An implant that elutes an investigational antiretroviral agent provided drug release that should be sufficient for HIV prophylaxis for 12 months or more, according to results of a phase 1 clinical trial just presented here at the International AIDS Society Conference on HIV Science.
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The islatravir-eluting arm implant was safe and generally well tolerated, with drug concentrations that remained above the target level needed for protection throughout the randomized, placebo-controlled study, said investigator Randolph P. Matthews, MD, PhD, senior principal scientist at Merck, Kenilworth, N.J.
“Based on this study, the islatravir-eluting implant appears to be a potentially important option for preexposure prophylaxis (PrEP) as an agent that could be effective with yearly dosing,” Dr. Matthews said in an IAS press conference.
This drug-eluting implant, inserted subdermally in the skin of the upper arm, could represent a “meaningful option” for many individuals at high risk of HIV infection, particularly those who have adherence challenges, said Dr. Matthews.
“Many at-risk individuals face adherence challenges with the existing daily oral PrEP therapy,” he added. “A high degree of adherence is required for it to be effective, and daily adherence is challenging for many, particularly for women.”
Islatravir, formerly known as MK-8591, is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) being evaluated in clinical trials not only for PrEP, but also for treatment of HIV-1 infection in combination with other antiretrovirals.
In preclinical trials, islatravir demonstrated high potency, a high barrier to resistance, and a long half-life, according to Dr. Matthews.
The phase 1, single-site, double-blind study included a total of 16 healthy adult volunteers who received implants of islatravir at one of two doses (54 mg and 62 mg) or placebo for 12 weeks.
Both active doses of islatravir led to concentrations above the target level at 12 weeks, and based on data modeling, the higher-dose implant would still be above the target level for at least a year, Dr. Matthews said in the press conference.
The projected duration above the target ranged from 12 to 16 months for the 62-mg dose of islatravir, and from 8 to 10 months for the 54-mg dose, according to the reported data.
All drug-related adverse events were mild or moderate in severity, and none of the volunteers discontinued the study because of an adverse event, Dr. Matthews said.
Taken together, these data support the continued progression of the implant clinical development program, said Dr. Matthews, who is an employee of Merck, which sponsored the study.
SOURCE: Matthews RP et al. IAS 2019, Abstract TUAC0401LB.