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February 28, 2011

Intermittent Truvada Protects Against Rectal Transmission of Emtricitabine-Resistant SHIV

The 184V reverse transcriptase mutation is one of the more common mutations that can be transmitted during HIV acquisition. Many recent papers have described the use of Truvada orally or as a topical gel for both pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP). Little data has been describe regarding the degree of protection that Truvada would convey in the face of virus with 184V mutation; however, data was presented today at the 18th Conference on Retroviruses and Opportunistic Infections that shows that Truvada does indeed provide complete protection despite the presence of 184V mutation.

Data were presented from the CDC in Atlanta, GA that evaluated the efficacy of Truvada against SHIV162p3-M184v using a rectal transmission model consisting of 14 weekly virus challenges. 184V mutated SHIV was shown to have >100 fold change resistance to emtricitabine (FTC), 0.3 fold change hyper-susceptibility to tenofovir (TFV) and 30-fold reduced viral fitness compared to wild type SHIV. 5 macaques were given human equivalent Truvada doses 3 days before and 2 hours after exposure. Infection was monitored by serology and PCR amplification of SHIV sequences from plasma.

All 5 of the macaques given Truvada were protected from infection with 184V-mutated SHIV during the trial period. Hypothesis regarding the continued efficacy of Truvada in the face of 184V mutation included residual activity by FTC, increased susceptibility to tenofovir or reduced viral fitness. Although the definite mechanism of continued activity of Truvada is yet to be understood, this data shows that Truvada remains a potent agent for prophylaxis of HIV despite presence of the 184V RT mutation.

Reference: Cong M-E, Youngpairoj A, Zheng Q, et al. Complete Protection against Rectal Transmission of an Emtricitabline-resistant SHIV162p3-184v Mutant by Intermittent Prophylaxis with Truvada. Presented Feruary 28, 2011, at the 18th Conference on Retroviruses and Opportunistic Infections; Boston, MA. Oral Abstract 31.

Source: Reporting from Boston for PRN News: A.C. Demidont, DO