Effect of Early HAART Initiation on Tumoral Response and Radiosurgery Outcomes in Primary CNS Lymphoma Patients with HIV/AIDS

Introduction: Primary central nervous system lymphoma (PCNSL) in patients with HIV/AIDS is difficult to treat due to severe immunosuppression, opportunistic infections, and reduced marrow reserve, which limit tolerance to intensive chemotherapy and radiotherapy. Radiosurgery offers a targeted treatment option, but its success depends on immune recovery, particularly adequate CD4 restoration through HAART. Additionally, molecular mediators such as MYC, CD44, and RGS13 influence tumor biology, immune evasion, and radiosensitivity, underscoring the need for an integrated therapeutic approach. Methods: We retrospectively analyzed 89 patients with HIV/AIDS-associated PCNSL who underwent stereotactic radiosurgery. Clinical variables included demographics, CD4 count at diagnosis and prior to radiosurgery, ART status, treatment combinations, and survival outcomes. Subgroup analyses stratified outcomes by CD4 thresholds (< 100 vs ≥ 100 cells/µL) and timing of HAART initiation. In addition, we explored the functional relevance of MYC, CD44, and RGS13 as described in prior patent publications and translational studies, focusing on their implications for proliferation, survival signaling, and therapeutic resistance. Results: Patients treated with radiosurgery alongside HAART had significantly better survival than those receiving radiosurgery alone. A CD4 count ≥ 100 cells/µL before treatment was key for durable response, local control, and survival. Early HAART initiation promoted immune recovery and enhanced radiosurgical benefit, consistent with guideline recommendations on optimizing immunity before cytotoxic therapy. Molecular findings linked MYC and CD44 to resistance and aggressiveness, while RGS13 may influence B-cell signaling and radiosensitivity. Conclusion: The study shows that immune restoration through HAART is essential for successful radiosurgery in HIV/AIDS-related PCNSL. Optimal outcomes require early HAART initiation and CD4 recovery (≥ 100 cells/µL), while radiosurgery alone is insufficient. Future trials should integrate radiosurgery with immune-based and molecularly guided strategies to improve survival.