Immediate Initiation of ART May Slightly Decrease Cancer Risk for HIV-Positive Individuals

March 15, 2021
Maggie L. Shaw

As part of the study, investigators looked into the long-term risk of cancer as affected by immediate initiation of antiretroviral therapy (ART).

Investigators looking into the 10-year risk of cancer as affected by immediate initiation of antiretroviral therapy (ART) among ART-naïve individuals living with HIV found the risk of both AIDS-defining and non–AIDS-defining cancers to be only slightly lower than for those who started ART later.

Their findings appear online today in Annals of Internal Medicine.

The team from University Hospital Basel and University of Basel in Switzerland extracted their data from the D:A:D study (Data collection on Adverse events of anti-HIV Drugs), which is investigating incidences of non-AIDS conditions and how they may be related to ART. For their final analysis, they analyzed outcomes among 8318 persons living with HIV, who had a median (interquartile range [IQR]) age of 36 (29-43) years and initiated ART with 1 of 3 strategies:

  • At CD4 cell level less than 350 x 109 cells/L or an AIDS diagnosis
  • At CD4 cell level less than 500 x 109 cells/L or an AIDS diagnosis
  • Irrespective of CD4 cell count

Overall, for the 2006 to 2016 study period encompassing 64,021 person-years of follow-up, there were 231 cases of non–AIDS-defining cancer and 272 of AIDS-defining cancer. The risk for AIDS-defining cancers compared with non-AIDS–defining cancers was lower if ART was started immediately following a diagnosis, but not by very much: 2.50% (95% CI, 2.37%-3.38%) vs 2.97% (95% CI, 2.37%-3.50%), respectively. Immediate initiation of ART was defined as starting treatment within 6 months of a diagnosis.

These results carry over into starting ART at the predetermined CD4 levels, which show higher risks:

  • CD4 cell level less than 500 x 109 cells/L:
    • Non-AIDS–defining cancers: 3.09% (95% CI, 2.60%-3.58%)
    • AIDS-defining cancers: 2.80% (95% CI, 2.37%-3.38%
  • CD4 cell level less than 350 x 109 cells/L:
    • Non-AIDS–defining cancers: 3.27% (95% CI, 2.80%-3.65%)
    • AIDS-defining cancers: 3.51% (95% CI, 2.99%-4.09%)

“It is unclear to what extent delayed ART initiation, with its consequences of continued HIV replication and immune deterioration, contributes to the increased risk for cancer in HIV-positive persons,” the authors stated as their reason for initiating this substudy of D:A:D data.

They added that there have been guidelines for immediate initiation of ART since 2015 and that previous research shows a 57% relative reduction of serious events, both related and unrelated, in patients living with HIV. However, half of patients in non–resource-limited settings who ultimately receive a diagnosis fail to begin therapy right away.

Stratifying by CD4 count at initiation did not produce improved outcomes in this multinational prospective cohort study, as evidenced by the 10-year absolute risk differences:

  • Less than 500 x 109 cells/L:
    • AIDS-defining cancers: 0.32 percentage point (95% CI, 0.21 to 0.44 percentage point)
    • Non-AIDS–defining cancers: 0.12 percentage point (95% CI, –0.01 to 0.26 percentage point)
  • Less than 350 x 109 cells/L:
    • AIDS-defining cancers: 1.00 percentage point (95% CI, 0.67-1.44 percentage points)
    • Non-AIDS–defining cancers: 0.29 percentage point (95% CI, –0.03 to 0.73 percentage point)

The combined overall risks for any cancer were 5.37% (95% CI, 4.63-6.19%) following immediate ART initiation, 5.82% (95% CI, 5.15%-6.60%) when ART was started at a CD4 count below 500 x 109 cells/L, and 6.65% (95% CI, 5.95%-7.35%) when ART was started at a CD4 count below 350 x 109 cells.

All of the participants included in this final analysis had at least 1 CD4 and viral load measure while ART-naïve, 77.3% were male, the median (IQR) baseline CD4 count was 410 x 109 cells/L (260-583 x 109 cells/L), and the median (IQR) baseline HIV RNA level was 4.6 log10 copies/mL (3.9-5.0 log10 copies/mL). The median follow-up was 8.3 years for the 3 treatment strategies evaluated. This analysis also saw 212 study participants who died during the course of the study and 627 developing a non–AIDS-defining disease (eg, Hodgkin lymphoma, lung cancer, anal cancer, etc).

“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, our findings are relevant,” the authors conclude. “In summary, we observed 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.”

Of particular note is that the risk of non–AIDS-defining cancers rose if an individual had ever smoked, was older than age 35, and had a low CD4 count, whereas the risk of AIDS-defining cancers rose with a high viral load and being classified as a man having sex with another man.


Chammartin F, Lodi S, Logan R, et al. Risk for non–AIDS-defining and AIDS-defining cancer of early versus delayed initiation of antiretroviral therapy. Ann Intern Med. Published online March 15, 2021. doi:10.7326/M20-5226