Merck announced new interim data from the Phase 2a trial (NCT04003103) in adults evaluating the safety, tolerability and pharmacokinetics (PK) of the once-monthly oral islatravir tablet -- the company’s investigational oral nucleoside reverse transcriptase translocation inhibitor (NRTTI) -- for pre-exposure prophylaxis (PrEP). Interim findings demonstrate that once-monthly oral islatravir achieved the pre-specified efficacy PK threshold for PrEP at both of the two doses studied (60 mg and 120 mg). In the interim analysis using blinded data, both monthly doses of islatravir were found to have an acceptable tolerability profile. These data are shared as a late-breaking oral presentation during the virtual 2021 HIV Research for Prevention Conference (HIVR4P 2021) and featured in the official press conference of HIVR4P 2021. In the ongoing Phase 2a randomized, double-blind, parallel assignment, placebo-controlled, multicenter trial in adults at low-risk for acquiring HIV-1 infection, participants were randomly assigned (2:2:1) to one of three oral once-monthly therapy groups: islatravir 60 mg, islatravir 120 mg, or placebo. Participants received islatravir or placebo once monthly over a 24-week blinded therapy period, followed by a 12-week blinded period (sponsor is unblinded after this stage to allow for interim evaluation of safety), and a 32-week unblinded follow-up in the islatravir groups to characterize the terminal elimination phase. Outcome measures for safety, tolerability and PK were analyzed. At the time of interim data analysis, 76.8% (n=192/250) of the planned participants had been randomized and dosed. Of these participants, 32.8% (n=63/192) were male, 67.2% (n=129/192) were female, 30.2% (n=58/192) were Black or African American, and 16.1% (n=31/192) were Hispanic or Latinx. In a review of blinded safety data, most adverse events (AEs) were mild or moderate with the most common (reported in > 4% of participants) including headache (7.3%), diarrhea (5.7%), nausea (4.7%), abdominal pain (4.2%), and upper respiratory tract infection (4.2%). Two participants discontinued due to AEs currently categorized as potentially drug-related, including sensation of a foreign body in the throat (mild severity) and rash and pruritus (moderate severity). Interim PK analysis of islatravir triphosphate (the active form of islatravir) concentrations in peripheral blood mononuclear cells (PBMCs) showed that the trough concentrations (the lowest level between doses) following either 60 mg or 120 mg monthly doses remained above the pre-specified PK threshold for HIV-1 prophylaxis of 0.05 pmol/106 PBMCs. Islatravir PK exhibited approximately linear dose proportionality at both study doses. A preliminary PK analysis of mucosal tissue (rectal, cervical and/or vaginal) obtained from a subset of study participants (n=54) suggests rapid and sustained distribution of islatravir to sampled tissues. This ongoing Phase 2a study is fully enrolled and the primary analysis of the full dataset is estimated to be available in late 2021.