Whether, and how, co-occurring HIV-1 infection (HIV) and tuberculosis (TB) impact cardiovascular status, especially in adolescents with perinatally acquired HIV (APHIV), have not been examined. We hypothesized that APHIV with previous active TB have worse cardiac efficiency than APHIV without TB, which is mediated by increased inflammation. Arterial elastance (Ea) and ventricular end-systolic elastance (Ees) were assessed by cardiovascular magnetic resonance, and ventriculoarterial coupling (VAC) estimated as Ea/Ees ratio. Inflammation was measured by high sensitivity C-reactive protein (hsCRP). Previous TB in APHIV was associated with reduced cardiac efficiency, related to an altered ventriculoarterial coupling. However, we did not find evidence of hsCRP mediated effects in the association between prior TB and cardiac efficiency. The clinical significance of these findings requires further study, including a wider range of biomarkers of specific immune pathways.