Dutch doctors explore intersection of aging and HIV
23 September 2014 - The widespread availability of potent anti-HIV combination therapy (commonly called ART or HAART) in Canada and other high-income countries has greatly reduced rates of death from AIDS-related infections. ART is so beneficial that researchers increasingly expect that some young adults who begin ART shortly after becoming HIV positive and who are engaged in their care and treatment and who do not have pre-existing serious health conditions will likely live into their 80s.
Aging
As the population of HIV-positive people ages, biomedical issues unrelated to HIV become more of an issue. These issues are called comorbidities and have to do with the declining health of major organ-systems, including the following:
- brain
- bones
- heart and blood vessels
- kidneys
- liver
- lungs
As the HIV epidemic matures in high-income countries, it is important that scientists undertake studies of older HIV-positive people so that their health and research needs can be explored, understood and addressed.
Choosing the right people
Most studies that have been done to try to understand HIV and aging have not used a comparable group of HIV-negative people. That is, such studies have compared HIV-positive people to an average HIV-negative person. However, HIV-positive people (and people at high risk for HIV) tend to have certain behaviours and characteristics that may place them at heightened risk for comorbidities. For instance, surveys have found that rates of smoking among HIV-positive people are generally greater than among HIV-negative people.
Scientists in Amsterdam have sought to remedy this shortcoming by recruiting people for their study of aging and HIV. They have not only recruited HIV-positive people for their study, called AGE h IV, but also HIV-negative people of a similar age and sexual orientation who had what the scientists called similar "lifestyle and sexual risk-taking behaviour to [HIV-positive] study participants."
In analysing their data collected so far, the Amsterdam scientists found that some HIV-positive people were more likely to have the following comorbidities:
- higher-than-normal blood pressure
- heart attacks
- peripheral artery disease
- dysfunctional kidneys
One of the reasons for the excess number of comorbidities among HIV-positive people was that there were more risk factors, such as being overweight and smoking tobacco. However, HIV infection itself also played a role in the development of comorbidities.
Readers should note that despite the effect of HIV, there are steps that can be taken to reduce the risk and impact of comorbidities.
In this CATIE News bulletin, we explore some of the findings from the Dutch study.
Study details
Participants were extensively surveyed, had their medical records reviewed, underwent physical exams and other assessments, and had their blood drawn for complex tests.
The scientists compared health-related data collected from two groups of people as follows:
- 540 HIV-positive people
- 524 HIV-negative people
In general, participants were in their early 50s and were mostly male (87%) and men who had sex with men (71%). Most of the HIV-positive participants had been living with the virus for 12 years and the vast majority had been taking ART for "many years." Their average CD4+ count was around 565 cells/mm 3 and HIV viral load was less than 50 copies/ml.
Hepatitis B or C virus co-infection was uncommon; fewer than 4% of participants had these viruses.
Data were collected between 2010 and 2012.
Results-Overall findings
Scientists found that participants who currently smoked tobacco were distributed as follows:
- HIV-positive people - 32%
- HIV-negative people - 25%
An increasingly used assessment in clinical trials is the waist-to-hip ratio. This assessment measures the circumference of the body at the waist and hips and compares them. A high waist-to-hip ratio suggests a large belly and excess belly fat. HIV-positive people (84%) were more likely to have a higher-than-normal waist-to-hip ratio than HIV-negative people (62%).
The proportions of participants who stated that they were physically active were as follows:
- HIV-positive people - 44%
- HIV-negative people - 53%
All of these differences were statistically significant; that is, not likely due to chance alone.
Comorbidities
Overall, scientists found that HIV-positive people were more likely to have a greater number of age-related comorbidities, as shown below:
- HIV-positive people - 70%
- HIV-negative people - 62%
In general, HIV-positive people had comorbidities occur about five years earlier than HIV-negative people. Furthermore, each age-related comorbidity was more common among HIV-positive people than HIV-negative people, as follows:
Higher-than-normal blood pressure
- HIV-positive people - 45%
- HIV-negative people - 31%
Heart attack
- HIV-positive people - 4%
- HIV-negative people - 2%
Peripheral artery disease
- HIV-positive people - 3%
- HIV-negative people - 1%
Kidney dysfunction
- HIV-positive people - 4%
- HIV-negative people - 2%
These differences were statistically significant.
Risk factors
Researchers found that the following factors were linked to an increased risk for age-related comorbidities:
- older age
- having a family history of specific comorbidities
- smoking tobacco
- having had a CD4+ count that was less than 200 cells/mm 3 for a prolonged period in the past
We explore these linkages later in this bulletin.
