Ask Dr. Jeff
Question: Last year I had an HIV genotype resistance test that said I had resistance to the non-nucleosides (Viramune, Sustiva, and Rescriptor), so I switched off of Viramune and on to a protease inhibitor. Now I got another resistance test and it does not show resistance to Viramune. What is going on? Was the first test wrong? Can I go back on Viramune now?
Answer: HIV drug resistance tests have some very significant limitations. First, they only give information about only the most common strains of HIV that you have, those that make up over 20% of the total HIV in your blood. Second, they provide good information about only the drugs you are on at the time the test is done.
Your experience is not at all uncommon. After a person stops an anti-HIV medication they have become resistant to, some mutations tend to drift into the background and are not detected by resistance tests. (Other mutations, such as those to AZT, may persist in large numbers of HIV viruses long after someone stops a specific anti-HIV medication.) This is because when a person is not taking any anti-HIV medications, the original, non-resistant strains of HIV tend to grow back. These non-mutated viruses are often called "wild type."
So, do the viruses with mutations disappear? Most people think they do not. So, when you restart a drug you had been resistant to in the past, those resistant HIV viruses that are still lurking around will rapidly grow and become the dominant strain in the body. This is because the non-resistant, wild type strains would be kept from growing by the medications.
Recently, however, a couple of studies reported that people with resistant HIV who were switching to a new combination had a better response if they first stopped all medications for 3 months, compared to people who switched right away. The theory proposed was that some resistant strains of HIV might actually disappear for good, when the wild type virus was allowed to grow without any medication. But, this was a small number of people, and during the time off of drugs, viral loads went very high and T helper cells dropped significantly in many of the people. Subsequently, other research showed that you could still find the resistant HIV strains in circulating blood cells in people who stopped drugs for 3 months. To try to determine if there is any benefit to stopping therapy for a few months when switching to a new regimen, the AIDS Clinical Trials Group (ACTG) is beginning a large trial.
Another problem with genotype tests for resistance is that the level of resistance that the test reports is based on how people with the same mutation did on particular medications. But, resistance is not usually an all-or-none phenomenon, particularly for the nucleosides and protease inhibitor classes of drugs. For example, it has been shown that adding Norvir to Crixivan, when people are resistant to Crixivan, results in suppression of HIV in a significant number of people. This can be explained by the higher Crixivan level in the blood due to the addition of Norvir. So, the virus might be resistant to lower levels of a drug, but still sensitive to higher levels of the same drug.
It is also important to remember that since not all strains of HIV within your body carry the same mutations, when treatment options are limited it may be reasonable to use drugs that have been used in the past. In your situation, though, it is likely that a non-nucleoside drug would not be helpful in a combination because, for the non-nucleoside analogue class of medications, resistance does appear to be more of an all-or-none phenomenon.
This article was provided by Seattle Treatment Education Project. It is a part of the publication STEP Perspective.