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Changes in HIV-related cancers reflect changes in HIV patient care

The incidence of Kaposi’s sarcoma among HIV patients has declined in the antiretroviral era, but the cancers are now presenting in older patients, after treatment starts, and in patients who have undetectable levels of HIV RNA.

Changes were also seen in the appearance of non-Hodgkin lymphoma, which is now occurring in patients with higher CD4 counts and lower HIV viral loads.

Although the findings of this large database study were largely driven by the fact that more patients are on antiretroviral therapy (ART) and in active clinical care, biological forces may also be at work, wrote Elizabeth L. Yanik, PhD, of the National Cancer Institute, Rockville, Md., and her associates (Am J Clin Oncol. 2016 Aug 9. doi: 10.1200/JCO.2016.67.6999).

“For example, cancers that develop in patients with HIV infection after immune recovery may manifest genetic or epigenetic changes that facilitate evasion from the immune system … [and] given that human herpesvirus-8 and Epstein-Barr virus are genetically heterogeneous, another possibility is that patients in whom Kaposi’s or non-Hodgkin lymphoma develops after immune reconstitution may be infected with more pathogenic strains.”

Dr. Yanik and her colleagues mined data from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). The 24,901 patients have been followed from 1996-2011. Among them, 446 cases of Kaposi’s sarcoma (KS) and 258 cases of non-Hodgkin lymphoma (NHL) developed. Overall, KS and NHL incidence rates decreased 5% and 8% per year, respectively.

The proportion of KS diagnosed during routine care increased significantly, from 32% to 49%, reflecting the fact that more HIV patients continue to enter active clinical settings. The diagnostic setting of NHL did not change significantly over the study period, with 64% of cases being diagnosed in routine care in the latter years. From the beginning to the end of the study period, patient median age at diagnosis increased for both KS (from 37 to 42 years) and NHL (from 40 to 46 years).

The authors said this is a direct result of changing care patterns. “The proportion of KS cases diagnosed among patients who received ART increased not because KS incidence increased in patients who received ART but because of the growing fraction of the HIV population administered ART.”

As the study period progressed, more cases of KS appeared 6 months or longer after ART initiation, from 26% in the early years to 60% in the latter years. This change didn’t occur with NHL cases; 68% of them were diagnosed at least 6 months after ART began.

The mean CD4 count at diagnosis increased with time for both KS and NHL. During 2007-2011, 15% of KS cases and 24% of NHL cases were diagnosed at CD4 counts of 500 cells/mL or more, whereas less than half were diagnosed at CD4 counts less than 200 cells/mL, the authors observed.

Both cancers began to appear during periods of decreased viral load as the study progressed, although the decrease was only significant for NHL. However, from 2007 to 2011, 29% of KS cases and 51% of NHL cases were diagnosed when HIV RNA was suppressed to 500 copies/mL or lower.

Again, the authors related this to improved clinical care. “These clinical characteristics and the changes in the underlying HIV population are inherently related. Improvements in ART access and earlier initiation lead to earlier suppression of HIV RNA and, ultimately, higher CD4 counts,” they said.

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On Twitter @Alz_Gal

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The incidence of Kaposi’s sarcoma among HIV patients has declined in the antiretroviral era, but the cancers are now presenting in older patients, after treatment starts, and in patients who have undetectable levels of HIV RNA.

Changes were also seen in the appearance of non-Hodgkin lymphoma, which is now occurring in patients with higher CD4 counts and lower HIV viral loads.

Although the findings of this large database study were largely driven by the fact that more patients are on antiretroviral therapy (ART) and in active clinical care, biological forces may also be at work, wrote Elizabeth L. Yanik, PhD, of the National Cancer Institute, Rockville, Md., and her associates (Am J Clin Oncol. 2016 Aug 9. doi: 10.1200/JCO.2016.67.6999).

“For example, cancers that develop in patients with HIV infection after immune recovery may manifest genetic or epigenetic changes that facilitate evasion from the immune system … [and] given that human herpesvirus-8 and Epstein-Barr virus are genetically heterogeneous, another possibility is that patients in whom Kaposi’s or non-Hodgkin lymphoma develops after immune reconstitution may be infected with more pathogenic strains.”

Dr. Yanik and her colleagues mined data from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). The 24,901 patients have been followed from 1996-2011. Among them, 446 cases of Kaposi’s sarcoma (KS) and 258 cases of non-Hodgkin lymphoma (NHL) developed. Overall, KS and NHL incidence rates decreased 5% and 8% per year, respectively.

The proportion of KS diagnosed during routine care increased significantly, from 32% to 49%, reflecting the fact that more HIV patients continue to enter active clinical settings. The diagnostic setting of NHL did not change significantly over the study period, with 64% of cases being diagnosed in routine care in the latter years. From the beginning to the end of the study period, patient median age at diagnosis increased for both KS (from 37 to 42 years) and NHL (from 40 to 46 years).

