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Günthard

Fakultäten » Medizinische Fakultät » Infektionskrankheiten und Spitalhygiene, Klinik für » Prof. Dr. Huldrych Günthard » Günthard

Completed research project

Title / Titel Long-term trends and transmission of individual drug resistance mutations as defined by the IAS-USA mutation list in the Swiss HIV cohort Study and dependence on changing antiretroviral treatment regimens
PDF Abstract (PDF, 14 KB)
Summary / Zusammenfassung Background
The introduction of combination antiretroviral therapy has dramatically increased both the life expectancy and the quality of life of HIV-1 infected individuals. The development of new antiretroviral drug classes further increased the treatment options, but HIV drug resistance remains an important cause of treatment failure. Detailed longitudinal analyses are thus in need in order to identify the characteristics of resistance mutations and to optimize long term treatment strategies.
Study Aims
Our aim is to longitudinally study (i) the prevalence of individual drug resistance mutations in patients failing antiretroviral treatment and (ii) to study the incidence of transmitted individual drug resistance mutations. A particular focus of the project lies in linking longitudinal changes of resistance to changes in antiretroviral treatment regimens.
Study Design
We will use various statistical methods to analyze genotypic resistance test results from eligible patients. In order to increase sample sizes, we expect to retrospectively sequence approximately 1000 available blood samples in patients failing antiretroviral therapy for this study.
3. Background
Introduction of combination antiretroviral therapy (cART) has been very successful in reducing morbidity and mortality of HIV-1 infected persons in the developed world over the last 15 years [1-3] Today, it is believed that HIV-infected patients potentially may reach almost the same life expectancy as HIV negative patients with chronic diseases (e.g. Hypertension, Diabetes Type II, etc) [4]. However, the emergence and transmission of HIV drug resistance is still a major threat to long-term efficacy and may potentially jeopardize the treatment success achieved so far in the long run [5, 6].

Over the recent years various new antiretroviral drugs have been introduced into clinical practise with considerable success by reducing toxicity and side effects as well as by increasing virological response rates significantly [7-10]. We have recently demonstrated that against earlier predictions, in Switzerland prevalence of drug resistance has decreased over time most likely due to improved antiretroviral treatment [11]. In addition, we have also observed that again, against earlier predictions, transmission of drug resistant viral strains has not increased; instead it remained stable over time [12].

To date, detailed longitudinal analyses of the long term evolution of individual drug resistance mutations from representative high quality integrated clinical and genotypic drug resistant databases are lacking. Such data however, is of importance and in conjunction with changes of antiretroviral drug regimens over time will be of great help to further improve long term antiretroviral treatment, respectively to help further understand emergence of resistance in “real world settings”. Over the last years the Swiss HIV Cohort Study (www.shcs.ch) has set up one of the most comprehensive genotypic drug resistance databases representative of a whole country that in combination with the large clinical SHCS database allows to address population based resistance studies of high quality [11, 13-18].

Significance of the project
This project will help to decipher the occurrence and the relevance of individual drug resistance mutations at the population level over time. With the unique quality of the SHCS database being representative of the Swiss HIV epidemic [19], long term treatment strategies can be developed and further improved.
Such treatment strategies are necessary for the following reasons:
1) The drug pipeline may decline in the following years, so in the future – despite the currently successful period – incidence of drug resistance may reemerge due to a shortage of new drug supply.
2) In resource limited settings availability of different drugs is substantially limited today and most likely will remain so, thus initial treatment strategies may be crucial for prevention of drug resistance and long-term success of ART.
Project leadership and contacts /
Projektleitung und Kontakte
Prof. Dr. med. Huldrych Günthard, MD (Project Leader) huldrych.guenthard@usz.ch
Prof. Dr. med. Bruno Ledergerber, PhD bruno.ledergerber@usz.ch
Dr. Alexandra Scherrer, MD alexandra.scherrer@usz.ch
Wan-Lin Yang, PhD student wan-lin.yang@usz.ch
Funding source(s) /
Unterstützt durch
SNF (Personen- und Projektförderung), Private Sector (e.g. Industry)
Swiss HIV Cohort Study
In collaboration with /
In Zusammenarbeit mit
participating centers of the Swiss HIV Cohort Study Switzerland
Duration of Project / Projektdauer Jun 2011 to Dec 2013