Long-acting cabotegravir and rilpivirine (LA-CAB/RPV) have been incorporated into the treatment of people living with HIV (PLWH), but evidence on their metabolic impact in real-world settings remains limited. This retrospective study analyzed the lipid profiles of 39 PLWH who switched from daily oral antiretroviral therapy to LA-CAB/RPV. Lipid parameters were compared before and seven months after the switch. No significant differences were observed in total cholesterol, LDL cholesterol, or triglycerides, indicating that LA-CAB/RPV did not worsen the lipid profile. However, HDL cholesterol increased significantly from 49.4 ± 11.5 mg/dL to 53.0 ± 11.9 mg/dL (p = 0.0065). Viral suppression and CD4 counts remained stable throughout the study period. These findings suggest that switching to long-acting injectable cabotegravir and rilpivirine maintains virological and immunological control without adversely affecting the total cholesterol, LDL cholesterol, or triglycerides, and is associated with an improvement in HDL cholesterol. LA-CAB/RPV therefore appears to be a metabolically safe therapeutic option for PLWH, with a potentially favorable effect on cardiovascular risk factors.