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New Directions in Individualizing ART
A Positive Look Ahead: New Directions in Individualizing ART

Released: August 09, 2023

Tristan J. Barber
Tristan J. Barber, MA, MD, FRCP
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Key Takeaways
  • Efforts to improve the quality of life for people living with HIV remain a key reason to individualize ART.
  • There are several investigational agents and future ART strategies offering different routes of administration and less-frequent dosing.
  • Further data are needed in vulnerable populations (eg, racial and ethnic minority groups, women, older persons, and children) to improve our data pool so we can truly individualize therapy for everyone we meet.  

The landscape of antiretroviral therapy (ART) is ever evolving. Here, I review investigational agents and future strategies that may improve our ability to individualize ART regimens for people living with HIV and address much needed gaps in the literature to allow us to customize care for all.

2-Drug Regimens

With investigational antiretrovirals (ARVs), we are seeing a coalescence of 2-drug regimens at the forefront. In the pipeline are several potent 2-drug combinations: oral doravirine with islatravir, and oral and injectable lenacapavir-based regimens (eg, oral lenacapavir in combination with islatravir).

Some of these investigational regimens lack the traditional nucleos(t)ide reverse transcriptase inhibitor backbones that have been associated with long-term toxicity, such as kidney or bone issues with tenofovir disoproxil fumarate and increased cardiovascular risk with abacavir. 

Dosing Frequency

Efforts to improve the quality of life for people living with HIV remain a key reason to individualize ART. Many are seeking regimens with reduced dosing frequency. Currently, we have a long-acting, intramuscular ART regimen available with dosing every 8 weeks, and going forward, we see the development of an oral, once-weekly ART regimen and a subcutaneous ARV given every 6 months, albeit currently coadministered with an oral daily tablet. It is worth noting that complete ART regimens that can be given every 6 months are being explored.

Treatment Modalities

An ART implant is a new treatment modality under investigation that could offer patients the ability to control replication of their virus without taking daily oral medicines. Instead, the drug is released for longer periods, such as a year or more. If this comes to fruition, it could represent—in reality—a functional cure from the relief of needing to take daily medicines. Other investigational treatment modalities include gastric residence devices, vaginal rings, patches, and broadly neutralizing monoclonal antibodies. 

Genetic Profiling

Aside from new ART agents and alternative treatment modalities on the horizon, genetic profiling is another tool that can assist in individualizing ART. 

We have seen genetic profiling in HIV management before with HLA-B*5701 testing to look for allergies to abacavir. In a wider sense, genetic profiling may have the potential to facilitate ARV dosing, ensuring that people get the right dose considering interpatient variabilities in drug metabolism and differences in body composition. In addition, genetic profiling could be used to identify markers to predict those who might be more at risk for an ARV-related adverse event such as weight gain.

Addressing Gaps 

Women and Racial and Ethnic Minorities
Although we have seen more effort to include greater diversity in gender, gender identity, and racial and ethnic background in clinical trials, I think it is fair to say that we still see an overrepresentation of White men. This continues to be an unmet need. Going forward, we need to ensure more representation of diverse populations in studies, including participants from resource-limited settings. 

Other Vulnerable Populations 
In addition to other aspects of diversity, more data on new agents and approaches to individualize ART in other vulnerable populations are needed, including in the pediatric population, older persons, and people who are pregnant or breastfeeding. These groups are often excluded from clinical and implementation studies. We need to improve our data pool so we can truly individualize therapy for everyone we meet. 

Switch Studies in Persons Not Virologically Suppressed 
Finally, many ART switch studies are performed in people who have been virally suppressed for 6 months or longer. We need a better understanding of how to offer people who cannot achieve viral suppression—for one reason or another—the opportunity to benefit from new treatment approaches. 

Your Thoughts?

Which investigational agents or potential treatment modalities are you most excited about? How will it affect your ability to individualize ART regimens for your patients? Join the discussion by posting a comment.