Antiretroviral Therapy

Antiretroviral Therapy

Physicians use viral loads and T-cell/CD4+ counts as approximate guides for starting treatment. There are no magic numbers, but the International AIDS Society recommends antiretroviral therapy when:

• The patient has a symptomatic HIV infection, no matter what the test results are
• The viral load rises above about 30,000 copies/mL, no matter what the T-cell/CD4+ count is
• The T-cell/CD4+ counts fall below 350 x 106/L (350/ul), no matter what the viral load is
• The viral load is between 5000 and 30,000 copies/mL and the T-cell/CD4+ cell count is between 350 and 500 x 106/L

Patients with a viral load below 5000 copies/mL and a T-cell/CD4+ count above 500 x 106/L are at low risk for short-term (3 year) clinical progression of disease. Whether therapy should be started or not in these patients depends on potential side effects, the patient's willingness to adhere to the strict therapy regimen, and other factors such as health insurance coverage.

When antiretroviral drugs are effective, the viral load should decrease to an undetectable level within 30 to 90 days of initial treatment. The T-cell/CD4+ count should simultaneously increase, usually by about 100 cells/cc during the first year.

Resistance Testing

Resistance testing evaluates whether HIV has evolved resistance to particular drugs. This test can help physicians decide on an initial antiretroviral regimen and help guide choices when treatment must be changed.

There are two types of drug resistance tests:

• Genotype assays examine the HIV's genetic material and identify particular mutations responsible for resistance. Generally, the viral load must be above a certain value (i.e., greater than 1000 copies/mL) for genotype testing to be useful. If genotype testing reveals a mutation known to cause resistance to a particular drug, the patient's drug therapy must be managed accordingly.
• Phenotype assays measure the ability of the virus to grow and replicate in the presence of varying concentrations of drugs. A virus that grows well in the presence of even a high concentration of drug indicates resistance.

There are many different types of both genotype and phenotype assays, many of which still need to be clinically tested and adequately standardized before becoming commercially available.

Despite the reliability of these tests, problems with drug resistance assays include the following:

• They are expensive.
• Turnaround time is usually several weeks, which is too slow for treating the fast-evolving HIV.
• Negative results are difficult to interpret. The assays cannot detect all resistant genotypes or phenotypes.

As of June 2000, the American Medical Association recommends resistance testing to help determine a patient's initial antiretroviral regimen only if there are factors that indicate an increased risk for resistance.

For example, there is some concern that HIV in women who are pregnant and in newborn children is more likely to develop resistance than in the general HIV-positive population. Patients should consult with their physicians to find out if they are at high risk for resistance, and if so, how resistance testing may benefit them.

The American Medical Association cautions that decisions to change therapy should be based primarily on a confirmed increase in viral load and the patient's treatment history. Resistance testing should be considered only as an additional source of information that may or may not be helpful