Integrated Genomic Surveillance of HIV (IGS-HIV)
formerly Molecular Surveillance of HIV (MolSurv-HIV)
Date: 15/08/2024
Study lead Unit 18: Dr. Kirsten Hanke and Dr. Karolin Meixenberger
Study lead Unit 34: Dr. Uwe Koppe
Tasks
In spring 2023, the Molecular Surveillance of HIV (MolSurv-HIV) was renamed Integrated Genomic Surveillance of HIV (IGS-HIV). The Integrated Genomic Surveillance of HIV new diagnoses is an important part of the national program for monitoring the German HIV epidemic. As part of IGS-HIV, HIV sequences are obtained to analyze the current HIV infection incidence using molecular epidemiology.
The main study objectives are
- the continuous analysis of transmitted primary HIV resistance,
- monitoring of circulating HIV variants,
- identifying and characterizing transmission networks,
- and detecting, investigating and evaluating regional and national HIV outbreaks.
For this purpose, the sample material of the InzSurv-HIV study is used, where serum or plasma is currently available for analysis of about 60% of all newly reported HIV diagnoses. In an automated procedure, viral RNA is isolated and different HIV genome regions are amplified using RT-PCR. A total of four amplicons are generated, which include 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 resistance and tropism determination. The amplicons are sequenced using Illumina-based next-generation sequencing (NGS).
Continuous analysis of transmitted primary HIV resistance
When a new HIV infection occurs with a virus that is resistant to antiretroviral therapy (ART), it is referred to as primary HIV resistance or TDR (transmitted drug resistance). In this case, the resistance mutations have developed prior to infection and the resistant virus was transmitted to another person. The resistance mutations can affect the efficacy of individual active substances or entire substance classes. This may limit the selection of active substances for initial antiretroviral treatment of the newly diagnosed person. The identification and interpretation of resistance mutations in the HIV sequence 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 are constantly being developed and approved for ART or pre-exposure prophylaxis (PrEP). This means that monitoring possible new resistance profiles remains an important task in order to be able to take them into account in resistance algorithms and therapy guidelines. Due to the high public health relevance of primary HIV resistance, continuous monitoring of the development and transmission of resistant HIV in Germany is an official duty of the RKI and also part of the "Strategy for Containing HIV, Hepatitis B and C and Other Sexually Transmitted Infections" of the Federal Ministry of Health (BMG). The results of the resistance analyses are reported annually to the European Centre for Disease Prevention and Control (ECDC) of the World Health Organization (WHO).
Monitoring of HIV variants in circulation
The monitoring of HIV variants in the IGS-HIV is mainly limited to the determination of the subtype of HIV-1 group M infections, since infections with other HIV-1 groups and HIV-2 are very rare in Germany. Subtype determination is usually done with web tools (e.g. REGA HIV-1 Subtyping Tool, COMET HIV-1 Tool, Geno2Pheno Subtyping Tool). If the assignment is not clear, 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 in Germany provides important insights into the infection dynamics and endemic spread of certain virus variants. Furthermore, some HIV subtypes show limited sensitivity to certain antiretroviral drugs due to natural polymorphisms, and there are reports of subtype-specific properties with regard to transmission or pathogenesis in certain populations or risk groups. Continuous monitoring of HIV diversity is therefore of great importance for the coordination of diagnostic and therapeutic guidelines.
Identification and characterization of transmission networks
Reconstructing related transmission events leads to a deeper understanding of the HIV epidemic and its dynamics. The insights gained can help to recommend targeted prevention measures in the future or to evaluate measures that have already been implemented. 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 presented in the form of a tree structure. Phylogenetic analyses are carried out using both maximum likelihood methods and Bayesian statistical methods. The latter, for example, allow sequence data to be linked to epidemiological data, which in turn enables the calculation of reproduction numbers (Re), which can be used to measure the spread of the virus in defined risk groups. In addition, Bayesian analyses can be used to depict the temporal and phylogeographic dynamics of the HIV epidemic.
Detection, investigation and assessment of HIV outbreaks
HIV outbreaks or sub-epidemics are defined as high-frequency transmissions, usually with a single virus variant, which therefore stand out in phylogenetic analyses as distinct, very compact clusters. Once an outbreak has been identified, the relevant public health stakeholders are informed so that possible measures can be initiated. These may include, for example, low-threshold testing and counseling services or interventions such as the increased provision of condoms or sterile injection materials.
Information for participants of the InzSurv-HIV & IGS-HIV
In order to fulfill our duties as formulated in the Infection Protection Act in the best possible way, we use modern molecular methods. Viral RNA is isolated from serum/plasma and then amplified and sequenced. We process both regular serum/plasma samples and filter cards on which serum or plasma has been dropped (DSS/DPS). In the case of the latter, the higher fragmentation and degradation of viral RNA is increasingly proving to be a problem. Therefore, since July 1, 2020, we have been gradually switching from filter cards to regular serum or plasma samples.
For successful HIV sequencing, we require at least 500 µl serum/plasma and the sample material should be as unaffected as possible by longer storage or freeze-thaw cycles.
During a pilot phase, it has been shown that weekly or event-driven direct shipment by mail is logistically advantageous for many senders.
If you are interested in switching from DSS/DPS to serum/plasma or have not yet sent samples to the RKI but would like to send samples in the future, please feel free to contact us.
Instructions for sending serum/plasma samples by post can be found here:
We will provide you with the shipping material for serum/plasma samples free of charge. Sample transport by courier or post is also free of charge for you.
Contact details
Shipping management
Sabrina Neumann
Phone: +49 (0)30-18754-2243
Fax: +49 (0)30-18754-2605
E-mail: Molsurv-HIV [at] rki.de
Principal Investigator Unit 18 (Molecular Epidemiology)
Dr. Kirsten Hanke
Phone: +49 (0)30-18754-2639
Fax: +49 (0)30-18754-2605
E-mail: Molsurv-HIV [at] rki.de
Dr. Karolin Meixenberger
Phone: +49 (0)30-18754-2277
Fax: +49 (0)30-18754-2605
E-mail: Molsurv-HIV [at] rki.de
Head of Studies Unit 34 (Epidemiology)
Dr. Uwe Koppe
Phone: +49 (0)30-18754-2262
E-mail: InzSurv.HIV [at] rki.de