A West African PrEP cohort study, published in Clinical Infectious Diseases, has found that men using event-driven PrEP had poorer adherence and a higher risk of acquiring HIV compared to those using daily PrEP. Men who acquired HIV during the study described major difficulties adhering to the event-driven regimen, particularly in relation to planning for sex and remembering to continue to take their PrEP for two days after having sex.
The authors highlight that in the context of West Africa, men had fewer opportunities for sex with male partners and sex could happen at a moment’s notice, making it difficult to plan for. They argue that their findings indicate that men “should be informed, before choosing between event-driven and daily PrEP, of the specific adherence difficulties with the former regimen... Those who choose event-driven PrEP should then receive enhanced support to guarantee adequate adherence.”
The roll-out of PrEP in West Africa has been slow due to economic constraints, hostility towards sexual minorities, and a lack of research on PrEP in the region. To address this gap, the CohMSM-PrEP demonstration study was designed to assess if men who have sex with men (MSM) in West Africa found oral PrEP acceptable, and whether they were able to use it effectively. It was conducted from 2017 to 2021 in Burkina Faso, Côte D’Ivoire, Mali and Togo. Early data from the study showed a significant reduction in HIV incidence, from 10.0 per 100 person-years among other MSM not taking PrEP to 2.3 per 100 person-years among the study participants. Despite this positive finding, incidence among the PrEP users in the study was still higher than nearly every other PrEP study among MSM worldwide. To understand why this was the case, Dr Christian Laurent and his colleagues from the CohMSM-PrEP Study Group analysed the final dataset to understand who acquired HIV during the study and what factors may have been associated with it.
The CohMSM-PrEP study enrolled HIV-negative MSM aged 18 or older who were at high risk of acquiring HIV. At any study visit, participants could choose between daily or event-driven PrEP, switch between these regimens, and discontinue or restart PrEP as they wished. Regardless of which regimen they chose, participants attended monthly medical and peer support appointments at an MSM-friendly clinic for their first four visits, then every three months thereafter. For those following the event-driven regimen, adherence was deemed adequate if the participant reported perfect adherence to the 2+1+1 dosing schedule: two pills taken two to 24 hours prior to sex, one taken 24 hours after the first dose, and another taken 48 hours after the first dose. For those on daily PrEP, adherence was adequate if the participant reported taking at least four pills in the week prior to having sex. Participants with difficulties adhering to PrEP were invited to attend support groups.
A total of 647 participants enrolled in the study, with the median time of participation being just over two years (25.6 months). The median age was 25, and nearly half of participants (46%) had a wife or girlfriend. On average (median), participants had had two male sexual partners in the previous three months, and only 43% reported using condoms every time they had sex during the same time period.
Of the total 5371 visits, event-driven PrEP was chosen in 72% of visits and daily PrEP was chosen in 26% of visits. Adherence was deemed adequate to prevent HIV infection in 44% of the 2677 adherence assessments of event-driven PrEP users, and 75% of the 1057 adherence assessments of daily PrEP users. This difference was statistically significant, meaning there is strong evidence that inadequate adherence among men on the event-driven regimen was not solely due to chance.
Twenty-five men acquired HIV during the study – 18 of whom were using event-driven PrEP, 6 switched between event-driven and daily PrEP, one was using daily PrEP, and two had discontinued PrEP for several months. HIV incidence was highest among those who had discontinued PrEP at 7.9 per 100 person-years, followed by 2.4 per 100 person-years for event-driven PrEP, and 0.6 per 100 person-years for daily PrEP.
After controlling for a range of factors, the analysis found that HIV incidence was 4.4 times higher for participants using event-driven PrEP compared to daily PrEP, 5.3 times higher among those who did not consistently use condoms in the previous 3 months, and 6.5 times higher among those participants who perceived themselves as having a moderate risk of acquiring HIV from a regular male partner compared to those who perceived themselves as having no risk.
Of the 25 participants who acquired HIV during the study, 20 reported having sex without having taken any PrEP, nine reported having sex when they hadn’t taken enough PrEP to protect themselves against HIV and 12 had missed study visits. Blood samples taken from the men when they had been diagnosed with HIV indicated that only two had detectable levels of PrEP in their bloodstream. One of these men had developed resistance to emtricitabine (one of the drugs used for PrEP), which was attributed to poor adherence.
Fifteen of the men were interviewed to better understand the context in which they acquired HIV. Most had a good understanding of the event-driven dosing schedule, but described difficulties in adhering to it, particularly in relation to planning for sex:
“Imagine, you go out for a party, a night out… it [sex] falls in your lap, what do you do? It’s a little complicated”.
Participants also found it difficult to remember to take PrEP in the two days after having sex. Participants felt that changes in routine caused by work, travel or alcohol use constrained their ability to adhere:
“It is not all that easy to use it [PrEP], or to remember, because there are moments, you might be traveling or you might be indisposed, but seeing as you should take it too, if you don’t pay attention, you can forget”.
Participants didn’t necessarily use condoms when they had forgotten to take their PrEP, which could explain later acquisition of HIV.
“Yes, in the beginning I replaced it [PrEP] with condoms, but well, almost every time I took condoms with me, but it happened one day that I didn’t take them”.
Laurent and co-authors speculate that the lower number of male sexual partners among their participants than in previous studies may indicate that West African MSM have less opportunity to meet male sexual partners, and therefore experience more difficulty in planning for when sex might happen.
However, they also caution that the choice of event-driven PrEP or daily PrEP was not randomised for participants. It is possible that men who were generally more averse to taking medication opted for the event-driven regimen, meaning they may also be less likely to adhere, which might bias the results.
Although these findings indicate that event-driven PrEP may be less effective for MSM in West Africa, the authors argue that it is still crucial to increasing the number of PrEP users. Without it, it is likely that a greater number of MSM would not start PrEP and remain at high risk of acquiring and passing on HIV. However, they argue that their results highlight a need to ensure that West African MSM – and MSM in similar contexts – are properly informed of the specific adherence challenges associated with event-driven PrEP and the risk of acquiring HIV if they do not adequately adhere to it. Those who do choose to use event-driven PrEP should receive enhanced support.
Laurent C et al. Human Immunodeficiency Virus (HIV) Seroconversion Among Men Who Have Sex With Men Who Use Event-driven or Daily Oral Pre-exposure Prophylaxis (CohMSM-PrEP): A Multi-country Demonstration Study From West Africa. Clinical Infectious Diseases, ciad221, online ahead of print, 13 April 2023.