Thai researchers have discovered that patients who fail treatment with a commonly used, inexpensive, first-line antiretroviral therapy (ART) are also usually resistant to other, similar drugs, leaving progressively fewer options for replacement therapies. Since catching treatment failure early is key to preventing further resistance, this research, published in the Feb. 1 issue of Clinical Infectious Diseases and currently available online, also argues for greater access in the developing world to tests that detect when the amount of virus in a patient's blood is increasing.
Combined antiretroviral therapy has dramatically changed the course of HIV disease, with a substantial reduction in illness and death both in developed and in developing nations. In Thailand, where a 2004 estimate put the number of HIV-infected people at 600,000, a generic, fixed-dose, combined pill of three antiretroviral agents has been available since 2002. In 2004, it was estimated that 60,000 Thai citizens would take this combination of stavudine, lamivudine, and nevirapine, known as d4T/3TC/NVP.
Lead author Somnuek Sungkanurparph, MD, of RamathibodiHospital in Thailand, and co-authors found that when this combination stopped working, it was nearly always because the virus had developed mutations that also make useless several other drugs of the same type.
Ideally, if a patient developed resistance to one or more of the elements in d4T/3TC/NVP, then he or she would simply switch to a different combination of drugs. However, in Thailand and other resource-limited countries, economics often determines what types of drugs are available. Some drugs that, in a developed country, might serve as a second regimen are either unaffordable or unavailable.
A small number of drugs do exist that are available and affordable in Thailand and that could serve as a second regimenif the drug-resistant virus is caught before it gets out of hand. Sungkanurparph found that when levels of virus in patients' blood were high, nearly two-thirds of them developed multiple drug resistance that limited the options for second-line therapy. When levels were low, only about one-third did.
Unfortunately, the test to detect how much virus is in a patient's blood is not widely available or affordable in many developing countries. Without this tool, which allows early detection of treatment failure, physicians can not change antiretroviral medications in time to stay ahead of resistance. In order to prevent sickness and death from HIV in developing countries, the accessibility of both ART and the virus-detection test need to be increased.
"In settings where antiretroviral agents are limited, prevention strategies for HIV resistance are crucial," said Sungkanurparph. "Early detection of virological failure provides more options for the second regimen and better treatment outcomes."
Source: Infectious Diseases Society of America (IDSA)