Background: Effective combined antiretroviral therapy (cART) has improved life expectancy among people living with HIV-1 infection. Treated HIV-1infection increases the prevalence of metabolic syndrome (MS). Despite sub-Saharan Africa having among the highest rates of HIV-1 infection, the effects of MS in HIV-1-infected individuals on cardiovascular risk is poorly explored. The aim of the study was to assess whether MS and/or HIV-1 treatment correlates with large elastic artery stiffness in HIV-1-infected patients treated with first-line cART. Methods: The study sample comprised of 102 subjects free of cardiovascular disease and major risk factors divided into two groups based on HIV-1 infection, treatment, and MS status: HIV-1 + /cART + /MS + (n = 12); HIV-1 + /cART - /MS + (n = 16); HIV-1 - / MS + (n = 10); HIV-1 + /cART + /MS - (n = 42); HIV-1 + /cART - /MS - (n = 32); HIV-1 - / MS - (n = 39). MS was established according the International Diabetes Federation definition. Large artery stiffness was measured using applanation tonometry to assess aortic pulse wave velocity (aPWV) and aortic augmentation index at heart rate of 75 bpm (AIx@HR75). cART included lamivudine/zidovudine and nevirapine or efavirenz. Results: The prevalence of MS in the HIV-1-infected patients was 28%. There were no significant differences in aPWV in the non-MS groups. However, in subjects with MS, aPWV was significantly higher in the HIV-1 cART patients (9.0 ± 1.9 m/s) compared with both controls (7.5 ± 1.8 m/s; P = 0.018) and untreated HIV-1 patients (7.7 ± 1.3 m/s; P = 0.023), and these differences remained after adjustment for blood pressure and sex. Aortic PWV was significantly elevated (P = 0.009) in HIV-1 cART patients with MS compared to their counterparts without MS. Untreated HIV-1 patients with MS also demonstrated increased aPWV compared to their counterparts without MS (P = 0.05). Aortic AIx@HR75 was, on average, ~ 5% higher in HIV-1 cART patients with MS (28.3 ± 62% compared with untreated HIV-1 patients with MS (23.5 ± 9%; P = 0.075). Sub-group multivariate analysis identified MS as an independent predictor of increased aPWV in HIV-1 cART patients. Conclusions: Our study established that presence of MS in HIV-1 patients on treatment was associated with increased aPWV and hence increased arterial stiffness in sub-Saharan African HIV-1 patients on first-line cART.