Aggregation behavior of conventional surfactants; SDS (anionic) and CTAB (cationic) in aqueous medium has been investigated in the presence of anti-HIV drugs; Emtricitabine (ECT) and Lamivudine (LMV) using conductometry, UV–Visible spectroscopy, and fluoroscence measurements over a temperature range of T = (298.15–313.15) K. The CMC values calculated from the conventional study i.e. conductance measurements corroborate very well with those obtained from spectroscopic techniques i.e. UV–Visible spectroscopy and fluorometry. The calculated CMC values have been used to determine thermodynamic parameters such as standard changes in enthalpy of micellization (ΔHmo), entropy of micellization (ΔSmo) and free energy of micellization (ΔGmo) using pseudo-phase separation model. These parameters have been analyzed in terms of the hydrophobic-hydrophilic interactions present in the surfactant-water-drug ternary system. It has been observed from the thermodynamic analysis that both the drugs favor micellization of studied ionic surfactants (SDS and CTAB) in aqueous medium, with Lamivudine exhibiting a more pronounced effect. Further, the micellar stability of studied systems has been analyzed in terms of enthalpy-entropy compensation graphs. This in-depth exploration of anti-HIV drug-surfactant interactions holds promising implications for enhancing pharmaceutical formulations in the context of HIV infection diseases. Display omitted