Understanding Treatment Failure
Adherence and Drug Resistance Play Crucial Roles
July 2009–Growing numbers of patients in Asia are experiencing treatment failure, a problem that occurs when antiretroviral therapy (ART) can no longer stop HIV from multiplying. Treatment failure is directly linked to whether a patient consistently takes all antiretroviral doses on time (known as adherence) and to antiretroviral drug resistance.
Drug resistance itself is a complex process in which the HIV virus slowly learns how to escape the effect of an antiretroviral and continues multiplying. This is achieved through developing genetic mutations that create a "smarter" mutant virus. Ongoing research is teaching us more about the relationship between adherence and the way resistance to individual antiretroviral drugs develops.1
Treatment educators in Viet Nam use a block game called Jenga to illustrate how the health of an HIV-infected person can be unbalanced by failure to adhere to drug regimens and by other treatment and care issues.
Antiretrovirals can be categorized by their potency, defined as their ability to prevent HIV from multiplying. They also have different genetic barriers to resistance, a measure of how many mutations it takes for the virus to figure out how to escape the effect of the drug. A high genetic barrier means that the virus has to acquire many mutations to avoid being suppressed; a low genetic barrier means that it only needs to acquire a few mutations to keep multiplying. For example, ritonavir-boosted lopinavir (Kaletra, Aluvia) is very potent and has a high genetic barrier to resistance because at least six mutations are needed to prevent it from working. But while nevirapine is potent, it has a low genetic barrier to resistance because only one mutation is needed to stop it from working. This means that high levels of adherence (for example, more than 95 percent of all doses) are needed to prevent resistance from developing.
When antiretroviral doses are skipped or when only one or two out of three drugs are taken at a time, this leads to uneven drug levels in the body. HIV then has a chance to multiply and acquire mutations. The more frequently this happens, the greater the chance that the drugs will not work anymore, even when taken correctly and on time.
The overall goal of ART is to prevent HIV from multiplying for as long as possible using the same antiretroviral regimen. Adherence together with individual drug characteristics will influence if or when treatment failure occurs.
1 Gardner EM, et al. Antiretroviral medication adherence and the development of class-specific antiretroviral resistance. AIDS. 2009; 23:1035–046
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