Evidence is mounting that HIV infection accelerates aging process
Clinicians need to emphasize wellness
Increasing numbers of studies in recent years have suggested that older HIV-infected individuals are impacted by comorbid conditions and are aging at an accelerated rate. While research needs to continue before a clear picture of the disease's impact on aging can be drawn, some of the latest findings offer clues and a warning for HIV patients and their providers.
The impact of HIV infection on older populations is gaining new attention from researchers, public health organizations, and clinicians worldwide.
"Even three years ago, this was hardly on the radar scope, but now we have a greater appreciation of the magnitude of the problem, and it's certainly challenging," says Krisann K. Oursler, MD, an assistant professor in the department of medicine at the University
of Maryland School of Medicine in Baltimore, MD. Oursler also is deputy director of the infectious disease clinic at the Veterans Affairs Maryland Health Care System in Baltimore.
Oursler's latest study involving HIV and older adults found that a 50-year-old, HIV-infected patient with chronic pulmonary disease functioned equivalently to a 68-year-old chronic pulmonary disease patient who is not infected with HIV.1
"So basically, among adults with chronic pulmonary disease, HIV-infected adults have worst function than HIV-negative adults, using multivariable models that adjusted for smoking and other comorbidities," Oursler says.
While lung cancer was not included in the study's analysis, investigators did look at chronic obstructive pulmonary disease (COPD), emphysema, and asthma, she says.
"Lung disease is worse in HIV-infected individuals," Oursler says. "If one individual is HIV-negative and has lung disease for five years, and another person who is HIV positive has lung disease for five years, it is possible that the person with HIV has lung disease that progresses more rapidly, but only longitudinal research measuring lung capacity will tell us this answer."
Oursler and co-investigators are collecting longitudinal data to look at the change in function over time to see if there is an accelerated decline with aging.
The same study looked at other comorbidities and aging, including cardiovascular disease. But it did not show a differential effect of cardiovascular disease between those HIV-infected and non-infected patients, although other research has suggested this occurs.
"It is possible that there is a ceiling effect and we didn't see a difference in cardiovascular disease because this was measured by self-reports and self-reports were not able to distinguish a difference," Oursler says.
Oursler and co-investigators are continuing research involving HIV-infected people and cardiovascular disease to see if there are differences in exercise performance.
In another new study in which the median age of HIV-infected men was 43 years, investigators found that HIV-infected men have a greater risk of cardiovascular disease. The study used computed tomographic (CT) scans for early detection. Older HIV patients had more common incidental findings.2
Research presented last fall at the 2010 Infectious Diseases Society of America (IDSA) annual meeting concluded that older HIV-positive adults tended to have low CD4 counts despite continuous virologic suppression and a median of three years of antiretroviral treatment. This suggests the need for early HIV diagnosis and treatment initiation among older adults.3
These findings also point to the need for HIV clinicians to focus on health prevention messages and screenings to help older patients improve long-term function.
"It's a lifelong challenge," Oursler notes.
Action now, impact later
When Oursler sees an HIV-infected patient in his or her late 50s, she will ask, "What do you want to be doing when you're 67 and 77 years old? Do you want to be in a nursing home, debilitated and frail? Do you want to be on oxygen and bedbound?"
What these patients do now will impact their lifestyle and activities in 10 to 20 years, she adds.
"That's where our emphasis on patient education needs to be: being physically active, smoking cessation, and HIV providers focusing on primary health care strategies to improve the quality of people's lives as they age with HIV," Oursler says.
While it was enough a few years back to simply keep HIV patients alive long enough to become middle-aged, now the goal is to give them better quality years as they age, Oursler notes.
"This is something that is a whole separate field of medicine and expertise," she adds. "We need to be continuing to collaborate with other specialties."
HIV clinicians might consult with geriatric physicians and other specialists who have been dealing with patients' comorbidities and aging issues for far longer than this has been an issue in the HIV clinical care.
"I work with geriatricians and have learned so much from them," Oursler says. "In the gerontology literature there is a whole host of knowledge the impact of age-related comorbidity on function."
Researchers are beginning to find clues into how HIV infection impacts the aging process. One possible explanation involves the virus' impact on naïve CD4 T-cells. Specifically, HIV infection appears to accelerate the T-cell division rate that leads to shorter telomere lengths.
A new study, published in PLoS One, found that HIV-1 infection among a treatment-naïve cohort is associated with significant telomere shortening within two subsets of naïve CD4 T-cells across age groups.4
Even with normal, healthy aging, we see signs that some T-cell subsets are older in terms of their telomere length," says Tammy Rickabaugh, PhD, assistant researcher at the AIDS Institute and University of California Los Angeles (UCLA) Department of Medicine in Los Angeles, CA.
"The problem with an older person getting infected with HIV is we're seeing signs that even with younger people, HIV accelerates some of this aging," she adds. "There are shorter telomere lengths in younger people who are infected with HIV when compared with healthy peers."
For people who are older and whose T-cell telomere lengths already are shorter because they are older, then it's possible the impact of HIV infection could result in a cumulative impact.
"One group in our study was in the range of 39 to 58 years, and they also showed aging," Rickabaugh says. "It did appear their lengths were a little shorter; they also showed signs of looking older than age-matched healthy individuals, but we need to look at more people."
The study took a look at cell numbers before subjects were treated with antiretroviral therapy (ART) and one year after ART. One of the groups of naïve cells did not come back fully after ART, Rickabaugh notes.
"There may be some issues that treatment is not able to correct," she adds. "Basically what we see is even on successful ART, some individuals still will present with clinical diseases such as certain types of cancer, cardiovascular diseases, frailty, and certain clinical manifestations."
The immune system remains important in fighting off some of the diseases and maintaining health, she says.
Research literature highlights the phenomenon of a decline in immune function as people age, Oursler says.
"An 80-year-old who never is sick would have less immune function than someone much younger," she says. "Add on the impact of HIV infection and the question is how does the decline due to aging combined with HIV affect the individual?"
References
- Oursler KK, Goulet JL, Crystal S, et al. Association of age and comorbidity with physical function in HIV-infected and uninfected patients: results from the Veterans Aging Cohort Study. AIDS Pat Care & STDs. 2011;25(1):13-20.
- Crum-Cianflone N, Stepenosky J, Medina S, et al. Clinically significant incidental findings among human immunodeficiency virus-infected men during computed tomography for determination of coronary artery calcium. Am J Cardiol. Dec. 30, 2010; [Epub ahead of print].
- Yong LK, Adeyemi O. Characteristics of Immunologic Non-Responders Among Older HIV-Infected Patients. Poster 1073. Presented at the Infectious Diseases Society of America's (IDSA's) 48th Annual Meeting, held Oct. 21-24, 2010, in Vancouver, Canada.
- Rickabaugh TM, Kilpatrick RD, Hultin LE, et al. The dual impact of HIV-1 infection and aging on naïve CD4 T-cells: additive and distinct patterns of impairment. PLoS One. 2011;6(1):1-9.
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