13th Conference on Retroviruses and Opportunistic Infections Denver, Colorado - February 5-8, 2006

Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 32LB

J Garcia-Lerma, R Otten, S Qari, E Jackson, W Luo, M Monsour, R Schinazi, R Janssen, T Folks, and Walid Heneine
CDC, Atlanta, GA, US

BACKGROUND: Chemoprophylaxis with ART 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 (TDF) using macaque models of simian human immunodeficiency virus (SHIV) mucosal infection suggest that TDF is not sufficiently protective at concentrations equivalent to those currently used in humans. Here, we investigated whether TDF/emtricitabine (FTC) combination protects macaques from rectal SHIV challenge, and whether this protection is sustained during repeated virus exposures.

METHODS: One group of 6 rhesus macaques was injected subcutaneously with 22 mg TDF and 20 mg FTC per kg once daily. The FTC dose is comparable to that approved for humans; 6 control animals did not receive any antiretroviral treatment. All animals were subjected to weekly rectal exposures with a low dose of SHIV_SF162p3 (10 TCID₅₀; 3.8 x 10⁵ 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. Historic data on control macaques using this repeat exposure model shows that 4 virus challenges infect ~75% of the animals.

RESULTS: Of 6 controls, 4 (67%) became infected after 4 challenges (median = 2.5; range = 2 to 4). In contrast, all 6 animals treated with TDF/FTC were fully protected. After 10 additional virus challenges, 1 of 2 remaining controls became infected while all 6 TDF/FTC-treated animals remained uninfected.

CONCLUSIONS: TDF/FTC combination provides a high level of protection against repeated virus challenges, demonstrating that chemoprophylaxis with potent antiretrovirals is an effective strategy for preventing sexual HIV transmission.

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2006-02-05
32LB

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