Background Lymphoma is a hematologic malignancy that occurs at a higher rate among individuals infected with the human immunodeficiency virus (HIV). HIV-associated lymphomas (HAL) are typically aggressive and heterogeneous. Despite advances in antiretroviral therapy (ART), real world data from the Middle East remain limited. In this study, we present a retrospective analysis of HIV-associated lymphoma cases managed at a tertiary center in Saudi Arabia, with a focus on subtype specific outcomes, ART status, associated infections and treatment response.

Methods Retrospective data were collected for 22 HIV-positive patients with lymphoma diagnosed between January 2017 and March 2025 at a tertiary center in Riyadh, Saudi Arabia. Clinical, pathological and treatment related data were collected from medical records. Overall survival (OS) was calculated from the date of diagnosis to death or last follow-up using the Kaplan-Meier method.

Results This study included 22 patients of whom 21 were male and 1 female. The median age at diagnosis was 41 years (range 20–79). B symptoms were reported in 86% and 19 patients (68%) had stage III–IV disease. Nearly all (94%) had elevated LDH levels. Median IPI score was 2 (range 1–4) and CNS-IPI was 3. Median CD4 count at diagnosis was 60 cells/μL (range 5–147) and about 12 patients (54.5%) were already started on ART. HIV viral load was detectable in 88%, 12 of these patients had >10,000 copies/ml. We noted associated infections included CMV in 9 (41%), EBV in 8 (36%) and HBV in 5 (23%). Regarding lymphoma type, DLBCL was the most common (10 patients, 45.5%), followed by plasmablastic lymphoma in 5 (22.7%), PCNSL in 4 (18.2%), Burkitt lymphoma in 2 (9%) and one case of T-cell lymphoma (4.6%). CNS involvement was documented in 7 patients, while 15 patients had extranodal disease. Chemotherapy regimens varied by subtype, R-CHOP was most used (8 patients, 36.4%). Five patients (22.7%) received HD-MTX and 3 (13.6%) received dose-adjusted EPOCH. MATRix was given to 2 and one received Dara-CODOX-M/IVAC regimen. Rituximab was included in 16 cases (72%). Only one patient underwent ASCT and remained in remission. Two patients died of septic shock before chemotherapy. Of the 18 evaluable patients, 11 (61.1%) achieved complete remission (CR), 3 (16.7%) had partial remission (PR) and 4 (22.2%) had refractory or progressive disease. Median overall survival (OS) was 12.2 months. Survival at 1-year and 2-year were 59.1% and 40.9%, respectively. By lymphoma subtype, plasmablastic lymphoma had the worst prognosis, with a median OS of 4.8 months and no patients surviving beyond two years. Burkitt lymphoma had better outcomes; median OS was not reached and 2-year OS was 66.7%.

Conclusions Our findings highlight the aggressive behavior of HIV-associated lymphomas, which remain a major clinical challenge despite the availability of ART. Most patients presented with low CD4 counts and advanced disease. While the combination of frontline chemoimmunotherapy with ART resulted in prolongation of overall survival, management of relapsed and refractory cases remains difficult and represents an area of unmet need. Notably, our overall survival was lower than what has been reported in global cohorts. To our knowledge, this is the first study of its kind from the Middle East. Ongoing efforts are essential to refine treatment approaches and improve long term outcomes in this high-risk population.

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2025
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