Lung Cancer Risk in HIV Tied to Immune Dysfunction

Accumulated exposure to low CD4/CD8 ratios was highly predictive of the risk for lung cancer among US veterans with HIV, according to a longitudinal follow-up study reported in The Lancet.¹

Low CD4 and CD8 cell counts have long served as markers of immune dysfunction, and persistence of low ratios of CD4/CD8 have correlated to higher risk of all-cause mortality not associated with AIDS in HIV-positive individuals.^2,3 The increased risk of pneumonia associated with HIV also increases the risk of lung cancer in this population.^4,5 

“We conducted preliminary investigations into low CD4/CD8 ratio measures and other cancer types and presented these results at the Conference on Retroviruses and Opportunistic Infections (CROI) in 2016,” explained study author Keith Sigel, MD, assistant professor of medicine at the Mount Sinai Health System in New York.  “Lung cancer is the leading cause of cancer death among HIV-infected persons, and HIV has been found to be independently associated with lung cancer risk. There may be a unique mix of mechanisms driving the excess lung cancer risk observed in the setting of HIV.”

The investigators identified 277 lung cancers from data taken from 21,666 participants with HIV enrolled in the Veterans Aging Cohort Study (VACS) between January 1, 1998, and December 31, 2012. They found that HIV RNA was significantly associated with greater lung cancer risk at the time-updated 12-month period and after 24 months’ follow-up (P =.004). Episodes of pneumonia at 12-month-lagged follow-up also correlated significantly with increased lung cancer risk (P =.0004).

“Among non-AIDS-defining cancers we only found significant associations (after adjustment) with lung cancer and anal cancer,” Dr Sigel noted. Of the 277 participants who developed lung cancer, baseline characteristics pointed to their being older, non-Hispanic white, more likely to smoke, and more likely to have a diagnosis of chronic obstructive pulmonary disease (COPD) or other lung disease.  

Dr Sigel noted that although association was highest with lung cancer, risk of other cancers is also likely to be increased by the presence of HIV. “We are continuing these investigations using updated cancer incidence data, as our power to detect an effect was lower with other cancer types,” Dr Sigel said. “We intend to further evaluate the role of low CD4/CD8 ratio measures in the development of other prevalent cancers among HIV-infected persons.”

An accompanying commentary by Makinson and Reynes⁶ pointed out several implications of the current study, most prominently that CD4/CD8 ratios and history of bacterial pneumonia are important markers that can be used to stratify HIV patients at greatest risk for lung cancer. Those identified should undergo screening computed tomographic imaging of the chest. They further suggest that early treatment of HIV with antiretroviral therapy is one of the best methods for reducing lung cancer risk by helping to reduce CD4/CD8 ratios.

References

1. Sigel K, Wisnivesky J, Crothers K, et al. Immunological and infectious risk factors for lung cancer in US veterans with HIV: a longitudinal cohort study. Lancet HIV. 2016;Dec 1. http://dx.doi.org/10.1016/S2352-3018(16)30215-6
2. Serrano-Villar S, Sainz T, Lee SA, et al. HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality. PLoS Pathogens. 2014;10:e1004078. http://dx.doi.org/10.1371/journal.ppat.1004078
3. Serrano-Villar S, Perez-Elias MJ, Dronda F, et al. Increased risk of serious non-AIDS-related events in HIV-infected subjects on antiretroviral therapy associated with a low CD4/CD8 ratio. PloS One. 2014;9:e85798. http://dx.doi.org/10.1371/journal.pone.0085798
4. Sigel K, Wisnivesky J, Gordon K, et al. HIV as an independent risk factor for incident lung cancer. AIDS. 2012;26:1017-1025. doi: 10.1097/QAD.0b013e328352d1ad
5. Shebl FM, Engels EA, Goedert JJ, Chaturvedi AK. Pulmonary infections and risk of lung cancer among persons with AIDS. J Acquir Immune Defic Syndr. 2010;55:375-379. doi: 10.1097/QAI.0b013e3181eef4f7
6. Makinson A, Reynes J. A novel marker of lung-cancer risk in people with HIV. Lancet HIV.  2016;Dec 1. http://dx.doi.org/10.1016/S2352-3018(16)30218-1