Evidence Against Accelerated Aging Among People Living With HIV: A Top HIV Clinical Development of 2015
The pace of aging for people living with HIV has been a major topic of discussion among HIV researchers and thus a major cause of worry for many HIV-positive patients. Reports concluding that HIV infection causes a quickening of our built-in obsolescence have led to a belief that people living with the virus are walking metabolic time bombs at heightened risk for heart attacks, strokes, fractures, dementia, frailty and other sucky aspects of getting old.
Much of the work looking at the relationships between HIV infection and adverse outcomes have come from cohort studies, where confounding is hard to avoid or account for. Traditional risk factors such as smoking, crack use, head injuries and depression are more prevalent among HIV-infected people and jack-up the rates of events of interest. Statistical methods adjust for known confounders, but some of these are less obvious and/or not captured in study surveys and medical records.
While confounders could explain higher event rates for HIV-infected compared to uninfected populations, they would be less able to account for any increased risk over time as people age. Two studies published this year examined changes in rates of events across age groups to see if there was a relative increase in those with HIV -- a result that would be expected if a cumulative effect of HIV-mediated inflammation is present.
The first was an analysis from Denmark, which uniquely enrolls practically all its HIV-positive citizens in a longitudinal cohort and also has a robust health registry of all Danes. Over 5,800 HIV-infected cases were matched -- by year of birth, sex and entry into their respective registries -- with 53,000 population controls.
As expected, the HIV-positive population had higher excess and relative rates of diseases associated with aging, including cardiovascular disease (CVD), cancers associated with HIV or smoking, severe neurocognitive disorders, chronic kidney disease, chronic liver disease and osteoporotic fractures. However, overall, age-standardized and relative risks for CVD, cancer and neurocognitive disorders did not appreciably change with time after HIV diagnosis or initiation of antiretroviral therapy. The age-standardized and relative risks of kidney disease did increase, but then plateaued after diagnosis of HIV infection. The authors conclude, "The findings from our study do not suggest that accelerated aging is a major problem in the HIV-infected population."
A separate U.S. Veterans Aging Cohort Study also looked at age and the major events associated with aging (myocardial infarction, end-stage renal disease, and non-AIDS cancers) among HIV-infected (n=30,564) and -uninfected controls (n=68,123). Again, there was a greater risk for these outcomes for the HIV-positive participants, but they occurred at similar ages as those without HIV.
The Bottom Line
Contrary to early studies and the conventional wisdom they spawned, these analyses of large datasets do not find evidence of accelerated aging of HIV-infected individuals. Conditions associated with getting older occurred at similar ages for the HIV positive and negative, and over time there was no evidence of significant widening of the risk differential for these diseases.
Clearly, HIV-positive persons suffer from CVD; cancers; and neurocognitive, renal and liver problems more than those without the virus. However, while HIV may well play a role in this disparity, accumulating data suggest that the preponderance of traditional factors -- including the more obvious, such as smoking, and the less measurable, such as stress -- are the main actors.
The message to our patients should be that any nihilism regarding the inevitability of accelerated aging as a consequence of HIV infection is misguided and that much of their fate continues to lie in their own hands. Clean living and adherence to HIV medications will go a long way. While getting old is tough, it beats the alternative -- as my patients rightly complain I say way too often.
What are some other top clinical developments of 2015? Read more of Dr. Wohl's picks.
David Alain Wohl, M.D., is an associate professor of medicine in the Division of Infectious Diseases at the University of North Carolina and site leader of the University of North Carolina AIDS Clinical Trials Unit at Chapel Hill.