Team Antivirals
Our clinical research on antiretroviral therapy (ART) includes both academic and industry-sponsored in vivo studies evaluating new antiretroviral drugs (ARVs) as well as new strategies for the use of approved drugs. These studies are performed at the clinical HIV unit at Department of Infectious Diseases, Karolinska University Hospital.
The unit has so far been involved in pivotal phase II-IV studies of almost all approved ARVs. The clinical drug-studies are headed by Dr Anders Thalme at a fully-equipped GCP-based trial unit, which includes also 2.5 research nurses. We are also involved in cohort studies of ART in low-middle income countries.
Studies on HIV drug resistance have been done since the 1990-thies. Today direct sequencing of the pol gene is aimed at in all newly diagnosed patients and in all patients failing ART. The sequences are uploaded in the InfCare HIV database and also in the international databases EuResist and Spread. In 2006, we co-founded the EuResist consortium with experts in virology, infectious diseases, bioinformatics and computer science. The database (db) is today one of the world´s largest HIV DR db incl. clinical/laboratory data and viral sequences. A bioinformatic engine has been developed integrating DR data with clinical information and treatment history to predict successful ART regimes after a failure. Data from partners in low income countries are added.
Since several years protocols for next generation sequencing have been developed for near full length genomic sequencing of HIV-1 and for analysis of drug resistance in minor viral variants. Special focus is put on the most frequent subtypes: HIV-1B, HIV-1C and HIV-1A, and plasma specimens are obtained from the Swedish cohort and from international cohorts.
As part of our interest for HIV cure approaches, a substantial effort is directed towards improving the quantification of the proviral DNA as well as understanding its regulation. Techniques to be evaluated include HIV RNA scope with automated cell counting, TILDA, Proximity ligation assay, Single molecular FISH and Super rolling circle amplification.
We have shown that different HIV-1 subtypes may respond different to ARVs and drug resistance mutations may deviate. Therefore we are testing all new ARVs with regard to ex vivo sensitivity, biochemical studies and molecular modelling using binding kinetics and inhibition assays.
Research Team Leader
Anders Sönnerborg
Research team leaderMD, PhD. Educated at Karolinska Institutet. Professor in Infectious Diseases/Clinical Virology since 1998. Acting director, Unit for Infectious Diseases and Dermatology. Senior consultant at Departments of Infectious Diseases and Clinical Virology, Karolinska University Hospital. Former scubadiver, soccer and ice-hockey player. Now more relaxed with interest in our cultural heritage, foreign cultures and the archipelago.
Research team members
Anders Thalme
I am MD, PhD and specialist in infectious diseases with special focus on HIV. I have the overall responsibility for the medical care at the HIV unit. I am involved in several pivotal of new antiretroviral drugs sponsored by the industry as well as strategic trials with already approved drugs.
Emmi Andersson
Senior physician MD, PhDI am MD and consultant in Infectious Diseases and Clinical Microbiology. In my PhD project I am studying HIV-1 infection in Sweden with epidemiological and molecular approaches in a close collaboration between the experimental and clinical units of prof Sönnerborgs research group. I focus on surveillance of transmitted drug resistance with comparative studies of traditional Sanger sequencing and modern NGS technique. Data are analysed with regard to drug resistance mutations in minor viral variants and phylogenetic analysis including identification of transmission cluster. Also we will use the data for the development and evaluation of new and better methods to estimate time-from-infection and the proportion of undiagnosed HIV-infections in Sweden. The latter is done in collaboration with European Center for Disease Control and prof Andrew Philips at University College London.
Duncan Njenda
Postdoctoral researcherI am PhD student in joint Karolinska Institutet- Stellenbosch University Double Degree program. I obtained my master degree in Medical Virology, Stellenbosch University, South Africa. My expertise is in virology and molecular biology. My PhD program is to identify resistance mechanisms against protease inhibitors in South African HIV-1C patients’ high throughput system biology approach. I aim to integrate molecular biology, biochemistry, virology and structural biology to understand the resistance mechanisms.
Lena Mattsson
Research nurseI am a research nurse supporting the researchers/clinicians in both clinical trials of antiretrovirals as well as academic clinical trials.
Liselott Njie
Research nurseI am a research nurse supporting the researchers/clinicians in both clinical trials of antiretrovirals as well as academic clinical trials.
Techniques
Phase I-IV clinical studies, database, bioinformatics, High throughput sequencing, NGS, ex vivo sensitivity assay, biochemistry (binding kinetics, inhibitory assays, moleuclar modelling
Collaborations
- Swedish National InfCare HIV cohort
- EuResist, www.euresist.org
- European Society for Translational Antiviral research, http://www.esar-society.eu/
- Nordic HIV cure consortium
- University of Sienna
- University of Cologne
- Max-Planck Institute for Bioinformatics
- University of Missouri
Funding
- Stockholm County Council
- Swedish Physicians Against AIDS Foundation
- Swedish Research Council
- NIH
- Karolinska Institutet Research Foundation Grants