Islatravir

Islatravir (4′-ethynyl-2-fluoro-2′-deoxyadenosine, EFdA, or MK-8591) is an investigational drug for the treatment of HIV infection.^[1] It is classified as a nucleoside reverse transcriptase translocation inhibitor (NRTTI).^[2] Merck is developing a subdermal drug-eluting implant to administer islatravir.^[3][4]

Islatravir

Names
IUPAC name 2′-Deoxy-4′-ethynyl-2-fluoroadenosine
Systematic IUPAC name (2R,3S,5R)-5-(6-Amino-2-fluoro-9H-purin-9-yl)-2-ethynyl-2-(hydroxymethyl)oxolan-3-ol
Other names EFdA; MK-8591; 4′-Ethynyl-2-fluoro-2′-deoxyadenosine
Identifiers
CAS Number	865363-93-5
3D model (JSmol)	Interactive image
ChemSpider	4983885
PubChem CID	6483431
UNII	QPQ082R25D
CompTox Dashboard (EPA)	DTXSID601046407
InChI InChI=1S/C12H12FN5O3/c1-2-12(4-19)6(20)3-7(21-12)18-5-15-8-9(14)16-11(13)17-10(8)18/h1,5-7,19-20H,3-4H2,(H2,14,16,17)/t6-,7+,12+/m0/s1 Key: IKKXOSBHLYMWAE-QRPMWFLTSA-N
SMILES C#C[C@]1([C@H](C[C@@H](O1)n2cnc3c2nc(nc3N)F)O)CO
Properties
Chemical formula	C12H12FN5O3
Molar mass	293.258 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

In 2021, FDA placed a partial clinical hold for several studies under Islatravir.^[5] The reason was a decline in CD4 T cells under therapy. Merck announced to restart the study program in 2023 with a decreased dose, however studies of islatravir for pre-exposure prophylaxis (PrEP) will be discontinued.^[6]

In 2024, results from a phase II study combining islatravir with lenacapavir indicated that the regimen shows promise as a possible weekly oral regimen.^[7]

Biological activity

Islatravir has activity against HIV in animal models,^[8] and is being studied clinically for HIV treatment and prophylaxis.^[9] Islatravir is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) that unlike other such inhibitors, inhibits HIV through multiple mechanisms,^[8] providing rapid suppression of the virus, when tested in macaques and mice.^[10] Nevertheless, there are HIV strains resistant to islatravir and research is ongoing.^[11][12]