Real-world efficacy and safety of PD-1 inhibitors in patients living with HIV and cancer: a retrospective cohort study.

OBJECTIVE

Programmed cell death protein 1 (PD-1) inhibitors have established a cornerstone in cancer therapy; however, there remains a lack of data regarding their use in people living with human immunodeficiency virus (HIV) infection (PWH), especially in patients with low CD4+ T-cell counts or baseline detectable HIV RNA. This study assessed the real-world efficacy and safety of PD-1 inhibitors in PWH presenting with concurrent malignancies, specifically capturing individuals with advanced baseline immunosuppression (CD4+ T-cell count < 100 cells/μL, n = 4) or with detectable HIV RNA (n = 9).

METHODS

From January 2022 to December 2024, patients diagnosed with cancer and treated with PD-1 inhibitors (camrelizumab, sintilimab, or tislelizumab) were enrolled. The included population was divided into an HIV-positive group and an HIV-negative group based on HIV status. Demographic details, clinical data, and cancer status were collected. Using propensity score matching (PSM) to adjust for baseline imbalances, we compared median progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs) between the two groups. Cox regression analysis was conducted to evaluate the influence of multiple variables on treatment response.

RESULTS

From 90 enrolled patients (70 HIV-positive, 20 HIV-negative), PSM selected 56 (37 HIV-positive, 19 HIV-negative) for final analysis. The ORR and DCR were comparable between the HIV-positive and HIV-negative groups (16.2% vs. 15.8% and 51.4% vs. 47.4%, respectively). Median PFS was 11.5 months (95% CI: 6.8-16.2) for the HIV-positive group and 16.9 months (95% CI: Not evaluated (NE)-40.4) for the HIV-negative group. For the lung cancer subgroup, the ORR and DCR were 23.5% and 70.6% among 17 HIV-positive patients vs. 30.0% and 50.0% among 10 HIV-negative patients. The respective median PFS was 14.5 months (95% CI: 4.9-24.2) and 17.2 months (95% CI: NE-36.0). Multivariable Cox regression analysis confirmed that HIV status was not independently associated with PFS in the overall cohort. Among the four patients with low baseline CD4+ T-cell counts, the DCR was 25.0% (one stable disease [SD], three progressive disease [PD]). Among those with detectable baseline HIV RNA (n = 9), four achieved SD and five experienced PD, yielding no objective responses. In the matched cohort, TRAEs were predominantly grades 1-2; severe (grade ≥ 3) toxicities occurred in three of 56 patients (5.4%), all within the HIV-positive group. Four patients-all from the HIV-positive group-discontinued immunotherapy due to TRAEs. HIV virological control was maintained without rebound throughout the study; overall CD4+ T-cell counts remained largely stable, with all patients presenting with baseline advanced immunosuppression (CD4+ T-cell count < 100 cells/μL) demonstrating robust immune restoration by week 24.

CONCLUSION

This retrospective study indicated that PD-1 inhibitors are effective and generally well tolerated in PWH with concurrent malignancies. HIV status was not an independent prognostic factor for treatment outcomes, and robust immune restoration was achievable even in patients with advanced baseline immunosuppression. Although severe (grade ≥ 3) TRAEs and treatment discontinuations occurred exclusively within the HIV-positive cohort, overall toxicity rates remained low. Larger prospective studies are required to further validate these findings in patients with low CD4+ T-cell counts or unsuppressed viral loads.