HIV Treatment Alerts - October 2003
Fehmida Visnegarwala, MD

Q: I am a 44-year-old male and have had HIV for 8 years. I have always been on combination HIV drugs, but have switched around a lot because of side effects or better (simpler) drugs coming along. Right now, I am on Videx, Epivir, and Sustiva. I get bad leg cramps pretty frequently and sometimes feel weak in my arms. Is this anything I should worry about?

A: You should worry about both your symptoms. Your leg cramps are associated with high-frequency signals from nerves that usually last for seconds or minutes. Stretching the muscle may make it better. Muscle cramps can be caused by dehydration, low sodium in the body, kidney failure, or low thyroid activity. However, the most common cause of your cramps is peripheral neuropathy most probably caused by taking Videx. HIV disease itself and drugs such as Videx (ddI), Zerit (d4T), and Hivid (ddC)—the "d drugs"—are known to cause "distal symmetric peripheral neuropathy" (DSPN). This usually affects the feet first and then gradually climbs up the legs and then involves the hands and arms. DSPN caused by HIV usually gets better when HIV treatment is begun, but often there are other underlying causes such as heavy alcohol use, diabetes, or kidney failure that must be addressed. The DSPN caused by HIV medications is thought to be related to the toxicity of these drugs in nerves. The diagnosis of DSPN can be made using specific tests. However, your doctor will likely look for decreased or absent ankle reflex (done with a knee hammer) and/or vibration sense (done with a tuning fork).

The weakness in your arms is a little more worrisome and suggests you may have a local problem in your neck, which can be ruled out with an imaging study (CT or MRI) of the neck. If the above is normal, then an "electromyography" test may help diagnose the problem, whether it is chronic inflammatory demyelinating polyneuropathy (CIDP), Guillain-Barré-like syndrome (sometimes associated with the use of d drugs), and/or mononeuritis multiplex (see the following question). If Guillain-Barré-like syndrome is suspected, then the Videx needs to be discontinued. The management of DSPN will include drugs such as tricyclic anti-depressants, or gabapentin (brand name: Neurontin) and pain management. L-carnitine (1500 mg 3 times a day) has been shown to help in some studies.

Finally, it may be useful to check the level of lactic acid in your blood. For this test, blood must be drawn correctly: do not do any vigorous exercise the day before, come in fasting, and rest in the waiting room for at least 20 minutes. Your doctor or nurse must make sure blood is drawn without the use of a tourniquet and immediately placed on ice and transported to the lab within 20 minutes. Lactic acidosis may be associated with fatigue and weakness, as well as cramps, rapid breathing, nausea, belly pain, diarrhea, and tingling or pricking sensations on the skin.

Q: My T cells have recently slid to 314 and I am considering therapy for the first time. I heard that I should take HIV drugs that are from at least 2 or 3 different "families." Is this true?

A: If you have had a stable CD4 for a long time and your viral load is less than 50,000, and you have no symptoms such as weight loss, fevers, chronic diarrhea, or enlarged glands, then the first thing to do is 1) confirm that your T cells are still less than 350 AND 2) make sure you feel truly ready to get on therapy. If so, then you should talk to your doctor about HIV drugs. The decision to start HIV therapy in someone like you (who is not acutely ill) should never be hasty. Starting HIV treatment will mean taking every dose of your drug everyday without missing a single dose for a very long time. If you do not adhere to your medications, it is likely that your virus may accumulate drug-resistance mutations and eventually not respond to the drugs you are on. This would require changing that regimen, which usually means more pills, more side effects, and even less chance of successfully controlling the virus.

So if you are ready to start and we have confirmed that your T cell count is indeed less than 350, we should talk about your drug options. The goal of HIV therapy is to get the HIV viral load under 50 within 12 to 24 weeks and keep it there as long as possible. The current US government treatment recommendations for a preferred first-line regimen are to combine drugs from 2 classes: either a boosted protease inhibitor (Kaletra) OR Sustiva plus any 2 nucleoside reverse transcriptase inhibitors (nukes). Certain nukes should not be combined, such as Retrovir/Zerit, Videx/Zerit, and Ziagen/Viread. The triple nuke regimen of Trizivir (Ziagen, Epivir, and Retrovir in 1 pill) is not recommended if your viral load before starting therapy is more than 100,000. Also, there is more doubt about the strength of this regimen because all the drugs are from 1 class; an advantage is the low pill burden (1 pill twice a day).

Currently, there is no favorable information for treating with 3 classes of drugs. In fact, it may be dangerous because it could increase toxicity and decrease adherence. Besides the preferred regimens described above, there are several alternative drugs that are effective. HIV therapy must be individualized based on many factors such as patient lifestyle, pill burden, future drug options, drug toxicities, patient cardiovascular risk, costs, etc.

Q: After a long period (8 months) of chronic pain almost everywhere, a doctor told me I may have mononeuritis multiplex. What exactly is this and is it related to my HIV or HIV drugs? I am an African American female, 28 years old, and am taking Viramune, Zerit, and Epivir.

