Editor’s Note: Islatravir is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) currently under development, while lenacapavir belongs to a new class of capsid inhibitors, both featuring long half-lives and highlighted as part of long-acting treatment strategies. Previously, the clinical development of islatravir was temporarily halted due to adverse events involving reductions in CD4 cells and lymphocytes. However, after dose adjustments, the combined use with lenacapavir in a phase 2 trial revealed positive outcomes at the recent CROI conference, promising the first all-oral weekly treatment plan for HIV patients. Infectious Disease Frontier interviewed Dr. Amy Colson, the study’s Principal Investigator and Director of Research at the Community Resource Initiative, at the event.
Infectious Disease Frontier: What research findings were presented at the conference?
Dr. Amy Colson: The study we discussed today was a phase two trial that explored the effectiveness of a once-weekly oral combination therapy consisting of Lenacapavir and Islatravir, compared to the standard daily oral regimen of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF). Participants who had maintained viral suppression on B/F/TAF for at least 24 weeks, with a CD4 count above 350, were randomized in an open-label fashion to either continue with their current regimen or switch to the new weekly combination of Islatravir and Lenacapavir. Our findings at the 24-week mark showed that virologic suppression was maintained equally in both groups at a rate of 92%. Only one participant on Islatravir experienced a detectable viral load, attributed to unique circumstances, yet showed a promising decrease in viral load over time.
Infectious Disease Frontier: Can you elaborate on the safety performance of Islatravir in this study, especially regarding any dosage adjustments from previous research?
Dr. Amy Colson: Of course. Concerns related to CD4 count and lymphocyte declines observed at higher doses of Islatravir in previous studies prompted us to select a lower dose of 2 milligrams per week for this trial. Using data from earlier trials, pharmacokinetic/pharmacodynamic (PK/PD) models helped us understand the relationship between Islatravir’s dose and CD4 count declines. Our results indicated no significant difference in CD4 or lymphocyte counts between the Islatravir-Lenacapavir group and the B/F/TAF group throughout the study, confirming the absence of associated toxicities at the chosen dosage.
Infectious Disease Frontier: Does the study include monitoring for resistance mutations, considering the novel treatment regimen?
Dr. Amy Colson: As the majority of participants maintained viral suppression, extensive resistance testing was not necessary. However, for the single case with detectable viremia prior to receiving the treatment, resistance testing showed no mutations against either Islatravir or Lenacapavir, indicating a low risk of developing resistance with this regimen.
Infectious Disease Frontier: How do you compare the advantages or disadvantages of this weekly oral regimen with existing long-acting injectable treatments?
Dr. Amy Colson: Both options have their unique benefits tailored to patient preferences and lifestyles. Some patients appreciate the convenience of less frequent clinic visits for injections, while others prefer a weekly oral option that offers discretion and avoids the daily reminder of their condition. The key advantage is providing choices to patients, enabling a personalized approach to treatment that accommodates different needs and preferences.
Dr. Amy Colson
MD, MPH
Research Director at AccessHealth MA
