A 43-year-old man in Toronto, Canada was infected with HIV despite regularly taking pre-exposure prophylaxis (PrEP)/Truvada.
According to a letter to the editor – titled “Multidrug-Resistant HIV-1 Infection despite Preexposure Prophylaxis” – published by The New England Journal of Medicine, “PrEP with emtricitabine (FTC)–tenofovir disoproxil fumarate (TDF) has been shown to be efficacious in preventing human immunodeficiency virus type 1 (HIV-1) infection in men who have sex with men and in whom adherence to treatment is high, as measured by levels of tenofovir diphosphate (TFV-DP) in dried blood spots.”
The authors – David C. Knox, M.D.; Peter L. Anderson, Pharm.D.; P. Richard Harrigan, Ph.D.; and Darrell H.S. Tan, M.D., Ph.D. – nonetheless stated that “a case of HIV-1 infection despite FTC-TDF–based preexposure prophylaxis.”
The man, who reported having sex with men, began to receive oral daily FTC-TDF in April 2013. Based on pharmacy dispensation records, he had “perfect” adherence to preexposure prophylaxis over 24 months. He had seven nonreactive fourth-generation HIV screening tests over the next 21 months.
It was also stated that “genotypic and phenotypic testing of a plasma sample obtained… revealed multidrug resistance… The M184V mutation, which compromises FTC activity, in addition to several thymidine analogue mutations, revertant substitutions, or both, which slightly decrease TDF susceptibility, probably explain this failure of PrEP. The multiple thymidine analogue mutations detected are unlikely to have been selected in the short duration of drug exposure; this suggests that resistance was transmitted rather than acquired after drug exposure.”
The authors conclude that “incident HIV is possible despite adherence to PrEP when persons are exposed to FTC-resistant virus, TDF-resistant virus, or both. We recommend that patients be counseled regarding the use of preexposure prophylaxis as part of a combination approach to HIV prevention.”