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Improving the HIV Pre-Exposure Prophylaxis (PrEP) Cascade


Pim Brouwers, Ph.D.
Division of AIDS Research


The objective of this initiative is to develop and test interventions to improve the screening, engagement, and retention of high-risk populations in HIV pre-exposure prophylaxis (PrEP) clinical care, and to support both adherence to PrEP drug regimens and persistence on PrEP drug regimens among persons at high-risk for HIV infection in the United States.


The Food and Drug Administration approved the first HIV preventive medication in 2012, and the Centers for Disease Control and Prevention published clinical practice guidelines in 2014, in which they recommended PrEP for HIV negative people at substantial risk for infection. The use of oral antiretroviral medications as HIV PrEP confers a strong preventive benefit to individuals who are at-risk for HIV infection when taken with high adherence.

PrEP clinical care follows a cascade that is analogous to the HIV treatment cascade. The PrEP cascade includes (1) targeting PrEP to the highest risk individuals, (2) screening individuals as PrEP candidates, (3) linkage to PrEP care, (4) initiation of a PrEP regimen, (5) retention in PrEP clinical care, and (6) adherence (taking medicines as prescribed) and persistence (continue to take medicines over time independent of adherence) to the PrEP medication regimen.

Unfortunately, gaps may occur at each step of the PrEP cascade. Studies indicate low awareness of oral PrEP among high-risk groups to whom PrEP would be targeted. Uptake of oral PrEP in the United States has been limited to date. An analysis of pharmacy claim data in 2014 found fewer than 4000 PrEP prescriptions nationwide.1  A cohort study reported that only 75% of those with risk behavior indicating a need for PrEP chose to initiate it.2  Although 93% of the cohort study participants who initiated PrEP were retained in care after three months, drug assay data indicated that the most common drug concentration pattern was clinically significant PrEP drug levels followed by discontinuation, indicating problems with persistence to the oral PrEP regimen.

Novel approaches to PrEP delivery such as long-acting injectable formulations and vaginal rings are currently undergoing testing in clinical trials. If approved for use, these formulations may facilitate PrEP uptake by expanding the available delivery options, in addition to reducing the adherence burden associated with oral PrEP.  Delivery of novel PrEP formulations in the future would benefit from efforts to improve screening, engagement, and retention of high-risk groups in PrEP clinical care.

There is a lack of proven interventions to support engagement and retention in PrEP clinical care at this time. Engagement of the highest-risk populations in PrEP care may require new screening tools and novel efforts to address risk perceptions among relevant key populations. Highly targeted delivery of PrEP is also critical to furthering its cost-effectiveness. Advancing strategies to retain individuals in all facets of PrEP care (appointments, HIV tests, and medication adherence/persistence) will also be vital to optimizing the preventive impact of PrEP.

This initiative aims to support research to strengthen the HIV PrEP cascade through efforts to target, engage, and retain the highest-risk populations in PrEP care. Such efforts include, but are not limited to research to:

  • Improve the targeting and screening of high-risk populations for potential PrEP use;
  • Develop and test interventions for linkage and retention of high-risk groups in PrEP care; and,
  • Support uptake, adherence, and persistence to PrEP drug regimens among high-risk groups.

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