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  IAS 2017: Conference on HIV Pathogenesis
Treatment and Prevention
Paris, France
July 23-26 2017
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An Open Label Multiple Dose Phase 1 Assessment of Long Acting Rilpivirine - Long-Acting Rilpivirine Suppresses Replication in Rectal Explants
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Long-Acting Rilpivirine Suppresses Replication in Rectal Explants
9th IAS Conference on HIV Science (IAS 2017), July 23-26, 2017, Paris
Mark Mascolini
Injection of long-acting rilpivirine (LA RPV) inhibited replication of HIV up to 4 months in rectal explants analyzed as part of a phase 1 study [1]. The long-acting nonnucleoside inhibited HIV replication modestly in cervical explants 2 months after the first injection. Development of LA RPV for preexposure prophylaxis (PrEP) stopped in phase 2a.
Long-acting injected PrEP stirs interest because it may limit adherence challenges seen with oral and topical PrEP. Although research on LA RPV PrEP has stopped, long-acting cabotegravir PrEP has reached phase 2b/3 trials.
The MWRI-01 trial, headed by the University of Pittsburgh's Ian McGowan, aimed to evaluate the safety and acceptability of LA RPV given as an intramuscular injection [1]. Exploratory analyses assessed cervical, vaginal, and rectal explant HIV infection [see reference 2] after exposure to LA RPV.
The trial randomized 8 women and 4 men to three arms receiving either 1200 mg (two arms) or 600 mg (one arm). After a baseline 1200-mg injection, women in arm 3A and men in arm 3B received repeat 1200-mg injections at months 2 and 4. Researchers collected samples for pharmacokinetic/pharmacodynamic analysis at baseline and months 1 through 6. Ex vivo explant analyses assessed the inhibitory impact of LA RPV on subtype B and C wild-type (nonmutant) HIV-1.
Three quarters of participants were white and the others black or mixed race. Age averaged 26.8 years in the 8 women and 33.3 years in the 4 men. Body mass index averaged 22.8 kg/m(2) in women and 28.0 kg/m(2) in men.
There were 2 grade 3 adverse events (both in men) and no grade 4 events. All 12 participants had injection site pain, rated grade 1 in 2 participants and grade 2 in 10 participants.
In arm 3A women, geometric mean ratio (GMR) for rilpivirine area under the concentration-time curve (AUC) remained stable at 1.31 with the second dose and 1.20 with the third dose. In arm 3B men, GMR rose from 1.04 with the second dose to 1.66 with the third dose. The researchers rated rilpivirine accumulation with three 1200-mg doses as modest but significant in all matrices.
In the rectal explant analyses, inhibition of both subtype B and subtype C virus persisted up to 4 months after the last injection of LA RPV. Suppression proved greater with subtype C than subtype B (slope for log10 p24 pg/mg -0.83 with subtype C and -0.32 with subtype B). In cervical explants, the researchers recorded viral suppression only at 2 months after the first injection (slope for log10 p24 pg/mg -0.16).
1. McGowan I, Dezzutti CS, Siegel A, et al. An open-label multiple dose phase 1 assessment of long-acting rilpivirine. 9th IAS Conference on HIV Science (IAS 2017), July 23-26, 2017, Paris. Abstract TUAC0103.
2. McGowan I, Dezzutti CS, Siegel A, et al. Long-acting rilpivirine as potential pre-exposure prophylaxis for HIV-1 prevention (the MWRI-01 study): an open-label, phase 1, compartmental, pharmacokinetic and pharmacodynamic assessment. Lancet HIV. 2016;3:e569-e578.