PrEParing for the Unexpected: Mechanisms and Management of HIV pre-exposure Prophylaxis Failure

Abstract

Pre-exposure prophylaxis (PrEP) for HIV is a proven and effective tool for preventing HIV. However, there are instances where individuals taking PrEP have contracted HIV infection. Most of these cases are due to nonadherence to the drug, while other cases of apparent PrEP failure are due to unrecognized HIV infection at baseline. Importantly, there are also now at least three well-documented cases of PrEP failing despite adequate adherence; these are cases of PrEP 'breakthrough'. This article outlines the potential mechanisms of PrEP failure, as well as how to identify and manage these patients. Finally, we provide a perspective on the future of PrEP as a key tool in preventing HIV worldwide.

Pre-Exposure Prophylaxis Failure With a Multiple Drug-Resistant HIV-1 Clade C Virus in Brazil

“…For example, its efficacy has been investigated and demonstrated in men who have sex with men, transgender women, heterosexual populations, and individuals who use injection drugs. 1 In addition, population-level reductions in HIV incidence have been associated with a successful implementation of PrEP programs in elevated-risk populations. 2,3 PrEP failures are highly uncommon in individuals capable of maintaining high adherence as determined by drug plasma levels.…”

Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylaxis: a case report

“…The reason for PrEP breakthrough in this case remains unclear despite a comprehensive analysis of the most likely etiologies of PrEP failure. 21 Patient self-report and pharmacologic measures over a prolonged period of time, made possible by the novel method of segmental hair analysis, 7 support high and consistent levels of adherence. Plasma TFV and FTC levels at the visit 12 weeks prior to his HIV diagnosis confirm adequate dosing in the days prior to that visit, TFV-DP and FTC-TP levels in a DBS sample indicate ≥ four doses per week adherence over the six weeks prior to HIV diagnosis, and drug levels in the segments of hair in the first, second and third months prior to HIV diagnosis are consistent with 7 days per week adherence (i.e.…”

Determinants of adherence to daily PrEP measured as intracellular tenofovir diphosphate concentrations over 24 months of follow-up among men who have sex with men

“…1 Adequate adherence to PrEP is key to its effectiveness in preventing HIV. 2 Therefore, WHO advises brief adherence counselling at each PrEP visit. 3 Insight into determinants of PrEP adherence may help clinicians to focus their counselling efforts on those who are more likely to be less…”

“…Adequate adherence to PrEP is key to its effectiveness in preventing HIV 2. Therefore, WHO advises brief adherence counselling at each PrEP visit 3.…”