International AIDS Society

TDF/FTC Delays, Does Not Prevent Infection With TDF-Resistant SHIV

Author: Mark Mascolini

29 August 2013

Taking oral tenofovir/emtricitabine (TDF/FTC) before and after rectal exposure to simian HIV (SHIV) resistant to TDF delayed but did not prevent infection with that virus in rhesus macaque monkeys.

Daily TDF/FTC protected HIV-negative heterosexuals, men who have sex with men, and injection drug users from becoming infected with HIV in four placebo-controlled trials. The strategy did not work in two trials of high-risk women because of poor adherence.

Because TDF is widely used to treat HIV infection in regions that may use TDF/FTC preexposure prophylaxis (PrEP) to protect people from HIV infection, US researchers assessed the protective potential of oral TDF/FTC in macaques exposed to SHIV carrying the K65R mutation, which renders virus resistant to TDF. SHIV is a lab-made virus consisting of simian immunodeficiency virus (SIV) cytoplasm and nucleus inside an HIV coat.

Six macaques received a weekly dose of oral TDF/FTC 3 days before rectal SHIV exposure, then another dose 2 hours after exposure. Six macaques not treated with TDF/FTC served as controls. All animals were exposed to escalating weekly doses of K65R-bearing SHIV for up to 28 weeks.

TDF/FTC PrEP significantly delayed acquisition of K65R-bearing SHIV in treated animals. But by the end of follow-up 4 of 6 treated macaques had become infected with the resistant virus.

The researchers believe their findings “highlight the need to closely monitor PrEP efficacy in areas with prevalent K65R.”

Source: Mian-er Cong, James Mitchell, Elizabeth Sweeney, Shanon Bachman, Debra L. Hanson, Walid Heneine, J. Gerardo García-Lerma. Prophylactic efficacy of oral emtricitabine and tenofovir disoproxil fumarate combination therapy against a tenofovir-resistant simian/human immunodeficiency virus containing the K65R mutation in macaques. Journal of Infectious Diseases. 2013; 208: 463-467.

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