Slow Uptake of PrEP: Behavioral Predictors and the Influence of Price on PrEP Uptake Among MSM with a High Interest in PrEP

Pre-Exposure Prophylaxis (PrEP) has been found to be an effective biomedical intervention for HIV prevention [1‐4]. The World Health Organization (WHO) recommends PrEP for people who are at substantial risk of HIV infection, for example men who have sex with men (MSM) [5]. In the past years, efforts have been made to make PrEP accessible, for example by setting up national PrEP implementation guidelines [6, 7]. Despite its effectiveness and these efforts, the accessibility of PrEP varies greatly per country [8], the uptake of PrEP has been low [9], and the full potential of PrEP at population level has not been reached yet [10]. In the Netherlands, it is estimated that there are currently 3500 individuals on PrEP [8], of which 95% are MSM [11], while it is estimated that 10,000 MSM meet eligibility criteria for PrEP [12, 13]. To increase uptake, it is therefore important to identify facilitators and barriers of PrEP use. While earlier studies investigated behavioral and psychological factors of PrEP uptake, such as sexual risk behaviors, perceived HIV risk, and stigma [14‐17], the influence of actual price changes on PrEP use has not been fully investigated, especially not in contexts where universal health care coverage of PrEP is not (yet) available.

Previous studies found several behavioral factors to be related to PrEP use. Compared to MSM who were not using PrEP, PrEP users were more likely to have had a recent STI diagnosis, have used post-exposure prophylaxis (PEP) before, have had condomless anal intercourse, have used recreational drugs or practiced chemsex (i.e., use of certain stimulants in the context of sex), have had sex with HIV positive sex partners, and have a greater number of sex partners [18‐21]. In terms of demographic characteristics, PrEP users were found to be of middle age and to have a higher income [18, 20]. While it is reassuring to see that MSM at higher risk of HIV are more likely to be interested in PrEP and to use PrEP, overall PrEP remains “underused”, and some population strata at higher risk are less likely to use PrEP [22‐24].

The slow uptake of PrEP so far has been explained by structural and psychosocial barriers, including lack of access to PrEP, doubts about effectiveness, concerns about side-effects, and expected stigma [25‐29]. Moreover, the costs of PrEP have been noted as one of the main barriers for PrEP uptake in cross-sectional analysis [30‐37]. Notably, in a report drawing on data from 32 European and Asian countries, the price of PrEP was the most common barrier for PrEP uptake [38]. With prices of around € 500 per month for patented Tenofovir-Emtricitabine formulations in Europe and $1600 per month in the U.S., branded PrEP is likely unaffordable for most people in many countries.

In recent years, PrEP has however become more affordable and accessible as a result of the introduction of generic formulations of PrEP and the inclusion of PrEP in health care packages or insurance coverage [8, 39]. PrEP uptake may increase as it becomes more affordable, and this hypothesis is further supported by the finding that uninsured MSM are less likely to use PrEP [23, 40], if PrEP is included in health insurance coverage. Yet, even though the affordability of PrEP is increasing, current pricing may still be a barrier for certain individuals and groups, notably MSM with lower incomes.

In the current study we examine whether the costs of PrEP indeed predict PrEP uptake, alongside behavioral and demographic characteristics. As of 1 January 2018 the price of PrEP in the Netherlands decreased from € 500, to € 50, per month, as a result of the introduction of generic formulations of PrEP [39]. This introduction of generic PrEP allowed us to look more closely into the effects of price on the uptake of PrEP. At the time of our study, PrEP was not included in reimbursement schemes of the national health insurance. The primary way of obtaining PrEP was to buy PrEP at the pharmacy on prescription from the general practitioner [41]. Formal PrEP services, offering PrEP in a co-payment scheme, were implemented in the public health centers as of July 2019, after data collection of our study was finished [11, 42].

The aim of this study was to investigate what sociodemographic and behavioral factors predict PrEP uptake. We in particular investigated whether the price decrease of PrEP, from € 500,- to € 50,- per month, resulting from the introduction of generic formulations of PrEP, is associated with an increased PrEP uptake. This study found that a better perceived financial situation, having ever had PEP treatment, and the price decrease of PrEP were significantly related to PrEP initiation. This is in line with our hypotheses and findings of earlier studies. However, while earlier cross-sectional studies reported the price of PrEP to be an important overall barrier for intended PrEP uptake [30‐38], we found more specifically that the price decrease of PrEP was only related to an increase in PrEP uptake among participants with an average perceived financial situation. This might indicate that the current price reduction of PrEP (from € 500 to € 50 per month for the Dutch context) did not impact MSM in more unfavorable nor more favorable financial situations, likely for different reasons. MSM in a favorable perceived financial situation may use PrEP anyway, regardless of price level, because the use of PrEP does not have a substantial impact on their financial situation. On the other hand, MSM in an unfavorable perceived financial situation may find the price of € 50 per month still too high and may be not be able to afford PrEP at this price. This indicates a need for the inclusion PrEP in health insurance or the implementation reimbursement schemes to increase PrEP uptake among less affluent MSM [23, 40].

