Back Back
Switching for PI Intolerance
Optimizing ART for a Patient With PI Intolerance and a History of Resistance and Nonadherence

Released: June 21, 2017

Expiration: June 20, 2018

Activity Information

Activity

Progress
1
Course Completed
Continue

In this HIV cases series, we highlight common patient case scenarios and the critical decision making that goes into selecting optimal patient management strategies. This case features a virologically suppressed man who is requesting a change from a boosted PI–based ART regimen due to GI toxicity. He has a history of adherence issues and virologic failure with resistance.

Case Details
A 52-year-old man was diagnosed with HIV 10 years ago and initially treated with efavirenz (EFV) plus emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF). He experienced initial virologic suppression; however, a lack of consistent adherence to his ART resulted in virologic failure. At failure, he was found to have M184V and K103N mutations and was placed on darunavir (DRV)/ritonavir (RTV) plus FTC/TDF. For the past 2 years, he has maintained virologic suppression but has complained of GI symptoms that he associates with his DRV/RTV. Neither symptomatic treatment nor a trial of atazanavir/cobicistat (COBI) has improved these symptoms. He states that he would very much like to consider other ART options.

Principles of Switching for a Patient With Adherence Concerns and Underlying Resistance
In considering an ART switch for this patient, I would suggest sharing with the patient the principles of switching ARVs in virologically suppressed individuals. First and foremost is the importance of maintaining viral suppression. To do this, the existence of underlying resistance and how this might limit treatment options should be considered. The case patient has an M184V mutation, which confers resistance to FTC and lamivudine, and the K103N mutation, which confers resistance to EFV and nevirapine.

Another important consideration is that, unlike other drugs, pharmacologically boosted PIs can often maintain viral suppression even if a patient’s ART regimen only includes 1 or even no other fully active agents. This is somewhat less likely to be the case with drugs with lower barriers to resistance, such as NNRTIs and first-generation INSTIs, the latter including COBI-boosted elvitegravir and raltegravir (RAL). This point was clearly demonstrated in the SWITCHMRK study, which randomized virologically suppressed patients to either continuation of their current boosted PI–based regimen or a switch to a RAL-based regimen and demonstrated a higher rate of virologic failure in those who switched to the RAL-based regimen, particularly if they had underlying NRTI resistance. Consequently, treatment guidelines advocate caution in switching virologically suppressed patients from a boosted PI to an alternative class if they have a history of treatment failure with resistance. For this patient, discussion would need to emphasize that, in general, a switch from a boosted PI with a history of M184V mutation would be associated with some risk.

Selecting a New ART Regimen
If after this discussion the patient still felt strongly about switching, one could consider emerging data with dolutegravir (DTG), an INSTI with a higher barrier to resistance than other drugs in its class. Analysis of a small data set from the SAILING study showed that for viremic, treatment-experienced patients who were treated with DTG and had only 1 active NRTI in their background regimen, virologic suppression was achieved in 12 of 12 individuals. For patients in this study who were treated with RAL and had only 1 active NRTI in their background regimen, virologic suppression was achieved in only 9 of 13 individuals.

An extrapolation of data from the large SWORD 1 and 2 maintenance studies could also be considered. These studies demonstrated that virologic suppression was maintained in 95% of patients who either remained on their stable regimen or switched to DTG plus rilpivirine (RPV). Although this was a robust data set using a treatment that would not be affected by the presence of M184V, it is important to note that the study excluded those with any history of virologic failure. Moreover, one would have to assume that this regimen would be effective for the case patient despite the presence of K103N mutation, which in vitro does not confer resistance to RPV.

Although more data and additional options may be on the horizon for patients who are suppressed on a boosted PI–based regimen and want to switch to another option despite underlying resistance, it is important to share with the patient that data remain limited in this setting and any switch would need to be done with caution and close monitoring. Based on current data, I would likely consider DTG plus FTC/TAF the most viable PI-sparing regimen for this patient.

Your Thoughts

Would you feel comfortable switching this patient from a boosted PI–based regimen? If so, what regimen would you consider? Please share your experiences and insights by joining the conversation in the comments box below.

Continue

Poll

1.
How likely would you be to switch the case patient to a regimen that did not contain a boosted PI?
Submit