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Treatment Simplification
How New Data From CROI 2017 May Inform Treatment Simplification Options

Released: April 20, 2017

Expiration: April 19, 2018

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In this HIV cases series, we will highlight common patient case scenarios and the critical decision making that goes into selecting optimal patient management strategies. This case features a virologically suppressed young woman exploring a regimen switch and discusses how data recently presented at CROI 2017 may affect the treatment simplification options available to her.

Case Details
A 27-year-old female inquires about simplifying her HIV regimen. The patient has consistently attended her clinic appointments and has been highly adherent on a first-line regimen of atazanavir (ATV)/ritonavir (RTV) plus emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) for 3 years with no evidence of virologic failure or ARV resistance. Although she does not want to risk losing control of her HIV infection, she is increasingly unhappy with the number of different medications she has been taking after recently enrolling in a holistic medicine course.

Key Considerations
It is not uncommon for patients doing well on older ARV regimens to request easier or newer alternative regimens from their providers, even when they have successfully suppressed viral replication for years. For the provider, the top priority when considering such a switch must be maintaining virologic suppression, and an important corollary is preserving future treatment options by avoiding virologic failure and treatment-emergent resistance.

As clinicians, it is important first to understand the patient’s reasons for requesting a treatment switch, which should include a discussion of the benefits and drawbacks of the current regimen. This then leads to an assessment of what options are appropriate for the individual patient going forward. This case is somewhat atypical in that the patient is requesting a regimen with fewer active drugs rather than fewer pills. Paradoxically, such a switch may require the patient to take more pills since there are as yet no 2-drug combination tablets that would be considered an appropriate treatment regimen. That said, are there dual therapy options that might be reasonable as switch strategies? New data presented at CROI 2017 suggest that 2-drug regimens may, in the future, be viable switch options, as discussed below.

Evolving Data on Simplification Strategies
Current switch strategies used in clinical practice typically involve changing from one 3-drug combination (usually comprising older ART agents) to another (usually comprising newer drugs combined into a single tablet). One newer approach involves switching from a 3-drug combination to a regimen consisting of fewer drugs. At its extreme, some have proposed that a single drug may suffice, but recent data clearly show that such an approach is a bad idea, as studies of dolutegravir (DTG) monotherapy led to frequent virologic failure, often with viral resistance. By contrast, data from other trials suggest that DTG-based dual therapy may be an effective switch strategy for some patients.

The noncomparative, single-arm ANRS 167 LAMIDOL trial showed that switching patients on virologically suppressive 3-drug regimens to the 2-drug combination of DTG and lamivudine (3TC) maintained virologic suppression in 97% of patients through 40 weeks of follow-up. Although these results are preliminary, they are encouraging and indicate that this approach may be a viable option in the future if larger studies validate these initial findings. A 2-drug DTG plus 3TC regimen would also be appealing for its lack of food restrictions/requirements and for the possibility of meaningful cost savings, as 3TC is available as a generic drug.

Data from a second 2-drug ART switch study involving DTG were also presented at CROI—from the phase III SWORD 1 and 2 studies that compared continuation of a fully suppressive 3-drug regimen with a switch to the 2-drug regimen of DTG paired with rilpivirine (RPV). After 48 weeks of follow-up, the 2-drug regimen maintained virologic suppression in 95% of patients and was well tolerated with no emergent integrase resistance mutations in the small number of patients with confirmed virologic failure. Overall, the study results demonstrated that, compared with a suppressive 3-drug ART combination regimen, a switch to DTG plus RPV resulted in:

  • Noninferior efficacy (ie, HIV-1 RNA < 50 copies/mL)
  • Comparable (but numerically higher) frequencies of any adverse event (AE), serious AEs, and drug-related grade 3/4 AEs (not surprising, as ongoing tolerated therapy infrequently produces new AEs)
  • A modest increase in frequency of drug-related grade 1/2 AEs and AEs leading to study withdrawal
  • Significant improvement in bone markers

There are some issues that may influence interest in the DTG plus RPV regimen, most notably the food requirements for RPV absorption and potential RPV-associated drug–drug interactions, particularly the fact that RPV cannot be coadministered with proton pump inhibitors. In this particular patient, it is also important to discuss the fact that RPV is not a recommended drug in pregnancy, an issue that needs to be mentioned to female patients with childbearing potential.

If the patient is adamant in wanting to change her regimen, reasonable options might include using newer combination tablets that would keep her on an HIV PI-based regimen (eg, darunavir/cobicistat plus FTC/tenofovir alafenamide) or suggesting she switch to a single-tablet regimen as an alternative. Neither choice would reduce the total number of drugs she is receiving, but either would reduce the number of tablets she was required to take. If neither of these options is acceptable to the patient, changing to one of the aforementioned 2-drug combinations might be reasonable, as long as the patient understood that this would not be an approved recommended regimen (because of the limited data supporting such a change) and was agreeable to a more careful follow-up strategy to ensure early detection of treatment failure.

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Which management strategy would you recommend in the case patient discussed in this commentary?
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