While having ever had PEP treatment was a significant predictor of PrEP initiation, other variables related to sexual risk behavior, such as number of sex partners in the past 6 months, history of STIs, condom use, and substance use were not significantly related to PrEP initiation after 6 months. These variables are considered key indicators for PrEP use and eligibility for PrEP, as they reflect an increased risk of HIV, and we therefore expected these to be significant predictors of PrEP initiation. A possible explanation for the lack of such a relationship is that participants in our sample overall had a high prevalence of sexual risk behaviors; most would be eligible for PrEP. Hence, their sexual risk behaviors are unlikely to distinguish between those who start taking PrEP or not (i.e., ceiling effect). This is in line with an earlier study that found that despite being an appropriate candidate for PrEP, and contemplating PrEP use, MSM do not always initiate PrEP use [9]. It was argued that PrEP initiation could be increased if PrEP providers apply motivational interviewing techniques to help MSM decide on PrEP use. It is important to recognize the role of healthcare providers in PrEP initiation. In our study we found that having had PEP treatment is related to PrEP use. This might be a result of the Dutch national guideline that instructs health care providers to encourage MSM to continue PrEP use directly after a PEP treatment [6]. This indicates that health care providers should be trained to recognize eligible candidates for PrEP and to be confident to prescribe PrEP to them.

Notably, only 45.6% of the participants in our study were using PrEP after 6 months follow-up. In this sample, we expected a higher PrEP uptake because of the high interest in PrEP among the participants. In the context of the Transtheoretical Model of Change, as applied to the PrEP cascade by Parsons et al. [9], most participants in our study were either in the stage of PrEP contemplation (i.e. willing to take PrEP) or the stage of PrEParation (i.e. intending to take PrEP), because the participants were recruited on a website where they could find detailed information on how to obtain PrEP. Thus, interest and knowledge would not be limiting factors to procure PrEP for the participants in this sample. MSM moved from the PrEParation stage to the action stage as soon as the price of PrEP dropped. Also other studies found large gaps between interest in PrEP and PrEP uptake [9, 50, 51]. It seems that structural barriers play a larger role in explaining this gap compared to psychosocial and behavioral factors. For example, among young Latino MSM it was found that structural syndemic factors, such as poverty and unstable housing, limit PrEP uptake despite high interest in PrEP [50]. In our study we found that the perceived financial situation and the price of PrEP were the most important factors in predicting PrEP uptake.

There are a few limitations to this study. We recruited participants using convenience sampling, limiting the representativeness of this study for the whole MSM population. The sample consisted mostly of highly educated MSM who were born in the Netherlands. MSM with lower education levels and migrant MSM may face other challenges when accessing PrEP. It is important to study the specific needs of these MSM subgroups, in particular because non-Western migrant MSM in the Netherlands have an increased risk of acquiring HIV [52]. Still, our study highlights that even among non-minority MSM in the Netherlands the price of PrEP and their financial situation are significant factors determining access to PrEP. The findings relate specifically to MSM with a high interest in PrEP, and are therefore mostly relevant for explaining the gap between a high interest in PrEP and a low uptake of PrEP [38]. Another limitation of this study is related to the assessment of the price of PrEP. We used the price of PrEP in pharmacies in the Netherlands to construct a variable for the price of PrEP that could be included in the regression analysis. However, some participants obtained PrEP informally (e.g., via pharmacies abroad), so the price of PrEP in pharmacies in the Netherlands may not have influenced their PrEP initiation. Monitoring of prices for PrEP at the time of the study in online pharmacies and through health care providers showed prices quite similar to the reduced price in the Netherlands, with a lower bound of € 30,- in Thailand and average prices around € 50,-. Another limitation is that the variable “price of PrEP” may not merely reflect the change in the price of PrEP, but may also reflect time effects. We did an additional analysis (see online supplementary material C) to control for possible time effects, and found no evidence that participants were more likely to use PrEP later in time. This indicates that the effect of the variable “price of PrEP” indeed captures an effect of the price drop of PrEP.

A strength of this study is that it is the first to collect data over a time span in which the price of PrEP significantly changed, allowing us to investigate the relationship between an actual, real-world change in the price of PrEP and PrEP uptake. These findings are not only relevant for the Netherlands, but also for other countries. In 2019, PrEP was not included in reimbursement schemes in 37 (out of 53 reporting) countries in Europe, underscoring that costs of PrEP likely continue to impact PrEP use [53]. We further expect that the results of our study remain relevant in the future, even when the price of branded PrEP may be (further) lowered, as new types of formulation (e.g., Emtricitabine/tenofovir alafenamide; [54]) or administration (e.g., injectables, implants [55]) may result in new pricing barriers. Pricing barriers may also continue to exist after the introduction of generic formulations of PrEP, because generic formulations of PrEP are not always substantially cheaper than branded Truvada [56].

To optimize PrEP uptake among MSM with a high interest in PrEP with limited financial resources, the cost of PrEP play an important role. The introduction of lower price generic formulations of PrEP led to an increase in PrEP uptake in the Netherlands. However, PrEP continued to be used by MSM in a favorable perceived financial situation. MSM in an unfavorable perceived financial situation may be more likely to use PrEP if it is available free of charge, through health insurance, or fully reimbursed, through a government scheme.