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Mortality High With Non-AIDS Cancers in EuroSIDA Despite HAART
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12th European AIDS Conference, November 11-13, 2009, Cologne, Germany
Mark Mascolini
More than 40% of EuroSIDA cohort members with a non-AIDS cancer died during 1.5 years of follow-up, and the cancers caused most of those deaths [1]. Higher CD4 count at cancer diagnosis lowered the death risk, while smoking, anemia, and injecting drug use raised the risk.
Non-AIDS cancers emerged as a leading cause of death in HIV-infected people when highly active antiretroviral therapy (HAART) began controlling opportunistic infections and AIDS malignancies [2-4]. In the prospective D:A:D cohort study, lower CD4 count, older age, current or past smoking, active HBV infection, earlier calendar year, and longer treatment with antiretrovirals predicted a higher risk of death with a non-AIDS cancer [2].
This new EuroSIDA study involved 305 people diagnosed with a non-AIDS cancer after entering the cohort. Oncogenic viruses accounted for 47% of these cancers (including anal and other HPV-associated cancers, Hodgkin lymphoma, and liver cancer), epithelial cancers (including gastrointestinal, lung, breast, and prostate cancer) accounted for 40% of non-AIDS cancers, and other cancers (including melanoma and hematologic cancers) accounted for 13%. The investigators had to make these groups because they would not have enough statistical power to yield useful data if they analyzed individual cancers.
Of the 305 cohort members with a non-AIDS cancer, 281 (92%) were taking HAART when diagnosed with cancer. Most study participants (83%) were men, and 57% got infected with HIV through gay sex. Median age at cancer diagnosis stood at 42 (interquartile range [IQR] 33 to 49), and median CD4 count measured 300 (IQR 190 to 501). Half of the study group smoked, and 43% had anemia.
Through a median follow-up of 1.5 years (IQR 0.5 to 4.1), 129 people (42%) died. At 2 years of follow-up, 36% with a viral cancer, 40% with an epithelial cancer, and 49% with "other" cancers had died. Of the 95 people with a known cause of death (74% of 129), the non-AIDS cancer caused 78 deaths (82% of 95). Thus non-AIDS malignancies caused at least 60% of the 129 deaths in this study group.
Statistical analysis accounting for numerous risk factors determined that people with epithelial and "other" cancers had an 84% higher death risk than people with viral cancers (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.06 to 3.22). The investigators proposed that the more invasive nature of epithelial and "other" cancers and the relative lack of effective treatment for these cancers explain the higher mortality. French researcher Dominique Costagliola suggested that the EuroSIDA team should weigh the individual impact of lung and liver cancer in this cohort, since those cancers account for most non-AIDS cancers in the French HIV population.
Ever smoking more than doubled the death risk in this study group (HR 2.20, 95% CI 1.06 to 4.54), while anemia almost doubled the risk (HR 1.87, 95% CI 1.0 to 3.51). Getting infected with HIV by injecting drugs (rather than gay sex) doubled the risk of death, but this association stopped short of statistical significance (HR 2.09, 95% CI 0.97 to 4.05).
Every CD4 count doubling cut the death risk by one third (HR 0.66, 95% CI 0.55 to 0.78). Starting combination antiretroviral therapy did not independently affect the risk of death in this analysis, which factored in HCV or HBV infection, gender, race, age, baseline viral load, AIDS, and year of cancer diagnosis.
The EuroSIDA investigators noted that this analysis is limited by lack of data on chemotherapy or surgery for cancer, as well as sparse data on some risk factors.
References
1. Kosa C, Reekie J, Bogner JR, et al. Survival and prognostic factors for patients with non-AIDS-defining malignancies (NADM). 12th European AIDS Conference. November 11-13, 2009. Cologne, Germany. Abstract PS3/3.
2. Monforte A, Abrams D, Pradier C, et al; Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study Group. HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS-defining malignancies. AIDS. 2008;22:2143-2153. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715844/?tool=pubmed.
3. Grulich AE. Cancer: the effects of HIV and antiretroviral therapy, and implications for early antiretroviral therapy initiation. Curr Opin HIV AIDS. 2009;4:183-187.
4. Stebbing J, Duru O, Bower M. Non-AIDS-defining cancers. Curr Opin Infect Dis. 2009;22:7-10.
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