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Project Inform Community Alert

August, 1999

Table of Contents:


A Warning and a Promise

Recent discussions about the possibility of some people going off therapy have had both good and bad consequences. On the positive side, they renew hope that HIV may not necessarily require a lifetime of uninterrupted therapy and offers a hint that people may be able to overcome drug resistance. But the downside is that many people skim over the fine points of the discussion and have begun to use simple drug holidays whenever they like.

The notion of simple drug holidays -- taking a weekend or day off here and there -- is as much a bad idea today as it ever was. Repeated, short-term drug holidays will greatly increase the chances of developing resistance to anti-HIV drugs. In short, those who want to live long and healthy lives should avoid short little drug holidays.

So what is the scientific discussion about? Researchers are talking about structured interruptions of therapy. This means that the effort to stop treatment is part of a plan, with a goal in mind, not a matter of whimsy or personal convenience. Three general hypotheses will soon be tested. All call for interrupting therapy for a specific length of time, at a pre-planned point in time, in hopes of achieving a particular treatment goal.

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In one hypothesis, researchers hope to determine if cycling people on and off therapy according to a set of rules might trigger a stronger immune response against HIV, and over time, make a person less dependent upon drugs to control viral load. A second hypothesis asks whether months-long interruptions in therapy might overcome drug resistance. The third hypothesis simply asks whether people suffering from serious side effects or severe drug weariness might give their bodies a rest from therapy without doing more harm than good. For now, there are no hard answers to these questions, only a few crumbs of intriguing data from small, short studies.

The Promise?

Project Inform, working with New York's Treatment Action Group, Los Angeles-based Foundation for AIDS and Immune Research and an international team of researchers, will do everything in our power to get answers as quickly as possible. We are jointly sponsoring an international scientific meeting at the end of July to help coordinate research on treatment interruption. We will share information as soon as it becomes available and continue to work as advocates, making sure the research gets done as well and as soon as it can.


ABT-378 Reaches Expanded Access Program

ABT 378 is a new protease inhibitor being developed by Abbott Laboratories that offers some significant advantages over the company's current product, ritonavir. A very small expanded access program will begin by mid-September for people no longer responsive to available therapies.

According to the manufacturer, the program will serve only a few hundred people in the US because of limited drug supplies. First priority will be given to people who have fewer than 50 CD4+ cells and/or an active opportunistic infection. Second priority, supply permitting, will be for people with CD4+ counts between 50 and 100. Third priority, supply permitting, will be for people with CD4+ counts between 100 and 200. A much larger expanded access program will extend availability of the drug to more people in early 2000. Because of the limited size of the program beginning in September, it's important to apply as soon as possible. Those interested should call Project Inform's National HIV/AIDS Treatment Hotline at 1-800-822-7422 for information.

ABT-378 is also available through clinical studies. Abbott reports many slots are still available, primarily for people who have failed only a single protease inhibitor and who have not yet used a non-nucleoside reverse transcriptase inhibitor (delavirdine, efavirenz or nevirapine).


Experimental Drug Combinations

The Federal Guidelines recommend that anti-HIV drugs be used in combination, typically including two drugs of the Nucleoside Analog Reverse Transcriptase Inhibitor class and one Protease Inhibitor or one Non-Nucleoside Reverse Transcriptase Inhibitor. Some doctors and patients have experimented with other combinations, such as using more than three drugs, using all three classes of drugs at once or combining multiple protease inhibitors. The information about these combinations is based on small studies. Some may be beneficial, while others may produce unwanted interactions or require changes in dosing, for the better or the worse. Using experimental combinations without considering known and unknown risks may jeopardize a person's current health status and future treatment options.

Why Consider These Combinations?

The most common reason for exploring these combinations is to construct effective regimens for people who are no longer responding to proven first and second line combinations. Some studies of third line therapy involve up to seven drugs, including drugs of every class.

Another motivation is to simplify drug dosing. Sometimes, combining two protease inhibitors may increase the blood levels of one or both drugs, thus reducing the number of pills needed, the number of times a day drugs are taken, or changing the associated food restrictions associated. This only works well with certain combinations, such as ritonavir plus saquinavir or indinavir. Combining some drugs often offers no advantages: it simply increases the number of pills a person must take. While using novel combinations to simplify regimens is an important goal for some people, limited data are available on how to best do this. Patients and doctors need to be well informed, lest they do more harm than good.

