Further research is needed to unravel the precise mechanisms underlying the contrasting effects of female sex hormones on HIV-1 sub-subtype A6, CRF02_AG, and subtype B. Continued investigation can shed light on the interplay between host factors, viral genetics, and viral replication. By understanding these subtype-specific interactions, healthcare providers and researchers can develop more effective therapeutic approaches and preventive interventions, ultimately advancing the goal of reducing HIV-1 transmission and improving patient outcomes. In conclusion, the replication activity of HIV- 1 sub-subtype A6 and CRF02_AG is influenced by female sex hormones, while HIV-1 subtype B is not affected. The contrasting effects highlight the complexity of HIV-1 replication and the importance of considering subtypespecific factors in therapeutic and preventive strategies. Further research is warranted to explore the underlying mechanisms and translate these findings into clinical applications.