of the pol genome region (protease, reverse transcriptase, integrase) and the envelope protein. These genome regions cover the currently relevant positions for genotypic determination of drug resistance and tropism. The amplicons are sequenced using Illumina-based Next Generation Sequencing (NGS) methods.
If a new HIV infection occurs with a virus that is resistant to antiretroviral therapy (ART), this is referred to as primary drug resistance or transmitted drug resistance (TDR). In this case, the drug resistance mutations developed before infection and the drug resistant virus was transmitted onwards. Drug resistance mutations can impair the effectiveness of single drugs or entire drug classes. This can limit the choice of drugs for the first line antiretroviral therapy of the infected person. The identification of drug resistance mutations in the HIV sequence and the interpretation of the HIV drug resistance is carried out using web tools (e.g. Stanford HIVdb Genotypic Resistance Interpretation Algorithm, HIV-GRADE algorithm). New drug classes and new drugs in established drug classes for ART or for pre-exposure prophylaxis (PrEP) are constantly being developed and approved. As a result, the observation of possible newly emerging drug resistance profiles remains an important task in order to be able to take them into account in drug resistance algorithms and treatment guidelines. Due to the high public health relevance of TDR, the continuous monitoring of the emergence and transmission of drug resistant HIV in Germany is an official task of the RKI and also part of the "Strategy to contain HIV, hepatitis B and C and other Sexually Transmitted Infections" of the Federal Ministry of Health (BMG). The prevalence of drug resistance is reported annually to the European Center for Disease Prevention and Control (ECDC) of the World Health Organization (WHO).
The monitoring of the circulating HIV variants in the IGS-HIV essentially focuses on determining the subtype of the HIV-1 group M infections, since infections with other HIV-1 groups and HIV-2 are very rare in Germany. The subtype is usually determined using web tools (e.g. REGA HIV-1 Subtyping Tool, COMET HIV-1 Tool, Geno2Pheno Subtyping Tool). If the assignment is not unequivocal, a phylogenetic analysis with reference sequences is carried out. The HIV epidemics in different regions of the world are dominated by different subtypes and recombinant forms, so that monitoring HIV diversity provides important information on infection dynamics and the endemic spread of certain virus variants in Germany. In addition, due to natural polymorphisms, some HIV subtypes show reduced susceptibility to certain antiretroviral drugs, and there have been reports of subtype-specific properties in terms of transmission or pathogenesis in certain populations or risk groups. The continuous observation of HIV diversity is therefore of great importance for the coordination of diagnostic and treatment guidelines.
The reconstruction of related transmission events leads to a deeper understanding of the HIV epidemic and its dynamics. The knowledge gained helps to recommend targeted preventive measures in the future or to evaluate measures that have already been taken. The identified HIV transmission chains and clusters are usually postulated based on the genetic distance of the analyzed sequences and the statistical support for the branches (bootstrap and posterior values). The results are displayed as a tree structure. The phylogenetic analyzes are carried out using both maximum likelihood methods and methods of Bayesian statistics. The latter, for example, enable the linking of sequence data with epidemiological data, which in turn enables the calculation of reproduction numbers (Re) with the help of which the distribution dynamics in defined risk groups can be measured. In addition, the temporal and phylogeographical dynamics of the HIV epidemic can be statistically estimated and visualized using Bayesian analyses.
HIV outbreaks or sub-epidemics are high-frequency transmissions with usually a single virus variant, which therefore stand out as distinct, very compact clusters in phylogenetic analyses. Once an outbreak has been detected, the responsible public health actors are informed so that possible measures can be initiated. These can include, for example, low-threshold testing and counseling services or interventions such as the increased provision of condoms or sterile injection materials.
In order to fulfill our mandate formulated in the Infection Protection Act in the best possible way, we use modern molecular processes. Viral RNA is isolated from serum/plasma and then amplified and sequenced. We process both regular serum/plasma samples and filter cards onto which serum or plasma has been dripped (DSS/DPS). In the case of the latter, the higher fragmentation and degradation of the viral RNA is proving to be increasingly problematic. Since July 2020, we have therefore been gradually switching from filter cards to sending in regular serum/plasma samples.
For a successful HIV sequencing we need at least 500 µl serum/plasma and the sample material should be damaged as little as possible by storage or freeze-thaw cycles.
In the course of a pilot phase, it has been shown that a weekly or event-related direct mailing is logistically advantageous for many senders.
If you are interested in switching from DSS/DPS to serum/plasma or have not yet sent any samples to the RKI but would like to send us samples in the future, please feel free to contact us.
A quick guide to sending serum/plasma samples by post can be found here:
You will receive the shipping material for serum/plasma samples from us free of charge. Sample transport by courier or post is also free of charge for you.
Shipping management
Sabrina Neumann
Telephone +49 (0)30-18754-2243
Fax: +49 (0)30-18754-2605
Email: Molsurv-HIV [at] rki.de
Heads of InzSurv-HIV & IGS-HIV
Dr. Kirsten Hanke
Telephone +49 (0)30-18754-2639
Fax: +49 (0)30-18754-2605
Email: Molsurv-HIV [at] rki.de
Dr. Karolin Meixenberger
Telephone +49 (0)30-18754-2277
Fax: +49 (0)30-18754-2605
Email: Molsurv-HIV [at] rki.de
Date: 22.01.2024
