XIX International AIDS Conference


WEPDC01 Sheep Rings and Other Things: New Directions in ARV for Prevention
  Oral Poster Discussion Session : Track C
Venue: Mini Room 6
Time: 25.07.2012, 13:00 - 14:00
Co-Chairs: Sharon Hillier, United States
Helen Rees, South Africa
 
 

13:00
WEPDC0101
Abstract
Powerpoint
Sustained release tenofovir and maraviroc from intravaginal ring in sheep
T.J. Smith
Auritec Pharmaceuticals, Santa Monica, United States
T. Smith, United States

13:05
WEPDC0102
Abstract
Sustained-release saquinavir from an intravaginal ring in sheep
R.A. Willis1, A.M. Malone1, J.A. Moss2, M.M. Baum2, K.L. Vincent3, M. Motamedi3, S. Kennedy2, J. Gilman1, I. Butkyavichene1, C. Nguyen1, T.J. Smith1
1Auritec Pharmaceuticals, Pasadena, United States, 2Oak Crest Institute of Science, Pasadena, United States, 3University of Texas Medical Branch, Galveston, United States
R. Willis, United States

13:10
WEPDC0103
Abstract
Development of a new intravaginal ring technology for the extended delivery of the microbicide tenofovir with and without the contraceptive levonorgestrel
T. Johnson1, M. Clark2, J. Clark1, N. Shelke1, G. Doncel3, D. Friend2, P. Kiser4
1University of Utah, Bioengineering, Salt Lake City, United States, 2CONRAD, Eastern Virginia Medical School, Obstetrics & Gynecology, Arlington, United States, 3CONRAD, Eastern Virginia Medical School, Obstetrics & Gynecology, Norfolk, United States, 4University of Utah, Bioengineering; Pharmaceutics and Pharmaceutical Chemistry, Salt Lake City, United States
M. Clark, United States

13:15
WEPDC0104
Abstract
Powerpoint
Sustained release raltegravir from an intravaginal ring in sheep
A. Malone1, J. Moss2, R. Willis1, M. Baum2, J. Gilman1, I. Butkyavichene1, S. Kennedy2, C. Nguyen1, T. Smith1,2
1Auritec Pharmaceuticals, Santa Monica, United States, 2Oak Crest Institute of Science, Pasadena, United States
A. Malone, United States

13:20
WEPDC0106
Abstract
Powerpoint
Population-level benefits from providing effective HIV prevention means to pregnant women in high prevalence settings
D. Dimitrov1, M.-C. Boily2, J. Marrazzo3, E. Brown1
1Fred Hutchinson Cancer Research Center, Vaccine & Infectious Disease Division, Seattle, United States, 2Imperial College London, Department of Infectious Disease Epidemiology, London, United Kingdom, 3University of Washington, Division of Allergy & Infectious Diseases, Seattle, United States
D. Dimitrov, United States

13:25
WEPDC0105
Abstract
Powerpoint
High maraviroc concentrations in rectal secretions after oral dosing do not prevent rectal SHIV transmission in macaques
I. Massud, W. Aung, A. Martin, S. Bachman, J. Mitchell, F. Deyounks, E. Kersh, C.-P. Pau, W. Heneine, J.G. Garcia-Lerma
Center for Disease Control and Prevention, Atlanta, United States
J. Garcia-Lerma, United States

13:30
Moderated discussion



Powerpoints presentations
Sustained release tenofovir and maraviroc from intravaginal ring in sheep - Thomas J Smith

Sustained release raltegravir from an intravaginal ring in sheep - Amanda Malone

Population-level benefits from providing effective HIV prevention means to pregnant women in high prevalence settings - Dobromir Dimitrov

High maraviroc concentrations in rectal secretions after oral dosing do not prevent rectal SHIV transmission in macaques - J. Gerardo Garcia-Lerma



Rapporteur report

Track C report by Christopher Hurt  


The main focus of this session was to describe exciting recent advances in drug-eluting intravaginal ring (IVR) technology, using sheep as the pre-clinical animal model. In one variant currently under development, a silicone IVR houses a drug delivery “pod” which can be adapted for a variety of different medications, including ARVs. Data were presented from 4 different studies, evaluating drugs from 4 different ARV classes. Sustained deliveries of tenofovir, saquinavir, raltegravir, and maraviroc (MVC) were demonstrated over 28-days, as determined in cervicovaginal lavage, tissue, and plasma levels. Dual-therapy IVRs with antiretrovirals and hormonal contraceptives are a particularly attractive approach for empowering women to have control over both their sexual and reproductive health. A novel device using polyurethane tubing either permeable to water or with a controlling membrane to titrate specific release rates, was explored with tenofovir alone or in combination with levonorgestrel. In vitro release testing and in vivo tests in sheep (and rabbits) demonstrated the ability to sustain drug concentrations in cervicovaginal fluid and tissue, at high levels over a 90-day period.

Two “other things” were discussed, besides sheep rings. In a model of transmission designed to assess the population-level impact of microbicide use in high prevalence settings, consistent use of a 70% efficacious microbicide by 60% of non-pregnant women was predicted to prevent up to 39% of new infections in women and 11% of new infections in men, over a 10 year period. Up to 10% of mother-to-child transmission cases could be prevented, as well, if HIV is acquired in pregnancy. Expanding the intervention into pregnant women appeared to have a higher overall impact.

Excitement about IVR technology was tempered a bit by negative data on the ability of 2 doses of MVC to prevent rectal SHIV infection, in a macaque study. Six animals received 300mg MVC 24 hours before virus exposure, and another 2 hours thereafter; 4 animals served as controls. Despite overall favorable pharmacokinetics in plasma and rectal secretions similar to those seen in humans, 5 of 6 MVC-treated animals were infected during five rectal SHIV exposures along with 3 of 4 controls. The faster rate of dissociation of MVC from the CCR5 receptor of macaques, compared with humans, may in part explain these findings. Seven-day dosing studies are underway, with explant challenges.




   

    The organizers reserve the right to amend the programme.


Contact Us | Site map © 2012 International AIDS Society