The risk of Hodgkin's lymphoma and anal, liver and lung cancers all remain higher for HIV-positive than HIV-negative individuals in the post-HAART era, according to an analysis of US veterans. Results were presented as a poster at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago this week.
These non-AIDS-defining cancers were commonly occurring at CD4 cell counts that would not automatically lead a doctor to recommend treatment based on current guidelines, and in the case of prostate cancer, half of diagnoses occured in people with CD4 cell counts above 350 cells/mm3, the upper threshold of immune damage at which many people might be offered HIV treatment.
The incidence of the AIDS-defining cancers Kaposi’s sarcoma and non-Hodgkin’s lymphoma has fallen significantly since effective antiretroviral therapy became available. However, there has been no such fall in new diagnoses of some non-AIDS-defining cancers in HIV-positive patients.
Indeed, there is evidence that the incidence of certain malignancies has actually increased in recent years, possibly because of long-term immunosuppression (see recent reports from the 2007 IAS conference and a meta-analysis published recently).
Investigators from the US Department of Veterans’ Affairs wished to see if rates of non-AIDS-defining cancers were higher amongst HIV-positive patients than their age, gender and race matched HIV-negative peers.
Electronic medical records were used to identify HIV-positive and matched HIV-negative patients who received care at Veterans’ Affairs facilities between 1997 and 2004 (within the "HAART era".) Diagnoses of malignancies (cancers) were identified; the resultant incidence rates for malignancies were compared between HIV-positive and HIV-negative individuals. Only newly diagnosed malignancies were included; patients with previous diagnoses were excluded from the analysis.
A total of 33,420 HIV-infected patients were followed for a median of 5.1 years, with 66,840 HIV-negative individuals followed for a median of 6.4 years.
Incidence rates of non-AIDS-defining cancers were 1260 per 100,000 person years in HIV-positive patients and 841 per 100,000 person years in HIV-negative patients. This corresponds to a 60% greater risk of developing a non-AIDS-defining cancer for HIV-positive versus HIV-negative patients (incidence rate ratio [IRR], 1.6; 95% CI: 1.5 – 1.7).
The incidence of anal cancer (IRR 14.9; 95% CI: 10.1 – 22.1), Hodgkin’s lymphoma (IRR: 4.6; 95% CI: 3.6 – 6.6), liver cancer (IRR: 2.8; 95% CI: 2.2 – 3.5), and lung cancer (IRR 2.0; 95% CI: 1.7 – 2.2) were particularly elevated in HIV-positive individuals compared to HIV-uninfected patients.
Investigators then compared the CD4 cell counts of HIV-positive patients who developed non-AIDS-defining cancers with the CD4 cell counts of those HIV-infected patients who remained cancer free. They found that median CD4 cell counts were significantly lower in HIV-positive patients developing anal cancer (154 cells/mm3 vs. 270 cells/mm3, p 3 vs. 270 cells/mm3, p = 0.03). However, development of prostate cancer was actually associated with a higher CD4 cell count (370 cells/mm3 vs. 270 cells/mm3, p
“In the highly active antiretroviral therapy era, the incidence of non-AIDS-defining malignancies is significantly higher among HIV-positive than HIV-negative veterans, adjusting for age, race and gender”, conclude the investigators.
They add, “some non-AIDS-defining malignancies appear to be associated with mild immunosuppression.”
Potential explanations include longer survival on HAART with only partial immune recovery, high incidences of active Epstein-Barr virus (EBV) – a virus that has been associated with some cancers, including types of non-Hodgkin's lymphoma – and human papillomavirus (HPV), some types of which are associated with risk of anal and cervical cancer. The researchers also speculated that there might be direct cancer-causing effects of long-term HIV infection.
Bedimo RJ et al. Incidence of non-AIDS-defining malignancies in HIV-infected vs. non-infected veterans in the HAART era: impact of immunosuppression. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, abstract H-1721, Chicago, 2007.