The AIDS Beacon™

With the help of antiretroviral medications today, individuals who are HIV-positive have a good prognosis for living many years after being diagnosed. However, one of the most common reasons that treatments fail is due to the development of drug resistance. According to AIDS Community Research Initiative (ACRIA), up to 30 percent of new HIV infections contain strains that are resistant to one or more antiretroviral drugs currently available.

Johns Hopkins School of Medicine states on its Web site that HIV is prone to making mistakes during replication, which are known as mutations. If the virus mutates while a person is on antiretroviral drugs, the phenomenon known as drug resistance can occur. The more frequently the virus mutates, the greater the likelihood that drug-resistant mutant viruses will be present in the body.

One goal of antiretroviral drug therapy is to inhibit replication of the virus by blocking the activity of the proteins reverse transcriptase and/or protease. This will prevent mutations from occurring.

Antiretroviral drugs have a unique shape that allows them fit in a “lock and key” position on reverse transcriptase and/or protease proteins. When mutations occur, the shape of the receptors on these proteins changes, which prohibits antiretroviral drugs from binding to them.

If the virus is allowed to replicate, it will continue to infect new CD4 cells (immune white blood cells) in the host’s body. When HIV infects humans, it mainly targets these immune cells and decreases their quantity, making it harder for the body to fight infections.

Antiretroviral drugs are usually given in combinations of three or more. The purpose of this is to increase the likelihood that replication and mutations will be inhibited. A three drug combination can lower viral load (HIV viral levels in the blood) up to 99.9 percent, according to ACRIA and a group of physicians and researchers who study new treatments for HIV and AIDS.

If the virus is resistant to one of the drugs, it may not be resistant to the others in the mixture and therefore will still be effective. However, cross-resistance is also a possibility. If the virus becomes resistant to one drug, it can also become resistant to other drugs in the same class.

Preventing Drug Resistance

The best way to prevent drug resistance is to adhere to the dosages and protocols provided by physicians. There is no guarantee that a complete adherence will prevent drug resistance from occurring. However, missing doses greatly increases the chances of drug resistance taking place.

Patients should also be conscientious about following the directions on the prescription labels, especially with regards to specific dietary requirements when taking the medication. Some medications need to be taken without food. The presence of food in the digestive tract may decrease absorbance levels into the bloodstream, ultimately increasing the chances that HIV will resume replication.

People experiencing diarrhea or vomiting should report these symptoms to their physicians. These symptoms can cause medications to be excreted from the body before they can be fully absorbed, thus increasing the risk of developing drug resistance.

Drug Resistance Tests

Physicians may conduct a drug resistance test to determine which antiretroviral medications would be most effective for different patients. Typically, information about previous drug regimens, CD4 count, viral load, and results of previous drug resistance tests are taken into consideration when deciding which medications are best for a patient.

Phenotype and genotype testing are used to determine drug resistance. Results are found to be most useful when both of these tests are conducted.  During phenotype testing, a blood sample is taken and exposed to current drug treatments. The samples are then analyzed to see which drugs are most effective in preventing HIV from replicating in its presence. Genotype testing analyzes HIV for the presence of specific mutations that are known to be drug resistant. By examining the individual’s genetic mutations in HIV, physicians can determine to which antiretroviral drugs the individual is most susceptible.

When Drug Resistance Occurs

There are three ways physicians determine if drug resistance has occurred. First, physicians determine whether the viral load in the blood is at a detectable level several months after starting a certain antiretroviral therapy. Second, physicians can also measure whether viral load levels change from undetectable to detectable levels. Finally, they can measure whether viral load levels increase while on a drug regimen. Any of these instances may indicate that resistance has developed.

Patients should discuss any of these occurrences with their physician, who will then determine what measures should be taken. Factors that may play a part in the physician’s recommendation include what antiretroviral medications have been taken in the past, which medications a patient is resistant to, CD4 levels, and which medications the patient has not used yet.

Current drug treatment may not always be discontinued if drug resistance has occurred. There are different degrees of resistance, some of which a drug will still work but not as effectively as it once did.

Drug resistance is problematic in many new HIV infections across the globe. Researchers are looking for new ways to help combat this problem. With strict adherence to antiretroviral medications, the probability of drug resistance occurring is greatly reduced.