# Incidence of severe immune-related adverse reactions in patients with HIV and cancer receiving immune checkpoint inhibitors: a systematic review and meta-analysis

## TL;DR

This study finds that immune checkpoint inhibitors are generally safe for HIV-positive cancer patients, with a 9% risk of severe immune-related side effects.

## Contribution

The study provides the first meta-analysis of severe immune-related adverse events in HIV-positive cancer patients treated with immune checkpoint inhibitors.

## Key findings

- The pooled incidence of severe immune-related adverse events in HIV-positive cancer patients is 9%.
- CD4+ T cell count does not significantly affect the risk of severe immune-related adverse events in these patients.
- The safety profile of immune checkpoint inhibitors in HIV-positive patients is comparable to HIV-negative patients.

## Abstract

With the continuous advancement of various treatment modalities, such as antiretroviral therapy, the life expectancy of people living with HIV (PLWH) is approaching that of the general population. Consequently, the annual incidence of non-AIDS-defining malignancies in this population is increasing. Immune checkpoint inhibitors (ICIs) block T cell suppression, enabling T cells to kill tumor cells. They also restore the function of HIV-specific CD8+ T cells and enhance their ability to clear cells with latent HIV infection. However, it is unclear if this will create an immune imbalance in the PLWH population, thereby increasing the likelihood of more severe immune-related adverse events, which is a common concern. Thus, this study aimed to assess the incidence of serious immune-related adverse events associated with ICI use in PLWH with cancers. This will provide clinicians with reliable evidence to optimize therapeutic decisions and ensure patient safety.

A thorough systematic search of three major databases (PubMed, Embase, and Web of Science) was conducted from database inception to July 13, 2025. We extracted the necessary data and their corresponding 95% confidence intervals (CIs) for use in the subsequent meta-analysis. Statistical analyses were performed using the R software (version 4.5.1).

This meta-analysis included 18 studies involving 813 patients. The final results indicated that without considering CD4+ T cell counts, the incidence rate of severe immune-related adverse reactions was 9% (95% CI: 0.08–0.12). The rate is relatively close to the spectrum of irAE incidence observed with ICI therapy in HIV-uninfected cancer patients. We further stratified CD4+ T cell counts by extracting data from seven studies. The findings showed that the incidence of severe immune-related adverse events was 13% (95% CI: 0.08-0.21) in those with a CD4+ T cell count <200 cells/μL, versus 11% (95% CI: 0.09-0.15) in those with ≥200 cells/μL. There was no statistically significant difference between the two groups (p=0.4444).

Preliminary data from this study show that the pooled incidence of severe irAEs induced by ICIs is approximately 9% in ART-treated and clinically stable PLWH with cancer. The rate is relatively close to the spectrum of irAE incidence observed with ICI therapy in HIV-uninfected cancer patients. Furthermore, subgroup analysis based on CD4+ T cell count revealed no statistically significant difference in the incidence of severe irAEs between the groups. Therefore, current evidence does not indicate that baseline CD4+ T cell count is an absolute contraindication to ICI therapy in PLWH with cancer. Taken together, these findings provide preliminary support for an acceptable safety profile of ICIs in PLWH with cancer. Combined with observed preliminary antitumor activity, the results justify further prospective studies. However, the wider confidence interval for the incidence in the subgroup with CD4+ T cell count <200 suggests greater uncertainty in this population, warranting closer monitoring in clinical practice.