Daily oral PrEP clinical trials to date have shown that adherence is the one single factor that influences most PrEP effectiveness. High levels of drugs found in the participants’ blood had a direct correlation with high levels of protection. On the other hand, ensuring those high levels of adherence have proved a very serious challenge in some contexts. Finding ways to ensure that high (if not perfect) levels of adherence are met should therefore the first area of focus.
2. Measuring adherence
Numerous methods for measuring adherence are available, with different costs, difficulties and reliability. A variety of approaches are presented. Placing adherence to PrEP in the context of combination prevention will be intellectually challenging but is essential for
3. Measuring impact and modelling incidence
Comparing observed HIV incidence to that of comparison populations either observed or modelled.
4. Secondary endpoints
Sexual behavior, pregnancy, drug resistance, STIs, selected factors from users’ perspectives.
5. Primary study populations
The choice of populations to be covered in a PrEP demonstration project should be context dependent, based on the greatest need within the country/region where the demonstration project is to take place. These may include may include sero3discordant couples in generalized epidemics, men who have sex with men and sex workers in concentrated epidemics, and other high3need groups (such as mobile populations, truckers, etc.) in concentrated epidemics. In addition, geographies of needs/risks may be considered.
6. Study design and sample size, length of project
The precise study design, sample size and length of project should be defined based on the specific setting and population where the project is to take place. A rough estimate of 600 to 800 individuals for each demonstration project group, and of at least 12 and if possible 24 months for the duration of the project should be considered as a minimum. A number of parameters that may need to be considered in refining these parameters are listed in this document.
7. Daily dosing, periodic dosing and intermittent dosing
Placing PrEP in the context of combination prevention reflects more accurately the realities of people’s lives but complicates the administration and the measurement of the intervention. PrEP works best when taken daily. The aim should be to be as close as possible to this target. Intentional intermittent dosing is not endorsed.
8. HIV testing, retesting and drug resistance
Ensuring that an individual does not start PrEP if HIV positive or discontinues immediately when seroconverting is critical both for the person’s own safety and for the population at large, to avoid the risk of developing drug resistance. At this point however, as long as the specific recommendations detailed in this document are followed, it appears that resistance may not pose too serious a threat in regards to PrEP. Indeed, this is a drug used in uninfected people. Specific recommendations on initial testing protocol and retesting can be in the document.
9. Other safety issues (side effects, pregnancy and breastfeeding)
The monitoring of side effects and other potential safety issues is a critical component of a PrEP demonstration project.
10. Sustainability
The most useful evidence drawn from these demonstration projects will be grounded in the reality of existing health systems, and therefore working jointly with the health system from the early stages will be beneficial for eventual uptake of PrEP on a larger scale. For that purpose, the demonstration projects should include three additional steps (i) identifying the functions / services that the health system would need to implement the components of a wider program, (ii) carrying out an assessment about the readiness of the health system/sector to carry out PrEP, (iii) carrying out a costing exercise for the program as a whole and for individual program components.
