Effective antiretroviral therapy alters the landscape
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"Over time, Kaposi's sarcoma and non-Hodgkin lymphoma occurred at higher CD4 counts (P<0.05) and lower HIV RNA values (P<0.05), and Kaposi's sarcoma occurred more frequently after ART initiation [defined as the first concurrent use of three or more different antiretroviral medications] (P=0.02 for trend)," investigators wrote in the Journal of Clinical Oncology.
"Patients and health care providers should maintain clinical vigilance for the development of Kaposi's sarcoma and non-Hodgkin lymphoma in patients with normal CD4 counts and low viral load," lead author Elizabeth Yanik, PhD, of the National Cancer Institute, Rockville, Md., told MedPage Today in an email.
Investigators identified 466 Kaposi's sarcoma diagnoses and 258 non-Hodgkin lymphoma diagnoses, including 135 diagnoses of diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma subtype. Overall, most cases were among white men.
Data were gathered from a population of 24,901 individuals with HIV in eight U.S. clinical cohorts that make up the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS), and categorized over three calendar periods, beginning with 1996 (when combination ART came into widespread use) to 2001, 2002 to 2006, and 2007 to 2011.
Median age at diagnosis increased over time from 37 years for Kaposi's sarcoma and 40 years for non-Hodgkin lymphoma (1996-2001), to 42 years for Kaposi's sarcoma and 46 years for non-Hodgkin lymphoma (2007-2011).
"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."
The proportion of cancers diagnosed following initiation of ART increased in recent years, investigators found. Kaposi's sarcoma diagnoses increased significantly, from 55% during 1996-2001 to 76% during 200-2011.
Overall, the proportion of patients with non-Hodgkin lymphoma who received ART was higher but stable over time (83% overall, and similar patterns were observed in the 82 DLBCL cases diagnosed during care. Of all non-Hodgkin lymphoma diagnoses, 68% occurred at least 6 months after ART initiation and this remained fairly consistent over time.
Data also reflected the expanding proportion of HIV patients in routine clinical care, which one study suggests has increased from 61% in 2000 to 82% in 2008; Yanik and colleagues reported that the proportion of Kaposi's sarcoma routine care diagnoses (n=196) increased from 32% in 1996 to 2001 to 49% in 2007 to 2011 (P=0.005 for trend), and the proportion of non-Hodgkin lymphoma diagnoses (n=150) remained relatively stable at 58%.
"The bottom line is that ART dramatically decreases the risk of cancer – particularly Kaposi's more so than lymphoma – but because we're seeing more people with HIV infection living longer ... clinicians need to be aware that even patients who are doing well on their HIV drugs may develop these cancers," said Paul Volberding, MD, in an interview with MedPage Today. Volberding, director of the University of California San Francisco AIDS Research Institute, was not involved in this study.
"If you see Kaposi's today in someone who is not yet on therapy, it will often go away when they start therapy, but patients who develop it while they're on antiretroviral therapy need the tumor treated directly," he added. "That's not an issue with lymphomas, which would be treated standard cancer chemotherapy."
It is still unclear whether HIV-associated cancers that develop among patients effectively treated with antiretroviral therapy differ biologically from cancers that develop among HIV patients not on therapy [who have uncontrolled viremia and severe immunosuppression], Yanik told MedPage Today. The JCO paper did not discuss treatment of these cancers.
In an editorial podcast that accompanied the paper by Yanik and colleagues, Richard Fowler Little, MD, a hematologist and oncologist in Bethesda, Md., suggested that Kaposi's sarcoma tumor biology may not necessarily be altered in the setting of high CD4 cell levels, and that ongoing HIV-related inflammatory factors may have a role, even in patients with undetectable HIV RNA and high CD4 cells. He also pointed to a possible role for viral epitodes directed against human herpesvirus-8, which confer the risk of Kaposi's sarcoma even in HIV negative patients. Finally, incomplete immunoreconstitution can allow opportunistic infections with Kaposi's sarcoma even in patients with CD4 cells in the normal range.
When treating lymphomas in these patients, Little cautioned HIV clinicians to collaborate closely with oncologists and to beware of drug-drug interactions, noting that protease inhibitors given with standard ABVD chemotherapy regimen (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine) may result in excessive toxicity. He recommended replacing protease inhibitors with one of the newer integrase strand transfer inhibitors.
This work was supported by the National Cancer Institute and the National Institutes of Health.
Some authors report consultancies, speaking fees, research grants and/or honoraria from ABIVAX, Gilead Sciences, Merck, Bristol-Myers Squibb, Janssen, AbbVie, ViiV Healthcare, Bristol-Myers Squibb, and Mallinckrodt.
Some authors report consultancies, speaking fees, research grants and/or honoraria from ABIVAX, Gilead Sciences, Merck, Bristol-Myers Squibb, Janssen, AbbVie, ViiV Healthcare, Bristol-Myers Squibb, and Mallinckrodt.
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Primary Source
Clinical Journal of Oncology
Source Reference: Yanik EL, et al "Changes in clinical context for Kaposi's Sarcoma and Non-Hodgkin lymphoma among people with HIV infection in the United States" J Clin Oncol 2016; DOI: 10.1200/JCO.2016.67.6999.
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