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.
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.
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