Delayed Start of HIV Therapy Tied to Small Increase in Risk of AIDS-Related Cancers

By Megan Brooks

March 16, 2021

NEW YORK (Reuters Health) - Delaying the initiation of antiretroviral therapy (ART) in HIV-positive patients is associated with a small increase in risk for AIDS-related cancer, according to new research that supports long-standing guidance to start ART immediately regardless of CD4 cell count.

Only about half of HIV-positive patients start ART when their CD4 cell count falls below 500 cells/L, "mainly due to late diagnosis of HIV. Our findings underline the importance of early HIV diagnosis and immediate lifelong antiretroviral therapy," Dr. Heiner Bucher, with University Hospital Basel, Switzerland, told Reuters Health by email.

Dr. Bucher and colleagues assessed the 10-year risk for non-AIDS-defining and AIDS-defining cancer with immediate versus deferred ART initiation (at CD4 counts <500 and <350 cells/L) in 8,318 HIV-positive adults (median age, 36 years) enrolled in a large, prospective, observational study.

During 64,021 person-years of follow-up, there were 231 cases of non-AIDS-defining and 272 cases of AIDS-defining cancer, they report in Annals of Internal Medicine.

At 10 years, with immediate ART initiation, the estimated risks for non-AIDS-defining and AIDS-defining cancer were 2.97% and 2.50%, respectively, versus 3.09% and 2.80%, respectively, when ART was delayed until the CD4 count was <500 cells/L, and 3.27% and 3.51%, respectively, when ART was delayed until a CD4 count of <350 cells/L.

Compared with starting ART immediately, the 10-year absolute risk differences for non-AIDS-defining and AIDS-defining cancer were 0.12 percentage point and 0.32 percentage point, respectively, for starting ART at a CD4 count <500 cells/L and 0.29 percentage point and 1.00 percentage point, respectively, for starting at a CD4 count <350 cells/L.

"Delayed initiating of antiretroviral therapy is likely to increase the risk of AIDS-defining cancer and other cancers in HIV-positive individuals, although when taking other factors that may contribute to increase cancer risk into account (like smoking)," Dr. Bucher told Reuters Health.

The absolute risks are small, however. The researchers calculate that 332 patients would have to be treated immediately (rather than deferring ART to a CD4 <350 cells/L) to prevent one case of non-AIDS-defining cancer over 10 years. To prevent one AIDS-defining cancer over 10 years, 100 would have to be treated immediately. Likewise, 80 patients would need to be treated immediately to prevent one person from developing any cancer over 10 years.

However, these findings are "relevant," they say, "considering the high morbidity and case fatality of cancer in HIV-positive persons and the expected increase in cancer-related illness in the aging HIV population."

"Cohort data indicate that, in high-income countries, non-AIDS-defining cancer is the leading cause of death in HIV infection. Although current guidelines recommend immediate initiation of ART in persons with newly diagnosed HIV infection, about half of such persons in non-resource-limited settings initiate ART at CD4 counts below 500 cells/L," they write.

This study, they conclude, shows that "strategies promoting deferral of ART initiation in ART-naive, HIV-positive persons are associated with a small increase in risk for AIDS-defining cancer. The study adds further supportive evidence that early ART may reduce risk for non-AIDS-defining cancer."

SOURCE: Annals of Internal Medicine, online March 15, 2021.