Introduction. Chemotherapy of HIV infection remains the only means of treating the disease. The process of development new and improving previously developed drugs is therefore considered a priority. One of the preclinical stage of drug efficacy testing is research in the virus-cell model system in vitro. The aim. To evaluate the antiviral efficacy of nucleoside reverse transcriptase inhibitors (NRTIs) 6HP and 3TC during HIV-1 replication in the neoplastic MT-4 cell line. Materials and methods. Two variants of the CD4+ T-lymphocyte MT-4 cell line (MT-4/1 and MT-4/2) transformed by Human T-lymphotropic virus type 1 (Retroviridae: Orthoretrovirinae: Deltaretrovirus: HTLV-1), with different levels of HIV-1 replication were used. Drugs ammonium-3’-azido-3’-deoxythymidine-5’-carbomoylphosphonat (6HP) and 2’,3’-dideoxy-3’-thiacytidine (3TC) were used to suppress the virus. Results and discussion. The replication activity of HIV-1 was observed to be higher in the MT-4/2 line than in the MT-4/1 line for different strains of the virus. The use of each of the substances separately showed a more significant inhibition of viral activity in MT-4/1 than in MT-4/2 cells. When used together, the inhibition level was almost the same in all cases and ranged from 87‒96% for the MT-4/1 line and 83‒89% for the MT-4/2 line. High efficacy was observed when using lower concentrations of drugs compared to individual use. Conclusion. The combined use of NRTIs 6НР and 3TС is promising for the treatment of HIV-infected patients at different stages of infection and with different levels of viral load.