SAN FRANCISCO—All official guidelines on HIV treatment either recommend drug-resistance testing or suggest considering such testing depending on the individual patient, Brad Hare, M.D., said at a meeting on HIV management sponsored by the University of California, San Francisco.
But deciding whether to use genotypic or phenotypic assays can be difficult, said Dr. Hare, a physician in the positive health program at the university.
Genotypic drug-resistance assays identify the presence of specific mutations in the HIV genome. Drug resistance is then inferred through an algorithm or a database analysis that matches these mutations to patterns of drug resistance.
Phenotypic assays use viral isolates or recombinant virus derived directly from the patient's plasma. The analysis derives from a culture-based system, and the concentration of a specific drug needed to inhibit viral replication can be quantified. In general, genotypic testing holds the edge early in a patient's disease, before the virus develops complex patterns of resistance. Phenotypic testing tends to be better late in a patient's infection, when the patient may see more regimen failure due to virus with complex mutations. (See box.)
Both tests may be required in complicated patients.
Results are available in days.
Is less technically complex than phenotypic assay.
Has proven value in predicting short-term virologic outcome.
Mutations may precede phenotypic resistance.
Can detect mixtures of resistant and wild-type virus.
Is less expensive than phenotypic assay.
Is an indirect measure of resistance.
Requires a viral load ≥1,000 copies/mL.
May not detect viral species with <20% prevalence.
Requires interpretation.
Cannot assess interactions between mutations.
Correlates of resistance are less clear for some (especially new) drugs.
Cannot test new drugs immediately.
Is a direct measure of resistance.
Results are similar to assays of bacterial resistance.
Results are easily understood.
Can be used for any drug.
Requires no knowledge of genotypic correlates of resistance.
Assesses effects of interactions between mutations.
Able to test new drugs immediately.
It takes weeks to get results.
Results may oversimplify the situation.
Resistance thresholds are not defined for all drugs or standardized for different assays.
Does not take into account the activity of drugs in combination.
Requires a viral load ≥500-1,000 copies/mL.
May not detect minor species.
Is more expensive than genotypic assay.