Oral pre-exposure prophylaxis (PrEP) based on tenofovir disoproxil fumarate/emtricitabine (Truvada)has set a high bar for prevention effectiveness, but a range of alternative PrEP products are in development, Raphael Landovitz of the University of California told the HIV Research for Prevention conference (HIVR4P 2018) in Madrid last week. They variously promise less frequent dosing, multi-purpose uses and different modes of action, although the development process for each has its challenges.
Speaking at the same plenary session, Craig Hendrix of Johns Hopkins University made an eloquent plea for research to continue into PrEP formulations which are topical (applied vaginally or rectally, at the site of potential HIV exposure) rather than systemic (spreading the drug throughout the body). Topical products such as films, inserts or gels would provide immediate, rather than long-term protection. However, the US National Institutes of Health is reducing its investment in topical PrEP research.
Landovitz said that there had been hope that the CCR5 entry inhibitor maraviroc, an oral tablet that is sometimes used as part of antiretroviral therapy, could also be used as part of PrEP. However, a study found that rectal tissue samples of men who had taken maraviroc could be more easily infected with HIV in a test tube than tissue samples of men taking other PrEP regimens. For this reason, maraviroc has not been taken forward for further development.
Tenofovir alafenamide (TAF) is a newer, modified formulation that causes less kidney and bone side-effects than tenofovir disoproxil fumarate (TDF) and is included in a number of fixed dose combinations for antiretroviral therapy. Landovitz said that while TAF is an attractive option for HIV treatment, it remains to be seen whether it will work well for PrEP. TAF delivers high levels of tenofovir to cells, without requiring high levels in blood plasma. This explains the reduced side-effects, but could also mean that protective levels of the drug are not reached in rectal and vaginal tissues.