15th International HIV Drug Resistance Workshop 13-17 June 2006, Sitges, Spain

BLUNTED VIRAEMIA AND SLOW DRUG RESISTANCE EMERGENCE IN RHESUS MACAQUES FAILING CHEMOPROPHYLAXIS WITH EMTRICITABINE

Antivir Ther. 2006, 11:S52 (abstract no. 44)

JG García-Lerma, S Qari, R Otten, J Johnson, C Kim, E Jackson, M Monsour, R Janssen, TM Folks and W Heneine
Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA

BACKGROUND: Chemoprophylaxis with antiretroviral drugs like tenofovir and emtricitabine as a strategy to prevent HIV transmission is being explored. However, drug resistance emergence and viral and immunologic dynamics in persons who become infected while on prophylaxis are currently not defined. Macaques failing antiretroviral prophylaxis provide suitable models to assess such parameters. Here, we describe findings in macaques infected with SHIV during chemoprophylaxis with emtricitabine.

METHODS: Four Rhesus macaques became infected with SHIV during chemoprophylaxis with emtricitabine. Animals received a dose of emtricitabine equivalent to that used in humans (20 mg/kg once- daily) and became infected after a median of 11 weekly rectal exposures with a low dose of SHIV_SF162p3 (10 TCID₅₀; 3.8×10⁵ virus particles). Virus load dynamics and immunologic responses were monitored in these animals and were compared with those seen in 9 untreated controls infected after a median of 2 exposures. Emtricitabine resistance was monitored by sequencing of SIV RT and by a sensitive real-time PCR assay for M184V.

RESULTS: Mean peak viraemia in the 4 emtricitabine-treated animals was 2.2 log₁₀ lower than in controls (4.5 ±0.4 log₁₀ versus. 6.7 ±0.3 log₁₀) and remained low during a follow up period of 6 to 14 weeks. Two emtricitabine-treated macaques had undetectable virus loads at weeks 7 and 6, while all controls had detectable viraemia up to 7 weeks. Sensitive testing detected low frequency of M184V in two animals 8 and 15 weeks after the first detectable plasma RNA or 7 and 12 weeks after seroconversion, respectively. Seroconversion was delayed by 3 weeks compared to controls in only one emtricitabine-treated animal with the lowest viraemia.

CONCLUSIONS: Breakthrough infections with SHIV during chemoprophylaxis with emtricitabine is associated with wild type virus and a substantial reduction in viraemia. Selection of drug resistance is slower than previously seen in monotherapy of established infections. This provides opportunities for early discontinuation of prophylaxis before drug resistance emerges.

2006-06-13
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