It's a good article, not sensational as some of the press releases have been, but I would not expect that from Dr. Kotler, an expert on nutritional aspects of AIDS. I should have posted this awhile ago.
Dr Donald Kotler has suggested that lipodystrophy may not be a direct side-effect of protease inhibitors at all, as severe and progressive malnutrition and altered fat distribution were common complications of HIV in the past prior to the availability of protease inhibitors. Kotler analyzed changes in body composition recently using MRI scans and also used anthropometric measurements since 1984 and found accumulated fat in the visceral compartment in patients on "modern" therapies. Not all patients were on protease inhibitors and some patients included were LTNP (long term survivors, never treated.) All the patients had low or undetectable plasma viral burdens. There are many patients on protease inhibitor therapy with no evidence of the syndrome. The estimates, from 2% to 64% indicate more research is necessary, especially to set standards to diagnose the condition. healthcg.com "Wasting/Endocrine Disorders" healthcg.com
"Truncal Obesity, "Crix-Belly" - Is it what it appears to be.or something else?" healthcg.com
Kotler believes that the changes may be a result of the body's immune response to HIV and that the mechanism of weight loss related to HIV is the same as for any chronic infectious disease, i.e., it occurs as a consequence of pro-inflammatory cytokine activities-tumor necrosis factor (TNF), interleukin-1 and interleukin-6. Cytokines affect intermediary metabolism and promote protein depletion and fat synthesis. The changes may be related to hypogonadism, a frequent development in HIV-infected individuals, more common in late stage disease.
"The obvious goal of treatment is to restore the balance between protein (muscle) synthesis and degradation, by stimulating the former-by the use of anabolic agents, or by retarding the latter-by the use of cytokine inhibitors such as thalidomide."
Several studies have found that anabolic steroids or growth hormone in HIV infection result in increased lean mass rather than fat and I think there will be studies presented in Geneva that show that human growth hormone decreases lipodystrophy.
Thalidomide can decrease TNF production and is being used in some conditions associated with inflammation and excess cytokine production. A study treating HIV related malnutrition showed a gain of lean mass as opposed to fat, however one of the side effects of Thalidomide was a rise in plasma viral burden.
Dr. Kotler does not believe that antiretroviral therapy should be discontinued if lipodystrophy develops, and he advocates aggressive treatment for hypertension, hyperlipidemia and diabetes and changes in diet and exercise. He doesn't know of any "hard evidence" that these changes can be treated or reversed although there are anecdotal reports and several studies will be presented in Geneva showing reversals in lipodystrophy and hyperlipidaemia in patients who switched to Viracept. Several studies have found more lypodystrophy in patients on Ritonavir/Saquinavir and some on Crixivan. Agouron has found about 10 cases on Viracept, out of 1000- 1500 patients in clinical trials.
"Treatment Issues" talked with Joseph Sonnabend, M.D., about the many factors that could increase the risk of coronary heart disease in people with HIV besides protease inhibitors. He also mentioned that the tendency toward increased heart attack in people with HIV was noted many years ago, long before protease inhibitors. However protease inhibitors may magnify the risk through their effect on blood lipids.
aegis.com
Dr. Sonnenbend thinks the elevated triglycerides are due to increased levels of alpha interferon and possibly increased levels of TNF, normally present in untreated HIV.
- TNF is made by the immune system and has been found to increase in HIV infection and to correlate with the progression of the disease.
-People with untreated advanced HIV have high levels of TNF and interferon-alpha.
-Both TNF and interferon, at lower levels, inhibit the lipoprotein lipase enzyme that is necessary for the triglyceride metabolism, according to Dr Sonnenbend.
-Giving AZT to such people lowers alpha-interferon and triglyceride levels.
-Giving protease inhibitors also lowers the alpha-interferon levels but does not reduce triglyceride levels, as one would expect.
-_Remune lowers levels of TNF (According to Immune Response).
- Question: Will patients treated with HAART and Remune have lower triglycerides because Remune lowers TNF which lowers triglycerides?
I don't even know if they are looking at this or if it is relevant.
He says a risk factor that has been overlooked is that many people with HIV infection receive androgenic and anabolic steroids that are known to increase the red blood cell mass which increases the blood viscosity and this added plaque can contribute to heart attacks.
Dr. Sonnebend says: "Maybe we should emphasize the sorts of things that we would do with the person who is not HIV-infected who came in with low HDL, high total cholesterol and triglycerides. He says "I suppose we have been so focused on HIV as the killer that we forget the other things that can get you too. HIV doctors haven't taken them all that seriously till now." Several studies have reported cholesterol lowering drugs help although it is not known if successfully treating the cholesterol and lipids will affect lipodystrophy. Dr. Sonnenbend says patients should monitor hematocrit, testosterone and lipid levels. He prescribes cholesterol lowering drugs, such as Lipitor or Zocor and recommends exercise and diet. More studies are required on treatment of this disorder.
An article by Henry describing two young men on protease inhibitors with severe coronary artery disease has been mentioned often. However one of the patients was on protease inhibitors for only 4 weeks, hardly long enough to cause this. The other patient, on PI's for five months, had a family history of heart disease, but he did also develop the cervical pad.
There was an article published recently in the Archives of Internal Medicine (1998;158:1238-44) that found that many primary care doctors do not follow cholesterol guidelines. In one study of 603 people with heart disease, 67% of patients did not receive cholesterol lowering drugs, and 45% were not counseled on their diet or lifestyles. So....all the more reason for patients who are HIV+ to be treated by specialists or physicians experienced in HIV treatment, imo.
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