Rilprivirine and dolutegravir intravaginal rings for the prevention of HIV transmission: in vitro and in vivo studies

Human immunodeficiency virus (HIV) poses a large burden on global health. Through the development of highly active antiretroviral therapy (HAART), HIV infected individuals are living longer lives with undetectable viral loads. In spite of the advancement in treatment, the incidence of new HIV infections continues to increase. Emphasis has now shifted to preventative strategies including intravaginal rings (IVR). The objective of this study was to manufacture IVRs with 10%w/w of rilpivirine (RPV) or dolutegravir (DTG). Based on success of manufacturing, the next steps were in vitro and in vivo release studies with the goal to have sustained release for a minimum of 30 days. Both in vitro release studies surpassed 30 days of zero order release. RPV achieved 100% release and DGT achieved 60% release. In vivo mice pharmacokinetics studies were promising since the concentrations of RPV and DTG were above the IC90 locally for the duration of the 28 day study. Plasma concentration of RPV did not reach the IC90 at any point during the study. Overall, RPV and DTG are possible ARTs to be further evaluated for the prevention of HIV using an IVR. Additional studies are needed to determine the efficacy and the possibility of combination IVRs.Doctor of Pharmac