Intermittent ART Raises Risk for AIDS-Associated Malignancy

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Summary and Comment

Intermittent ART Raises Risk for AIDS-Associated Malignancy

SMART study participants who received intermittent ART had elevated rates of Kaposi sarcoma, lymphoma, and lung cancer, but the numbers were too small for results to be statistically significant.

The SMART study (stopped prematurely in 2006) outlined the substantial risks associated with intermittent antiretroviral therapy (ART) designed to keep CD4 counts above 250 cells/mm³ (ACC Nov 29 2006). A separate report now describes the patterns of malignancies seen in this study.

During 4 years of follow-up, 71 malignancies were diagnosed among the 5472 study participants. Thirteen were AIDS-defining malignancies: 8 Kaposi sarcomas, 3 non-Hodgkin lymphomas, and 2 Hodgkin lymphomas. The risk for any AIDS-defining malignancy was significantly higher with intermittent antiretroviral therapy (ART) than with continuous ART, although no significant differences were seen for specific types of such malignancies. The strongest predictor of developing an AIDS-defining malignancy was having experienced a previous one: 7 of the 13 patients who developed Kaposi sarcoma or lymphoma had a history of one of these conditions before enrolling in the study.

Most non–AIDS-defining malignancies (including skin, prostate, and colon cancer) were diagnosed with similar frequency in both arms of the study. Lung cancer diagnoses were more common in the intermittent-treatment group, but the difference did not reach statistical significance.

Nineteen study participants died of cancer (3 of AIDS-defining malignancies and 16 of non–AIDS-defining malignancies), but no significant differences in cancer mortality could be established between the treatment arms.

Comment: Despite this study’s size, not enough cancer cases occurred for researchers to fully describe patterns of malignancy associated with intermittent ART. However, intermittent treatment does seem to have been particularly risky for patients with histories of AIDS-related malignancies (which can develop even in patients with relatively high CD4-cell counts). The suggestion of a higher rate of lung cancer in the intermittent-treatment group is interesting; it recalls data from other sources that suggested that uncontrolled HIV infection may be an independent risk factor for lung cancer (ACC Jul 2 2007).

— Abigail Zuger, MD

Published in AIDS Clinical Care September 24, 2007