The latest PrEP formulation to receive a trial is a small
topical insert or mini-suppository containing the two drugs TAF and
elvitegravir. The insert is no bigger than a medium-sized HIV pill. Presenter
Dr Charles Dobard of the US Centers for Disease Control and Prevention (CDC) said the
formulation as an insert has several advantages: it can be carried around
discreetly and used when needed, and the fact that it is topical, and has low systemic
absorption, means there should be minimal toxicity.
The same technology, but containing the non-antiretroviral-based prophylactic
substances carrageenan and griffithsin, was presented at the
HIV R4P conference last year.
The rationale presented for combining the nucleoside reverse
transcriptase inhibitor TAF and the integrase inhibitor elvitegravir is that
the two drugs act at different stages of the HIV life cycle and so might offer
good protection as both PrEP and post-exposure prophylaxis (PEP). It should
also be noted that when elvitegravir is taken as an oral drug, it needs boosting by cobicistat or
ritonavir and perhaps as a result, it has struggled to compete with
dolutegravir. When it is used topically it does not need boosting and so there may be more market potential. And, of course, both drugs are manufactured by
Dobard first presented the results of dose-finding
studies that indicated that an insert containing 20mg of TAF and 16mg of elvitegravir
produced the best drug levels in tissues. These studies also showed that there
was virtually no drug detected in blood plasma, suggesting that the two were
being absorbed directly into mucous membrane tissues with little systemic absorption.
The inserts were given vaginally to six female rhesus macaques four hours before they were challenged with the monkey-adapted virus SHIV. The challenges continued weekly for 13 weeks. In addition, eight monkeys received a placebo insert and weekly challenges.
Seven of the eight monkeys receiving
placebo were infected (87.5%), all but one in the first four weeks, but only
one of the six receiving the TAF/elvitegravir insert was infected, in the ninth week (16.7%). This represents
92% efficacy in preventing SHIV infection. Dobard commented that this was roughly
the same efficacy as had been seen in a previous study using 1% tenofovir gel as
Studies are now ongoing to see if the insert is as effective
when dosed 24 hours in advance of exposure, or as PEP four hours after
exposure. The insert is also designed to work for rectal use too, but no
studies have yet been completed.