A: Mononeuritis multiplex (MM) is uncommon and often difficult to diagnose. A diagnosis would need to be confirmed with an "electromyography and nerve conduction test," where small needles are placed in your muscle and a small amount of electrical current is given to check your nerves. Mononeuritis multiplex involves the large nerves and develops over months to years. The most common causes of this disorder are low blood supply (involving small blood vessels that feed the nerves) or "demyelination" (loss of the insulation around the nerves). In HIV, the MM usually occurs early in disease state, though in patients with advanced disease this syndrome has been associated with CMV disease. In those with early disease, the cause is thought to be an autoimmune process (the immune system is reacting to some of the body's own proteins). It is unlikely that your symptoms are caused by your HIV drugs. Zerit and most nukes can cause peripheral neuropathy, but this is not related to MM.

Since you are African American woman there is a small chance that you may have "sarcoidosis," which may present with MM. If your doctor has not found any other symptoms then it is unlikely. If you have chronic hepatitis C, then a related condition called "cryoglobulinemia" may lead to MM. If not done already, it will be important to be checked for diabetes. The good news is that you may not need to change your therapy and even though you are dealing with a lot of pain, MM usually resolves on its own over time. Many patients with MM experience a lot of weakness associated with this disease. Pain management and not overexerting yourself are the mainstays of treatment. A vitamin B-12 shot and taking vitamins daily might be a good idea as well.

Q: Is there a relationship between high triglycerides and high blood sugar? I have both of these and have been on HIV medications for 6 years. Will this get worse? I am taking Glucophage for the high blood sugar, which my doctor says is early diabetes. I am a 38-year-old, white male, 5'10" and 180 pounds.

A: There is a definite relationship between high triglycerides and high blood sugar. Triglycerides are fat particles produced by absorption from the gut after eating; they can also be produced in the liver. These are broken down into smaller particles by a substance in the body called "lipoprotein lipase," which needs insulin for its action. So, when there is lack of insulin (as in diabetes) these fat particles are not chewed up and therefore float around in the blood leading to high triglycerides. There are other related metabolic problems, but this is a rather simple explanation of a very complex interaction that occurs in the body.

You have been on HIV medications for 6 years. I wonder if this has included protease inhibitors (PIs). There is a known link between new or worsening diabetes in patients treated with PIs. This is related to the development of insulin resistance caused by these drugs. Insulin resistance means that if your body normally needed 20 units of insulin to digest all the sugar that you absorbed after eating a fast food hamburger, you may now require 80 units to digest the same amount of sugar. You need more insulin to do the same work. High triglycerides, insulin resistance, high blood pressure, low HDL ("good") cholesterol, and central obesity (fat in the gut, resembling a pear shape) are all linked to the "metabolic syndrome" or "syndrome X." Having syndrome X and insulin resistance is bad over the long term. It is a risk factor for future cardiovascular events such as heart attacks and strokes.

So first things first: if you are on a PI, then you should be switched, if possible, to regimen containing a non-nuke (like Sustiva or Viramune) or to a triple nuke regimen (like Trizivir). Medical studies have shown that diabetes gets better and may even reverse when you stop taking PIs. If you are unable to switch from PIs, then perhaps switching to Reyataz is an option because it affects fats and insulin less than other PIs.

Among the drugs used for diabetes, metformin (brand name: Glucophage) is known to reduce insulin resistance. However, it carries a small risk of lactic acidosis, which could be a problem if you are using either Zerit or Videx. The other class of drugs that might help manage your diabetes is the insulin-sensitizing drugs. These include rosiglitazone (brand name: Avandia) or Pioglitazone (brand name: Actos). These drugs not only have the advantage of treating insulin resistance but actually may improve HIV-associated lipodystrophy.

Besides drug treatment, the 2 cornerstones for management of diabetes and syndrome X are diet and exercise. Your ideal body weight is around 150 pounds. So a well-controlled diet with a nutritionist's help will be extremely important. Detailed dietary recommendations can be found on the American Diabetes Association website (www.diabetes.org). Regular exercise not only will help your diabetes control, improve your weight control, and decrease your risk of heart attack, but will also decrease your risk of osteoporosis (brittle bones), which is an important complication of HIV disease and/or HIV therapy. If you have not been in an exercise program, starting a program such as brisk walking, jogging, cycling, or swimming for about 25 to 45 minutes several days a week will help. You may need medical clearance to join a more intensive exercise program such as the Houston Body Positive Wellness Program (www.montrose-clinic.org/BodyPos.htm).

Fehmida Visnegarwala, MD, is an assistant professor of medicine at Baylor College of Medicine, and the Director of Education and Research at Houston’s Thomas Street Clinic.

Send your questions for physicians to rita@centerforaids.org or by mail: Questions, P.O. Box 66306, Houston TX 77266-6306.

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Copyright © 2003 - Research Initiative Treatment Action (RITA!). Reproduced with permission. RITA! is published by The Center for AIDS. Contact Thomas Gegeny, MS, ELS, Editor, RITA! for permission to reproduce RITA!. tom@centerforaids.org. http://www.centerforaids.org

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