Prompt treatment and better screening could prevent many cancer deaths in patients taking HIV therapy

Many cancer-related deaths in patients taking antiretroviral therapy are potentially preventable, a US study published in the online edition of AIDS suggests.

A low CD4 cell count, detectable viral load, late diagnosis of cancer, and not receiving cancer treatment were all associated with an increased risk of mortality.

“Our findings could be explained by poor cancer awareness, inadequate screening practices, or lack of prompt therapy,” write the investigators.

They suggest “HIV-infected individuals may require novel cancer prevention and treatment strategies that incorporate key prognostic factors such as those found in our study, including suppression of HIV RNA, prevention of CD4 cell decline and cancer screening initiated at younger age than in the general population.”

The investigators conducted their study because other research has shown that cancer is an increasingly important cause of death among people with HIV. They wished to identify the predictors of mortality in patients taking HIV therapy.

Their study population included 20,677 patients who received HIV care at eight sites across the US between 1996 and 2009.

Overall, 1454 patients were diagnosed with cancer and 650 were taking antiretroviral therapy at the time their malignancy was diagnosed. The cancers were diagnosed an average of three years after HIV therapy was started.

Almost half the cancers (49%) were AIDS-related, 34% were non-infection-related, and 17% were infection-related. Many of the cancers were diagnosed late (46% at stage IV).

At the time of cancer diagnosis, the patients had a median age of 44 years, 21% were co-infected with hepatitis B or C, 38% were smokers, 18% were injecting drug users, and 15% had alcohol dependency issues.

The patients had very weak immune systems when they started HIV therapy. Median CD4 cell count at this time was only 47 cells/mm³. Viral load was high at the time antiretroviral therapy was initiated (5.4 log₁₀ copies/ml).

CD4 cell count increased with antiretroviral treatment, but was still only 207 cells/mm³ at the time of cancer diagnosis. Overall, 85% of patients had a viral load of below 400 copies/ml at some time between initiating HIV therapy and the diagnosis of their cancer.

A total of 305 individuals died, and this provided a mortality rate of 20.6 per 100 person years.

Mortality rates were highest for non-Hodgkin lymphoma of the central nervous system (90.6 per 100 person-years), liver cancer (84 per 100 person-years), and lung cancer (68 per 100 person-years).

Factors associated with an increased risk of death were older age (p < 0.01), stage IV cancer at the time of diagnosis (p < 0.01), and a lower CD4 cell count at the time of diagnosis (p = 0.01).

Characteristics associated with improved survival were: receiving cancer therapy (p < 0.01), a viral load below 400 at the time of cancer diagnosis (p < 0.01) and diagnosis with an infection-related cancer (p < 0.01).

These findings were altered little when the investigators restricted their analysis to patients with a known cancer stage at the time of diagnosis, or to patients whose cancer was stage IV when it was detected.

“We found that in a large cohort of over 20,000 HIV-infected persons…more than 3% of patients receiving antiretroviral therapy develop cancer,” comment the researchers.

Many of the factors associated with an increased risk of death were potentially modifiable. Therefore, the investigators believe that their findings have implications for the treatment and care offered to HIV-positive patients. They write: “Our results support earlier initiation of combination antiretroviral therapy and aggressive cancer screening and treatment practices to maintain immunological function, obtain optimal viral suppression, control viral co-infections, detect cancer at an earlier stage, and provide appropriate cancer therapies.