Combination antiretroviral therapy (cART) program in low- and medium-income countries (LMIC) like Cameroon is according to the public health method with a standardized regimen for all people living with HIV (PLHIV). Insight into inflammation patterns and metabolic disorders is needed to understand the pathophysiology of HIV and age-linked diseases. However, minimal data is available on residual inflammation and targeted metabolic disorder in the populations on first-generation anti-HIV drugs like zidovudine and lamivudine that have more toxic side effects. Therefore, this study aimed to identify immune aging in people living with HIV-1 on cARTcompared to HIV-1 Negative Control using a proteomics and metabolomics approach. Plasma blood samples were obtained from therapy naïve PLHIV, PLHIV on ART for more than five years, and healthy HIV-negative controls. Samples were analyzed for 92 markers of inflammation and 72 targeted metabolites of the tricarboxylic acid. Several tests were performed to compare the groups under study. Principal component analysis reveals a general clustering of the patients in the ART group with those in the healthy control group. Four inflammatory markers, including OPG, CXCL9, CXCL10, and CCL25, were found to be significantly different (p < 0.2) between the groups after Mann Whitney test, and higher levels of TNFSF14, IL-15RA and CCL23 were found in the ART group compared to healthy controls after Kruskal Wallis test. Ten metabolites, including butyric acid, azelaic acid, fructose, glucuronic acid, inositol phosphate, arachidonic acid, pyruvic acid, citric acid, lactic acid, and X3.4 dihydroxylbutyric acid (p<0.05) were observed to be significantly different between the groups. Pathway analysis shows viral protein interaction with cytokine and cytokine receptor pathway, cytokine-cytokine receptor interaction pathway, and chemokine pathway as the top three pathways linked to inflammation but the most significant pathways with p-value<0.05 were identified to be “Toll-like receptor signaling pathway,” “Intestinal immune network for IgA production” and “Cytosolic DNA-sensing pathway.” These markers and metabolites are linked with age-related comorbidities, including cardiovascular diseases and hepatitis C.