Should we fear resistance from tenofovir/emtricitabine preexposure prophylaxis?

PURPOSE OF REVIEW

To review current data on HIV-1 resistance arising from the use of fixed dose combination tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for preexposure prophylaxis (PrEP) to prevent HIV-1 infection.

RECENT FINDINGS

Resistance to tenofovir (TNV) or FTC is infrequently selected by TDF/FTC PrEP if started before HIV-1 infection has occurred, but is much more common when inadvertently started during undiagnosed acute infection. Mathematical modeling predicts that the number of HIV-1 infections averted by the use of PrEP far exceeds the increase in drug-resistant infections that could occur from PrEP. Studies in macaques show that TNV-resistant virus but not FTC-resistant virus can cause breakthrough infection despite TDF/FTC PrEP. FTC resistance with M184 V/I occurs more frequently than TFV resistance with K65R in seroconverters from clinical trials of TDF/FTC PrEP.

SUMMARY

The benefit of preventing HIV-1 infections with TDF/FTC PrEP far outweighs the risk of drug-resistant infection, provided PrEP is not started in persons with undiagnosed HIV-1 infection. We should respect but not fear HIV-1 resistance from TDF/FTC PrEP and recognize that most TNV or FTC resistance will arise from its use for antiretroviral therapy (ART). Preventing ART failure or detecting it early is most important for preventing the spread of HIV-1 resistance to TDF/FTC and preserving its effectiveness for both PrEP and ART.