Danish study raises questions about accelerated aging in HIV
20 July 2015
In the past decade reports have suggested that some HIV-positive people are at heightened risk for aging-related issues including the following:
- heart attack
- stroke
- some cancers
- severe organ injury and dysfunction
- fractures
This has led some researchers to theorize that perhaps HIV infection is associated with accelerated aging.
A team of researchers in Denmark has been pondering the potential effect of HIV on the aging process. They think that if HIV does accelerate the aging process then the risks of developing severe age-related diseases should increase over time as people with HIV live longer.
To explore the issue of HIV and aging, the Danish team analysed health-related data collected over a period of 20 years from both HIV-negative and HIV-positive people. They found that while age-related diseases were relatively common among HIV-positive people, overall severe age-related complications were not common. Thus the team concluded that accelerated aging was not linked to HIV. Later in this CATIE News bulletin we explore this conclusion as well as possible limitations of the Danish study.
Study details
In Denmark, several large databases exist to capture health-related information from citizens and residents. The information in these databases can be analysed by researchers who are studying different health conditions. Danish researchers are known for their close monitoring of the HIV epidemic in that country.
In the present study, data were gathered from HIV-positive people from January 1995 to June 2014. People who were diagnosed with age-related conditions before the start of the study were excluded from analysis.
The researchers focused on trends. Specifically they sought to assess the length of time it took for one of the age-related conditions they were monitoring to occur. They relied on hospitals and clinics to make a diagnosis and record this diagnosis. In cases where participants had died, the research team also made use of analysing data from death certificates.
The diseases on which the team focused were as follows:
- heart attack
- stroke
- virus-associated cancers, including lymphoma, Kaposi's sarcoma (KS), liver cancer and cancers of the anus, cervix, penis and vulva
- smoking-related cancers, including cancers of the lung, head and neck and bladder cancer
- other cancers
- chronic brain dysfunction
- chronic kidney dysfunction
- chronic liver dysfunction
- fractures due to osteoporosis
Data from 5,897 HIV-positive people were analysed and their average profile at the time they entered the study was as follows:
- 76% men, 24% women
- age – 37 years
- common routes of HIV infection (percentages do not add up to 100 due to rounding): men who had sex with men – 46%; people who injected street drugs – 10%; heterosexual contact – 37%; other routes – 6%
- co-infection with hepatitis C virus – 15%
- CD4+ cell count – 300 cells/mm 3
Data from HIV-positive people were compared to data from 53,073 HIV-negative people. In other words, data from each HIV-positive person were compared to data from nine HIV-negative people.
Results—Overall
In general, HIV-positive people were more likely to have severe forms of age-related diseases than HIV-negative people. Here is the distribution of the specific conditions monitored by the research team:
Heart attack
- HIV-positive people – 3%
- HIV-negative people – 2%
Stroke
- HIV-positive people – 4%
- HIV-negative people – 3%
Chronic kidney dysfunction
- HIV-positive people – 2%
- HIV-negative people – 0.7%
Chronic liver dysfunction
- HIV-positive people – 2%
- HIV-negative people – 0.7%
Chronic brain dysfunction
- HIV-positive people – 2%
- HIV-negative people –0.4%
Osteoporosis-related fractures
- HIV-positive people – 8%
- HIV-negative people – 6%
Virus-associated cancers
- HIV-positive people – 5%
- HIV-negative people – 0.5%
Smoking-associated cancers
- HIV-positive people – 2%
- HIV-negative people – 1%
Other cancers
- HIV-positive people – 3%
- HIV-negative people – less than 4%
Statistical analysis found that among HIV-positive people the relative risk of developing certain events or conditions was generally greater than among HIV-negative people, as follows:
- heart attack – two-fold elevated risk
- stroke – two-fold elevated risk
- virus-associated cancer – 14-fold elevated risk
- smoking-associated cancer – two-fold elevated risk
- other cancers – 17% increased risk
- chronic neurocognitive problems – five-fold elevated risk
- chronic kidney dysfunction – four-fold elevated risk
- chronic liver dysfunction – four-fold elevated risk
- osteoporosis-related fractures – two-fold elevated risk
In reviewing the results, readers can see that in most cases the specific conditions as well as the risks for them were elevated among HIV-positive people. However, overall, relatively small proportions of HIV-positive people had severe forms of these diseases.
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.”
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)
—Sean R. Hosein
REFERENCES:
- 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 .
- Petoumenos K, Law M. HIV-infection and comorbidities: a complex mix. Lancet HIV . 2015; in press .
- 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.
- 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.
- 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.
- 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 . Available from: http://www.ncbi.nlm.nih.gov/pubmed/26150497
From Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE's Information Network at http://www.catie.ca
Source: CATIE: CANADIAN AIDS TREATMENT INFORMATION EXCHANGE
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