Investigating the combination of Temsavir and entry inhibitors on HIV replication: Synergistic and antagonistic effects observed against various R5-tropic envelopes

HIV is still a pandemic; antiretroviral therapeutics for preventing and treating HIV infection continue to present significant challenges. The demand for new drugs and effective treatments remains ongoing. Here, we investigated the effects of combining Temsavir with other HIV entry inhibitors, including CD4 mimetic BNM-III-170, T20 or enfuvirtide, Ibalizumab, and Maraviroc. Our results show that TMR demonstrates both synergistic and antagonistic activity when combined those other entry inhibitors, depending on the concentration and the specific envelope used. Results suggest that while low-dose combinations, especially using Temsavir and CD4 mimetic, exhibited antagonistic effects, Temsavir showed synergy at low and medium concentrations in combination with enfuvirtide, Ibalizumab, and Maraviroc. These results are promising for the potential of co-administrating antiretrovirals for HIV treatment and highlights the importance of developing advanced antiviral strategies. On the other hand, the variable responses against different R5-tropic envelopes underscore the complexity of designing universally effective combination antiviral therapies.