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Review Details Current Understanding, Future Directions of DLBCL in Patients With HIV


Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin subtype in individuals living with HIV.

A new review highlights the characteristics, treatment, and prognosis of diffuse large B-cell lymphoma (DLBCL) in people living with HIV (PWH).

Due to potential interactions and overlapping toxicities of antiretroviral and antineoplastic drugs, authors stress that collaboration between HIV specialists and hemato-oncologists is crucial for treating PWH with non-Hodgkin lymphoma (NHL).

The review’s findings were published in Cancers.

HIV-related lymphomas are a major cause of morbidity and mortality in individuals living with HIV, while DLBCL “is the most common NHL subtype in PWH,” the researchers explained.

Prior to the introduction of combined antiretroviral therapy (cART), patients with this condition were typically treated with standard-dose chemotherapy. However, toxicity rates were high and outcomes were poor. What’s more, before this treatment was introduced, PWH had a 60- to 200-fold increased risk of developing NHL compared with a healthy population. The risk of developing DLBCL specifically was 98 times greater in PWH than in the general population.

From 1986 to 1995, DLBCL had an incidence rate of 63% in PWH, but this fell to 35% to 37% in the late-cART era of 2006 to 2015.

The advent of cART resulted in enhanced immunity, superior functional status, and a greater tolerability to chemotherapy among individuals with HIV-related NHL. It also contributed to a delayed age at DLBCL diagnosis. However, the condition still occurs earlier in this cohort of patients than in the general population.

“Patients with HIV-related DLBCL are currently treated with the same regimens as those given to the general population, achieving similar response rates,” the authors noted.

Despite these outcome improvements, PWH who also have DLBCL have different survival rates than those in the general population with only DLBCL. In addition, it’s been shown that NHL in individuals with HIV is associated with other viral infections, like Epstein–Barr virus. Around 31% of PWH and DLBCL test positive for Epstein-Barr virus.

Although an infection with HIV raises the risk of NHL, “retrospective specific epidemiology data about DLBCL in PWH are hard to find nowadays, due to most of the studies reporting heterogeneous data about NHL or lymphoid neoplasms in general,” the researchers said.

Studies have been able to show HIV-related DLBCL is more common among men. Risk factors of developing NHL in those with HIV include a high viral load and low CD4+ T-cell count.

DLBCL in patients with HIV does present with some unique characteristics compared with the general population. For example, these patients have more frequent plasmacytoid features, and DLBCL of the central nervous system in patients living with HIV is also typically of the immunoblastic type.

The central nervous system is involved in around 13% to 20% of HIV-related NHL cases, the authors wrote. Because of this, “for most patients with HIV-related DLBCL, staging should also include evaluation for CNS involvement, with cytologic and flow cytometric analysis of the cerebrospinal fluid.”

However, more research is needed to better understand the differences between DLCBL in PWH and the general population, the researchers said.

When it comes to the treatment of relapsed/refractory HIV-related lymphomas, the researchers caution several factors should be taken into consideration before turning to allogeneic hematopoietic stem-cell transplantation. These include immunosuppressive drug and antiretroviral agent interactions, the potential of graft-versus-host disease, and the high risk of infectious complications.

Overall, “the inclusion of PWH treated with cART in clinical trials and the implementation of novel therapies in this group of patients are still a challenge,” the authors concluded. “Interdisciplinary collaboration between hematologists and HIV specialists is crucial for the optimal treatment of both conditions, minimizing risk of adverse outcomes in the patient.”


Huguet M, Navarro JT, Moltó J, Ribera JM, Tapia G. Diffuse large B-cell lymphoma in the HIV setting. Cancers. Published online June 15, 2023. doi:10.3390/cancers15123191

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