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Individualizing and Simplifying ART
ART Simplification Through Treatment Individualization

Released: November 07, 2023

Nagalingeswaran Kumarasamy
Nagalingeswaran Kumarasamy, MBBS, FRCP, PhD
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Key Takeaways
  • What is simple for one person may not be for another. Personal preference and potential adverse effects should help determine what ART regimen is best for an individual.
  • Rapid ART initiation and same-day ART help simplify decisions and improve treatment adherence.
  • Active, continuous support from the clinic and an individual’s personal support network are key to maintaining ART adherence and virologic suppression. 

Antiretroviral therapy (ART) is lifelong. People living with HIV must take these drugs every day to see the benefits of viral load suppression and increased CD4+ cells. This is why ART simplification is so crucial: It is much easier to adhere to lifelong therapy when the regimen is not so complex.

Fortunately, in resource-limited settings, we now have a single-tablet regimen available, a combination of dolutegravir, lamivudine, and tenofovir disoproxil fumarate (TDF), which is recommended by the WHO in their guidelines. Other single-tablet regimens that are more accessible in other parts of the world include combinations of bictegravir, emtricitabine, and tenofovir alafenamide (TAF), or dolutegravir, abacavir, and lamivudine. Compared with older ART regimens, with harsh adverse effects and complex dosing regimens, taking a single, fixed-dose tablet once daily makes it much easier for people living with HIV to adhere to long-term ART.

Simplification Is Individualization
Having already simplified ART from a sophisticated multidrug regimen to a single pill, how can we simplify it further? The next level of simplification—of frequency, at least—is a long-acting, injectable form of ART. With long-acting (LA) ART, specifically, LA cabotegravir plus rilpivirine, rather than taking a daily pill, people living with HIV can get an injection every 2 months and still remain virologically suppressed. Even longer-acting ART is currently in development.

But the availability of LA ART shows how simplifying treatment has now become a matter of tailoring it to the individual. Some feel that LA ART relieves the burden of pill fatigue, but others prefer to take tablets every day. In my clinic in Chennai, India, when I tell people about LA ART, approximately 50% of them are very receptive to it.  On the other hand, the remaining individuals are accustomed to taking their ART every day orally, are doing well, and do not want to disrupt their daily routine. Other people do not want to visit the clinic every 2 months or are unable to. It is possible that these people would be receptive to an LA ART formulation that lasts 6 months, but until that becomes available here, the best option for them may be a daily pill.

Minimizing the Impact of ART on People’s Lives
Aside from personal preference, another factor to consider when prescribing an ART regimen is the potential for adverse effects. Research demonstrates that long-term use of TDF carries a risk of renal dysfunction and may cause bone mineral density loss, increasing risk of osteoporosis and osteopenia. So healthcare professionals may also need to modify the ART regimen they prescribe based on an individual’s medical history or to prevent adverse effects.

In my resource-limited setting, TDF is a component of preferred therapy, along with lamivudine and dolutegravir, but for some people, a switch to TAF-containing ART may be best. TAF is associated with less bone and renal toxicity than TDF.

We have been looking at various other adverse events like weight gain, particularly with the integrase inhibitors.  Studies are ongoing to ask, “In someone who has weight gain, might switching to another class of regimen prevent or reverse weight gain?” So far, that has not been seen.

Alternatively, clinical trials have shown that 2-drug therapies are just as efficacious as a three-drug regimen. A 2-drug regimen could be considered another method of simplifying ART by reducing lifetime exposure to antiretroviral drugs. Lamivudine and dolutegravir 2-drug therapy has been approved by the FDA for use in the United States and is also available in resource-limited settings. However, this regimen is not recommended for people who are coinfected with HIV and hepatitis B or for individuals being treated for active opportunistic infections, such as tuberculosis.

The goal is to optimize therapy to minimize adverse effects and the impact of ART on people’s lives. This is a critical aspect of ART simplification based on each individual’s needs—one size does not fit all.

Simplifying Initiation to Improve Adherence
In my practice, we have implemented WHO guidelines for rapid ART initiation, which is defined as initiation of ART within 7 days of HIV diagnosis. If someone comes into the clinic who just tested positive, we reconfirm the diagnosis, counsel them, and do a detailed clinical examination to rule out opportunistic infections like tuberculosis, fungal infections, or bacterial infections. If needed, we put them on the appropriate opportunistic infection prophylaxis or treatment and stabilize them before initiating ART. If they do not have any symptoms or opportunistic infections, they can start ART. If they are agreeable, they can even start ART on the same day. This helps prevent loss to follow-up and greatly reduces the risk of transmission to their partners by rapidly suppressing viral replication.

Improving Adherence Support
In my clinic here in Chennai, we follow a very large number of people living with HIV. The rate of viral suppression in our clinic is approximately 91% with the fixed dose combination of dolutegravir/lamivudine/TDF. This is much higher than the global rate of viral suppression, estimated to be approximately 65%, and the rate of viral suppression in the United States, estimated to be approximately 66%. I think what sets us apart is the type of adherence support and psychosocial support we provide. For people who are not adhering to ART, we schedule frequent visits to the clinic to monitor their viral loads and so they can receive continued adherence counseling.

HIV infection still carries a lot of stigma in many regions, so we provide multiple counseling cycles and increased social support to make sure that people living with HIV accept that they have to start and continue treatment. This is an ongoing process, not a one-time counseling.

Furthermore, in India, people generally live in nuclear families, with a father, mother, children, and grandparents in one home. With that dynamic in mind, we think of counseling not only for the patients but also for their caregivers at home. With consent, we also educate the families about newer therapies, antiretroviral drugs, and how they can continuously provide psychosocial support and care to their family members living with HIV.

If we think of ART simplification as removing barriers to ART adherence, I believe that tailor-made counseling for not just the individual, but their support system as well, makes all the difference.

Your Thoughts?
How do you individualize ART in your clinic? Do you see individualization as an effective way to simplify ART? Leave a comment below to join in the discussion.