Inflammation
HIV infection is associated with increased inflammation. The Dutch scientists found that HIV-positive people had significantly greater levels of proteins in the blood suggestive of elevated inflammation, such as the following:
- high-sensitivity C-reactive protein (hsCRP)
- soluble CD14 (sCD14)
- soluble CD163 (sCD163)
Having elevated levels of sCD14 or hsCRP (but not sCD163) was linked to a greater risk for age-related comorbidities.
ART
Current or past use of the following anti-HIV drugs was not linked to a significantly increased risk for any age-related comorbidities:
- abacavir (Ziagen, and in Kivexa, Epzicom, Trizivir and Triumeq)
- d4T (stavudine, Zerit)
- ddI (didanosine, Videx)
In context
As reported earlier, the Dutch scientists found that the following factors were linked to an increased risk for age-related comorbidities:
- older age
- having a family history of specific comorbidities
- smoking tobacco
- having had a CD4+ count that was less than 200 cells/mm 3 for a prolonged period in the past
People can't change their age or their families, but those who smoke tobacco can ask their doctor, nurse and/or pharmacist for advice and support when trying to quit. Tobacco smoke injures the lungs, affects the heart and blood vessels, and increases the risk of diabetes and many other complications, including cancer.
The other finding from the Dutch study, about injury that can arise from immune deficiency (low CD4+ cell count), suggests that starting ART as early as possible in the course of HIV disease is associated with better health and long-term results. ART can help preserve the immune system and the health of other organ-systems.
The findings from the Dutch study are particularly interesting because of the similarities between the HIV-positive and HIV-negative people. It shows that some differences between these two populations are not necessarily as huge as might be imagined. The present analyses from the AGE h IV study are cross-sectional in nature. That is, they cannot prove cause and effect. However, the study is an important step in the process of understanding the impact of HIV on aging and vice versa. The AGE h IV study has gone to great lengths to accrue participants who are similar in characteristics whether or not they have HIV. This is an immense strength not seen in many studies and underscores the validity of their findings. Due to the composition of the AGE h IV cohort, it is vital that it continue to get funding for many years. Assessing participants over several years as they age-a longitudinal study- has much potential to increase the knowledge base that doctors, nurses and pharmacists can turn to when helping HIV-positive people achieve the long-term benefits of ART and healthy living. Long-term monitoring is also significant because some co-morbidities of aging with HIV may not appear until participants are in their late 60s or early 70s.
However, the general findings seen in the present Dutch study have been confirmed by some other studies.
Turning the tide
As previously mentioned, although some risk factors for comorbidities cannot be reversed, such as age and family history, many other risk factors for poor health can be changed with help from doctors, nurses and pharmacists. To find out more about changes to improve heart health, see CATIE's HIV and cardiovascular disease fact sheet.
-Sean R. Hosein
Resources:
Report to the NIH about Aging and HIV
The CIHR Comorbidity Agenda
CIHR's HIV Comorbidity Research Agenda: Relevant Research Areas
HIV and Aging - Healthy living tips for people 50 and over living with HIV
HIV and Aging - CATIE Webinar Series: Building Blocks
Factsheets on HIV and aging in Canada - Canadian AIDS Society
Evidence-informed recommendations for rehabilitation with older adults living with HIV: a knowledge synthesis
REFERENCES:
- Lohse N, Hansen AB, Pedersen G, et al. Survival of persons with and without HIV infection in Denmark, 1995-2005. Annals of Internal Medicine . 2007 Jan 16;146(2):87-95.
- Samji H, Cescon A, Hogg RS, et al. Closing the gap: increases in life expectancy among treated HIV-positive individuals in the United States and Canada. PLoS One . 2013 Dec 18;8(12):e81355.
- May MT, Gompels M, Delpech V, et al. Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy. AIDS. 2014 May 15;28(8):1193-202.
- Lohse N, Gerstoft J, Kronborg G, et al. Comorbidity acquired before HIV diagnosis and mortality in persons infected and uninfected with HIV: a Danish population-based cohort study. Journal of Acquired Immune Deficiency Syndromes. 2011 Aug 1;57(4):334-9.
- Hansen AB, Lohse N, Gerstoft J, et al. Cause-specific excess mortality in siblings of patients co-infected with HIV and hepatitis C virus. PLoS One . 2007 Aug 15;2(8):e738.
- Schouten J, Wit FW, Stolte IG, et al. Cross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-infected and uninfected individuals: the AGE h IV Cohort Study. Clinical Infectious Diseases . 2014; in press .
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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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