Monthly islatravir for PEP and PrEP: 12 pills a year could cover unmet need for HIV prevention in billions of people globally

The most important study at CROI 2020 could easily turn out to be one that looks at using the NRTTI islatravir (EFdA) for HIV prevention.

Islatravir has the potential to change the way we think about PrEP and PEP due to its high potency and long-acting formulations (that include daily, weekly and monthly oral dosing and an annual implant).

Animal studies already showed 100% efficacy using weekly doses (at >0.43 mg/kg) at preventing SHIV infection after rectal challenge.

This is now further supported by results from CROI 2020 of a macaque study, presented by Martin Markowitz from the Aaron Diamond AIDS Research Center that looked at whether islatravir could work as PEP.

The study included 12 rhesus macaques that were challenged rectally with high dose SHIV. Then, 24 hours later, half received a total of four weekly doses of islatravir (3.9 mg/kg) and half were untreated controls.

This was a multistage study using the same animals. After seven weeks follow-up from the last dose, animals were rechallenged with SHIV and stepped down to three weekly doses, then two, then a single dose, all with the same seven week washout.

Islatravir produced 100% protection when 4, 3, or 2 weekly doses were given. However, all control animals quickly became infected. After the single dose, 4/6 animals were still protected, but 2/6 became viraemic (at days 14 and 49). However, lowest intracellular drug levels achieved in these animals were significantly lower than levels seen in human studies (using a 60 mg once-monthly dose). This led the presenters to speculate that a single PEP dose 24 hours after exposure might still provide higher levels of protection.

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These early results present a strong case for fast track development and regulatory review of the monthly oral formulation of islatravir for PreP. It is possible to go further to say there is actually a public health urgency for this.

Once-monthly oral PrEP could cover a vast unmet need for HIV prevention for people unable or unwilling to use daily PrEP. People who are reluctant to use daily PrEP – 365 pills a year – might rethink their decision if HIV was prevented by taking only 12 pills over a year.

Phase 3 efficacy studies should be run in regions of the world and in populations where HIV incidence is still highest. Following the FDA decision on F/TAF, they will clearly need to include women.

Also, and it is never too early to plan for pricing and access, a highly effective single pill that could be used as PEP or for monthly protection as PrEP, has a potential market that includes multiple billions of people globally who are sexually active.

A market this size can plan for pricing similar to that for current daily generic PrEP.