 |
|
|
| |
PrEP GSK744 Integrase Administered Monthly Perhaps Quarterly Prevents HIV-Infection in Monkeys
|
| |
| |
Long-Acting Integrase Inhibitor Shields Macaques From Anal Simian HIV - written by Mark Mascolini - (03/04/13).......
GSK1265744 is a dolutegravir analog that can be packaged in nanoparticles (GSK744LAP) permitting monthly or perhaps even quarterly dosing in humansPrEP Once a Month or Up to Once Every 3 Months with Integrase Inhibitor GSK744
Antiviral Characteristics Of S/GSK1265744, An HIV Integrase Inhibitor (INI) Dosed By Oral Or Long-acting Parenteral Injection....once monthly or 3 months dosing/PrEP/HAART
ICAAC Sept 9-12 2012
http://www.natap.org/2012/ICAAC/ICAAC_12.htm
IAC: Pharmacokinetics, Safety and Tolerability of the HIV Integrase Inhibitor S/GSK1265744 Long Acting Parenteral Nanosuspension Following Single Dose Administration to Healthy Adults - (07/25/12)
New Agents for the Treatment of HIV-1: Is the pipeline opening up?
http://www.natap.org/2012/IAS/IAS_105.htm
"Long-Acting Parenteral Formulation of GSK1265744 Protects Macques against Repeated Intrarectal Challenges with SHIV"
Chasity Andrews from the Aaron Diamond AIDS Research Center in NYC reported results from a study of 16 rhesus macaques were challenged with SHIV, 8 received placebo & 8 were administered GSK744, were injected intramuscularly. Macaques were challenged with SHIV (monkey HIV) intrarectally. All 8 macaques who received GSK744 remain averimic, without HIV, during the rectal challenge phase and the subsequent followup 10-week phase. All 8 macques who received placebo were infected during the challenge phase, results are significant with a p=.0001. Proviral DNA was not detected in PBMCs from any GSK744LAP-treated macaques in post challenge followup phase. Proviral DNA was detected in PBMCs from all placebo animals in followup phase. Virus-specific antibody responses were not detected in any GSK744LAP-treated macaques throughout the study, but were detectable 1-3 weeks after first plasma RNA detection in all placebo animals. GSK744 plasma concentrations in protected macaques were comparable to those in humans. Animals were dosed at week -1 and week 3, animals were challenged weekly for up to 8 weeks with SHIV (monkey HIV) or until infection was confirmed. Dosing was decided after a PK study and plasma levels remained high, substantially above IC90, in 6 macaques receiving GSK744 during challenge and in 2 macaques levels fell to at or below IC90 during the last challenge at week 7.
SUMMARY/CONCLUSIONS
GSK744LAP prevented rectal transmission of SHIV162P3 in rehesus macaques repeadtedly exposed to the virus
- full necropsy will be performed to determine if the animals are locally infected, but systemic virus dissemination is contained
Future GSK744LAP studies in macques:
- determine the minimum protective dose of GSK744LAP against intrarectal challenges
- proof-of-concept PrEP studies in female macques
GSK744LAP is a promising next-generation PrEP agent that has a PK profile suitable for monthly to quarterly injections
link to webcast
http://webcasts.retroconference.org/console/player/19409?mediaType=podiumVideo
|
| |
|
|
|
|
|
