Human immunodeficiency virus (HIV) is one of the most genetically divergent viruses. In this doctoral thesis, we wished to describe the HIV epidemic in Slovenia and to characterize Slovenian samples. We included samples obtained from more than half of HIV-positive individuals diagnosed with HIV in Slovenia in diverse time frames. We confirmed subtype B as the most prevalent HIV subtype, identified in over 80% of samples. We observed that subtype B epidemic was mainly due to local transmission, because the majority of individuals (66%) belonged to large transmission clusters. Persons belonging to large clusters had statistically significant association with the following: Slovenia reported as most likely country of HIV acquisition, HIV diagnosis after the year 2004, and no surveillance drug resistance mutations detected. On the contrary, we did not find an association with homo/bisexual HIV mode of transmission and recent HIV infections. However, more than half of large transmission clusters were exclusively male clusters and two clusters encompassed only individuals declaring themselves as men who have sex with men (MSM). We estimated the origin of the oldest phylogenetic cluster in the year 1986 and with this the start of Slovenian subtype B epidemic in the late 1980s. Non-B subtypes were detected less often, the most prevalent was subtype A. Two thirds of persons infected with non-B subtype reported heterosexual mode of HIV transmission vs. 11% of persons infected with subtype B. In addition, non-B subtype was seen more often among women and immigrants, and persons who reported to have acquired HIV in a stable relationship with the source. Near full-length genome sequence was obtained for a selected set of samples with unassigned HIV subtype. We obtained 11 near full-length genomes and two sequences of > 7.000 base pairs. Seven sequences were identified as “pure” subtypes or already characterized circulating recombinant forms (CRFs). The remaining six sequences were determined to be unique recombinant forms (URFs); four displayed a single recombination event and two exhibited a complex recombination pattern involving several subtypes or CRFs. Finally, three HIV strains were recognized as having epidemic potential and could be further characterized as new CRFs.