Islatravir PrEP didn’t protect against M184V mutation in macaque study

Results from a macaque study showed that although implants that slow-released a low dose of islatravir protected animals against rectal exposure to wild-type SHIV, it failed to protect against SHIV with the M184V mutation. [1]

This study is important because although islatravir is no longer being developed as PrEP, it is structurally very similar to the investigational NRTTI MK-8527, which is now entering phase 3 studies as a once-monthly oral formulation of PrEP.

The results were presented by Charles Dobard from the US CDC in Atlanta and colleagues.

The study included 11 animals that were exposed rectally to either wild-type (n=6) or SHIV with M184V (n=5), twice weekly, for up to four weeks, and compared to untreated macaques. No infections occurred after exposures to wild-type SIV compared to 4 out of 5 animals that were infected after a median of three exposure to M184V. The difference was highly statistically significant (p=0.0091).

However, the results were not thought likely to have clinical significance for the development of MK-8527 because of the very low incidence of M184V in the general population (in most settings).

The practical implications from this study were also difficult to interpret because study increased the infectiousness of the SHIV challenge by four-fold in order to adjust for the reduced viral fitness associated with the M184V mutation.

Also, M184V is not commonly reported in viral transmission studies because in the abscense of drug pressure it usually quickly reverts to wild-type virus.