Abstract—In South Africa, the proportion of patients admitted to hospitals with Adverse Drug Reactions (ADRs) range between 2-21.4% and between 1.7 to 25.1% of hospital in-patients are reported to have developed ADRs in hospitals. Drugs are therefore responsible for significant mobility and mortality amongst people in South Africa. The use and uptake of medicines results in ADRs due to medicine’s toxicity and interactions with other medicines. A large number of ADRs are preventable. This research aims to investigate the association between Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathways involved in cellular response to drugs and occurrence of Adverse Drug Reactions (ADRs). A Pearson’s Product-Moment Correlation (PPMC) was run to assess the relationship between the frequency of ADRs and biological pathways for 33 drugs that included 18 HIV drugs commonly called Anti-Retrovirals (ARVs), 5 anti-tuberculosis (TB) drugs and 10 drugs frequently implicated in ADRs (DFAs) comprising of 3 opioids, 2 loop diuretics, 2 beta agonists, 2 low molecular heparins and 1 systemic corticoid. The ratios of biological pathways/ADRs for ARVs, TB drugs and DFAs were found to be 0.02, 0.33 and 0.06 respectively. ARVs had on average more ADRs (165.22±3.94) compared to TB drugs (67.60±29.17) and DFAs (160.9±49.99). However, TB drugs were linked to a comparatively larger number of KEGG biological pathways (22±9.95) compared to ARVs (3.94± 0.74) and DFAs (9.50±1.79). Further research is required to understand the importance of these research findings towards the development of more effective drugs characterized by reduced prevalence of ADRs.