Foundations of ART Management in Heavily Treatment–Experienced Patients

Now, we will discuss switching therapy in those who are virologically suppressed but who have underlying resistance. We have learned over the last few years that in this population, regimens can often be simplified. To do so, we must take advantage of the fact that certain drugs with high barriers to resistance may not require all of the drugs in the background regimen to be fully active.

The US Department of Health and Human Services guidelines do comment on the potential role of proviral DNA genotyping in this setting, since there is not a sufficient level of plasma HIV-1 RNA to assay.¹ This test can be used if there is a question about underlying resistance when the treatment history of the person is uncertain. The recommendation is not stronger because there is no real evidence to validate a benefit in this setting. If a proviral DNA genotypic resistance test is obtained, I would encourage anyone to interpret the findings with caution.

If a mutation is detected, there is most likely resistance to that particular drug. However, if no mutations are detected, resistance cannot be excluded.

When considering regimen modifications in patients who are virologically suppressed, it is very important to understand the patient’s drug resistance history, since it will not be possible to do routine resistance testing.¹ One needs to carefully review the patient’s treatment history and think about situations in which virologic failure may have occurred and what resistance may have emerged in those settings.

It is also important to review all available resistance testing. If there is uncertainty about treatment history or resistance history, a treatment modification should only be undertaken if the new regimen is likely to maintain suppression of resistant virus.

Within-class switches—such as from one NNRTI to another, from one PI to another, or from one high-barrier INSTI to another—usually will maintain viral suppression.

Caution is encouraged if considering switching from a boosted PI to another class if a full treatment resistance history is not known, especially if the new class does not include another high-barrier drug. In this situation, seeking out expert consultation may be a good idea to avoid the potential for viral rebound to occur.

One also needs to consider any adverse effects that a patient experienced while receiving previous therapies and current patient comorbidities. For example, if the patient has chronic hepatitis B virus (HBV) infection, the new regimen must include drugs that are active against HBV, such as tenofovir. Other comorbid conditions that might be affected by the change in therapy should be taken int consideration. Some of these are listed in the slide.