MedicalResearch.com Interview with:
Martin Markowitz MD
Clinical Director and Staff Investigator
Aaron Diamond AIDS Research Center
Aaron Diamond Professor at The Rockefeller University
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Cabotegravir ((CAB) is an inhibitor of HIV-1 integrase and is amenable to formulation in both oral and long acting injectable forms. In preclinical studies injectable CAB protected against low dose intrarectal challenge using an HIV-like virus in the rhesus macaque model.
These results support the clinical development of CAB as prevention. This study was a first attempt to establish a dosing regimen and evaluate safety and acceptability of intramuscular injections of CAB. The study was a placebo controlled blinded study of approximately 120 subjects with a 5:1 randomization active/placebo. Subjects received 800mg CAB given as 2 2mL injections or placebo every 12 weeks for 3 injections after a 4 week safety lead in of oral therapy. Safety acceptability and PK were assessed.
The main findings were that injections were associated with injection site reactions in the vast majority of participants that were mild to moderate and of short duration. Only 4 subjects who entered the injection phase discontinued due to injection intolerance. There were no additional safety signals and the participants considered the injections acceptable when asked to complete questionnaires. PK analysis found that despite modeling that suggested that the 800mg q 12 week dose would be adequate, this was not the case. More rapid uptake and release from the depot resulted in lower than anticipated drug levels at trough. Alternate dosing regimens are under study.
Another finding is that there were participants (14%) who had detectable drug in plasma detected at 52 weeks after last injection suggesting the presence of a tail in some individuals.
MedicalResearch.com: What should readers take away from your report?
Response:Cabotegravir long acting is a safe and acceptable medication that holds promise as a novel way to prevent HIV infection. Additional study is required to determine the optimal dosing schedule and ultimately efficacy as PrEP.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: In addition there is a need to understand what happens to individuals if CAB LA is stopped and there is a persistent tail. This raises the risk of drug resistance if infection occurs. As CAB is thought to have a high barrier to resistance this concern remains theoretical and efforts to prevent this are implemented in planned efficacy studies.
MedicalResearch.com: Is there anything else you would like to add?
Response: I am the recipient of grants from GSK and ViiV and have acted as a paid consultant to ViiV.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Safety and tolerability of long-acting cabotegravir injections in HIV-uninfected men (ECLAIR): a multicentre, double-blind, randomised, placebo-controlled, phase 2a trial
Markowitz, Martin et al.
The Lancet HIV , Volume 0 , Issue 0 ,
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