PROTEASE UNINHIBITED
FEB/96
In April, there will be three protease inhibitors available for your shopping delight in drug stores. Meanwhile, some things to keep in mind:
- Not all protease drugs are created alike. How strong they are, the kinds of resistance they cause, side effects, how well they work in combination with other drugs, and what kinds of antibiotics, anti-virals, antihistamines and birth control you can use at the same time are different with each drug.
- Two of these drugs, Crixivan (Merck) and Ritonavir (Abbott) are the strongest anti-HIV drugs to date. One study showed that people taking Ritonavir with under 100 T cells had significantly less chance of getting sick or dying in the following six months. This is the first time that any anti-viral has been shown to do this. And preliminary data suggests that these drugs may lower HIV in the lymph as well as in the blood.
- Taking protease drugs with other anti-virals, like AZT/3TC, ddI, d4T, etc, may make them stronger, and help the effect last much longer than just taking one protease alone. In small studies, adding AZT or AZT/ddC or AZT/3TC hit the virus much harder, for a longer period of time, in more people, and caused less AZT resistance. Just how long this effect lasts (1 year? 2 years?) - we have no idea.
- There is a lot of variation in how people respond to these drugs. In trials, some people have had fantastic T cell increases and viral load drops. Other people in the trials had very little response. We don't know why yet. Taking other anti-virals at the same time (see #3) increased how many people responded. Most of the big results reported in the media were in 40-60% of the people in the trials.
- Taking a protease drug requires a different kind of commitment from you than any previous anti-HIV drug. Be clear with yourself before starting that you can really commit to taking the drug as prescribed, each and every time. Why? Because anti-virals can only work if HIV is not resistant to them. Avoiding resistance for as long as possible is the key to getting the most out of the protease drugs. If you skip doses, even a few times, or take less than prescribed, your hiv may become resistant. In early protease trials, people who took lower doses developed many different kinds of HIV resistance, and now none of the protease drugs will work for them.
- Taking one can make you resistant to the others. Saquinavir can cause a partial resistance, but in some cases, full cross resistance. Taking either Crixivan or Ritonavir will make you resistant to all the other protease inhibitors. This is called cross resistance. It means you can probably only benefit from one of the powerful protease drugs. And, once your HIV gets resistant to whichever one you choose, no other protease drugs will work for you.
- SO it's worth taking your time to figure out your protease strategy. Check what drugs you can take with each of them, how often you have to take them, and what side effects you might expect. Consider getting a viral load test to measure what HIV is up to in your blood. Choose which drug(s) you want to try, if or what other anti-virals you want to take at the same time, and consider whether you can really commit to following your strategy 100%.
- How can you tell if your HIV is becoming resistant to a protease drug (or 3TC/AZT or ddI, etc)? By taking a viral load test. If your numbers are high, say 300,000, and you start a drug, your numbers should fall in a month. If they stay the same, or go up, then the drugs aren't working very well for you. It's more confusing if your viral load is low. Is the drug or your immune system or both, keeping your virus low? Talk to your doctor, and keep watching your viral load. In time we hope to have a better understanding of how to use the viral load test.
- Big unresolved questions: (some of them) What is the best drug combination to keep HIV and resistance low? No idea. What are the long term safety issues with the protease inhibitors? No idea. Lots of people agree that PWAs with high viral loads and symptoms, who have taken AZT and other drugs for years, might want to try protease. What about everyone else? What if your viral load is high, but you have no symptoms? Many argue that keeping HIV as low as possible is the key to survival. Others worry about getting strong resistance, before having any symptoms. What if viral load is very low - under 10,000? Taking combo anti-virals may keep it low, or maybe your immune system would do that anyway. Maybe a strong protease combo will kick you into some kind of remission, with no progression for years. Or maybe it will not change much, except to cause your HIV to become so resistant that you can't get any benefit from anti-virals if your T cells fall later. We have no idea.
Protease inhibitors seem to do great things in many people, but there are many unanswered questions about how best to use them. We have to push drug companies and doctors alike to collect the kind of information that will help us make the best decisions. Saquinavir is extremely expensive, and odds are that Crixivan and Ritonavir will be also. The companies promise useful, accessible patient assistance programs - don't hesitate to call them. Pressure local gov'ts for ADAP and Medicaid coverage. A drug is no help at all if no one can afford it.
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last modified: 5/12/96