HIV and Aging -- Inflammation

[Guest guest]

From Medscape...

HIV and Aging--Inflammation: An expert interview w/Dr Deeks

Many people with long-term HIV infection that is controlled with highly active

antiretroviral treatment (HAART) appear to have clinical manifestations of

premature aging, although this is a highly controversial topic. The fact that

chronic low-level inflammation persists during long-term effective

antiretroviral therapy is now well accepted. This phenomenon might be

contributing to some of the complications that are occurring in some

HIV-infected people.

G. Deeks, MD, is a professor of medicine in residence at the University

of California, San Francisco (UCSF), and codirector of the Population and

Clinical Sciences Core at the UCSF-GIVI Center for AIDS Research. He is a

leading expert on the immunopathogenesis of HIV. Much of his recent work has

focused on the persistence of low-level inflammation in the face of HIV

controlled with long-term HAART.

Dr. Deeks

Medscape: Is there a difference in the levels of inflammation between healthy

individuals and people with HIV that has been well controlled with HAART?

Dr. Deeks: Markers of inflammation are elevated in patients on HAART that has

been controlling the virus for years, but the effect is not particularly

dramatic. Many of the more common markers of interest are only approximately 50%

higher in treated patients than in people who are not infected with HIV.

Since we are talking a lot about aging, it is of interest that some of the

immunologic features of advanced aging appear to characterize the immune system

of patients who are otherwise doing well on treatment. For example, T cells in

treated patients have lower-than-normal levels of CD28, a molecule involved in T

cell function. This is also commonly seen the elderly.

Medscape: Does HIV itself contribute to inflammation?

Dr. Deeks: About 80% of patients on HAART with HIV RNA that is undetectable with

conventional assays have detectable virus when very sensitive research-quality

tests are used. Based on the few studies that have attempted to quantify virus

in tissues, it is clear that the overall viral burden is much higher in tissue

than in blood. The critical question is whether this virus has clinical

significance. For example, could it be causing chronic inflammation? There is

some disagreement in the field, but our data suggest that there is no strong

relationship between the amount of virus in the blood and the amount of T cell

activation.

Based on a number of studies in which nothing happened when standard regimens

were intensified with additional agents, we concluded that low-level cryptic

viral replication probably is not a major cause of inflammation and activation,

and, by extension, age-associated diseases in these patients. We struggled to

prove that HIV is the cause of this inflammation and we failed.

Medscape: Then what causes the persistent inflammation?

Dr. Deeks: There is robust literature in the elderly showing that there are

dramatic differences between those who are CMV [cytomegalovirus]-positive and

those who are CMV-negative. Those who are positive have reduce proliferative

regenerative capacity, low naïve to memory T cell ratios, low CD4 cell counts,

lots of activation, lots of interleukin-6, and C-reactive protein. These are all

markers of immunologic aging, or immunosenescence.

We see comparable effects in people infected with HIV who are on HAART. Despite

the lack of any obvious CMV disease, many patients, otherwise doing well, have

very high levels of CMV-specific T cells. We estimate that up to 30% to 50% of

circulating T cells are directed at CMV. These cells can certainly cause

inflammation. The level of inflammation probably depends on individual titers of

CMV and the extent of immune activation. We think that these factors are

underappreciated.

Medscape: What happens when you treat for CMV?

Dr. Deeks: In a randomized trial with valganciclovir conducted by my colleague

Dr. Hunt [professor of medicine at the University of California at San

Francisco], CMV levels went down and the amount of excess T cell activation that

was unexplained dropped by about 25%. This suggests that a large portion of

immune activation and inflammation is related either directly or indirectly to

CMV infection.

Medscape: So why not simply treat for CMV?

Dr. Deeks: Most of the available drugs that are active against CMV are " toxic. "

Acyclovir is a benign drug that is active against other viruses from the CMV

family, but it is not active against CMV. As Hunt says, " the juice

probably isn't worth the squeeze. " We clearly need new therapeutic

interventions.

Medscape: There probably are other factors contributing to this chronic

inflammation. What about interventions such as low-dose aspirin and statins?

Dr. Deeks: There are good data in other populations demonstrating the

anti-inflammatory benefits of aspirin, statins, and other drugs, but we simply

don't have that kind of data in an HIV population. Some studies are planned or

are underway.

For now, lifestyle changes such as diet and exercise may be the most useful

interventions. They have demonstrated efficacy in dampening immune

overactivation and restoring a more normal homeostasis.

Medscape: Does HAART have any anti-inflammatory value?

Dr. Deeks: Definitely yes. All of the information that I have seen consistently

shows that inflammation levels are much higher in people who are untreated than

in those who are treated. The effect of treatment can be profound. The problem

is that treatment does not fully restore values to what might be considered

normal.

It is hard to reverse the effect of inflammation. We need to prevent it. If the

infection starts in the 40s, or earlier, then 20 years later we are going to see

evidence of premature aging. Since people who start HAART earlier tend to have

less inflammation once therapy is successful, I think we should get people on

HAART earlier rather than later.

Dr. Deeks has disclosed no relevant financial relationships.

[CLOSE WINDOW]

Authors and Disclosures

Journalist

Bob Roehr

Bob Roehr is a freelance writer for Medscape.

[Guest guest]

I recently heard a talk by a holistic doctor about warding off Alzheimer's by reducing the inflammation in our body/ brain by eliminating the gluten in our diet. She said that many body problems and diseases are caused by inflammation. Since I have had symptoms of intolerance to gluten that she mentioned (bloating, gas, diarrhea), I though I would try eliminating gluten to see what happens. It seems to help, so far.

I am using bread made from brown rice, pasta made from rice or qinuoa, and rice or corn cereals.

I am a senior and have been on HIV meds for many years, now Atripla.

Has anyone else heard of this theory regarding gluten and inflammation, especially for HIV?

Ed

[Guest guest]

My three cents worth

I concur (re: gluten causes inflammation, gas, diarrhea, bloating).*

Wheat and cow milk products do not provide natural, hard-wired essential

nutrients. One can EXIST consuming them, but they don't work well for a

compromised immune system. Adequate calcium and vitamin D are readily available

in fruits, vegetables, nuts, seeds, avocados.

It's a huge subject and controversial for most people, even so called HIV

nutritionist specialists. We've been brain-washed by the mega-growers and

marketers with " milk - it does a body good' when the pure physiological facts

just don't add up in their favor.

I replaced wheat products with brown rice versions too. Now I don't have nearly

as many sinus issues, lung mucous and don't snore! Whenever I do eat wheat more

than once a day I have flatulence. Same goes for cow milk products. Goat's milk

is much easier to digest and lactose free.

* Read Dr. N. Graham's " 80-10-10 " for the critical data on the subject

(among others).

Steve Perkins, CNHP/CHNP (Certified Nutritionist)