Background: Doravirine (DOR) is a new-generation non-nucleoside reverse transcriptase inhibitor, which has emerged as an option for people living with HIV (PLWH) owing to its favorable efficacy and safety profile, unique resistance pathway and limited potential for drug-drug interactions. Methods: This retrospective chart review study aimed to better understand DOR-based treatment use in Greece, PLWH characteristics, and drivers of treatment switch. Eligible individuals were adult PLWH who were switched to a DOR-based regimen based on the physician’s decision. Individuals exposed to DOR at any time prior to switching to the DOR-based regimen were excluded. Results: From 12 July 2023 to 31 October 2023, 110 PLWH were consecutively enrolled across 6 public hospital clinics. At baseline (closest prior to or on the date of first DOR prescription), the mean age of PLWH was 49.3 years, 90.9% were males, 88.2% were asymptomatic, 86.5% were virologically suppressed, 33.6% were suffering from multimorbidity (excluding infections/infestations), 45.5% were receiving comedications for their comorbidities, and 5.5% were co-infected with Hepatitis C virus. Most PLWH (98.2%) were prescribed DOR plus two nucleoside reverse transcriptase inhibitors; 87.3% were prescribed DOR/Lamivudine/Tenofovir Disoproxil Fumarate fixed-dose combination. PLWH started DOR a median of 11.7 years after first-ever antiretroviral therapy initiation, corresponding to 2nd/3rd/≥4th antiretroviral line in 33.6%/33.6%/32.7% of participants, respectively; 60.9% of them were proactively switched to a DOR-based regimen. The most common reasons for switching were ‘regimen simplification’ (42.7%), ‘tolerability’ (26.4%) and ‘prevention of toxicities’ (18.2%). Conclusions: This study highlights the patterns of DOR use in real-life clinical practice in Greece among treatment-experienced PLWH. Physicians switch HIV-1-infected individuals from prior ART to DOR-based regimens to offer a simplified regimen or to avoid or prevent toxicity.