Long acting systemic HIV pre-exposure prophylaxis: an examination of the field

Abstract

Oral pre-exposure prophylaxis for the prevention of HIV-1 transmission (HIV PrEP) has been widely successful as demonstrated by a number of clinical trials. However, studies have also demonstrated the need for patients to tightly adhere to oral dosing regimens in order to maintain protective plasma and tissue concentrations. This is especially true for women, who experience less forgiveness from dose skipping than men in clinical trials of HIV PrEP. There is increasing interest in long-acting (LA), user-independent forms of HIV PrEP that could overcome this adherence challenge. These technologies have taken multiple forms including LA injectables and implantables. Phase III efficacy trials are ongoing for a LA injectable candidate for HIV PrEP. This review will focus on the design considerations for both LA injectable and implantable platforms for HIV PrEP. Additionally, we have summarized the existing LA technologies currently in clinical and pre-clinical studies for HIV PrEP as well as other technologies that have been applied to HIV PrEP and contraceptives. Our discussion will focus on the potential application of these technologies in low resource areas, and their use in global women's health.

Next-Generation HIV Pre-Exposure Prophylaxis Preferences Among Men Who Have Sex with Men Taking Daily Oral Pre-Exposure Prophylaxis

“…Nonoral forms of PrEP currently in development include long-acting injectables (LAIs), rectal microbicides (RMs), antibody infusions (AIs), and subdermal implants (SIs). 17 These modalities may appeal to populations that disproportionately experience barriers to daily oral PrEP. For example, formulations that do not require a daily pill may reduce PrEP stigmas associated with being HIV positive, gay, or ''sexually irresponsible.''…”

Extended-Duration MK-8591-Eluting Implant as a Candidate for HIV Treatment and Prevention

“…Even for cabotegravir and rilpivirine, large injection volumes and multiple injections are required to achieve pharmacokinetic profiles supportive of monthly dosing (17)(18)(19)(20). It is thus clear that novel formulation approaches capable of achieving extended-duration pharmacokinetics for molecules of diverse physicochemical properties, at practical injection volumes and with a limited number of injections, are highly desirable (15,(22)(23)(24).…”

Drug delivery in female reproductive health

“…A key perceived advantage of long-acting dosage forms is that adherence will be substantially improved compared with that seen with pericoital products such as tenofovir vaginal gel [1]. Desai and coworkers [2] examined the field of long-acting systemic HIV pre-exposure prophylaxis. These long-acting systems fall into one of two general categories: injectable and implantable.…”