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Personalized ART Treatment
Tomorrow’s ART, Today: Personalized Treatment for All People With HIV

Released: December 03, 2025

Tristan J. Barber
Tristan J. Barber, MA, MD, FRCP
Activity Information

Activity

Key Takeaways
  • Aside from viral load, many factors play into the choice of ART regimen for both initiation and switch, such as comorbidities, comedications, fear of stigma or discrimination, and individual preferences.
  • Ensuring that ART is reviewed at every visit and taking a person-centered and collaborative approach to HIV management is key to optimizing long-term health and quality of life for every person living with HIV.

In my experience, antiretroviral therapy (ART) is never one-size-fits-all. That is, healthcare professionals should always aim to select an appropriately individualized regimen for each person living with HIV when initiating therapy, and we should be open to modifying a virologically suppressive regimen if necessary. Here, I’ll discuss considerations for how to apply best practices in individualizing ART among people with HIV and identify how future ART agents may provide additional options for selecting optimized, individualized regimens.

Factors That Drive ART Choices
The first step is considering factors that drive ART choices. In addition to achieving sustained viral suppression, treatment must also be minimally impactful on an individual in terms of tolerability and simplicity. Matching the right regimen to the right person for optimized health-related quality of life allows for integration of ART into lifelong care and supports avoidance of stigma and discrimination.

Assessing ART preferences should be a routine part of every patient visit, involving counseling on options, supporting adherence, and ensuring that decision-making is shared and person centered.

Research shows that people with HIV want more involvement in decisions about their treatment. Key aspects of treatment to discuss include pill burden and size, dosing frequency, side effects, comorbidities, drug–drug interactions, pregnancy considerations, disclosure and privacy concerns, adherence history and lifestyle factors, inconvenience to social life, and food requirements.

It is also important to discuss social determinants of health when assessing ART, as they can play an important role in an individual’s ability to maintain ongoing engagement in care. These can include healthcare access, quality of healthcare, education, racism and discrimination, economic stability, housing availability, and environmental conditions.

ART Regimen Selection
For first-line therapy, global guidelines have harmonized around the use of a second-generation integrase inhibitor, combined with 1 of 2 nucleoside reverse transcriptase inhibitors (albeit with caveats for those with hepatitis coinfection, individuals who previously took pre-exposure prophylaxis, and those with a very high baseline viral load, low CD4 count, or preexisting resistance).

Potential weight gain and cardiometabolic, renal, and drug interaction issues should also be considered when choosing a regimen. People who are transgender may also have specific concerns about ART and gender affirming hormone therapy (GAHT), although for the most part, they can be reassured that ART and GAHT can be used together safely. I tell people that even if they are prescribed ART that has the potential for interactions with GAHT (such as protease inhibitors), adverse events can be monitored for, and hormone dosing can be adjusted based on clinical effects and measured concentrations.

However, even people with virologically suppressed HIV on stable ART can be candidates for ART switch. In the case of stable switch, factors to consider include new available options, current viral load, previous ART and prior regimens that failed, transmitted or acquired resistance, adherence, concomitant medications, and individual preferences. Comorbidities and pregnancy intention are also important factors.

Future ART Agents
The most recent ART innovations have been in the field of long-acting therapy, namely injectable cabotegravir and rilpivirine, but also lenacapavir for treatment-experienced people. What other options might soon be available?

I think the combination of subcutaneous lenacapavir with intramuscular cabotegravir looks promising and might offer a long-acting option for those with prior drug resistance. For people who prefer oral ART, there are new daily options: doravirine with the novel nucleoside reverse transcriptase translocation inhibitor islatravir is now looking favorable in naive and switch studies compared to bictegravir/emtricitabine.tenofovir alafenamide in phase III, and bictegravir/lenacapavir is in earlier development. In addition there are longer-acting once weekly oral options in development that utilize islatravir, both in combination with oral lenacapavir and with ulonivirine, a novel non-nucleoside.

Other long-acting agents in earlier stages of development include once-yearly lenacapavir, ultra-long cabotegravir, the capsid inhibitor VH499, and developmental integrase inhibitors: VH-184, GS-1219, and GS-3242.

I find the development of a third-generation integrase with activity against HIV with first- and second-generation integrase mutations particularly exciting given recent reports of an increase in population levels of detectable integrase resistance in some settings.

My hope is that increased options for long-acting ART will broaden access to these agents, although expanding access to the most vulnerable populations remains a key priority.

Your Thoughts
Now more than ever, we have the opportunity to provide person-centered and holistic care for people living with HIV. What questions do you ask your patients when assessing whether their ART regimen is the most optimal for them? Leave a comment to join the discussion!