Risk Factors for Cancer Mortality among People with HIV

Risk Factors for Cancer Mortality among People with HIV

SUMMARY: HIV positive people on antiretroviral therapy are more likely to die after cancer diagnosed if they have poor immune function as indicated by a low CD4 T-cell count or are unable to achieve undetectable viral load, according to a study published in the December 14, 2010 advance online edition of AIDS. Regular cancer screening starting at a younger age and prompt treatment could help improve survival in this population, investigators advised.

By Liz Highleyman

Several studies since the advent of effective combination antiretroviral therapy (ART) have indicated that people with HIV have a higher overall risk of cancer compared with their HIV negative counterparts.

Incidence of the AIDS-defining cancer Kaposi sarcoma (KS) has declined dramatically, but rates of some other cancers -- including anal cancer, liver cancer, and lung cancer -- have risen as HIV positive people live longer. This is especially true for cancers with infectious causes, for example human papillomavirus (HPV) for anal cancer and hepatitis B or C for liver cancer.

Chad Achenbach from Northwestern University and colleagues conducted a multi-site cohort study to evaluate survival and predictors of mortality after cancer diagnosis among more than 20,000 HIV positive individuals on combination ART. They analyzed all-cause mortality among patients receiving routine care at 8 U.S. clinical sites who were diagnosed with cancer between 1996 and 2009.

Cancers were classified as AIDS-defining (KS, non-Hodgkin lymphoma, and invasive cervical cancer) or non-AIDS defining cancers; the latter were divided into those related or unrelated to viral coinfections.

Results

Out of 20,677 people in the cohort, 1454 participants overall and 650 patients on combination ART were diagnosed with invasive cancer:

	AIDS-defining cancers: 49%;
	Non-infection-related non-AIDS cancers: 34%;
	Infection-related non-AIDS cancers: 17%;

Patients diagnosed with cancer had the following characteristics:

	Median age: 44 years;
	Median CD4 count at ART initiation: 47 cells/mm3.
	Median CD4 count at cancer diagnosis: 207 cells/mm3.
	38% smokers;
	21% with hepatitis B or C coinfection;
	18% current or past injection drug users;
	15% alcohol use issues.

46% of cancers were advanced (stage IV), indicating late diagnosis.

305 of patients with cancer died during a total of 1480 person-years of follow-up, for a crude mortality rate of 20.6 per 100 person-years.

The highest mortality rates were observed for the following types of cancer:

	Primary central nervous system non-Hodgkin lymphoma: 90.6 per 100 person-years;
	Liver cancer: 84.3 per 100 person-years;
	Lung cancer: 68.1 per 100 person-years.

Overall survival was 58% at 2 years after cancer diagnosis.

After adjusting for other factors, the risk of death was significantly higher among participants who were older and had stage IV cancer.

Conversely, the adjusted risk of death was lower among people with the following factors:

	Higher CD4 cell count at the time of cancer diagnosis;
	HIV RNA suppression (<400 copies/mL) on combination ART;
	Received any type of cancer treatment;
	Had AIDS-defining cancer (vs non-AIDS-defining);
	Had infection-related non-AIDS cancer (vs infection-related).

"Independent predictors of mortality after cancer diagnosis among HIV-infected persons include poor immune status, failure to suppress HIV RNA on combination ART, cancer stage, and lack of cancer treatment," the investigators concluded.

"Modification of these factors with improved strategies for the prevention and treatment of HIV and HIV-associated malignancies are needed," they recommended.

"HIV-infected individuals may require novel cancer prevention and treatment strategies that incorporate key prognostic factors such as those found in our study," they added in their discussion, including HIV viral load suppression, prevention of CD4 cell decline, and cancer screening starting at a younger age than the general population.

Investigator affiliations: Feinberg School of Medicine, Division of Infectious Diseases, and Center for Global Health, Northwestern University, Chicago, IL; Gillings School of Global Public Health, Department of Epidemiology, and Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC; University of Washington Department of Medicine; Center for AIDS Research; Department of Epidemiology, University of Washington, Seattle, WA; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Medicine and Center for AIDS Research, University of Alabama at Birmingham, Birmingham, AL.

1/7/11

Reference
CJ Achenbach, SR Cole, MM Kitahata, and others. Mortality after cancer diagnosis in HIV-infected individuals treated with antiretroviral therapy. AIDS (Abstract). December 14, 2010 (Epub ahead of print).