What is drug resistance testing?

Drug-resistance testing also has become a key tool in the management of HIV-infected individuals. Resistance testing is now routinely used in individuals experiencing poor responses to HIV therapy or treatment failure.

In general, a poor response to initial treatment would include individuals who fail to experience a decline in viral load of approximately hundredfold in the first weeks, have a viral load of greater than 500 copies per mL by week 12, or have levels greater than 50 copies per mL by week 24. Treatment failure would generally be defined as an increase in viral load after an initial decline in a person who is believed to be consistently taking his or her medications.

Because drug-resistant viruses can be transmitted, guidelines from the U.S. Department of Health and Human Services (DHHS) (https://aidsinfo.nih.gov/) and International Antiviral Society-USA (IAS-USA) have suggested that resistance testing be performed in individuals who have never been on therapy to determine if they might have acquired HIV that is resistant to drugs.

The goals of antiviral therapy are to enhance immunity and delay or prevent clinical advancement to symptomatic disease without inducing important side effects or selecting for drug-resistant virus. Currently, the best marker of a drug’s activity is a decrease in the viral load.

Ideally, prior to initiating treatment, the viral load and the CD4 cell count should be checked and the viral load test then repeated after approximately four weeks of treatment. If the patient is beginning a regimen that includes two to three drugs for which the patient’s virus does not appear to be resistant, it is expected that the amount of virus should decrease by at least a hundredfold during this interval.

The ultimate goal is for the viral load to decrease to undetectable levels which should occur by approximately 12-24 weeks. There are some individuals that despite taking all of their medications correctly will suppress their viral load to less than 200 copies/mL but not consistently undetectable levels. It is not completely known how to optimally manage this situation but many experts would continue to monitor on current therapy as long as viral load remains below 200 copies/mL.

Those who are not having an appropriate response to therapy need to be questioned to make sure that they are taking their medications correctly, and if not, why. If the viral load is not going to undetectable levels and the patient is taking the medications correctly, then it is likely that there is a resistant virus to some of the medications. Drug-resistance testing then should be performed and the patient managed as described in the next section.

Once the patient’s viral load is suppressed, they can often have viral load and CD4 cell counts performed less frequently (for example, every three to four months and in select cases every six months or possibly even less).

There are currently two main types of resistance tests available in the clinic: one that is called a genotype and the other a phenotype assay. The former looks for mutations in the virus and the latter the actual amount of drug it takes to block infection by the patient’s virus.

The genotype test is very helpful in those being screened for the presence of resistant virus prior to initiating treatment and those experiencing viral rebound on one of their first treatment regimens. The phenotype test is particularly useful in those who are highly treatment experienced and have substantial amounts of drug resistance, especially to the protease class. The information derived from these tests, along with a tropism test will ultimately tell the provider which of the many approved drugs are likely to be fully active against the specific patient’s virus.

Using this information, the goal is to include at least two and at times preferably three fully active drugs in the next regimen in order to optimize the chances of suppressing the viral load to undetectable levels. It is often useful to seek expert consultation in managing those with multidrug resistant virus.