By Liz Highleyman

Research to date has produced conflicting data regarding the occurrence of AIDS-defining and non-AIDS-defining malignancies in the HAART era. It is known that declining immune function increases the risk of AIDS-defining cancers (non-Hodgkin's lymphoma, Kaposi's sarcoma, cervical cancer), but the effect of immune deficiency or HIV infection itself on non-AIDS-defining malignancies is uncertain.

At the 14th Conference on Retroviruses and Opportunistic Infections last week in Los Angeles, researchers reported results of an analysis of fatal cancer in the large international D:A:D (Data Collection on Adverse Events of Anti-HIV Drugs) study, which includes more than 23,000 HIV positive patients followed since 1999.

Results

• Out of 1246 total deaths, 305 were due to cancer:

- 193 (63%) due to non-AIDS-defining cancers (1.79 per 1000 person-years);
- 112 (37%) due to AIDS-defining cancers (1.05 per 1000 person-years).

• Fatal AIDS-defining malignancies were:

- non-Hodgkin's lymphoma: 82 cases;
- Kaposi's sarcoma: 28 cases;
- cervical cancer: 2 cases.

• The most common fatal non-AIDS-defining cancers were:

- lung cancer: 62 cases;
- gastrointestinal (e.g., stomach, liver) cancer: 41 cases;
- hematological cancer (e.g., Hodgkin's lymphoma): 20 cases;
- anal cancer: 20 cases;

• The risk of dying due to either AIDS-defining or non-AIDS-defining cancers increased with lower CD4 cell counts.

• Patients with non-AIDS-defining malignancies had a higher median CD4 cell count at the time of death (211 vs 75 cells/mm3) and a higher median nadir (lowest-ever) CD4 count (87 vs 30 cells/mm3) than those with AIDS-defining cancers.

• While increasing age was a risk factor for cancer overall, patients developed AIDS-defining cancers at a younger age than non-AIDS-defining cancers (43 vs 52 years).

• Tobacco smoking was a significant risk factor for lung cancer.

• Active hepatitis B virus (HBV) infection was a significant risk factor for liver cancer.

• Patients with previous non-fatal AIDS-related illnesses had a significantly greater likelihood of dying from AIDS-defining cancers.

• Overall rates of AIDS-defining and non-AIDS-defining cancers were significantly lower in 2004-2005 compared with 1999-2001.

• Patients who died of cancer had similar CD4 counts in both periods, suggesting that other factors (perhaps earlier diagnosis and/or more aggressive treatment) accounted for the difference.

Conclusion

The researchers concluded that among patients with access to potent antiretroviral therapy, deaths due to non-AIDS-defining cancers are now more common than deaths from AIDS-defining malignancies.

Since lower CD4 counts significantly increase the risk of fatal cancer, they recommended that "prevention of development of advanced immunodeficiency and continued focus on reducing known risk factors (including smoking cessation and treatment of chronic hepatitis B virus infection) appear to be key strategies to prevent fatalities caused by malignancies in HIV-infected populations."

03/09/07

Reference
A D'Arminio Monforte, D Abrams, C Pradier, and other. HIV-induced immunodeficiency and risk of fatal AIDS-defining and non-AIDS-defining malignancies: results from the D:A:D Study. 14th Conference on Retroviruses and Opportunistic Infections. Los Angeles. February 25-28, 2007. Abstract 84 (oral).

Additional D:A:D Study Articles

Protease Inhibitor Therapy Increases Risk of Myocardial Infarction: D:A:D Study

Limited Impact of Antiretroviral Therapy on Risk of Liver-related Death: The D:A:D Study

Metabolic and Adverse Events Report from the 13th CROI

HCV or HBV Coinfection Are Risk Factors for Liver-Related Death in the D:A:D Study

Lipid Profiles in HIV-Infected Patients Receiving Combination Antiretroviral Therapy

14th CROI Main Page