The Vespa2 survey was conducted in 2011 in mainland France and the overseas departments (DOM) among people living with HIV (PLHIV) receiving outpatient care at hospitals. These geographic areas are highly heterogeneous and diverse, both socially and demographically as well as epidemiologically, but are governed by the same health insurance system and the same HIV treatment guidelines. The objective of this study was to analyze virological success (viral load <50 copies/ml) of treatment among PLHIV in the DOM, to compare it with that observed among PLHIV in metropolitan France, and to assess the impact of social and behavioral factors on treatment success (adherence, nationality, employment, resources, knowledge, confidentiality, and crack use). The comparative analysis focused on PLHIV diagnosed after 1996 and treated for at least 12 months, comprising 321 PLHIV receiving care in the French overseas departments and 1,246 PLHIV in mainland France. In the French overseas departments, virological success was observed in 78.7% of treated individuals, ranging from 69.9% in French Guiana (Cayenne) to 87.7% in Réunion; it was 90.4% in mainland France. Among the French overseas departments, French Guiana tended to have a less favorable outcome (ORa (ref. Martinique)=0.4; 95% CI: [0.1–1.1]) after adjusting for social and demographic characteristics; among these, only inactivity was associated with a lower outcome (OR (ref. self-reported employed) = 0.3 [0.1–0.9]). The gap with mainland France (OR for the French overseas departments (ref. mainland France) = 0.4 [0.3–0.5], adjusted OR = 0.7 [0.4–1.0], p = 0.054) was partly attributable to social and behavioral factors and adherence. Thus, a cluster of closely interrelated social factors explains these suboptimal treatment outcomes for patients in the French overseas departments, highlighting the importance of structural factors and suggesting the value of intensifying medical and social care.