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Tenofovir/FTC Prevents SHIV Transmission in Monkeys
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Reported by Jules Levin
15th Intl HIV Drug resistance Workshop, June 13-17, Sitges, Spain
"Prevention of rectal SHIV transmission in macaques by tenofovir/FTC combination"
"......animals were subjected to 14 weekly rectal exposures with a low dose of SHIV ....all six animals treated with tenofovir/FTC were fully protected after 14 challenges .....chemoprophylaxis with drug combinations will be more effective than single drugs in preventing sexual HIV transmission...."
Studies are ongoing in the USA & internationally to test prevention of sexual HIV transmission with tenofovir & tenofovir/FTC. Note from Jules Levin: while HIV vaccine research languishes & appears facing failure, HIV drug prophylaxis appears that it might be successful.
J Gerardo Garcia-Lerma1, R Otten1, S Qari1, E Jackson1, W Luo1, C Kim1, D Adams1, S Bashirian1, M Monsour1, D Delinsky2, R Schinazi2, R Janssen1, T Folks1, and W Heneine1
1Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA
2Emory University/VA Medical Center, Decatur, Georgia, USA
BACKGROUND: Chemoprophylaxis with antiretrovirals as a strategy to prevent the transmission of HIV is being explored, although information on the most effective antiretroviral intervention is not yet known. Available data on tenofovir using macaque models of SHIV mucosal infection suggest that tenofovir is not sufficiently protective at concentrations equivalent to those currently used in humans. Here, we investigated whether tenofovir/FTC combination or FTC alone protects macaques from repeated rectal SHIV challenge.
METHODS: Two groups of six Rhesus macaques were injected subcutaneously with either 22 mg tenofovir/20 mg FTC per kg or 20 mg/kg FTC alone once daily. Fifteen control animals including 6 real time controls did not receive any antiretroviral treatment. All animals were subjected to 14 weekly rectal exposures with a low dose of SHIV-SF162p3 (10 TCID50; 3.8x10-5th virus particles) which expresses an R5 tropic HIV-1 envelope that resembles naturally transmitted HIV-1 strains. Infection was monitored by serology and PCR amplification of SHIV gag and pol sequences from plasma and peripheral blood lymphocytes, respectively.
RESULTS
Fourteen of the 15 control animals became infected after a median of 2 challenges (range= 1-10). In contrast, all six animals treated with tenofovir/FTC were fully protected after 14 challenges (exact log-rank p-value=0.00013). In the FTC group, 4 of the 6 animals become infected after 5, 10, 12, and 13 challenges (exact log-rank P-value=0.005 compared to untreated animals). Using a cox proportional hazard model, the FTC-treated macaques were 3.9 times less likely to become infected than control animals (P-value=0.021).
CONCLUSIONS: Tenfovir/FTC combination provides high level protection against repeated virus challenges, demonstrating that chemoprophylaxis with potent antiretrovirals can provide an effective strategy for preventing sexual HIV transmission. Despite high antiviral activity, FTC alone did not provide full protection in this model suggesting that chemoprophylaxis with drug combinations will be more effective than single drugs in preventing sexual HIV transmission.
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