I'm often asked various questions from patients, nurses and physicians regarding HIV-related problems and their management. I always held the opinion that the more informed my patients are, the better acquainted they will be to assess their own needs and options. Many of the topics discussed in this month's installment of The Buzz are day-to-day and commonplace, covering clinical problems as well as new treatments and developing options.
A new class of agents is about to land in our lap. T-20 is part of this new group of drugs that stop the virus from latching or fusing with CD4-T cells; they are about to become part of our armamentarium against the virus within a very short period of time. I believe that as T-20 is used with shrewdness and discernment by clinicians, it can reduce the amount of virus in the blood and improve immune system functioning for patients who are in the most difficult of situations. That is, those with low T-cell numbers and high viral loads. One question I am also asked is: "Will this drug be used early on?" Perhaps, but probably not in many patients; the drug will be expensive and needs to be injected (like an insulin shot) twice daily by the patient.
Several studies were thought provoking, artful and provided some basis for using their design in clinical practice. One example was a study presented by Shlomo Stacznewski of Frankfurt, Germany, who successfully treated patients who either failed protease inhibitor treatment or had nucleoside-related (nuke) toxicity. Unique dual (double) protease inhibitor (PI) boosting with Kaletra plus saquinavir was used here. Other artful measures were incorporated in his work. First, for the patients who initially presented with resistance to PIs, they were placed on a treatment interruption or drug holiday until mutated virus reverted back to wild type (non-resistant or the older and native precursor virus) before starting on this new combination therapy. Second, he treated these individuals without any nuke backbone. The success of this approach, without the need for a nucleoside, is very tantalizing. I think this option should be placed on the table for patients in similar situations, but also needs much further study. (See "Kaletra/Sustiva" in Newsbriefs.)
Also, information about a new and useful tool, recently presented at the drug resistance meeting in Seville, Spain just prior to Barcelona, but later discussed there again, is a lab test called "replicative capacity" (RC). This measures the ability of the virus to replicate or reproduce and is an indicator of the fitness of the virus. Decisions about "when to start" treatment may potentially be made with the help of this test. Currently I am using the test in a different situation: if the RC is low in patients with high levels of resistance with detectable viral load, it may not be necessary to change that individual's therapy. This is because a low RC means low viral fitness and thus, immune function and T-cell count can continue to improve or be preserved. Much further work is necessary to research this new test device.
Finally, other new anti-viral drugs presented in Barcelona (discussed above and below in this article) will be useful and affect our management for many patients. They provide a great deal of hope for people because some of the newer treatments have distinct advantages over the older ones.
Several new protease inhibitors (PI) are on their way. A newly formulated version of amprenavir (Agenerase) -- its "pro-drug" or active component, called 908, is in clinical trials and we at Northstar Healthcare in Chicago are also participating in this research. It is a protease inhibitor that can be taken once daily when combined with small doses of ritonavir [Norvir] and has the added advantage of a low number of pills per dose. It will be much easier and tolerable for patients than the older form of this drug. (See "Agenerase Pro-Drug" in Newsbriefs.)
Another PI, atazanavir, is already available through expanded access. It is administered as only two pills once daily and has fewer side effects. It doesn't seem to cause elevations in cholesterol or triglycerides (another type of fat found in the blood) and causes less gastro-intestinal problems.
Tipranavir is a PI that has the advantage of being useful for people with resistance to other PIs. T-20, already discussed earlier in this article will be available by prescription early in 2003, as is FTC, a new nuke (see "T-20 Is Coming Too" in Newsbriefs this issue, also The Buzz, September/October issue).
First, let's not assume that the diarrhea is due to medications; an easy test to do would be laboratory analysis to check stools for parasites or infectious bacteria. If this test demonstrates infection, then have it treated. If negative, you can try various options, but one at a time. Often taking pancreatic enzymes that improve the digestive process can reduce diarrhea quite a bit. Acidophilus supplements to replace beneficial bacteria may also help. Calcium as a binder has also been found to be effective in some patients and some people take Tums, which contains reasonable amounts of calcium. Finally, many HIV-positive patients are lactose intolerant. Thus, reducing dairy from your diet may be helpful.
