A review of reported cases of HIV pre‐exposure prophylaxis failure with resultant breakthrough HIV infections. Issue 2 (3rd November 2020) - To, KW
Abstract : Objectives: Early randomized controlled trials (RCTs) have confirmed high efficacy of pre‐exposure prophylaxis (PrEP) for preventing HIV infection in men who have sex with men (MSM) with high HIV exposure risk. Nevertheless, some PrEP failure cases have been reported despite adequate drug adherence. This review aims to summarize the common features of PrEP failure cases and discuss the implications of upscaling PrEP programmes. Methods: A search based on articles and clinical trials was conducted through Medline and OVID, with keywords for accessing publications reporting 'true' PrEP failure in the presence of documented adherence to daily regimen of co‐formulated tenofovir disoproxil fumarate/emtricitabone. Results: Ten cases of 'true' PrEP failure were identified, all of which were preceded by continued practice of condomless anal sex, despite documented adherence. Dried blood spot and/or hair analyses provided supporting evidence of adherence in eight cases. There was strong association of PrEP failure with recurrent or multiple sexually transmitted diseases and infection with resistant HIV viruses. Seroconversion was usually atypical or delayed because of significantly suppressed viral load, making diagnosis a clinical challenge. Discussion: Although it is uncommon, 'true' PrEP failure can occur in a real‐world situation, contrary to the outcome of early RCTs. Failure to identify HIV infection while on PrEP can potentially lead to the emergence of drug‐resistant virus. To achieve effective HIV prevention, PrEP programmes should emphasize safer sexual practice in addition to drug adherence. Early identification of PrEP failure is crucial, which requires the development of highly sensitive assays and their clinical application.