HIV-1 genetic diversity and resistance profile might change according to the risky sexual behavior of the host. To show this, we recruited 134 individuals between the years 2015 and 2017 identified as transgender women sex workers (TWSW, n = 73) and Heterosexual Military Officers (HET-MO, n = 61). After obtaining informed consent, we collected a blood sample to perform the HIV genotyping, CD4 cell count, and viral load. We used bioinformatics approaches for detecting resistance mutations and recombination events. Epidemiological data showed that both groups reported sexually transmitted diseases and they were widespread among TWSW, especially syphilis and herpes virus (35.6%). Illegal drugs consumption was higher among TWSW (71.2%), whereas condom use was inconsistent for both HET-MO (57.4%) and TWSW (74.0%). TWSW showed the shortest time exposition to antiretroviral therapy (ART) (3.5 years) and the lowest access to ART (34.2%) that conducted treatment failure (>4 logs). HIV-1 sequences from TWSW and HET-MO were analyzed to determine the genetic diversity and antiretroviral drug resistance. Phylogeny analysis revealed 125 (93%) cases of subtype B, 01 subtype A (0.76%), 07 (5.30%) BF recombinants, and 01 (0.76%) AG recombinant. Also, TWSW showed a higher recombination index (9.5%, 7/73) than HET-MO (1.5%, 1/68). HET-MO only showed acquired resistance (26.23%, 16/61), whereas TWSW showed both acquired as transmitted resistance (9.59% for each). In conclusion, TWSW and HET-MO showed significant differences considering the epidemiological characteristics, genetic diversity, recombination events, and HIV resistance profile.