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

MD, 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.

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

I 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.

Lena Mattsson

I am a research nurse supporting the researchers/clinicians in both clinical trials of antiretrovirals as well as academic clinical trials.

Sofia Sandberg

I am a research nurse supporting the researchers/clinicians in both clinical trials of antiretrovirals as well as academic clinical trials.

Liselott Njie

I am a research nurse supporting the researchers/clinicians in both clinical trials of antiretrovirals as well as academic clinical trials.

Ujjwal Neogi

I obtained my doctoral degree from Department of Medicine Huddinge, Karolinska Institutet (KI) in 2013. Following my two year postdoc, I joined the Department of Laboratory Medicine as Assistant Professor in 2015, where my research focuses on bench-to-bedside clinical and translational research to understand the host and viral factors associated with disease progression and control in HIV-1. I intend to use high-throughput multi-omics and approach. Apart from this my research interests also include phenotypic drug sensitivity assay, viral fitness and spread of the HIV-1 epidemic in low- and middle-income countries.

Shambhu G Aralaguppe

Born and raised in Davangere, India. I obtained my master's degree from the University of Mysore, Mysore in 2011. I worked as a research fellow at JNCASR, Bangalore, India, where I learnt most of the molecular biology and virology techniques. Now I am a PhD student in Prof Sönnerborg's group since June 2015. I aim at genotypic and phenotypic characterization of HIV 1-C virus pertaining to adaptation and virulence. Along with this, I will also study the role of drug resistant mutations affecting pathogenesis of the virus. I am an amateur violinist in Carnatic classical music.

Duncan T Njenda

I 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. 

Nigus Fikrie Telele

M.Sc in Medical Parasitology and PhD in Medical Microbiology at Addis Ababa University, Ethiopia. I worked as a Lecturer and Assistant Professor in the Department of Microbiology, Immunology and Parasitology, School of Medicine, Addis Ababa University. Since 2011, I joined the Prof. Sönnerborg group at Karolinska Institutet and currently I am studying PhD on molecular epidemiology of HIV drug resistance and minority mutations using a large countrywide HIV cohort established at seven university hospital ART clinics in Ethiopia.

Amare Worku Kalu

MSc in Medical Microbiology from Addis Ababa University, Ethiopia, and worked as head of Microbiology/HIV service laboratories and ART program in AAU College of health sciences. Since 2011, I am involved in research activity based on a large multisite Ethiopian national HIV cohort. Using samples and data from this cohort, currently, I am working on my Ph.D. project in Karolinska Institutet with the aim to describe the molecular evolution of HIV-1 subtype C and its impact on therapeutic response in Ethiopia with Prof. Sönnerborg as the main supervisor.

Kamlendra Singh

I graduated in Physics from the Banaras Hindu University, Varanasi, a premier educational establishment of India. I am a trained structural biologist, biochemist and biophysicist. For the past 20 years, I have been studying the molecular mechanism of nucleic acid metabolism by bacterial, viral and mammalian replication enzymes. Major goals of my research are to understand the mechanism(s) of drug susceptibility and resistance, viral, bacterial and mammalian replication using advanced biochemical, biophysical and computational approaches. I have experience in basic research that unveiled the mechanistic details of the DNA/RNA polymerase reaction, the proofreading function, coordination between the polymerase and proofreading activities ensuring faithful replication, and nucleic acid unwinding by the helicases. More specifically, my research interests include Human Immunodeficiency Virus type 1 (HIV-1), Hepatitis C virus (HCV), Hepatitis B Virus (HBV), Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Foot-and-Mouth disease virus (FMDV), and Mycobacterium tuberculosis. My role in Sönnerborg group to oversee/conduct biochemical assays, and use computational techniques to understand molecular basis of drug resistance and susceptibility.

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