“PrEP is highly effective when taken as prescribed,” Nila Dharan, MD, PhD, FRACP, notes. “It is important to investigate cases of HIV acquisition once patients have been prescribed PrEP, to understand why this HIV prevention method has failed whether there were structural or logistical barriers, poor adherence, or true ‘failure’ of the medication to prevent HIV, even when taken appropriately. Once the challenges are identified, they can be addressed, so that new HIV infections are prevented.” For a study published in Clinical Infectious Diseases, Dr. Dharan and colleague’s examined HIV seroconversions among participants prescribed PrEP who were enrolled in the Expanded PrEP Implementation in Communities in New South Wales (EPIC-NSW). Between March 1, 2016 and April 30, 2018, 9,709 participants enrolled and 99% of them received PrEP. The researchers conducted follow-up to
identify HIV seroconversions through March 31, 2019. “We wanted to identify the reasons for HIV acquisition among people who were dispensed PrEP, such as not taking the medication as prescribed; being infected with a virus resistant to the drug(s) in PrEP; or being infected with HIV despite taking the medication as prescribed,” Dr. Dharan says. “The EPIC-NSW study is one of the largest PrEP studies to date, so it provided a unique opportunity to understand reasons for HIV acquisition among people receiving PrEP.”
HIV Acquisition Due Primarily to Poor Adherence
Among patients who received PrEP, 30 were diagnosed with HIV by March 31, 2019. The median age of patients diagnosed with HIV was 31 (interquartile range [IQR], 25-38), all identified as male, and most (97%) identified as gay. The median number of days from first PrEP supply to HIV diagnosis was 409 (IQR, 347-656). The researchers found no evidence that individuals who seroconverted were adequately adherent to PrEP, according to the study results. They also found that 63% of individuals who seroconverted to HIV had diagnoses of chlamydia, gonorrhea, syphilis, or new hepatitis C infection. One patient demonstrated resistance to emtricitabine at the time of HIV diagnosis, in the form of a M184V mutation (Table). “There was no evidence that any of the participants who acquired HIV while on the study were taking PrEP as prescribed, which means there was no evidence of true failures of the medication,” Dr. Dharan notes. “Importantly, most participants who reported why they were not taking PrEP as prescribed reported that they felt they not at high enough risk to warrant taking the medication. We also identified missed opportunities for HIV testing around diagnoses of STIs. It is important for physicians prescribing PrEP to discuss the patient’s perceived level of risk and address any possible reductions in adherence that may occur because of that perception. In addition, the use of event-driven PrEP dosing regimens or long-acting injectable medications for PrEP should be discussed with patients who feel their risk varies over time or who may have difficulty taking daily medications.”
Working With Patients to Facilitate PrEP Adherence
The study results point to several ways in which HIV prevention can be improved, according to Dr. Dharan. “First, clinicians prescribing PrEP should ensure that they discuss the circumstances of their patients to identify potential barriers to use,” she notes. “Second, they should also regularly discuss the use of PrEP in detail, including stopping and starting PrEP, to ensure patients understand the risks for HIV acquisition during times of perceived lower risk. On-demand regimens for PrEP, as well as new long-acting injectable medications, may be more suitable for patients with intermittent periods of risk or difficulty remembering to take oral medications.” An important finding is that “only one participant’s acquired HIV had a mutation conferring resistance to a PrEP agent at diagnosis, and this participant had indeterminate initial HIV test results, which may have been related to inconsistent PrEP use,” Dr. Dharan explains. “This shows that diagnosing HIV may be challenging when someone acquires HIV while being exposed to PrEP. It is therefore important to conduct serial follow-up testing if indeterminate HIV test results occur in the setting of PrEP exposure.” She also suggested directions for future research. “Understanding how best to keep individuals at risk for HIV acquisition on effective PrEP and facilitating appropriate dosing regimens for them is critical to improve real-world effectiveness,” Dr. Dharan says. “Research into how to facilitate re-uptake of PrEP around times of lower self-perceived risk is also a vital area for future studies.”
