This study assessed the effect of Human Immunodeficiency Virus and Antiretroviral Drugs (ARVs) on liver enzyme markers (Aspartate aminotransferase, Alanine aminotransferase and Alkaline phosphatase) and CD4 T-cells. A total of Seventy Five (75) individuals were enrolled into the study, which comprised Twenty Five (25) HIV negative (control), Twenty Five (25) HIV positive non-treated with ARVs and Twenty Five (25) HIV positive treated with antiretroviral drugs (ARVs). Females were found to be the majority of HIV infected patients and most patients were at the middle age of 20-39 years. AST and ALT were assessed according to the Reitman and Frankel’s (1957) method, while ALP was based on King Armstrong’s (1980) method and CD4 T-cells using a method assayed of Cassens et al., (2004). The result show a significant increase (p<0.05) in AST and ALT levels of HIV positive non treated group compared to HIV negative group (control). AST and ALT levels of HIV positive treated with ARVs is significantly higher in comparison to HIV positive non-treated group. But the ALP activity was significantly lower (p<0.05) in HIV positive treated group compared to non-treated group. Infection by HIV increases the activities of the three enzymes, which may be due to liver cells apoptosis caused by HIV infection, intact immune response to HIV replication which subsequently leads to hepatocellular necrosis and inflammation. But at the commencement of antiretroviral therapy the activities of the three afore-mentioned enzymes decreases which may be as result of decrease in the negative effect of the virus to the liver enzymes by ARVs. For clinical significance, it is necessary to investigate the activities of liver enzymes in HIV positive patients in order to monitor the diagnosis and advanced infection of the liver cells by HIV.Keywords: Aspartate aminotransferase, Alanine aminotransferase, Alkaline phosphatase, Human immunodeficiency virus and antiretroviral drug