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Individualizing ART: STIFF Cost
Switching ART Without a “STIFF Cost”: Individualizing ART in Patients Who Are Virologically Suppressed

Released: June 28, 2023

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Key Takeaways
  • There are several reasons to optimize ART in patients who are virologically suppressed, including simplification, tolerability, interactions, food/fluid requirements, fertility, and cost.
  • Single-tablet regimens, 2-drug regimens, and nonoral regimens offer growing options for ART individualization.
  • For more discussion of strategies to individualize ART, register here to join me and a panel of experts from around the world at our live symposium, either virtually or in person.

Thanks to the success of modern antiretroviral therapy (ART), the life expectancy of people whose HIV is treated continues to improve and is now approaching that of the general population.

Single-tablet regimens, 2-drug regimens, and nonoral regimens (eg, injectable cabotegravir, rilpivirine, lenacapavir) offer growing options for ART individualization, even after patients achieve virologic suppression.

“STIFF Cost”

Reasons to optimize ART in patients who are virologically suppressed can be summarized using the acronym “STIFF Cost.”

  • Simplification: Reduce pill burden and/or dosing frequency
  • Tolerability: Enhance tolerability and/or decrease toxicity
  • Interactions: Prevent or mitigate drug‒drug interactions
  • Food/fluid requirements: Eliminate food or fluid requirements
  • Fertility: Allow for optimal use of ART during pregnancy or in cases where pregnancy may occur
  • Cost: Reduce costs

Simplification is the most straightforward reason to understand, so let’s look at the others in turn.

Tolerability
Although newer antiretrovirals (ARVs) are more tolerable and associated with less serious adverse events, we still worry about more subtle, long-term adverse events.

For example, the use of abacavir, some protease inhibitors (PIs) (eg, darunavir [DRV]), and integrase strand transfer inhibitors (INSTIs) has been associated with an increased risk of incident cardiovascular events.

Significant weight gain has been observed in some individuals—particularly women and Black persons—after initiating or switching to ART regimens containing INSTIs or tenofovir alafenamide. However, current guidelines do not recommend switching ART if weight gain occurs because it is unclear if switching their regimen will reverse it. Fortunately, this is being examined in trials such as the DEFINE study of switching to a DRV-based regimen and the Do It Study of switching to a doravirine-based regimen.

Interactions
ARVs may interact with several medications, necessitating a change in therapy to avoid toxicities or changes to efficacy. For instance, to avoid decreased INSTI exposure, special consideration should be taken to separate INSTI dosing from polyvalent cations (eg, aluminum, magnesium, and calcium—often ingredients in multivitamin tablets; dosing separation recommendations may differ with each INSTI.

Anticoagulants and antiseizure medications are common culprits for drug interactions across several drug classes, including INSTIs, nonnucleoside reverse-transcriptase inhibitors, and PIs. Boosted PIs and cobicistat-containing regimens are subject to numerous drug‒drug interactions because of their ability to inhibit drug-metabolizing enzymes (eg, CYP3A4).

Healthcare professionals should consult the US Department of Health and Human Services guidelines, the University of Liverpool HIV Drug Interactions website, or tools such as HIV-ASSIST to remain diligent in managing drug‒drug interactions. 

Food and Fluid Requirements
Several ARVs require coadministration with food for optimal absorption (eg, rilpivirine, DRV). Therefore, it is imperative to assess food insecurity for each patient when selecting a regimen.

Occasionally, during a severe illness, patients are unable to take oral medications and/or require the use of enteral feeding tubes. In these cases, healthcare professionals should explore if liquid formulations are available or if ARVs can safely be crushed without affecting drug concentrations.

Fertility
Neural tube defects were an initial concern with use of dolutegravir-based regimens during pregnancy, but new data support the use of dolutegravir as a preferred component in initial regimens. Other ARVs recommended in pregnancy include raltegravir, atazanavir/ritonavir, DRV/ritonavir, or efavirenz with tenofovir disoproxil fumarate (TDF)/emtricitabine or TDF/lamivudine.

ART regimens with insufficient safety data in pregnancy (eg, 2-drug regimens) should be avoided because of the potential of fetal toxicity and/or altered pharmacokinetics—especially in the second or third trimester.

Cost
Finally, the cost-effectiveness of therapy for HIV treatment has been well established, but for patients for whom cost is an issue, we may consider including generic medications (eg, efavirenz or TDF). However, use must be balanced with the possibility of increased pill burden and/or tolerability issues.

Learn More
Clearly, there is much to consider when individualizing ART. To learn more, join me and a panel of experts from around the world as we discuss strategies for individualizing ART at our live symposium at IAS 2023 in Brisbane, Australia. You can participate in person or via live simulcast.

IMPORTANT NOTE: This live event will be available only to registered attendees of IAS 2023. If you have registered for IAS 2023 and would like to participate, please proceed to the in-person program or the conference online portal provided by the organizers. If you haven’t registered for the conference, you can do so here.

Unable to make it to the IAS 2023 meeting? Check out our encore virtual symposium here. 

Your Thoughts?

How do you approach individualizing ART in your practice? For what reasons do you switch ART regimens in persons living with HIV who are virologically suppressed? Join the discussion by posting a comment.