Highlights from the inaugural HIVR4P conference

Abstract

Injectable, longacting PrEP Excitement is building around the prospect of longacting injectable preexposure prophylaxis (PrEP), not only for prevention, but also for treatment. William Spreen (GlaxoSmithKline, Research Triangle Park, NC, USA) presented data for the PrEP dose rationale of the nanosuspension HIV integrase inhibitor cabotegravir (GSK744). Data from animal models and studies of volunteers showed that 800 mg injected intramuscularly every 12 weeks is predicted to yield drug levels correlated with robust antiHIV activity and protection against simian–human immunodeficiency virus rectal and vaginal challenge in non-human primates. This dose is under study in human phase 2 safety, acceptability, and pharmacokinetic trials. The second study (MWRI01—a phase 1 open-label safety, acceptability, pharmacokinetic, and pharmacodynamic study) is led by Ian McGowan (University of Pittsburgh School of Medicine, PA, USA). Healthy HIV-1 seronegative participants (two cohorts each containing 12 women, six men) received an intramuscular dose of either 1200 mg or 600 mg of the antiretroviral compound TMC278 LA (Janssen). Plasma and tissue (rectal, cervical, and vaginal) were obtained before and after exposure and participants were followed up for 4 months after receiving the compound. Safety, acceptability, and pharmacokinetics were all monitored, and tissue samples were taken and challenged ex-vivo with HIV-1. The investigators noted that exposure to TMC278 LA was associated with suppression of viral replication in rectal tissue that persisted for up to 4 months. However, viral suppression was not evident in vaginal or cervical tissues. “A single dose of the compound was safe and well tolerated, with dosedependent plasma exposure“, said McGowan. “The TMC278 tissue-toplasma ratio for rectal tissue was roughly twice that in vaginal or cervical tissues. This is the fi rst study to show prolonged suppression of explant viral replication after systemic antiretroviral exposure. There are now plans for multiple dosing studies.”