The risk of HIV drug resistance following implementation of pre-exposure prophylaxis.
OBJECTIVE
Results of trials determining if pre-exposure prophylaxis (PrEP) with antiretroviral drugs prevents transmission of HIV are expected soon. Tenofovir and emtricitabine--currently evaluated as PrEP--are popular in treatment of HIV. Drug resistance could, therefore, be critical in the use of PrEP. We review the literature regarding risks associated with drug resistance owing to PrEP.


RESULTS
Few studies addressed the issue of drug resistance to tenofovir and/or emtricitabine. Studies in HIV-1-infected individuals followed small numbers of patients for a short time. Studies in macaques were well designed, but used SHIV, which has an attenuated course of infection. The available information suggests that the probability of emergence of drug resistance is small. Infections that occurred despite use of PrEP had reduced peak viremia, which could reduce HIV transmissibility. Mathematical modeling suggests that, although transmitted drug resistance may under some circumstances increase, the benefits of PrEP outweigh the risks associated with resistance.


CONCLUSIONS
Tenofovir and emtricitabine are recommended in first-line treatment. The potentially limited impact of drug resistance should, therefore, be confirmed in daily practice. Surveillance of drug resistance is recommended in areas where PrEP is used. Patients that became infected despite use of PrEP should be closely monitored for virological failure.
van de Vijver
David A M C
DA
Department of Virology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands. d.vandevijver@erasmusmc.nl
Boucher
Charles A B
CA
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D063065:Organophosphonates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018570:Risk Assessment; D000068698:Tenofovir; D014766:Viremia / Q000188:drug therapy
D019380:Anti-HIV Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine