Thursday, October 22, 2009

CD4 cell count below 500 increases cancer risk for patients with HIV

Maintaining a CD4 cell count above 500 cells/mm3 will protect HIV-positive patients from a range of AIDS-defining and non-AIDS-defining cancers, French investigators conclude in a paper published online on October 8th in The Lancet Oncology. The investigators analysed the rates of the seven most common cancers in people with HIV and found that CD4 cell count was the strongest risk factor for several of them. Most of the patients in the study, which included data collected between 1998 and 2006, were taking antiretroviral therapy. “Our results suggest that combination antiretroviral therapy would be most beneficial if it restores or maintains the CD4 cell count above 500 cells/mm3, thereby indicating earlier diagnosis of HIV infection and earlier treatment initiation”, comment the authors. Current guidelines recommend that HIV treatment should be started when a patient’s CD4 cell count is in the region of 350 cells/mm3. The findings of the French study will support the arguments of clinicians who believe that there will be additional survival benefits if treatment is started before a patient's CD4 cell count falls below 500 cells/mm3. Infection with HIV is associated with an increased risk of developing a number of cancers. Since effective HIV therapy became available there have been falls in the incidence of the AIDS-defining cancers Kaposi’s sarcoma and non-Hodgkin’s lymphoma, but the number of cases of several non-AIDS-defining cancers has increased. Many of these non-AIDS-defining cancers are linked to other infections, but it is unclear what role CD4 cell count, viral load and the use of antiretroviral therapy have in the development or prevention of several malignancies. Therefore investigators examined the French hospital HIV database to determine the incidence of the seven most common cancers in patients with HIV and their relationship with CD4 cell count, viral load and use of HIV treatment. These cancers were Kaposi’s sarcoma, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, lung cancer, liver cancer, cervical cancer and anal cancer. A total of 52,278 patients with 253,353 person years of follow-up were included in the analysis. HIV treatment was used by 73% of patients for the total period of follow-up between 1998 and 2006. Kaposi’s sarcoma was the most commonly diagnosed cancer (565 patients, incidence 2.32 per 100 person years). The next most common was non-Hodgkin’s lymphoma, which was diagnosed in 511 patients (incidence 2.09 per 100 person years), followed by lung cancer (207 cases, incidence 0.85 per 100 person years). There were also 149 cases of Hodgkin’s lymphoma (incidence 0.61 per 100 person years), 119 diagnoses of liver cancer (incidence 0.49 per 100 person years) and 74 cases of anal cancer (incidence 0.30 per 100 person years); cervical cancer was detected in 69 patients (incidence 0.93 per 100 person years). Most cancers developed approximately six to eight years after a patient was first diagnosed with HIV. However, both liver and anal cancer were associated with a longer duration of HIV infection, being diagnosed an average of ten years after diagnosis with HIV. Patients diagnosed with Kaposi’s sarcoma and non-Hodgkin’s lymphoma had low nadir and current CD4 cell counts (below 200 cells/mm3). Moreover, although half of the patients diagnosed with these malignancies were receiving antiretroviral therapy, they had a high viral load suggested frequent virological failure. HIV treatment was being used by two-thirds of patients diagnosed with non-AIDS-defining cancers. These patients had a median CD4 cell count of 244 cells/mm3, and median viral load was approximately 500 copies/ml. Nearly all the patients diagnosed with anal cancer were taking antiretroviral therapy. These individuals had a nadir CD4 cell count of 68 cells/mm3, had a long duration of diagnosed HIV infection, had spent an average of two years with a CD4 cell count below 200 cells/mm3, and a year with a viral load above 100,000 copies/ml. Median CD4 cell count at the time anal cancer was diagnosed was 276 cells/mm3. The investigators tested the risk factors for all seven cancers using 78 statistical models. These showed a clear relationship between CD4 cell count and the development of all the cancers with the exception of anal cancer. Indeed, the risk of these cancers was significantly increased for patients with a CD4 cell count between 350 and 499 cells/mm3 compared to patients with a CD4 cell count above 500 cells/mm3. A high viral load (above 100,000 copies/ml) was associated with an increased risk of AIDS-defining cancers, whereas the use of antiretroviral therapy, even when immunological and virologic responses were controlled for, was protective. The risk of anal cancer increased by 30% each year a patient had a CD4 cell count below 200 cells/mm3 (RR = 1.3; 95% CI, 1.2 to 1.5, p = 0.0001), and by 20% each year viral load was above 100,000 copies/ml (RR = 1.2; 95% CI, 1.1 to 1.14, p =0.005). Taking antiretroviral therapy reduced the risk of cervical cancer by 50% (RR = 0.5; 95% CI, 0.3 to 0.09, p = 0.03), and a higher CD4 cell count also significantly reduced the risk of this malignancy (p = 0.0002). “Immunodeficiency increased the risk of all the cancers that we investigated”, write the investigators, who suggest “immune deficiency would impair the ability of host cells to limit expansion of tumoral cells or viral replication”. The investigators emphasise that prompt diagnosis of HIV and the early initiation of antiretroviral therapy could cut the risk of cancer. They also suggest “access to cervical cancer screening programmes should be offered to all HIV-positive women, and cancer-specific screening programmes, such as for lung cancer and for anal cancer, need to be assessed in HIV-infected patients.”


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