Cancer is an increasingly important cause of death in people with HIV

Over a third of deaths in HIV-positive patients in France in 2005 were caused by cancers, investigators report in a study to be published in the March 1^st edition of Clinical Infectious Diseases (now online). This represents a significant increase in the proportion of cancer-related deaths amongst French HIV-positive patients since 2000.

The investigators suggest that better cancer prevention, monitoring and care could help reduce the amount of death caused by malignancies in patients with HIV, and also stress the importance of keeping the CD4 cell count of HIV-positive individuals above 250 cells/mm³.

Thanks to HIV treatment, there has been a significant fall in the amount of HIV-related illness and death seen in HIV-positive individuals in industrialised countries. Rates of the AIDS-defining cancers such as non-Hodgkin’s lymphoma and Kaposi’s sarcoma have also fallen.

However, as patients with HIV live longer, it is expected that conditions such as heart disease, liver problems and non-HIV-related cancers will become increasingly important causes of death.

In 2000, a survey of French hospitals (the Mortalite study) revealed that 12% of all deaths in HIV-positive individuals were attributable to non-HV-related cancer and that cancers accounted for 29% of all deaths in patients with HIV.

Investigators repeated this survey in 2005.

A total of 1042 deaths were reported in 2005 among the 78,000 individuals receiving HIV care at hospitals participating in the study. This compared to 964 deaths in 2000.

Details of 1013 were available for analysis by the investigators. Overall, 76% of deaths were in men, the median age was 46 years, and the median duration of diagnosed HIV infection was twelve years. Most of the patients (87%) had received HIV treatment and 47% had a viral load below 500 copies/ml at the time of death. Median CD4 cell count was 161 cells/mm³, indicating moderately severe immune suppression, this was, however, higher than the median CD4 cell count of only 90 cells/mm³ recorded in patients dying in 2000.

The most frequent cause of death was an AIDS-defining illness (total number, 377, 36%, a fall from 47% in 2000).

In all 344 (34%) deaths were cancer-related. This represented a significant (p = 0.02) increase on 2000 when 29% of deaths were cancer-related.

Further analysis showed that 17% of deaths were caused by cancers that were not related to either HIV or hepatitis. Patients dying of such cancers had a median age of 49 years, had been diagnosed with HIV for a median of twelve years, had a median CD4 cell count of 200 cells, and 55% had a viral load below 500 copies/ml at the time of death.

A total of 64 deaths were caused by respiratory cancers, including 53 caused by lung cancer and twelve by cancer of the nose or throat. There was no change in the proportion of deaths caused by respiratory cancers in 2005 (5%) compared to 2000 (6%). Lifestyle factors appear to have been an important factor in these deaths as 90% of those dying of respiratory cancers were smokers and 34% drank excessive amounts of alcohol.

There was a significant increase in the proportion of deaths caused by digestive cancers in 2005 compared to 2000. This included ten cases of pancreatic cancer compared to just three in 2000.

The investigators noted that there were seven cases of breast cancer in 2005 compared to none in 2000, and there was also an increase in the number of deaths attributable to skin cancer (ten in 2005 compared to two in 2000). There was no change in the number of deaths attributable to anal cancer.

Death from liver cancer was mainly associated with hepatitis C infection. This contrasted to 2000 when hepatitis B virus was also an important cause of liver cancer-related death.

There was no difference in the proportion of deaths caused by non-Hodgkin’s lymphoma between 2005 (11%) and 2000 (10%). The CD4 cell counts of individuals dying of these cancers in 2005 and 2000 were also comparable (86 cells/mm³ vs 76 cells/mm³). However, almost one-third of patients dying of this type of cancer had a CD4 cell count above 200 cells/mm³ at the time of death.

Kaposi’s sarcoma accounted for 4% of cancer deaths in 2005 compared to 3% in 2000, a non-significant change. Fewer than 1% of cancer deaths in both 2005 and 2000 were caused by cervical cancer.

“We demonstrated that malignancies accounted for more than one-third of the causes of death in this population of patients. We also demonstrated that the proportion of deaths attributable to malignancies increased significantly since 2000,”,write the investigators.

They also emphasise that “the proportion of non-AIDS-related cancers also increased significantly from 2000 to 2005”. Other studies, such as the D:A:D study, have also found that non-AIDS-defining cancers are an increasingly important cause of death in patients with HIV. The investigators note similarities between the findings of their study and that of the D:A:D study, particularly that the median CD4 cell count of patients dying of non-AIDS-defining cancers was in the region of 200 cells/mm³.

The investigators conclude that “cancer prevention, screening, early diagnosis and improved management and surveillance should be included in routine long-term follow-up of HIV-infected patients and should have some immediate impact on mortality.” They also stress the importance of keeping the CD4 cell counts of HIV-positive individuals above 250 cells/mm³.