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Background Every day, around 7000 people still get infected with HIV worldwide. Antiretroviral (ARV) therapy reduced morbidity and mortality, and while early ART is expected to reduce incidence, transmission of HIV infection is still ongoing. Transmission investigations shed light on how to prevent HIV spread and on the origin of transmitted drug resistance (TDR). Clinical, socio-behavioral and therapy adherence factors influence the transmission of HIV and the efficacy of interventions. Objectives The main goal is to construct a cohort to analyze the prevalence and characteristics of TDR in newly diagnosed HIV patients and to describe and analyze risk factors associated with HIV infection and transmission of drug resistance in Portugal. Methods The BEST HOPE cohort includes patients at least 18 years old, with a new HIV diagnosis since September 2014 and a baseline drug resistance test. Data include clinical characteristics of the patients collected through a questionnaire and the HIV genomic sequence obtained from the drug resistance test. Additionally, patients from specific vulnerable groups - Men who have sex with Men (MSM) and Migrants - fill in a questionnaire concerning socio-behavioral factors associated with HIV infection. Patients are being recruited in 18 Portuguese hospitals, covering most regions of the country. Until now, we have collected data from around 250 HIV-positive patients, including 40 migrants and 85 MSM. This unique dataset will therefore combine viral genomic data with clinical and socio-behavioral data. A relational Access database was constructed for the purpose of this study to store all the collected data. Descriptive statistics will be performed using SQL and R statistical software. Moreover, we will analyze the different characteristics of epidemic hotspots using in-depth phylogenetic analysis, which takes into account control sequences available in Portuguese and public databases. Expected results Our study will provide an innovative molecular epidemiological perspective about the determinants of HIV transmission, with or without TDR. These results will be useful to inform Public Health entities for designing prevention policies. In this conference, we will present preliminary results concerning the molecular epidemiology and characteristics of TDR in Portugal and in specific vulnerable groups.