Treatment Review; Double Issue #26 & #27 November 1997

Compassionate use: A compassionate use program is when a drug is made available before it's approved to people who have few or no other options. They may have no other options because they've taken the other drugs in the same class and the HIV in their bodies has built up resistance to the drugs so they don't work any more. Or they may not be able to take the approved drugs because they can't tolerate the side effects.

For children: This program will provide abacavir to children with HIV infection who aren't responding to approved anti-HIV treatments or who cannot take them because of side effects. Children with a condition known as HIV-related encephalopathy can also qualify. Encephalopathy is when there's shrinking of the brain tissue, which can be caused by HIV or other infections. To participate the child must be HIV+ and 6 months to 14 years old. The child must have a viral load over 100,000 and a CD4% of less than 15% of their total lymphocyte count despite therapy with approved antiretrovirals for at least 4 weeks. Or the child must have a treatment limiting toxicity to AZT, 3TC and ddI. Doctors can contact the Glaxo-Wellcome Program Coordinator at (800) 501-4672.

For adults: This open label, compassionate use protocol will provide abacavir to adults with HIV infection who have failed or are intolerant to standard therapy. To qualify, you must have been previously treated with a combination of at least two antiretrovirals and one protease inhibitor. Or you must be unable to take any available therapy due to treatment limiting toxicity. The following recommendation is suggested by the drug company: abacavir should be given as part of a combination antiretroviral treatment including other antiretrovirals which you've never taken. To participate you must be HIV+ and 13 years or older with a T4 cell count under 100 and viral load over 30,000. You cannot be pregnant or nursing, have kidney or liver failure, or a serious medical condition such as diabetes, congestive heart failure, cardiomyopathy, or other heart problem. Doctors can contact the Glaxo-Wellcome Program Coordinator at (800) 501-4672.

Abacavir study results: Very little information is available from abacavir studies. In a study that only lasted 12 weeks, abacavir had a strong anti-HIV effect both on its own and combined with AZT. People in this study hadn't used any other anti-HIV drugs except AZT. No information is available about the anti-HIV effect of abacavir in people who have taken other anti-HIV drugs.

Side effects: Abacavir has only been studied in a small number of people. The side effects seen so far include increased fatigue, changes in liver function tests, headache, abdominal pain, constipation, diarrhea, nausea, vomiting, sleeplessness, skin rash, dizziness, and allergic reactions which may include skin rash and fever.

Resistance and abacavir: The changes in HIV that cause drug resistance are called mutations, and different mutations cause resistance to different drugs. In test tube studies, if the HIV already has some mutations that make it resistant to 3TC, ddI or ddC, more mutations are likely to occur so that the HIV may quickly become resistant to abacavir too.

Crossing the blood brain barrier: Some of the early encouraging news about abacavir was because the drug might cross the blood brain barrier and affect HIV in the CSF better than other anti-HIV drugs. CSF stands for cerebrospinal fluid which is in your spinal column and around your brain. A spinal tap where a small amount of that fluid is taken out is one way of measuring brain infection. New information shows that abacavir doesn't get into the CSF any better than the other anti-HIV drugs AZT, d4T and 3TC.

What does it add up to? For someone not responding to current treatments, trying to figure out which combination of anti-HIV drugs will work is very difficult. If you're already resistant to most nucleoside analogs, using abacavir as part of an anti-HIV drug combination may add very little or no anti-HIV effect. The result is that HIV then has an easier time getting resistant to the other anti-HIV drugs in the combination.

For example, if you start therapy with nelfinavir (Viracept) and abacavir because these are the only anti-HIV drugs you haven't tried, the abacavir might not do much to control the HIV. The risk is that your treatment will be the same as taking nelfinavir alone. Nelfinavir is a protease inhibitor. HIV develops resistance to protease inhibitors taken alone very quickly. Once the HIV is resistant to one protease inhibitor, it may also be resistant to other protease inhibitors as well. If possible, it would be better to use abacavir with at least two new anti-HIV drugs that have a good chance of working. For people who aren't in an emergency situation, waiting for other new treatment options would probably be better than taking abacavir right way.

What other options are there? Other new anti-HIV drugs are being developed. Compassionate use programs for two new anti-HIV drugs are planned to start by the end of 1997. These drugs are Sustiva (formerly known as DMP 266) and adefovir dipivoxil (formerly known as bos-POM PMEA, new trade name Preveon). See page 12 for details on these programs.

The Network has a Simple Facts Sheet on Understanding Drug Resistance in English and Spanish. Simple Facts Sheets on dozens of other topics are available at this site as well. If you'd like a printed version of any of these sheets you can also contact The Network at (800) 734-7104. Information for this article came from a National AIDS Treatment Advocacy paper, and from a Treatment Action Group Report. Call us to send you a copy of any of these publications as well.

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