Pre-exposure prophylaxis, or PrEP, is currently being studied as a potential method for a person who is at risk of HIV infection to reduce their risk of becoming infected. It involves taking anti-HIV medications on a regular basis.
There are several types of PrEP being investigated. PrEP drugs may be available in a variety of forms, including pills taken orally or gels inserted into the vagina or rectum. The drugs may need to be taken every day, or coitally (before and after sex), or intermittently (once or twice a week or month).
Most types of PrEP being studied use the antiretroviral drug tenofovir (called Viread when used in pill form) or combinations of tenofovir and FTC (sold as a fixed-dose co-formulation pill called Truvada).
While some PrEP clinical trials have had promising results, others have not. This has raised questions about how well PrEP will work, particularly among women.
Differences in adherence to PrEP among study participants has been suggested as one explanation for the wide range of effectiveness levels in completed clinical trials.
Measuring Adherence in Clinical Trials
Regular adherence to PrEP is likely needed to maintain high levels of drug in the body and maximize the protection provided by PrEP.
Therefore, an accurate measure of adherence among study participants is needed to correctly interpret study results and understand how well PrEP really works.
Adherence among study participants in PrEP clinical trials is normally measured in the following two ways:
- Self-report -- every month participants are asked by study investigators how well they have been adhering
- Pill or applicator counts -- every month participants are asked to return any unused pills or gel applicators to study investigators
Unfortunately, these two methods of measuring adherence are not very accurate and tend to overestimate how well participants are adhering to PrEP. Participants often self-report that they are adhering more frequently than they actually are and participants may not return all of their unused pills or gel applicators.
Overestimation of adherence among study participants through self-report or pill/applicator counts can lead to underestimation of the effectiveness of PrEP.
Drug Levels as a Measure of Adherence
Recently, some completed PrEP clinical trials have also measured adherence by looking at whether study participants who were supposed to be taking PrEP had detectable levels of anti-HIV drugs in their blood or other body fluids. This method of measuring adherence is more accurate than self-report or pill/applicator counts because it is a direct measure of exposure to the drug.
Using the levels of anti-HIV drugs in participants to estimate adherence has a few limitations. A participant's drug levels are generally only measured once a month during the clinical trial. Therefore, having detectable drug levels suggests that a participant was adhering to PrEP at the time the drug levels were measured; it does not necessarily reflect how good their overall adherence was in the past month since their last visit. Also, anti-HIV drug levels can remain detectable for a few days after taking PrEP pills, therefore having a detectable level of drug at a study visit means that a participant had taken PrEP within the past few days.
Recently released information on drug levels suggests that poor adherence may explain the low levels of PrEP effectiveness in some studies and why some study participants became infected with HIV while taking PrEP.