The authors said this is a direct result of changing care patterns. “The proportion of KS cases diagnosed among patients who received ART increased not because KS incidence increased in patients who received ART but because of the growing fraction of the HIV population administered ART.”

As the study period progressed, more cases of KS appeared 6 months or longer after ART initiation, from 26% in the early years to 60% in the latter years. This change didn’t occur with NHL cases; 68% of them were diagnosed at least 6 months after ART began.

The mean CD4 count at diagnosis increased with time for both KS and NHL. During 2007-2011, 15% of KS cases and 24% of NHL cases were diagnosed at CD4 counts of 500 cells/mL or more, whereas less than half were diagnosed at CD4 counts less than 200 cells/mL, the authors observed.

Both cancers began to appear during periods of decreased viral load as the study progressed, although the decrease was only significant for NHL. However, from 2007 to 2011, 29% of KS cases and 51% of NHL cases were diagnosed when HIV RNA was suppressed to 500 copies/mL or lower.

Again, the authors related this to improved clinical care. “These clinical characteristics and the changes in the underlying HIV population are inherently related. Improvements in ART access and earlier initiation lead to earlier suppression of HIV RNA and, ultimately, higher CD4 counts,” they said.

[email protected]

On Twitter @Alz_Gal

The incidence of Kaposi’s sarcoma among HIV patients has declined in the antiretroviral era, but the cancers are now presenting in older patients, after treatment starts, and in patients who have undetectable levels of HIV RNA.

Changes were also seen in the appearance of non-Hodgkin lymphoma, which is now occurring in patients with higher CD4 counts and lower HIV viral loads.

Although the findings of this large database study were largely driven by the fact that more patients are on antiretroviral therapy (ART) and in active clinical care, biological forces may also be at work, wrote Elizabeth L. Yanik, PhD, of the National Cancer Institute, Rockville, Md., and her associates (Am J Clin Oncol. 2016 Aug 9. doi: 10.1200/JCO.2016.67.6999).

“For example, cancers that develop in patients with HIV infection after immune recovery may manifest genetic or epigenetic changes that facilitate evasion from the immune system … [and] given that human herpesvirus-8 and Epstein-Barr virus are genetically heterogeneous, another possibility is that patients in whom Kaposi’s or non-Hodgkin lymphoma develops after immune reconstitution may be infected with more pathogenic strains.”

Dr. Yanik and her colleagues mined data from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). The 24,901 patients have been followed from 1996-2011. Among them, 446 cases of Kaposi’s sarcoma (KS) and 258 cases of non-Hodgkin lymphoma (NHL) developed. Overall, KS and NHL incidence rates decreased 5% and 8% per year, respectively.

The proportion of KS diagnosed during routine care increased significantly, from 32% to 49%, reflecting the fact that more HIV patients continue to enter active clinical settings. The diagnostic setting of NHL did not change significantly over the study period, with 64% of cases being diagnosed in routine care in the latter years. From the beginning to the end of the study period, patient median age at diagnosis increased for both KS (from 37 to 42 years) and NHL (from 40 to 46 years).

The authors said this is a direct result of changing care patterns. “The proportion of KS cases diagnosed among patients who received ART increased not because KS incidence increased in patients who received ART but because of the growing fraction of the HIV population administered ART.”

As the study period progressed, more cases of KS appeared 6 months or longer after ART initiation, from 26% in the early years to 60% in the latter years. This change didn’t occur with NHL cases; 68% of them were diagnosed at least 6 months after ART began.

The mean CD4 count at diagnosis increased with time for both KS and NHL. During 2007-2011, 15% of KS cases and 24% of NHL cases were diagnosed at CD4 counts of 500 cells/mL or more, whereas less than half were diagnosed at CD4 counts less than 200 cells/mL, the authors observed.

Both cancers began to appear during periods of decreased viral load as the study progressed, although the decrease was only significant for NHL. However, from 2007 to 2011, 29% of KS cases and 51% of NHL cases were diagnosed when HIV RNA was suppressed to 500 copies/mL or lower.

Again, the authors related this to improved clinical care. “These clinical characteristics and the changes in the underlying HIV population are inherently related. Improvements in ART access and earlier initiation lead to earlier suppression of HIV RNA and, ultimately, higher CD4 counts,” they said.

[email protected]

On Twitter @Alz_Gal

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Changes in HIV-related cancers reflect changes in HIV patient care
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FROM THE JOURNAL OF CLINICAL ONCOLOGY

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Key clinical point: Kaposi’s sarcoma and non-Hodgkin lymphoma are appearing in older, less- immunosuppressed patients.

Major finding: From 1996-2011, median patient age at diagnosis increased for both Kaposi’s sarcoma (from 37 to 42 years) and non-Hodgkin lymphoma (from 40 to 46 years).

Data source: The database study examined 446 cases of Kaposi’s sarcoma and 258 cases of non-Hodgkin lymphoma.

Disclosures: The National Cancer Institute headed the study; Dr. Yanik had no financial disclosures.