Due to the difficulty of registering adherence in this type of preventive strategy, three different indicators were used, which were subsequently correlated with each other.

People who chose to take HIV pre-exposure prophylaxis (PrEP) following the 'on-demand' schedule of administration did so at times when they were at risk of HIV transmission and the drug levels in their blood confirmed that they were taking it properly. This proves the efficacy of this preventive strategy in gay, bisexual and other men who have sex with men (GBHSH), according to the findings of the AmPrEP study conducted in the Netherlands.


PrEP consists of the use of antiretroviral drugs (currently, the only combination approved for this purpose is tenofovir disoproxil fumarate and emtricitabine; Generic Pharmaceutical equivalent [EFG]; Truvada®) to prevent HIV infection and is an intervention that It has been shown to be highly effective both in studies and in real settings. In addition, the IPERGAY trial showed that the efficacy would be the same in a daily PrEP regimen as in PrEP on demand, a regimen that consists of taking two pills 24 hours before sexual practice, a third 24 hours after the first two pills and another fourth 48 hours after the first dose (2-1-1).

The AmPrEP study began in 2015 and had 376 participants, two of whom were trans women and the rest were GBHSH men. When choosing the option of taking PrEP daily or on demand, 182 of the participants preferred the second regimen. In 2019, two HIV transmissions were reported among its participants. In one case the person had stopped taking PrEP before the infection occurred, but in the other the person became infected with HIV despite maintaining a good level of adherence. In both cases, the PrEP regimen chosen was daily administration.

These results point to a good efficacy of on-demand PrEP. However, determining the level of adherence to PrEP 2-1-1 is challenging as users' memory can fail to indicate whether they took it at risky times and drug levels in their blood are not. They can be used as a guide to know if they take it properly as the taking is irregular.

To avoid these complications, the researchers measured PrEP use in three different ways and correlated them. Thus, participants were offered an application that they should use daily to record PrEP use, anal intercourse without a condom, and type of sexual partner: stable, known occasional, or unknown occasional. In addition, in the quarterly appointments that the participants kept, they completed a questionnaire to see if they remembered their use of PrEP and its frequency in the previous three months, if they took it during anal intercourse without a condom, and with whom. In this way, the long-term memory of the participants could be correlated with the daily record obtained with the application.

As a third way to measure PrEP use, three dried blood samples were taken to determine drug levels in red blood cells rather than plasma: three, six, or nine months after starting PrEP and , subsequently, at 12 and 24 months. Thanks to these tests, it was possible to know if tenofovir had been taken in the previous six weeks. In the case of emtricitabine, as it was metabolized in a different way and its intracellular levels decreased faster, it only made it possible to determine whether it had been taken in the previous two days.


Of the 182 people who opted for on-demand PrEP, 141 used the app, so the remaining 23% (41 people) were not included in the analysis. Three differences were found between people who used the app and those who didn't. 41% of users who did not use it were at the lowest income level, while among those who did carry out a daily record, this percentage dropped to 26%. On the other hand, in this second group, 48% said they had a stable relationship compared to 27% of those who did not use the application. Finally, participants who did not identify exclusively as gay were less likely to use the app.

The 141 people who used the application registered a total of 8,224 days in which they had anal intercourse without a condom, which is equivalent to 4.6% of the total number of participant-days in the study and represents one day out of every 22. In general, at At the end of the study, it was found that 70% of the days in which an unprotected anal intercourse was maintained had been covered. According to the authors, this would demonstrate that for many users on-demand PrEP would be the most appropriate option if used to cover risk relationships.

According to the app's log, the 2-1-1 regimen was taken appropriately in 84% of sexual relationships with known casual partners and in 82% of sexual relationships with unknown partners, while participants did not take no dose (or only one) in 7.6% and 9.7% of the occasions, respectively. These data differed in the case of sexual relations with stable partners, as only 60% of the people took the regimen completely, while 33% took one or none of the planned doses. As the participants were not asked about their knowledge of the HIV status and viral load of their partners, this difference could be understood as a reflection of the participants' judgment about the risk of having sex with them, whether correct or not.

The quarterly questionnaire was answered by 94% of all participants and 90% indicated having used PrEP in the last three months. In that period, on-demand PrEP was taken an average of six times, but only in two out of six cases was there a risky anal intercourse, which would correlate with the estimate that one out of every 22 days would involve one of those relationships and would indicate how rare episodes are with risk of HIV transmission.

Blood samples were available from 98 participants averaging twice each, and upon analysis, the mean intracellular level was found to be 590 femtomols (fmoles) of tenofovir per sample. On the other hand, looking at emtricitabine levels, 69% of the samples reflected that the participants had not taken PrEP in the last 48 hours. Although this could contrast with previous studies carried out in gay men taking daily PrEP where an intracellular level of 700 fmoles of tenofovir per sample would be associated with adherence of at least four days a week and good efficacy, these levels could be found in people taking the 2-1-1 PrEP regimen. In addition, the application showed that in the 42 days prior to the blood sample an average of 10 pills were taken and the questionnaire increased that average to 13 pills.

On the other hand, a correlation was found between tenofovir concentrations with the number of days in which an unprotected anal intercourse took place by finding similarity between the graph that reflected tenofovir concentrations versus the reported number of PrEP doses in the six last few weeks before the blood sample was taken and the graph where those tenofovir concentrations compared with the number of days there was a risk relationship.

As had already been observed in other studies on PrEP, age was related to the lack of coverage of this prophylaxis, with men under 35 years of age showing a greater probability of having risk relationships on days not covered by PrEP. This risk was twofold in PrEP users who had sex with known sexual partners and who had heavy alcohol use.

In their conclusions, the authors indicate that, in the AmPrEP study, participants taking PrEP on demand did so adequately when they were at risk of acquiring HIV. Although these data may be very different from those seen in other studies, there are also others to support them and agree that daily and on-demand PrEP regimens have an identical degree of protection.


Source: Aidsmap / Own elaboration (gTt-VIH)

References: Jongen VW. Adherence to event-driven HIV PrEP among men who have sex with men in Amsterdam, the Netherlands. Analysis based on online dairy data, 3-monthly questionnaires and intracellular TFV-DP. Journal of the International AIDS Society 24: e25708, 2021

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