Multidrug-Resistant HIV Transmission Despite Adherence to PrEP

A man with documented good adherence to tenofovir/emtricitabine (TDF/FTC, Truvada) pre-exposure prophylaxis (PrEP) became infected with HIV carrying mutations that confer resistance to both FTC and TDF. The authors believe their case report shows that "incident HIV is possible despite adherence to preexposure prophylaxis when persons are exposed to FTC-resistant virus, TDF-resistant virus, or both."

When adherence to once-daily TDF/FTC PrEP is good, this strategy reliably protects men who have sex with men (MSM) and others from HIV acquisition. Health authorities in the United States and internationally recommend daily TDF/FTC PrEP as part of an HIV prevention package. The success of TDF/FTC therapy depends on HIV sensitivity to these antiretrovirals. But until this study, research had not addressed whether the success of TDF/FTC PrEP depends on sensitivity to one or both of these agents.

Researchers in Canada and the United States report the case of an HIV-negative 43-year-old Toronto MSM who began using daily TDF/FTC for PrEP in April 2013. Over the next 21 months, he had seven nonreactive fourth-generation HIV screening tests. Pharmacy records confirmed the man's report of perfect PrEP adherence over these 21 months and for the following three months. But after these seven negative screens, the man had (1) HIV-1 and -2 antigen/antibody-reactive, p24 antigen-reactive and Western blot-negative results, followed in seven days by (2) a screen-positive, p24 antigen-negative, Western blot-negative result.

This sequence of results supported the clinical suspicion that the man acquired HIV during receptive condomless anal sex that he reported with multiple partners in the weeks before the first result series. Viral deep sequencing also supported HIV infection within that exposure period.

Plasma assays on the day of the first suggestive tests showed a tenofovir concentration of 152 ng/mL, a level indicating recent TDF/FTC dosing. Dried blood spot analysis 24 days after the first tests recorded a tenofovir-diphosphate level of 2297 fmol/punch, a level consistent with long-term adherence.

Genotypic and phenotypic testing seven days after the first suggestive tests indicated multidrug-resistant HIV harboring (1) the M184V mutation, which makes virus resistant to FTC and (2) several thymidine analog mutations or revertant substitutions, which slightly decrease viral susceptibility to TDF. These mutations were unlikely to evolve during the short exposure to TDF/FTC. Therefore the authors conclude that the man became infected with resistant virus. Data from British Columbia indicate that 1.7% of patients carry virus resistant to FTC, TDF or both. Similar data are not available from Ontario, the province in which the case occurred.

The researchers conclude that infection with TDF/FTC-resistant HIV is possible in people adhering to daily TDF/FTC PrEP. They underline the importance of counseling PrEP candidates that PrEP is "part of a combination approach to HIV prevention."