After a decade of approval¹ and recommended use² of daily oral HIV pre-exposure prophylaxis (daily PrEP), challenges to daily PrEP use continue among gay, bisexual, and other men who have sex with men (MSM) at behavioral risk for HIV infection. Issues of reaching MSM³ and educating providers⁴ about addressing perceptions of this highly effective prevention method continue, even in the context of US Preventive Services Task Force Grade A recommendation⁵ and guidelines that recommend daily PrEP for any person who requests it.² Although PrEP use among White MSM has greatly expanded, racial and ethnic minority MSM are less likely to use PrEP.^6–8

Despite the many MSM who overcome barriers of PrEP knowledge and related health care access, some men with behavioral indications refuse daily PrEP when offered by a provider.^9–11 Previous research on this topic in the United States is sparse. A novel longitudinal approach with a small sample of young Black/African American (Black) MSM in 2016–2017 Atlanta¹² found that a variety of issues were involved in decisions to refuse oral PrEP relatively early in PrEP implementation within the United States. Concern for potential side effects, daily pill adherence, cost, and other issues changed over time for some men, with the emphasis on importance of provider–patient dialogue over time to tilt the balance toward acceptance of oral PrEP as a viable prevention option.^4,12–15

With new HIV prophylaxis products becoming available,² further behavioral research is needed to understand concerns about using PrEP among MSM in the emerging context of sexual event-driven (ie, 2-1-1 dosing)¹⁶ and long-acting injectable PrEP.¹⁷ In this quantitative analysis, we examine concerns reported by MSM who recently refused provider-offered daily oral PrEP to better facilitate uptake and use of various forms of HIV prophylaxis among MSM.

MSM who self-reported unprotected anal sex (ie, without condoms or PrEP use) and refusal of daily oral PrEP recommended by a provider in the past 6 months were recruited for this study primarily through provider referrals but also health clinics, community venues, and online outreach in Atlanta, Chicago, and Raleigh-Durham during 2019. Other eligibility requirements included 18 years or older, cisgender male identification, and a resident of 1 of the 3 metropolitan statistical areas noted. Study procedures were approved and monitored by the CDC Institutional Review Board (Protocol #7031).

Eligible and consenting MSM were enrolled and presented with a quantitative, self-administered, computer-based survey assessing their demographic characteristics, sexual risk and prevention behavior, and preferences for emerging future prevention methods among other issues. Specifically, participants were asked 3 key questions for this analysis, related to their main reason for recently refusing daily oral PrEP, likelihood of using various HIV prophylaxis options in the future, and belief that daily oral PrEP was good for all gay and bisexual men:

Analysis consisted of bivariate and multivariable logistic regression models of (1) demographic characteristics associated with the most common “main reason” for recently refusing daily oral PrEP offered by a provider and (2) the association of main reasons and demographic characteristics with preferred prevention method. We also analyzed the association of belief that PrEP is good for all gay and bisexual men with their reported likelihood of using prevention products in the future.

A decade into daily oral PrEP as a viable HIV prevention method for MSM, some men with behavioral indications continue to refuse to use it when offered to them by a provider. We found potential side effects, a daily pill regimen, and lack of adequate information about PrEP to be top reasons for refusing daily PrEP in a diverse sample of MSM. These findings are similar to previous hypothetical studies of MSM who had not been offered PrEP but said that they would not use daily oral PrEP if offered by a health provider.^4,12–15 Unlike many of the earlier hypothetical studies among men who had not been offered PrEP, however, MSM in our study who refused PrEP had fewer concerns about access and cost. Advancements in cost coverage over the past decade (eg, Medicaid expansion, federal and drug company medication assistance programs, and federal clarification that insurers must pay for all PrEP-related costs) are helping to ease financial concerns among MSM,^18–20 however not universally for states that have not expanded Medicare. Stigma of using PrEP was also not a common primary reason for men refusing PrEP²¹ as it was earlier in the era of PrEP implementation, as social norms adjust when more MSM use PrEP.^22,23

Among the top reasons for refusing daily oral PrEP recommended by a provider were potential side effects.^4,12–14,24 Provider training and social marketing efforts are needed to inform MSM about research on type and frequency of potential side effects and framing those side effects in perspective with other common medications prescribed by providers. Daily adherence is understandably a concern for some MSM who refuse daily PrEP; however, since late 2021,² providers may prescribe oral event-driven or long-acting injectable PrEP as alternatives to a daily adherence regimen. Provider training and community education on these new PrEP modalities may also be needed, as well as training on facilitating sexual health discussions with patients for a wider range of health providers who may serve MSM,²⁵ and discussions that should continue over time to ensure successful PrEP adherence and persistence or necessary adjustments.

Most MSM with behavioral indications who refuse daily oral PrEP offered by a provider reported that they are likely to use daily PrEP or other emerging prophylaxis methods in the future. This is promising for providers and health officials to continue to message and discuss PrEP options with their MSM patients despite their initial reluctance to use PrEP. Provider education on emerging HIV prevention products is a critical next step to inform ongoing discussions with MSM about the best PrEP alternatives for them²⁵ while considering that optimal prevention methods for an individual may change over time.²⁶

This study of MSM who refused daily oral PrEP recommended by a provider represents a first quantitative study on a unique sample that we are aware and, further, focused largely on Black MSM in 3 US cities. Given the small sample size (n = 93), some of the odds ratios have relatively wide CIs and are not entirely stable. Nevertheless, these results give practical direction to next steps for messaging for racial and ethnic minority HIV-negative MSM who are reluctant to use daily oral PrEP. More research is needed in larger samples of MSM who refuse PrEP offered by a provider to better understand the intricacies of why they refuse PrEP now and what are their intentions for HIV prevention in the future—especially in a new era of multiple available PrEP modalities. Another limitation is the hypothetical nature of multiple PrEP modalities at the time of the study, when only daily oral PrEP was available and recommended in the United States. Now that long-acting injectable and event-driven PrEP are available modalities; actual behavior can be assessed for those options and daily oral PrEP when offered by a provider. Nonetheless, our 2019 study of several products that would be available in the future provides insight into potential alternative preferences and relevant prevention messaging for MSM.

Implementation of daily oral PrEP has its challenges; some of those persist over time (eg, daily regimen, concern for side effects),^27–29 while other challenges are being addressed (eg, cost, access).^5,16,26,30 The advent of new HIV prophylaxis methods brings a greater variety of prevention opportunities for MSM, particularly men who have refused daily PrEP, although injectable and event-driven PrEP may have their own challenges for uptake and adherence. Most men who refuse daily PrEP when offered by a provider still indicate a likelihood of using some form of PrEP in the future. This is promising for HIV prevention providers and public health officials, indicating a need to continue to discuss and offer PrEP products to MSM under their care over time, further addressing the Ending the HIV Epidemic in the US initiative.³¹