| dc.description.abstract | ABSTRACT BACKGROUND: The World Health Organization (WHO) recommends all countries offering antiretroviral therapy (ART) to HIV-1 infected patients to establish surveillance systems in order to monitor the prevalence of transmitted HIV-1 drug resistance (TDR) as this may reduce the chances of treatment success. In Norway surveillance of TDR among persons newly diagnosed with HIV-1 infection was started in January 2006 by The Norwegian Institute of Public Health (FHI). The aim of this study was to investigate the prevalence of TDR in patients diagnosed with HIV-1 in Norway in 2011-12, and to explore potential differences in the pattern of TDR according to gender, transmission route, mutations identified, resistance to ART, viral subtype and whether the patients were infected in Norway or abroad. Finally the significance of resistance mutations obtained through epidemiologic surveillance was evaluated with regard to clinical treatment options with ART. METHODS: A retrospective observational study on data from the HIV- cohort database at Oslo University Hospital, Ullevål (OUS Ullevål) and from FHI was performed. Physicians diagnosing patients with a previously undiagnosed HIV-1 infection were asked to send plasma samples for genotypic resistance testing to OUS Ullevål, and the results of sequence analysis were sent anonymously to FHI. With WHOs list of mutations for surveillance of transmitted drug resistant HIV strains and Calibrated Population Resistance (CPR), a tool for analysis of HIV-1 sequence data sets from the Stanford HIV Drug Resistance Database, resistance mutations were identified. The WHO list is designed for epidemiologic surveillance, and does not give clinical guidelines on resistance against drugs, or consider the genetic barrier of a drug and the complex interactions of mutations. Therefore surveillance drug resistance mutations (SDRMs) identified by WHOs list do not automatically imply clinical relevance. Guidance for treating patients infected HIV-1 with antiretroviral therapy depends on clinical analysis carried out by a virologist and an infectious disease specialist based on the patient s medical history and recommendations from the International AIDS Society (IAS) and the Rega Institute for Medical research in addition to the Stanford HIV Drug Resistance Database. RESULTS: Resistance sequence analysis from plasma samples were obtained from 246 (48%) of 509 patients newly diagnosed with HIV-1 in Norway in 2011-12. 15 (6,1%) of 246 patients were infected with virus with one or more mutations coding for resistance. 8 (3,3%) had resistance mutations for non-nucleoside reverse transcriptase inhibitors (NNRTI), 3 (1,2%) for nucleoside and nucleotide reverse transcriptase inhibitors (NRTI) and 1 (0,4%) for protease inhibitors (PI). Almost half of the 15 patients were infected abroad, mainly in Sub- Saharan Africa. Non-B subtypes of HIV-1 was found in 7(70%) of the 10 cases with high- level resistance. The prevalence of cases with TDR of clinical significance was 4% of 246 patients, and 1,6% if only patients infected in Norway were included. DISCUSSION AND CONCLUSION: Results of epidemiologic surveillance of TDR in HIV- 1 infected patients in Norway in 2011-12 are in agreement with previous reports on primary HIV-1 resistance with a low but increasing prevalence. Almost half of the cases diagnosed with primary resistant HIV-1 were infected abroad, mainly in Sub- Saharan Africa. Thus the results of TDR among HIV-1 infected probably do not represent the actual situation in Norway. Not all the identified mutations were of clinical impact as the WHO list is designed for epidemiologic surveillance. Numbers of cases with TDR with mutations of clinical significance were only 4%. If only patients with resistant HIV-1 infected in Norway were included the numbers were even lower. | eng |