AT AIDS 2016

DURBAN, SOUTH AFRICA (FRONTLINE MEDICAL NEWS) – The rates of the AIDS-defining cancers Kaposi’s sarcoma and non-Hodgkin’s lymphoma have plummeted in the antiretroviral era, yet they are still the two top cancers in terms of cumulative incidence in HIV-infected patients by age 75, Benigno Rodriguez, MD, said at the 21st International AIDS Conference.

Lung cancer also remains a major concern in the HIV-infected population. Each of these three cancers carries about a 1 in 25 lifetime risk to age 75, the estimated lifespan of HIV-positive patients on combination antiretroviral therapy (ART), according to Dr. Rodriguez of Case Western Reserve University in Cleveland.

ART has resulted in a marked change in cancer trends among HIV-infected patients. The incidence of AIDS-defining cancers has decreased “massively,” Dr. Rodriguez observed; but because ART has extended the lifespan, patients are now living long enough to get other cancers. And they do so at a higher rate than that of the general population because of their impaired immune function, higher rate of risk factors such as smoking, and greater prevalence of oncogenic viral coinfections such as hepatitis B and C and Epstein-Barr virus.

The increase in the incidence and risk of colorectal, liver, and anal cancers among HIV-positive individuals since the introduction of combination ART can largely be explained by the population’s longer exposure to risk due to increasing survival, he said.

Dr. Rodriguez presented highlights of an analysis of cancer trends in North America during 1996-2009. The study was based on 86,620 HIV-infected persons with 475,660 person-years of follow-up and 196,987 subjects without HIV infection and with more than 1.8 million person-years of follow-up. Trends over time were assessed for nine cancers: Kaposi’s sarcoma, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, and melanoma, as well as anal, lung, colorectal, liver, and oropharyngeal cancers ( Ann Intern Med. 2015;163:507-18 ).

Examining trends in three periods – 1996-1999, 2000-2004, and 2005-2009 – the investigators looked at the impact of ART over time on rates of AIDS-related and non–AIDS-related cancers in HIV-infected patients and compared them to results in the general HIV-uninfected population.

By conducting a competing risk analysis, Dr. Rodriguez and his coworkers were able to estimate the cumulative lifetime risk of the various cancers by age 75, a metric that provides readily understandable information for counseling HIV-infected patients about their long-term cancer risk.

The measure “is more intuitive than using incidence rates,” Dr. Rodriguez said. In a study of 1,578 HIV-infected patients who received the hepatitis B vaccine, for example, those patients whose immune function did not to respond to the vaccine were more likely to be among the 6% of patients who subsequently developed cancer during up to 20 years of follow-up.

The findings on cancer trends in the ART era have clinical implications for cancer screening and prevention in HIV-infected patients. The high rates of smoking and lung cancer in this population make HIV-positive smokers a logical target for lung cancer screening. The rising risk of colorectal cancer – the cumulative lifetime risk to age 75 was 0.4% in 1996-1999, 0.7% in 2000-2004, and 1.3% in 2005-2009 – suggests a need for increased colorectal cancer screening in the older HIV-positive population.

Early and sustained HIV suppression with combination ART remains the only known method of preventing AIDS-defining cancers. Dr. Rodriguez and his coinvestigators in the Centers for AIDS Research Network of Integrated Clinical Systems demonstrated the crucial role of suppressing HIV in a study of 6,036 HIV-infected patients who started on ART and were followed for more than 21,000 person-years. Compared with HIV-infected patients with a 3-month lagged HIV viremia of no more than 50 copies/mL, patients’ risk of developing non-Hodgkin’s lymphoma was 2.1-fold greater if their 3-month lagged HIV viremia was 51-500 copies/mL and 3.56-fold greater if it exceeded 500 copies/mL ( Clin Infect Dis. 2014 Jun;58[11]:1599-606 ).

The study on cancer trends over time was funded by the National Institutes of Health. Dr. Rodriguez reported receiving honoraria from Gilead Sciences.