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Danish Study Raises Questions About Accelerated Aging in HIV

July 20, 2015

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Trends in Time

Researchers found that, overall, once participants were diagnosed with HIV and began to take potent combination anti-HIV therapy (commonly called ART or HAART) there was no further increase in the risk for the cluster of diseases studied.

Another way of viewing this finding is as follows: As a group, once participants began taking ART, there was no significant increase in the conditions studied as they aged.

These and other findings caused the Danish team to arrive at the following conclusion:

"[In the current] era, the cumulative effect of HIV-induced chronic inflammation on [the] risk of age-related diseases is small and does not support the notion that accelerated aging is a major problem in HIV-infected individuals."


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Points to Consider

1. Research With U.S. Veterans

Broadly similar findings to those of the Danish study have been reported from observational research in the U.S. in a study called the Veterans Aging Cohort Study Virtual Cohort (VACS). In that study, researchers analysed data from nearly 100,000 participants (31% were HIV positive and 69% were HIV negative). Participants were monitored from 2003 to the end of 2011. Researchers found that HIV-positive people were more likely to have age-related diseases than HIV-negative people. However, when such diseases were diagnosed, they occurred in people of similar ages regardless of HIV status. This latter finding suggests that HIV is not generally associated with accelerated aging.


2. Limitations of the Present Study

Scientists from Australia's leading research centre, The Kirby Institute, in Sydney, New South Wales, reviewed the findings of the Danish team. They stated: "The causes of long-term clinical outcomes in HIV-positive individuals are a complex mix of [the following factors]":

  • HIV infection
  • ART
  • co-infections such as hepatitis B and/or C viruses
  • smoking tobacco
  • alcohol and/or substance use

They noted that the latter factors (co-infections and use of certain substances) are, on average, "much more [common] in people with HIV than in those without."

The Australian scientists noted that the design of the Danish study rendered it difficult to discern which of the above-mentioned five factors contributed to the increased risk for severe age-related co-morbidities among the HIV-positive participants studied. This is a problem with many studies that seek to explore and understand aging and HIV.

To remedy this situation, the Australian scientists stated: "Data from well-matched HIV-positive and HIV-negative prospective cohort studies with detailed information about HIV, treatment, co-infection, and social, behavioural or lifestyle factors are needed to find out which of these factors increase the risk of age-related co-morbidities; however, such studies would need large numbers of participants with long follow-up." Such a study would also be very expensive.


3. A Potential Source of Bias

Another issue noted by the Australian reviewers is that there was "a consistent pattern of declining relative risk of these age-related co-morbidities with increasing age." They stated that the most likely explanation for this was what they called "survivor bias." They explained this term as follows:

"HIV-positive patients most at risk for [severe age-related diseases] do not survive to older age." The reviewers added, "These patients are likely to be individuals who do not respond well to antiretroviral treatment, have detectable viral load, and have low CD4+ cell counts, which are associated with an increased risk of all causes of death."


4. Now and for a Healthy Future

The Australian scientists also thought about the implications of an aging population of HIV-positive people -- what this might mean for health services now and in the future -- so they made several statements, including the following:

"For many people, HIV infection has now become a long-term manageable chronic illness, with the new challenge being the prevention and management of chronic illnesses that occur at increased rates."

Thus, aging-related research with HIV-positive people is critical. The type of study that the Australian scientists called for, one that collects very detailed information on tens of thousands of HIV-positive people and lasts for many years for the sole purpose of assessing age-related changes in health, is likely to be extremely expensive. Such a study will not be funded in the immediate future due to cost issues. Implicitly recognizing this fiscal reality, the Australian scientists gave the following prescription for doctors, nurses, pharmacists and health systems that can be implemented today:

"The keys steps to ensure healthy aging in HIV-positive individuals are:

  • early initiation of ART
  • achieve and maintain an undetectable viral load
  • reduce many of the traditional risk factors for aging-related health issues"

Indeed, the Australian scientists strongly encourage doctors and nurses to focus on helping their HIV-patients quit smoking because they see this as the largest contributor to ill health in this population. This is sound advice because an earlier Danish study found that HIV-positive nonsmokers were not at any significantly increased risk for a heart attack.

As the populations of high-income countries generally become older, aging-related research will become more urgent. New ways of assessing aging will emerge and some of this research could be applied to HIV-positive people before they begin to develop signs/symptoms of aging. So, for now, the present Danish study is not the final word on accelerated aging with HIV. Much research still lies ahead.


Resources

Quantification of biological aging in young adults -- Proceedings of the National Academy of Science

Management of Human Immunodeficiency Virus Infection in Advanced Age -- Journal of the American Medical Association

Long-term HIV infection and health-related quality of life -- CATIE News

Dutch doctors explore intersection of aging and HIV -- CATIE News

Geriatric syndromes found to be common among some people with HIV -- CATIE News

HIV and Aging: State of Knowledge and Areas of Critical Need for Research. A Report to the NIH Office of AIDS Research by the HIV and Aging Working Group

The CIHR Comorbidity Agenda -- Canadian Institutes of Health Research

CIHR's HIV Comorbidity Research Agenda: Relevant Research Areas

HIV and Aging -- Healthy living tips for people 50 and over living with HIV -- CATIE

HIV and Aging -- CATIE Webinar Series: Building Blocks

Mental Health -- from HIV in Canada: A primer for service providers

HIV and brain-related issues -- TreatmentUpdate 204

Factsheets on HIV and aging in Canada -- Canadian AIDS Society

Evidence-informed recommendations for rehabilitation with older adults living with HIV: a knowledge synthesis -- Canadian Working Group on HIV and Rehabilitation (CWGHR)


References

  1. Rasmussen LD, May MT, Kronborg G, et al. Time trends for risk of severe age-related diseases in individuals with and without HIV infection in Denmark: a nationwide population-based cohort study. Lancet HIV. 2015; in press.
  2. Petoumenos K, Law M. HIV-infection and comorbidities: a complex mix. Lancet HIV. 2015; in press.
  3. Gill MJ, Costagliola D. Myocardial infarction in HIV-infected persons: Time to focus on the silent elephant in the room? Clinical Infectious Diseases. 2015 May 1;60(9):1424-5.
  4. Rasmussen LD, Helleberg M, May M, et al. Myocardial infarction among Danish HIV-infected individuals: Population attributable fractions associated with smoking. Clinical Infectious Diseases. 2015 May 1;60(9):1415-23.
  5. Helleberg M, May MT, Ingle SM, et al. Smoking and life expectancy among HIV-infected individuals on antiretroviral therapy in Europe and North America. AIDS. 2015 Jan 14;29(2):221-9.
  6. Belsky DW, Caspi A, Houts R, et al. Quantification of biological aging in young adults. Proceedings of the National Academy of Sciences USA. 2015; in press.
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This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication CATIE News. Visit CATIE's Web site to find out more about their activities, publications and services.
 

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