Foundations of ART Management in Heavily Treatment–Experienced Patients

Let's transition to discussing heavily treatment–experienced patients.

This figure summarizes what we currently understand, based on the data we have already discussed.¹ The first question one might ask is: What is the likelihood of susceptibility to a boosted PI or DTG? If the patient is susceptible to both, there are many options, including DTG plus NRTIs, even with no fully active NRTIs. One may also choose a boosted PI plus NRTIs (with the same caveats about the number of active NRTIs) or a boosted PI plus INSTI.

If there is susceptibility to PIs only, then a boosted PI plus NRTIs should be chosen as the new regimen.

If there is susceptibility to DTG and not PIs, then the new regimen should consist of DTG plus 2 NRTIs. Although data are limited, it is likely that BIC should perform similar to DTG in these settings.

If there is no susceptibility to either PIs or DTG (which means there is no fully active drug with a high barrier to resistance), then ideally one would compose the new regimen of 2 (or preferably 3) fully active drugs.

When we consider highly treatment–experienced patients, we are thinking about those who don’t have a high-barrier drug to use, regardless of how many lines of treatment they have received, and what regimens they have failed. Therefore, the regimen we must compose will contain 2—or preferably 3—fully active drugs.

To construct a new regimen for highly treatment–experienced patients, we must determine which drugs are likely to be fully and partially active, based on available resistance data and inferred resistance data.¹ New drugs in new classes are a very important part of these new regimens. These new drugs are ibalizumab (a monoclonal antibody attachment inhibitor), fostemsavir (also an attachment inhibitor), and a drug in the advanced stages of development for treatment-experienced patients, lenacapavir, a capsid inhibitor.^12-14

In addition, we have older drugs like enfuvirtide (which we now rarely use because of toxicity) and maraviroc if the patient has HIV that is CCR5 tropic only.¹