Background Disparities in combined antiretroviral therapy (cART) outcomes have been consistently reported among people living with HIV (PLWHIV). The present study aims at investigating the mechanisms underlying those disparities among PLWHIV in France. Methods We used data from the Vespa2 survey, a large national cross-sectional survey, representative of HIV-infected people followed at hospitals in 2011. Among participants diagnosed ≥1996, HIV treatment-naive at the time of cART initiation and on cART for at least 12 months, the frequency of sustained virological suppression (SVS; undetectable viral load [<50 copies/ml] for at least 6 months) at the time of the survey, was assessed and its social determinants were measured through logistic regression, accounting for clinical and biological determinants of response to cART. Results Among 1,246 participants, 77.7% had achieved SVS. SVS was less frequent among those unemployed (0.6 [range 0.3-1.0]) and those with the lowest level of education (0.4 [range 0.2-0.9]). The late presenters, diagnosed at a CD4⁺ T-cell count <200/mm³ (0.5 [range 0.3-0.9]) and the late starters, diagnosed at a CD4⁺ T-cell count >200 but initiating cART at CD4⁺ T-cell count <200 (0.3 [range 0.1-0.8]) were less likely than the ideal starters (≥350 CD4⁺ T-cells/mm³ at cART initiation) to achieve SVS, as were those who reported suboptimal adherence versus those reporting optimal adherence (0.4 [range 0.2-0.7]). In bivariate analyses, material deprivation, discrimination and a weak social network were also associated with a poorer treatment response. Conclusions Structural social factors remain strong determinants of treatment response and should be addressed in a broad approach of care, but wider political issues should also be investigated.