Background:Neisseria gonorrhoeae (N. gonorrhoeae) is a gram-negative bacterium with a lipooligosaccharides (LOS)-based cell membrane. LOS is considered to supress HIV-1 replication by downregulating NF-κB, IRF3, and IFN-β. The aim of the study:To explore the effect of N. gonorrhoeae LOS on HIV replication in lymphocytes of naive HIV patients, as indicated by NF-κB, IRF3, and IFN-β expressions. Materials and methods: Naïve-HIV lymphocyte culture was divided into 5 groups. The treatment groups were exposed to N. gonorrhoeae LOS with doses ranging from 50 ng/ml, 100 ng/ml, and 200 ng/ml, respectively. The positive control group was exposed to 300 µM of tenofovir as the standard antiviral treatment, while the negative control group received only standard medium. At 24 hours post-treatment, the level of HIV p24 was determined using ELISA and the expressions of NF-κB, IRF3, and IFN-β was measured by flowcytometry. Results: The mean expression of NF-κB and IRF3 were significantly different among groups (p=0.025; p=0.020), while the expression of IFN-β and the level of p24 did not differ significantly (p=0.051; p=0.068). There was a strong and significant positive correlation between LOS concentration and NF-κB and IRF3 expression (r=0.704, p=0.003; r=0.759, p=0.001;). Conclusion: Exposure of lymphocytes from a naïve HIV patient to N. gonorrhoeae LOS significantly affected the expression of NF-κB and IRF-3.