Pre-Exposure Prophylaxis Using TMC278LA

While for certain diseases, the use of medications by healthy people has been proven to function as prophylaxis, i.e. malaria, it is still unknown whether PrEP can help prevent HIV infection from exposure during sex or injection-drug use. To address whether PrEP is safe and effective for use in humans, the traditional sequence of drug development steps should be followed as closely as possible. TMC278 (rilpivirine) is a new investigational non nucleoside reverse transcriptase inhibitor (NNRTI) discovered and in development by Tibotec, a division of Johnson \& Johnson. Data from clinical development (Phase IIB) suggest that TMC278 has a similar efficacy and better side-effect profile as compared to other, older, NNRTIs, such as efavirenz. Like TMC125 (etravirine), TMC278 is a diarylpyrimidine (DAPY - a class of molecule that resembles the pyrimidine nucleotides found in DNA, and which have shown potency in inhibiting the activity of HIV reverse transcriptase). Tibotec is currently investigating TMC278 in two formulations: an oral formulation for HIV treatment and, in early phase, a long acting (LA) injectable formulation for HIV treatment. The latter has also potential application for HIV transmission prevention. TMC278LA is an innovative drug formulation and its long apparent half life may allow administration of PrEP monthly rather than orally and daily, as for other ARV that are currently studied as PrEP agents. Therefore, a phase I/II, open-label, prospective, single arm, pharmacokinetic clinical trial in 100 HIV negative subjects (50% of whom will have to be of self-identified African ancestry and 50% females, approximately) is to be conducted. The study will examine whether a monthly dose of TMC278LA not exceeding 600 mg i/m over a time period of approximately six months, with a loading regimen of the first two i/m injections separated by two weeks, is safe and well tolerated by HIV-negative subjects. Investigation of drug pharmacokinetics in plasma and genital secretions will be also carried out in order to ensure optimal drug exposure during drug administration. 100 evaluable subjects will be enrolled, with approximately 50 of African ancestry, and 50 females. This will provide 50-subject-years of safety data in order to support a later large phase III global efficacy study.