se drugs you haven’t used before. Project Inform recommends “changing at least two elements of the combination therapy at the same time,” preferably choosing drugs never used before. You may think you have tried 'em all, but there could be some “overlooked options” still available to you, including still-experimental drugs (see “At the End of Your Rope?”, POZ, October 1997). In particular, consider using drugs shown by researchers to enhance each other’s effectiveness. Examples are ddI-hydroxyurea, delavirdine-indinavir, delavirdine-saquinavir, ritonavir-saquinavir, nelfinavir-saquinavir and nelfinavir-indinavir.
Try to select drugs to which you are less resistant. Even if they include some new drugs, most folks with lots of drug experience will still have to use drugs they’ve tried before. Thus, the issue is picking those drugs to which your HIV has the least resistance. In general, this is likely to mean the drugs you’ve used the least and/or which you’ve used in combos with some degree of effectiveness. In addition, some PWAs are now rushing to do drug resistance tests. There are two types: Genotypic, which looks at the genetic code of a person’s strain of HIV, and phenotypic, in which his or her virus is actually grown in a test tube and then exposed to various drugs. Results from these tests might provide useful information, especially when they seem to correlate with viral load and CD4 counts. But the ultimate usefulness is still uncertain. For example, many anecdotal reports indicate that the presence or absence of mutations found with genotypic testing (the cheaper and more widely used method) may not always correlate with viral loads. People with high viral loads don’t always show the viral mutations that would explain resistance to the drugs they’re taking. Conversely, people whose virus does have resistance-associated mutations may still have undetectable viral loads. Currently, most experts recommend against using these tests as a major determinant of therapy choice.
Make sure the drugs are getting into your blood. See the points on adherence, absorption and drug interactions, above.
Bring the load down hard and fast. Research from Dr. Dale Kempf and colleagues at Abbott Labs suggests that the time period antiretrovirals keep working depends on just how low the viral load goes after starting treatment. Some researchers also believe that a fast decraese in virus levels is preferable to a long, slow decline. If your viral load has not decreased by at least 10-fold (one log) within four weeks of starting therapy, discuss with your doctor the idea of adding another drug to the combination, at least until the load comes down to lower (hopefully undetectable) levels. If you have a long history of using single drugs, consider starting treatment with a four- or five-drug combination.
When your drug combo fails, the first step is researching all the possible options and discussing them with your physician. Once you clearly understand why drugs fail-and how to create the best possible new combo-you can greatly improve your chances of finding an effective treatment approach.