HIV Drug Resistance Testing

AIDS Survival Project recently hosted a Lunch and Learn on "HIV Drug Resistance Testing: Giving Medications the Best Chance for Success," presented by Laura Maroldo, RPA-C, Associate Director, Medical Affairs and Education with ViroLogic and West Midtown Medical Group in New York City.

Ms. Maroldo began her presentation by stating, "The goals of HIV treatment should be that it is potent, durable and tolerable. In addition, one wants a regimen to suppress HIV as much and as long as possible, restore immune function, preserve future drug options and improve the quality of life."

What Is "Treatment Failure"?

Treatment failure occurs when one's medications stop controlling HIV and as a result, viral load goes up and CD4 count goes down. As the immune damage continues, there is increased risk of opportunistic infections. Drug resistance occurs when genetic changes or "mutations" in the virus allow it to continue multiplying while one is taking HIV drugs. A single mutation can give HIV resistance to some drugs. For most drugs, however, several mutations are needed for HIV to become resistant. "Resistance," according to Ms. Maroldo, "is not all or nothing, but a matter of degrees." She continued by explaining that a mutation is a change in the structure or behavior of the virus, and its genetic code determines shape and characteristics. A mutation is a change in that genetic code, which changes the way HIV looks and behaves.

Why Does Resistance and Treatment Failure Occur?

Basically, for four reasons:

• A random occurrence

• Drug interaction decreasing effectiveness

• Malabsorption

• Nonadherence to the treatment regimen

Ms. Maroldo emphasized that nonadherence is the reason for most treatment failures. So what does this mean? Take your medications as directed!

Viral Fitness

The technical term for viral fitness is replication capacity (RC). The RC indicates how well HIV makes copies of itself and may be an important factor in the pace of disease progression.

All of this information is used for strategic planning to create a treatment plan and a diagnostic plan. The former should be individualized considering the following:

• Pill burden

• Number of doses per day

• Lifestyle

• Side effects

• Effectiveness (potency and durability)

• Preserving future drug options

• Overall quality of life

The diagnostic plan looks at not only the CD4 count and viral load, but includes resistance testing and fitness/RC testing.

When Is Resistance Testing Recommended?

• When drugs stop working

• When drugs don't work well enough

• For pregnant women starting treatment

• Chronic infection, treatment naive

There are three types of resistance:

1. Clinical resistance: HIV multiplies in your body even though you are taking antiviral drugs.

2. Genotypic resistance: The genetic code of HIV has mutations that are linked to drug resistance.

3. Phenotypic resistance: HIV multiplies in a test tube when antiviral drugs are added.

Genotypic testing is where the genetic code of the sample virus is compared to the wild type. The code is a long chain of molecules called nucleotides. Each group of three molecules, called a codon, defines a particular amino acid used to build a new virus.

Letters and numbers are used in combinations to describe mutations. An example would be K103N. The first letter, K, is the code for the amino acid in the wild type virus. The number 103 identifies the mutant codon. The second letter, N, is the code for the "changed" amino acid in the mutant sample.

According to the New Mexico AIDS InfoNet, "Phenotypic testing is where a sample of HIV is grown in the laboratory. A dose of one antiviral drug is added. The growth rate of the HIV is compared to the rate of wild type virus. If the sample grows more than normal, it is resistant to the medication. These results are reported as 'fold' resistance. If the test sample grows thirty times as much as normal, it would be reported as a '30-fold resistance.' Phenotypic testing is also a direct measure of resistance and is quantitative."

A virtual phenotype is a test that combines some element of both genotypic and phenotypic testing. After a genotype is done on the sample, phenotypic test results for other virus samples with a similar genotypic pattern are taken from a database. Less expensive and faster than running both tests individually, these results tell you how the virus is "likely" to behave.

Cross-resistance is where the virus is resistant to more than one drug. An example of this is cross-resistance between Crixivan and Norvir, both of which are protease inhibitors. So, it is important for you and your health care provider to take this into consideration when switching medications because of resistance.

These tests are widely available and are covered by most insurance, as well as Medicare and Medicaid (except in Texas and Mississippi). If a person is uninsured and is self-paying, there is a program through ViroLogic to help you find coverage for such tests. The toll-free number is 1-87-PHENOAID.