Not necessarily. If the bloating is being caused by an infection, it can easily be treated. Often bloating occurs due to dietary components such as greasy, high fatty foods, and "fast food." Also, because of lactose intolerance, dairy products may be the cause. Avoiding these can often help. Finally, I sometimes use metronidazole for some patients to reduce gas-producing bacteria in the gut.
A researcher from the Hospital Foch in Suresnes, France has recently discovered HIV activity in fat tissue, specifically within the fat cells of patients with lipodystrophy. If this finding correlates with fat redistribution problems, it may prove to have implications for possible treatments in the future. Research into affecting HIV replication specific to fat cells could also be investigated. Robert Gallo, the co-discoverer of HIV, stated that the finding may also explain why HIV is more difficult to eradicate. Presently, however, most experts believe that HIV and/or some of the anti-viral drugs affect the mitochondria and eventually lead to these fat-related abnormalities.
Every patient with fat-redistribution problems has different manifestations. Depending on the situation, various options can be attempted. Often changing the drug combination to medication that is less likely to worsen the condition is possible. I sometimes use medications that improve insulin sensitivity to reduce visceral (body cavity) fat. Also, various anabolic agents can be helpful in combating some of the body habitus changes, while using various anti-oxidant vitamins to improve mitochondrial function. Finally, don't underestimate the power of exercise to break down excess fat. A recent study has shown this to be quite advantageous when dealing with fat accumulation syndromes.
Currently the U.S. Food and Drug Administration (FDA) curtails its availability. Laws have been put in place to protect the public from many drugs with potential harmful effects. Thus all agents need to be studied adequately and the FDA has very high standards. New-Fill is an agent already proven and approved in other countries such as in Europe, Latin and South America, while safety and effect has also been presented in at least two international medical AIDS conferences. The suffering and disfigurement of lipodystrophy could be taken into account and perhaps some loophole could be used to allow for patient access under severe facial atrophy conditions.
When will it be available again to the major HIV-impacted community? Who is to say. A pharmaceutical company needs to step up to the plate and pursue distribution rights and studies to satisfy regulations. Still, some of my patients have found a way to continue getting access while some individuals are traveling to San Diego and seeing my friend Dr. Jorge Tagle in Tijuana for its administration.
I have been getting increased numbness and shooting pains in my legs. My doctor says this is from HIV. I am currently on Epivir, Zerit and Crixivan; I am undetectable and my T cells are 390. If my numbers are so good, why am I having these problems?
The nukes and more often, Zerit, have been implicated in causing or worsening the symptoms you describe. These symptoms are often referred to as peripheral neuropathy (distal symmetric type), and denotes damage that has occurred to the nerve endings. It can often be treated or reversed with either dose reductions of the offending drug, which in this case is probably Zerit, or by substituting another drug. Talk with your doctor about your treatment options. Some doctors prefer to treat neuropathy with medications such as amytriptiline or neurontin, which suppress the symptoms but unfortunately do not reverse the problem. Often vitamins such as folic acid and vitamins B1 and B6 are also helpful in improving the nerve function and reducing symptoms. In a small study done by the NIH (National Institutes of Health), acetyl-carnitine was found to repair the damage of peripheral neuropathy in HIV disease.
First, drugs such as "crystal-meth" or "Tina" and the other alphabet drugs are highly addictive. Once you're hooked it may not be easy to unhook. After getting high during an evening, being off them the next day presents with difficulties and lows that are so bad that it often leads to depression, anxiety and fatigue. Being on antiviral HIV medications may also have drug interactions. Eventually a host of psychological problems, not usually obvious to the individual himself using crystal, occurs. The metabolic changes occurring while being on them increase the body's breakdown of body mass and overworks the heart and cardiovascular system. Hence, wasting, lipodystrophy and a host of heart problems can and probably will eventually develop or worsen. Using recreational drugs also reduces the use of safe-sex practices. There is an epidemic of syphilis and hepatitis C on the rise; party drugs have added to this problem. Patients who are HIV-positive and get infected with hepatitis C then become confronted with a more complicated course that can be overwhelming and shorten one's life.
Daniel S. Berger, M.D. is Medical Director for Northstar Healthcare, Clinical Assistant Professor of Medicine at the University of Illinois at Chicago and editor of AIDSInfosource (www.aidsinfosource.com). He also serves as medical consultant and columnist for Positively Aware. Dr. Berger can be reached at DSBergerMD@aol.com or (773) 296-2400.