Another motivation for experimental combinations is to increase the overall potency of the regimen. The effect of combining the "right" drugs can be much greater than what would be expected from simply adding another drug. Some people seeking the strongest possible anti-HIV regimen may use all three classes of drugs. This approach runs the potential risk of using up options too quickly. If a person experiences viral breakthrough while on a regimen that includes all classes of drugs, s/he could develop resistance to any and all classes of drugs, thus greatly limiting future options.

For more detailed information on anti-HIV drug interactions, contact Project Inform's toll-free National HIV/AIDS Treatment Hotline at 1-800-822-7422 and request the Drug Interactions Fact Sheet.


Experimental Dosing Schemes with Protease Inhibitors

This chart is intended only to show what is known about some of the combinations and how people are currently experimenting with them. It should not be viewed as recommendations for dosing schedules as the ideal dosage may turn out to be quite different than that shown. It is also not a recommendation for any particular combination, even though it is clear that some combinations have a great deal more to offer than others. Even the most promising combinations have only been evaluated in small, short-term studies. The information on the chart might serve as a starting point for discussion among doctors, pharmacists and patients when considering an experimental combination.


 

AmprenavirDelavirdineEfavirenzIndinavirNelfinavirNevirapineRitonavirSaquinavir
Amprenavir APV No data available3EFV 600mg, 1x; APV 1,200mg, 3x8 (no clinical data)Standard DosesStandard Doses1No data available2APV 1,200mg, 2x; RTV 200mg, 2x4 (no clinical data)Standard Doses
Delavirdine DLVNo data available3 No data availableIDV 600mg, 3x; DLV 400mg, 3xStandard DosesNo data availableStandard Doses5Standard Doses
Efavirenz EFVEFV 600mg, 1x; APV 1,200mg, 3x8 (no clinical data)No data available IDV 1,000mg, 3x; EFV 600mg, 1xStandard DosesNo data availableStandard DosesUse with Caution6
Indinavir IDVStandard DosesIDV 600mg, 3x; DLV 400mg, 3xIDV 1,000mg, 3x; EFV 600mg, 1x Standard DosesIDV 800-1,000mg, 3x; NVP 200mg, 2xRTV 100mg or 400mg, 2x; IDV 400 or 800mg, 2x7Standard Doses
Nelfinavir NFVStandard Doses1Standard DosesStandard DosesStandard Doses Standard DosesRTV 400mg, 2x; NFV 750mg, 2xNFV 750mg, 3x; SQV 600 or 800mg, 3x
Nevirapine NVPNo data available2No data availableNo data availableIDV 800-1,000mg, 3x; NVP 200mg, 2xStandard Doses Standard DosesStandard Doses
Ritonavir RTVAPV 1,200mg, 2x; RTV 200mg, 2x4 (no clinical data)Standard Doses5Standard DosesRTV 100mg or 400mg, 2x; IDV 400 or 800mg, 2x7RTV 400mg, 2x; NFV 750mg, 2xStandard Doses RTV 400mg, 2x; SQV 400mg, 2x
Saquinavir SQVStandard DosesStandard DosesUse with Caution6Standard DosesNFV 750mg, 3x; SQV 600 or 800mg, 3xStandard DosesRTV 400mg, 2x; SQV 400mg, 2x 
1x = one time daily. 2x = two times daily. 3x = three times daily.




Footnotes

  1. Nelfinavir increases amprenavir levels by two to three times.

  2. Currently being studied. Amprenavir levels are expected to decrease.

  3. Currently being studied. Amprenavir levels are expected to increase.

  4. Several dosing schemes are being studied, including RTV 100mg 2x + APV 1,200mg 2x; and RTV 500mg 2x + APV 1,200mg 2x. Studies of APV+RTV both dosed once daily are also planned.

  5. Ritonavir dose can be reduced to 500mg or 400mg 2x if side effects are observed.

  6. Efavirenz reduces saquinavir (Fortovase®) levels by 60%. Studies are ongoing to determine if higher doses of saquinavir can be used in combination with efavirenz. It may be possible to use a combination of RTV+SQV+EFV with RTV 400mg 2x; SQV 400-800mg 2x and EFV 600mg 1x.

  7. For this combination, indinavir can be taken with food. Doses being studied include RTV 400mg 2x + IDV 400mg 2x; RTV 100mg 2x + IDV 800mg 2x; and RTV 200mg 2x + IDV 800mg 2x.

  8. The dose of amprenavir can be reduced to 1,200mg two times daily if RTV 100-200mg 2x or NFV 1,250mg 2x is also used.



  
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This article was provided by Project Inform. Visit Project Inform's website to find out more about their activities, publications and services.
 
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