September 16, 2009

The Role of HIV-Related Immune Depletion in Cancers

Having a CD4 count less than 500 was a significant additive factor in the risk of developing a non-AIDS-related cancer, according to a study published in the October 1 issue of Clinical Infectious Disease. Both low CD4 counts and high viral loads were implicated in an increased risk for AIDS-related cancers.

A number of non-AIDS-defining cancers—such as anal cancer and lung cancer—are on the rise recently in people living with HIV and appear to occur at higher rates than in HIV-negative people. Though researchers have identified some of the contributing factors for the increased risk, such as infection with human papillomavirus (HPV)—the cause of cervical and anal cancer—being more common in people with HIV, it is not entirely clear how HIV and its related immune dysfunction contribute to the increased risk.

To determine the impact of immune decline and viral replication on cancer risk, Mathias Bruyand, PhD, from the Institut National de la Santé et de la Recherche Médicale (INSERM) in Bordeaux, France, and his colleagues examined the medical records of 4,194 HIV-positive people enrolled in the ANRS Aquitaine Cohort study. During the course of the study period—January 1998 through December 2006—251 people developed at least one type of cancer. Of those individuals, 107 were diagnosed with an AIDS-defining cancer, such as Kaposi’s sarcoma or non-Hodgkin’s lymphoma, and 144 were diagnosed with a non-AIDS-defining cancer, such as lung cancer.

When Bruyand’s team looked at the factors associated with the development of cancer, they found that both a CD4 count less than 200 and a viral load more than 500 were associated with an increased risk for AIDS-related cancer. Moreover, the risk for cancer increased the longer a person spent with a CD4 count of less than 200.

For non-AIDS-related cancers, having a CD4 count below 500 was associated with developing this type of malignancy. Neither viral load nor antiretroviral (ARV) therapy was associated positively or negatively with the risk of developing non-AIDS cancers.

Of note, Bruyand and his colleagues found that currently having a low CD4 count, rather than a low CD4 count in the past that has since risen, was associated more strongly with an increased cancer risk. This means that people who once had CD4 counts below 500, but who went on HIV treatment and brought their CD4 counts back above 500, would theoretically reduce their risks of cancer.

In an accompanying editorial, Diego Serraino, MD, from the Istituto di Ricovero e Cura a Carattere Scientifico in Aviano, Italy, said that the data are an encouragement for both ARV therapy to help people maintain high CD4 counts and cancer prevention measures. “Combination of an appropriate antiretroviral regimen with prevention programs—antismoking campaigns and screening programs are, in my opinion, the priorities—is the main message of the study,” he wrote. “This is a message that I totally share.”

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