HIV-associated cancers less frequent in patients on ART

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Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) – two HIV-associated cancers – are less frequent, but still occur in patients undergoing antiretroviral therapy, according to a Northwestern University study.

Dr Chad Achenbach, assistant professor of medicine in the division of infectious diseases at Feinberg School of Medicine, Northwestern University co-authored the study. Achenbach is also a member of the Robert H Lurie Comprehensive Cancer Centre of Northwestern University.

Patients with HIV are at a much greater risk for developing Kaposi sarcoma and non-Hodgkin lymphoma because of a weakened ability to fight off other viral infections that may lead to these cancers. While the risk of these cancers has declined dramatically in recent decades thanks to antiretroviral therapy (ART), the incidence nonetheless remains significantly higher than in the general population without HIV.

In the observational study, which included close to 25,000 patients with HIV, investigators examined data starting from 1996, when potent combination ART came into widespread use, until 2011. They found that, as expected, the incidence of Kaposi sarcoma and non-Hodgkin lymphoma fell in the years after 1996.

But they also identified new trends in characteristics related to the diagnosis of these cancers. Over the course of the study, patients showed lower HIV RNA values and higher CD4 counts at the point of initial cancer diagnosis. A higher number of CD4 cells is typically a sign that the HIV virus is being controlled.

They also found that, over time, Kaposi sarcoma was more frequently diagnosed after a patient had initiated ART. (This wasn’t driven by an increase in the risk of cancer for patients on ART, but rather, by the growth in the portion of the HIV population receiving treatment.)

Overall, the investigators’ findings reveal that patients remain at risk for these HIV-associated cancers, even while responding well to HIV treatment.

The study also raises important questions for future research, including whether cases of Kaposi sarcoma and non-Hodgkin lymphoma that develop during HIV treatment are biologically or genetically different from those that arise when HIV is uncontrolled with profound immune defects. If so, it could indicate a need for finding new approaches to preventing, identifying and treating these cancers.

“This paper shows us the importance of studying the changing epidemiology of HIV-associated cancer in the current era of potent HIV therapies,” Achenbach said. “Interactions between the immune system and cancer are amplified in those with HIV. This gives us an opportunity to understand how a defective immune system alters cancer risk.”

Abstract
Purpose: The biology of HIV-associated cancers may differ depending on immunologic and virologic context during development. Therefore, an understanding of the burden of Kaposi’s sarcoma (KS) and non-Hodgkin lymphoma (NHL) relative to antiretroviral therapy (ART), virologic suppression, and CD4 count is important.
Patients and Methods: KS and NHL diagnoses during 1996 to 2011 were identified among patients with HIV infection in eight clinical cohorts in the United States. Among patients in routine HIV clinical care, the proportion of cases in categories of ART use, HIV RNA, and CD4 count at diagnosis were described across calendar time. Person-time and incidence rates were calculated for each category.
Results: We identified 466 patients with KS and 258 with NHL. In recent years, KS was more frequently diagnosed after ART initiation (55% in 1996 to 2001 v 76% in 2007 to 2011; P-trend = .02). The proportion of patients with NHL who received ART was higher but stable over time (83% overall; P-trend = .81). An increasing proportion of KS and NHL occurred at higher CD4 counts (P < .05 for KS and NHL) and with undetectable HIV RNA (P < .05 for KS and NHL). In recent years, more person-time was contributed by patients who received ART, had high CD4 counts and had undetectable HIV RNA, whereas incidence rates in these same categories remained stable or declined.
Conclusion: Over time, KS and NHL occurred at higher CD4 counts and lower HIV RNA values, and KS occurred more frequently after ART initiation. These changes were driven by an increasing proportion of patients with HIV who received effective ART, had higher CD4 counts, and had suppressed HIV RNA and not by increases in cancer risk within these subgroups. An improved understanding of HIV-associated cancer pathogenesis and outcomes in the context of successful ART is therefore important.

Authors
Elizabeth L Yanik, Chad J Achenbach, Satish Gopal, Anna E Coghill, Stephen R Cole, Joseph J Eron, Richard D Moore, W Christopher Mathews, Daniel R Drozd, Ayad Hamdan, Mary E Ballestas, Eric A Engels

Feinberg School of Medicine material
Journal of Clinical Oncology abstract


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