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Dr Michael Seah
Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.
Novel PrEP delivery
Trials in rhesus macaques showed it to be 100% effective as PrEP. Quarterly injections protected against rectal SHIV infection, while monthly injections were protective against repeated vaginal exposure.
Proposed dosage in man would be quarterly 800mg of GSK744 LA IM injection. Presented as 200mg/mL, it would be given as divided doses - 2x2mL gluteal injections).
Clinical evaluation in high risk MSM with phase 2 safety & tolerability trials begin in the northern hemisphere spring 2014.
Dapivirine (DPV) & Maraviroc (MVC) vaginal rings were trialled as a PrEP device in the MTN-013 study. Vaginal rings provide sustained drug delivery, minimal user action is required and they are discrete. The rings were well tolerated with primarily mild to moderate adverse effects. Abstract #41
With DPV, 100,000 fold higher concentration of drug was found in vaginal fluid compared to plasma. The levels of DPV in cervical tissue dropped to below the lower limit of quantification (LLOQ) 3 days after ring removal. Vaginal MVC levels were 2-4 times lower than DPV, and MVC plasma levels and cervical tissue were below LLOQ.
Researchers found that the anti-HIV activity of DPV ex-vivo from cervical biopsies correlated to the concentration of drug.
In the FAME-02 study, DPV film and gel were trialled as delivery mechanisms for vaginal PrEP. Abstract #42LB
Films were akin to Listerine strips that dissolve on contact. Researchers found that subjects had difficulty using the film, with sticking to the finger and poor placement noted on follow up. Cervical levels of DPV were equivalent to 1 month of vaginal ring use (10^6 pg/mL). Vaginal drug levels were about 4 fold higher - reflecting tissue surface adherence. Similar plasma levels were seen for both film and gel, comparable to the vaginal ring.
This study could provide lower cost, on demand PrEP for women. Modified film size/shape could improve placement issues.