February 24, 2016
HIV-positive people are not "aging faster" than HIV-negative people, according to results of a study comparing almost 6000 people with HIV and more than 53,000 people without HIV in Denmark.1 The new findings challenge the theory of "accelerated aging" with HIV infection.
Research over the past several years in the United States and Europe shows that HIV-positive people have higher rates of certain age-related diseases (like heart disease, some non-AIDS cancers, and kidney disease) than people the same age without HIV. These findings led some to suggest that faster or premature aging in HIV-positive groups explains their higher risk of these diseases. But many other factors could explain higher rates of age-related disease in people with HIV, including higher rates of traditional risk factors (like smoking) or ongoing immune system activation and inflammation in people with HIV, even in those who reach an undetectable viral load with antiretroviral therapy.
Denmark collects detailed health data on everyone in the country, including people with HIV. All HIV-positive people get free treatment at one of eight HIV centers throughout the country. Researchers took advantage of these nationwide health records to get a better understanding of age-related diseases in people with and without HIV infection.
The study involved all HIV-positive adults in Denmark who received care at some point between January 1995 and June 2014. Everyone was at least 16 years old and living in Denmark when they entered the study. The study group included people born outside Denmark and people who inject illegal drugs. For each of these HIV-positive people, researchers selected 9 people from the general population who matched the HIV-positive person in age, sex (man or woman), and year entering the study.
Next the researchers checked two national health databases to determine how many people in the HIV group and the general-population group got one of 9 serious age-related diseases during the study period: myocardial infarction (heart attack), stroke, virus-associated cancer, smoking-related cancer, other cancers, severe neurocognitive disease (HIV- and non-HIV dementia), chronic kidney disease, chronic liver disease, and osteoporotic fracture. (Osteoporotic fractures are broken bones that result from decreasing bone density.) The study did not include anyone who already had one of these conditions, except fractures.
Then the researchers used standard statistical methods to calculate the absolute risk (or rate) and the relative risk (or rate ratio) of a serious age-related disease during follow-up in several ways, including (1) the overall absolute risk and relative risk of such a disease in HIV-positive versus HIV-negative people, and (2) the change in absolute risk and relative risk with (a) increasing age, (b) longer time since starting combination antiretroviral therapy, and (c) longer time measured in calendar years. In making these comparisons, the researchers accounted for the possible impact of age, sex, calendar year, and country of origin.
The study included 5897 people with HIV matched to 53,073 HIV-negative people in the general population. Median age in both groups stood at 37 years, and three quarters of both groups were men.
Compared with the general-population group, HIV-positive people had a higher relative risk of all age-related diseases studied except for "other cancers." As expected, the absolute risks (the rates) of these diseases rose with older age in people with and without HIV. However, the relative risk of all these diseases -- except fractures -- fell with increasing age in HIV-positive people compared with HIV-negative people (Figure 1). In other words, increasing age did not make age-related diseases more likely in people with HIV.
Figure 1. Relative risk of eight major diseases fell with increasing age in HIV-positive people compared with HIV-negative people in a study of almost 59,000 people in Denmark. (HIV illustration from Servier PowerPoint Image Bank.)
Next the researchers looked at whether absolute risk or relative risk of these nine diseases increased with time since people tested positive for HIV. For these analyses, the researchers used statistical techniques to account for the impact of aging on risks of the nine diseases.
First, the absolute risk (the age-standardized rate) of heart attack, stroke, any type of cancer, severe neurocognitive disease, and chronic kidney disease did not change much with time since HIV diagnosis. Only the absolute risk of chronic liver disease and osteoporotic fracture seemed to increase slightly with time since HIV diagnosis. Compared with HIV-negative people, the relative risk of all age-related diseases except chronic liver disease and osteoporotic fracture was stable or decreased with time after HIV diagnosis.
Results were very similar when the researchers calculated absolute risk and relative risk of serious age-related diseases with time since these HIV-positive people started combination antiretroviral therapy.
Finally, the investigators examined risk of these diseases over six periods: 1995-1999, 2000-2002, 2003-2005, 2006-2008, 2009-2011, and 2012-2014. Except for chronic kidney disease, risks of these age-related diseases remained stable or fell over time in people with HIV. Because the absolute risk of chronic kidney disease rose after 1995-1999 both in people with HIV and in the general population, the relative risk has decreased with time.
This large and careful comparison of nine age-related diseases in people with versus without HIV contains mostly good news for HIV-positive people. The bottom-line message from this study is that people with HIV do have higher absolute risks (rates) of most of these diseases than people without HIV, but the relative risks (rate ratios) are not getting higher as people age. Importantly, when age was taken out of the analysis, the absolute risk and relative risk of most of these diseases did not increase (1) with increasing time since HIV diagnosis, (2) with increasing time since starting combination antiretroviral therapy, or (3) with calendar time (calendar-year periods starting with 1995-1999 and ending with 2013-2014).
Together all of these findings challenge the idea that people with HIV are "aging faster" than people without HIV. The findings appear to contradict the theory of "accelerated aging" with HIV infection. Two HIV experts who reviewed this study note that other recent research has made similar findings.2 A U.S. Veterans Aging Cohort Study showed the HIV-positive veterans had higher rates of myocardial infarction, end-stage kidney disease, and non-AIDS cancers than HIV-negative veterans.3 But these diseases occurred at similar ages in HIV-positive and negative veterans. Two European/U.S.4 and Dutch5 studies also found no hints of accelerated aging in people with HIV.
These studies and the Danish study1 do find that HIV-positive people have higher absolute risks (rates) of certain age-related illnesses than people without HIV. Although rates of these diseases do increase with increasing age regardless of HIV status, the relative risks (HIV-positives versus general population) do not seem to be higher with older age than with younger age. Other factors -- including inflammation caused by HIV and traditional risk factors like smoking -- probably explain the higher risks of these diseases in people with HIV. So HIV-positive people should work with their clinicians to avoid or reverse changeable risk factors linked to age-related diseases, including smoking, heavy alcohol drinking, lack of exercise, and infection with other sexually transmitted diseases including hepatitis B and C virus (HBV and HCV). HIV-positive people who do not have HBV infection should get the HBV vaccine.
At the same time, the Danish study1 and other work3-5 should relieve concern that HIV-positive people are somehow aging faster than HIV-negative people. In fact, much research now shows that people with HIV are living almost as long or as long as HIV-negative people -- if they take antiretroviral therapy and reach an undetectable viral load.
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