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Supplement Introduction

Winter 2005

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

Patrick G. Clay
This supplement was the brainchild of the late editor of Positively Aware, Charles Clifton. Charles and I met in (appropriately enough) San Francisco, during the Retrovirus conference in 2004 to discuss ways to educate patients about how their body breaks down medicines. The intent of this supplement is to provide foundational general knowledge about the pharmacokinetics and pharmacodynamics (see ABCs of Antiretrovirals) of antiretroviral medications. It also gives specific recommendations on currently available medicines. Why does your doctor prescribe Lexiva once a day for you and twice a day for your partner? Why do you have to eat with Reyataz and cannot eat with Crixivan? Why is Videx EC given sometimes at 250 mg and sometimes at 400 mg daily? These were just some of the questions Charles and I hoped to be able to answer with this supplement.

How much (milligrams) of a drug should be taken at one time? The answer most often times is: enough to work, but not too much to cause significant side effects. Most antiretrovirals are dosed to achieve in the body a level of drug that falls into what is called a "therapeutic range" (see Figure 1: Therapeutic Range). Taking enough of the medicine (having drug concentrations somewhere on the graph) will, in most cases, give you an effect. These effects can be good (therapeutic) or bad (toxic).

If the drug level is appropriate for the virus in your body, you could see a lowering of the viral load and/or increasing of the CD4 count. These would obviously be good therapeutic effects. Taking too much or not having enough of the medicine in your body (incorrect dosing or poor adherence) could result in either toxic effects or no effect. Neither of these are desired outcomes -- for you or your doctor! The paragraph below provides a more detailed explanation of the graph. It is important to understand these concepts, as they are pivotal to the information provided in this supplement.

Figure 1: Therapeutic Range
Sub-optimal levels: These are drug concentrations that are associated with a low chance of a therapeutic effect.
Therapeutic effect: In the case of antiretroviral drugs, it is the reduction of HIV-RNA, the increase in CD4 cells, and the prevention of opportunistic infections.
Therapeutic range: The size of the difference between doses or drug levels that cause a therapeutic effect versus a toxic effect.
Toxic effect: Toxicity from the drug
The drug concentration in the blood rises as you go from left to right along the x-axis or bottom of the graph. The actual amount (milligrams per milliliter of blood, see ABCs of Pharmacokinetics) varies depending on several factors including: the drug, prescribed dose, how long you have been taking the medicine and how long it has been since you took your last dose. The chance of the drug having an effect increases up to a maximal amount as you go from bottom to top or up the y-axis. As stated previously, for antiretrovirals this effect is measured by changes in T-cell count and viral load. You probably know that the most you can reduce your viral load is down to less than 50 copies per milliliter -- so there is a maximal effect the drug can have on your virus. Same with T-cells -- your body can only make so many over time and at some point you will have T-cells in the "normal" or non-HIV infected range. These two levels (undetectable viral load and normal CD4 count) represent a maximal effect of the anti-HIV medicines. What your maximal effect may be, however, is also dependent on your history of taking HIV medicines and how much damage the virus has already done to your body. You and your doctor should have talked about what the goals for your drugs are before you started taking them. Not everyone can or should use an undetectable viral load and "normal" T-cell count as goals.

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If the drug you take is not in sufficient quantity, you can get sub-optimal levels. At this drug concentration, you would likely not see a therapeutic (good) benefit from taking the medicine. Even though you don't get a positive effect, you can still see a negative one. For instance, taking low doses of Retrovir will not change your viral load or T-cells, but may still cause you to have anemia.

If too much medicine is taken, then the chance that you will have a toxic effect becomes more likely. An example of this is taking too much Crixivan. Very high levels of Crixivan can cause you to develop stones in your kidneys (very painful!). Not only is this drug's recommended doses (from the company and in this supplement -- see Protease Inhibitors) at levels that usually don't allow this to happen, drinking plenty of water immediately after the dose and during the day help minimize this risk

The challenge with HIV medicines is that the "therapeutic range" in many instances is still being discovered. What is the maximum level of drug that should be in the body daily to provide long term therapeutic effects? Sadly, this is not known for every drug. What doctors and researchers understand more clearly for most anti-HIV drugs is what dose of a drug is associated with toxicity. Manufacturers' and doctors' recommended and prescribed doses reflect this knowledge. This does not mean side effects cannot happen from having therapeutic levels of the drug in the body. As you are probably aware, long-term side effects of some of these medicines (lipodystrophy and diabetes, for example) may result from taking the proper amount of medicine and having therapeutic levels of the drugs. Unfortunately, long-term side effects from medicines, even when dosed appropriately, are not unique to anti-HIV drugs. Diabetics can develop resistance to their insulin and those with asthma who have to take steroids are all too familiar with long-term side effects of medicines. However, many side effects are related to the amount of drug in the body. Having the optimal amount of drug in your body and keeping it that way consistently over time may offer the most effective way to minimize side effects.

Though this supplement presents the most appropriate doses, levels and combinations of antiretrovirals, long-term therapeutic success is still only achievable with continual maximal adherence. The emphasis on honest communication with your doctor, pharmacist and nurse about your HIV medicines, other medicines you might be taking (especially ones available over the counter!) and how these medicines make you feel cannot be strong enough. This supplement is meant to help you understand more about what happens to the drugs after they are inside your body. It should be used as a reference when you are talking to your doctor about current or new medicines. It is the intent of the authors that by providing this educational material, we are able to increase your understanding of the medicines used to treat HIV. If by accomplishing a higher knowledge level about antiretrovirals in persons affected by this virus, we are able to improve one person's outcome or prevent one virus from becoming resistant -- then we will say this supplement was successful.

Lastly, this supplement provides many recommendations that are not found within the package inserts of medicines. Many of the recommendations made within are based on the authors', editor's and TPAN's current understanding of the currently approved anti-HIV medicines. This supplement in no way should supplant what your doctor has prescribed for you. At no time should you consider altering the dose, frequency or diet instructions for your anti-HIV medicines without first talking with and getting approval from your doctor. What we try to emphasize in this supplement are that these medicines are different in everyone and your doses are likely to reflect this. Only you and your doctor know what is best for you -- that is how your medicines are best managed.

Sincerely,
Patrick G. Clay, Pharm.D.
claypg@umkc.edu

Back to Winter 2005 contents page.


Got a comment on this article? Write to us at publications@tpan.com.

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!



  
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This article was provided by Positively Aware. It is a part of the publication Positively Aware. Visit Positively Aware's website to find out more about the publication.
 
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HIV Medications: When to Start and What to Take -- A Guide From TheBody.com
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