September 2015




A possible AIDS-related AMD connection

by Maxine Lipner EyeWorld Senior Contributing Writer

Patients with AIDS

Patients with AIDS are at increased risk of developing AMD (seen here).

Source: National Eye Institute

The risk AIDS patients face

Patients with acquired immune deficiency syndrome (AIDS) have a fourfold greater risk of developing AMD than their counterparts who have not been infected by HIV, according to Douglas A. Jabs, MD, MBA, professor of ophthalmology and professor of medicine, Icahn School of Medicine at Mount Sinai, New York. This is from study results published in the June 2015 issue of the American Journal of Ophthalmology, which considered the prevalence of intermediate-stage AMD in those with AIDS.

The desire to launch the study grew from mounting evidence that those with AIDS appear to be at increased risk for certain age-related diseases. It has become increasingly clear in the AIDS literature that HIV-infected persons who are antiretroviral-treated and immune- restored have a shortened lifespan and have an accumulation of age- related diseases like cardiovascular disease, non-AIDS cancers, diabetes, and dyslipidemia, Dr. Jabs said. Because we knew that there was accentuated aging in this population, we decided to look for AMD.

Considering prevalence

Included in the study was the cohort from a National Institutes of Health-funded longitudinal investigation, which began in 1998 with the idea of studying various ocular complications of AIDS. These were patients with AIDS, but many had been immune-restored and were immunologically recovered, Dr. Jabs said. When the study began in 1998, AMD wasnt one of the complications considered, but there were ocular photographs that had been taken. Spurred by a small pilot study that appeared to show an increase in AMD in such patients, investigators decided to examine the archived photographs they had collected for the large longitudinal investigation and grade them for AMD. The cohort included 1,825 patients with a median age of slightly more than 43 years. The prevalence of intermediate-stage AMD was about 10%, Dr. Jabs said. Investigators here also wanted to consider how this compared to what they might expect in the general population. To consider this, they compared the study results to those in the Beaver Dam Offspring Study, which was done at the University of Wisconsin, Madison. It estimated intermediate-stage AMD from photographs and had a roughly similar age distribution, Dr. Jabs said.

What we saw was that in an age- and gender-adjusted comparison, the risk of AMD was about fourfold greater in patients with AIDS than in the HIV-uninfected Beaver Dam Offspring Study, Dr. Jabs said.

The root of this appears to be changes in the immune system. If you look at people who are HIV-infected, antiretroviral-treated and immune-restored, their immune systems are not normal, Dr. Jabs said. They have chronic immune activation and systemic inflammation, and they have changes in their immune systems in terms of the percent of naive T cells and terminally differentiated effector T cells. The upshot is that their immune system looks like that of a 75-year-old person. The current hypothesis is that this chronic immune activation and systemic inflammation is pushing the immune system to appear as if it belongs to an older person. Meanwhile, it is well known that systemic inflammation is associated with conditions such as cardiovascular disease, Dr. Jabs said. There are also data to show that systemic inflammation is a risk factor for AMD. We think that the increased prevalence is due to the immune activation and systemic inflammation and the fact that these people are in this chronic immune-activated, systemically inflamed state.

Clinical implications

The clinical implications of all of this remain unclear. Dr. Jabs pointed out that the study only involved intermediate-stage AMD and that they dont know yet what the progression to the late stage will be. In addition, there are some data to suggest that antiretroviral medication used by AIDS patients actually reduces the rate of neovascularization in animal models, he said, adding that this may mean that the rate of progression could be less for those on such medication. I dont think we can make any therapeutic recommendations yet, he said. However, I do think that when physicians evaluate an HIV-infected person in an eye exam, they should look for evidence of AMD. Overall, Dr. Jabs hopes that ophthalmic practitioners come away with the understanding that AIDS patients may need particularly close scrutiny. I think this is another piece of evidence of the accentuated aging thats seen in patients who are HIV-infected, antiretroviral-treated and immune-restored, he said. It adds to the growing body of literature that these people need to be watched for non-AIDS age-related diseases. When it comes to treating the HIV itself, physicians are now doing a good job of expanding lifespans of infected patients, Dr. Jabs said, adding that due to age-related diseases, these are still not fully normal lifespans. But we need to start paying attention to the age-related conditions and not just think of them as strictly HIV-related problems, he concluded.

Editors note: Dr. Jabs has no financial interests related to this article.

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