Immediate ART combo to reduce infection-related cancer risk

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Immediate initiation of combination ART can reduce the risk of infection-related cancers in newly diagnosed HIV patients,s a University of Copenhagen analysis indicated.

Healio reports: “According to recent estimates, up to 40% of cancer cases among HIV-positive persons in the US are infection-related; an attributable fraction 10 times as high as in the general population,” Dr Álvaro H. Borges, clinical associate professor at the University of Copenhagen, Denmark, and colleagues wrote. “HIV-positive persons also have an increased risk of infection-unrelated cancer. Reduced control of oncogenic viruses and impaired immune surveillance of malignant cells may facilitate carcinogenesis during HIV infection.”

To determine the impact of ART on these cancers, Borges and colleagues re-examined data from the Strategic Timing of Antiretroviral Treatment (START) trial. In the study, researchers randomly assigned 4,685 HIV patients from 35 countries to receive immediate or deferred combination ART. After a 3-year follow-up, they found improved CD4 counts among those given prompt therapy. Borges and colleagues identified cancer events among START participants, categorised each as infection-related and infection-unrelated, and they calculated the impact of ART initiation on cancer incidence.

The researchers identified 14 cancer events among HIV patients who received immediate ART, and 39 among those with delayed treatment. Patients receiving immediate ART were less likely to develop infection-related cancers (HR = 0.26; 95% CI, 0.11-0.64), although this association was weakened for infection-unrelated cancers (HR = 0.49; 95% CI, 0.21-1.15). Patients in the deferred group were more likely to develop cancer after 1 year of follow-up, whereas annual incidence in the immediate ART group remained stable. After adjustment, the researchers identified older age, higher BMI, residence in a low-middle income region, baseline HIV RNA and baseline CD8 count as independent predictors of infection-related cancer; older age and baseline CD8 count were the only predictors of infection-unrelated cancer.

The researchers noted that immediate ART’s protective effect was primarily driven by a reduction in cases of Kaposi sarcoma and non-Hodgkin’s lymphoma. Further, their adjustments of the analysis model for CD4 counts did not impact the effect of immediate ART on infection-related cancers, and adjustments for HIV RNA levels played only a minor effect.

“These findings suggest that the benefit of immediate [combination ART] in reducing cancer goes beyond HIV RNA suppression and immune status as assessed by CD4 counts and seems to likely to be also mediated by other mechanisms impacting coinfections with pro-oncogenic virus and immune surveillance,” the researchers are quoted in the report as saying. “Further research is needed to identify mediators of the benefit of immediate [combination ART] initiation in reducing cancer risk.”

Abstract
Background: In the START study, immediate combination antiretroviral therapy (cART) reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 counts and HIV RNA between the study arms.
Methods: Incident malignancies in START were categorized into infection-related and infection-unrelated cancer. We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline covariates, cancer risk factors and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART.
Results: There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23 infection-related and 16 infection-unrelated) (Hazard Ratios; 95% CI; of immediate vs deferred cART initiation were 0.26; 0.11-0.64; for infection-related and 0.49; 0.21-1.15; for infection-unrelated cancer). Independent predictors of infection-related cancer were older age, higher BMI, low-middle income region, HIV RNA and baseline CD8 count. Older age and baseline CD8 count were independent predictors of infection-unrelated cancer. Adjustment for latest HIV RNA level had little impact on the protective effect of immediate cART on infection-related cancer. Adjustment for latest HIV RNA level, but not for CD4 count or cancer risk factors, attenuated the effect of immediate cART on infection-unrelated cancer.
Conclusions: Immediate cART initiation significantly reduces risk of cancer. Though limited by small sample size, this benefit doesn’t appear to be solely attributable to HIV RNA suppression and may be also mediated by other mechanisms.

Authors
Álvaro H Borges, Jacqueline Neuhaus, Abdel G Babiker, Keith Henry, Mamta K Jain, Adrian Palfreeman, Peter Mugyenyi, Pere Domingo, Christian Hoffmann, Tim RH Read, Sanjay Pujari, Michael Meulbroek, Margaret Johnson, Timothy Wilkin, Ronald Mitsuyasu

Healio report
Clincial Infectious Diseases abstract


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