11Highly-Active Antiretroviral Therapy (HAART) is the recommended treatment and management strategy for 12 HIV infection. Although the existing antiretroviral drugs are indispensably significant in improving the 13 quality of lives of HIV/AIDS individuals, the drugs still have many limitations including resistance, production 14 of toxicity, and their limited availability. These limitations continue to open new opportunities in the use of 15 ethnomedicine for the management of HIV/AIDS. With this, few researchers have made an effort to test the 16 inhibitory activity of crocodile serum as it has a unique and diverse molecular activity in preventing HIV-1 17 replication. In this study, a cell culture-based assay was utilized coupled with colorimetric enzyme 18 immunoassay to determine the HIV-1 reverse transcriptase activity. One HIV-1 seropositive serum was 19 processed for Peripheral Blood Mononuclear Cells (PBMC) co-culture from which HIV-1 isolates were obtained. 20 The HIV-1 reverse transcriptase activity after 21 days was 0.5928 pg/well. Moreover, a baseline Philippine 21 crocodile serum concentration of 0.5% vol/vol was used based on the previous study conducted by Hinay and 22 Sarol (2018) and the cell viability results showed no cell reduction of mononuclear cells after 72 hours 23 incubation. The inhibitory activity of the Philippine crocodile serum at 0.5% and 0.25% vol/vol concentrations 24 inhibited 65.68±2.93% and 69.92±0.45% respectively in post-infection interactions. In addition, the Philippine 25 crocodile serum in pre-infection interaction at 0.5% and 0.25% vol/vol concentrations inhibited 68.61±1.67% 26 and 69.95±2.24% respectively. As has been noted, the inhibitory actions of the Philippine crocodile serum 27 effectively regulate the HIV-1 replication in both pre-and post-infection interactions.28 29 Keywords: Philippine freshwater crocodile, HIV-1 co-culture, HIV-1 inhibition, HIV-1 reverse transcriptase 30 31 129 130 Data Management 131 The results of pre-infection and post-infection assays were expressed as means ±SD in triplicates. The 132 Percent (%) reduction of HIV-1 activity was computed using the following mathematic formula: 133 % inhibition = Absorbance of Negative control* -Absorbance of test sample**