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IAS 2013: People with HIV Who Use Statins May Have Lower Cancer Risk

HIV positive people who use statins to manage high cholesterol also may reduce their risk of developing non-AIDS-defining malignancies, according to study findings reported at the recent 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) in Kuala Lumpur.

A growing body of evidence indicates that people with HIV are more prone to develop age-related non-AIDS conditions such as cardiovascular disease at an earlier age. Data on cancer rates compared with the general population have been conflicting, but suggest higher risk of developing certain malignancies.

This may be due in part to chronic inflammation triggered by persistent HIV infection, and therapies that reduce inflammation -- such as statins, also known as HMG-CoA reductase inhibitors -- may therefore be beneficial. Recent general population studies have shown statin use is associated with reduced mortality independent of cardiovascular risk.

Vincenzo Spagnuolo from IRCCS Ospedale San Raffaele and colleagues looked at the link between statin use and cancer rates, hypothesizing that statins would be associated with reduced cancer occurrence.

This retrospective longitudinal analysis included 5357 ART-experienced HIV patients followed at San Raffaele Scientific Institute in Milan through October 2012. They were not taking statins when they started ART, and did not have cancer at the time of ART or statin initiation.

Nearly 80% of participants were men, the mean age was 47 years, and 30% were coinfected with hepatitis C. They had been infected with HIV for 15 years on average and on combination ART for 10 years. The median CD4 T-cell count at baseline was 293 cells/mm³, with a nadir (lowest-ever) level of 214 cells/mm³.

Participants were followed for a median of about 10 years between ART initiation and first cancer diagnosis, loss to follow-up, death, or last study visit, yielding 52,663 total person-years (PY) of follow-up data. Malignancies were classified as AIDS-defining (non-Hodgkin lymphoma, Kaposi sarcoma, or cervical cancer) or non-AIDS-defining (all others).

Results

• 375 patients (7%) developed any type of cancer during 52,663 PY of follow-up, for an overall crude incidence rate of 7.1 cases per 1000 PY:

o   194 people (52% of all cancer cases) developed AIDS-defining malignancies;

o   181 people (48%) developed non-AIDS malignancies.

• The most common non-AIDS cancers were Hodgkin lymphoma (12%), anal cancer (6%), liver cancer (5%), and lung cancer (4%).
• 740 patients (14%) used statins during follow-up, for a mean duration of about 25 months:

o   68% of these used rosuvastatin (Crestor);

o   10% used pravastatin (Pravachol);

o   7% used atorvastatin (Lipitor);

o   13% used more than 1 statin.

• 12 statin users (1.6%, or 1.3 per 1000 PY) developed cancer, compared with 363 non-statin users (7.9%, or 8.4 per 1000 PY) -- a statistically significant difference.
• All cancers that developed among statin users were non-AIDS-defining malignancies.
• 3.2% of patients with cancer used statins, compared with 14.6% of people who did not develop cancer.
• In a multivariate analysis, significant predictors of cancer development were older age, higher HIV viral load, higher CD8 cell count, and higher total cholesterol level.
• Factors significantly associated with a lower cancer risk were statin use, longer time on ART, and higher CD4 cell count.

"This study showed, in a large number of treated HIV-infected subjects, that the use of statins was associated with a 46% reduction in cancer occurrence over a 10-year follow-up," the researchers concluded. "[T]his effect appeared to be even stronger in relation to the AIDS-defining malignancies, which were not observed."

These findings support results of another recent study published in theMay 15, 2013 edition of Clinical Infectious Diseases.

Edgar Overton from the University of Alabama at Birmingham and colleagues evaluated whether statin use was associated with decreased risk of non-AIDS-defining events and non-accidental death among 3601 participants in the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort who were not taking statins at baseline.

Over 15,135 person-years of follow-up, 484 participants started statins. A total of 616 patients experienced non-AIDS events, with crude rates of 4.4 per 100 PY among those taking statins and 4.1 per 100 PY among those not on statins -- not a statistically significant difference. However, looking only at malignancies, statin use did predict a significant reduction.

"Although statin therapy was not associated with a reduction in time to all non-AIDS-defining event[s] or non-accidental death, it was associated with a statistically significant 57% reduction in non-AIDS-defining malignancies," the study authors concluded. "Confirmatory studies are needed to evaluate statin-associated reduction in risk of cancer and non-AIDS-associated morbidities."

8/14/13

References

V Spagnuolo, L Galli, A Poli, et al. Association between HMG-CoA reductase inhibitors (statins) use and cancer occurrence among HIV-1 treated patients. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur, June 30-July 3, 2013. Abstract WEPE504.

ET Overton, D Kitch, CA Benson, et al. Effect of statin therapy in reducing the risk of serious non-AIDS-defining events and nonaccidental death. Clinical Infectious Diseases 56(10):1471-1479. May 15, 2013.