ICAAC: Incidence of non-AIDS-defining cancers remains higher for HIV-positive individuals despite HAART

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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.

Glossary

AIDS defining condition

Any HIV-related illness included in the list of diagnostic criteria for AIDS, which in the presence of HIV infection result in an AIDS diagnosis. They include opportunistic infections and cancers that are life-threatening in a person with HIV.

lymphoma

A type of cancer that starts in the tissues of the lymphatic system, including the lymph nodes, spleen, and bone marrow. In people who have HIV, certain lymphomas, such as Burkitt lymphoma, are AIDS-defining conditions.

matched

In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

human papilloma virus (HPV)

Some strains of this virus cause warts, including genital and anal warts. Other strains are responsible for cervical cancer, anal cancer and some cancers of the penis, vagina, vulva, urethra, tongue and tonsils.

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.

References

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.