Dr. Jennifer Hoy
Infectious Disease/HIV Specialist and Medical Professor at Monash University Alfred Hospital, Australia. Member of the Australian Antiretroviral Guidelines Committee and the International Antiviral Society-USA (IAS-USA) Antiretroviral Guidelines Panel. Leading and participating in the development of new antiretroviral drugs and the prevention and management of opportunistic infections, with a primary research focus on complications related to aging in HIV-infected individuals and their pathogenesis, prevention, and management.
Infectious Disease Frontier: What principles do you follow, and what considerations do you have in transitional ART?
Dr. Hoy: Patients who have achieved virological suppression in clinical practice have met treatment goals but still need to maintain therapy. In these virally suppressed patients, there are various scenarios where transitioning treatment may be necessary. When considering a transitional ART, several principles and considerations should be observed. For example: assessing the previous treatment regimen to ensure virological suppression can be maintained post-transition, identifying the reasons for treatment change (whether due to treatment toxicity or virological failure), conducting resistance testing to gather evidence of resistance mutations after ART, understanding if the patient has other comorbidities like cardiovascular disease, chronic hepatitis B virus (HBV) infection, and whether the patient is pregnant. By addressing these considerations, we can ensure that the new treatment plan is appropriate and maintains virological suppression in the patient.
Infectious Disease Frontier: What advantages do you see in switching to INSTIs (Integrase Strand Transfer Inhibitors) in transition therapy? How do you view INSTIs’ impact on weight and cardiovascular disease?
Dr. Hoy: Numerous clinical trials have shown that INSTIs have strong antiviral efficacy, a high barrier to resistance, and good safety profiles with minimal drug interactions and side effects. Consequently, INSTIs have become the first-line recommendation in current international HIV treatment guidelines. Second-generation INSTIs, such as dolutegravir (DTG) and bictegravir (BIC), have an even higher resistance barrier, making them particularly suitable for patients with poor adherence, viral resistance, concurrent opportunistic infections, tumors, or long-term use of other medications. This means we can switch to an INSTI-based regimen with a high resistance barrier without losing efficacy. However, some studies have indicated that a small subset of patients may experience excessive weight gain with INSTIs. Currently, most patients are willing to gain some weight by using INSTIs, but it’s worth noting that a very small fraction of patients might experience significant weight gain, potentially increasing the risk of cardiovascular disease, metabolic syndrome, and other conditions.
The relationship between INSTIs and cardiovascular disease is a hotly debated topic, with two large-scale studies providing conflicting results. One study suggested a higher risk of cardiovascular events within the first six months of INSTI exposure, while another study presented opposite findings at the 30th Conference on Retroviruses and Opportunistic Infections (CROI) in February 2023, confirming that transitioning to INSTIs does not increase cardiovascular disease risk. Therefore, the debate regarding whether INSTIs increase the risk of cardiovascular disease remains unresolved.
Infectious Disease Frontier: Some research explores transitioning patients who have achieved virological suppression to simplified maintenance regimens. How do you view this transition therapy strategy?
Dr. Hoy: In January 2021, the U.S. FDA approved the first long-acting injectable regimen, Cabenuva (cabotegravir + rilpivirine), for the treatment of HIV patients who have achieved virological suppression following ART. This is the first approved long-acting treatment for HIV, requiring only a monthly intramuscular injection to maintain long-term viral suppression. Research suggests that under the right conditions, transitioning to this simplified drug regimen can be safe and effective while reducing dosing frequency (every four or eight weeks). Currently, in many countries, including Australia, the eight-week dosing regimen is the only option. Studies indicate that this regimen can maintain high rates of virological suppression. However, there are drawbacks: patients must visit the clinic every eight weeks, the two drugs in this regimen lack activity against chronic HBV infection, and there’s an increased risk of virological failure if a patient has previously experienced virological failure or resistance mutations with either drug in the regimen.
In summary, for many patients, this simplified treatment regimen reduces stigma, improves compliance among HIV/AIDS patients in need of ART, and enhances their quality of life. I believe that long-acting injectables have both advantages and disadvantages, but in the right circumstances, they are safe and effective.
