Abstract
Background:
Event-driven dosing of HIV preexposure prophylaxis (PrEP) using a 2-1-1 regimen is efficacious for men who have sex with men (MSM). However, data are limited on the prevalence, correlates, and patterns of non-daily PrEP use in the U.S.
Setting:
Nationwide online survey.
Methods:
We distributed a survey to assess experiences with PrEP, including non-daily use, in May 2019 on geosocial networking sites commonly used by MSM.
Results:
Among 9,697 respondents, mean age was 43 years, 67% were non-Hispanic white, and 90% were MSM. Nearly all (91.0%) had heard of PrEP, 40.1% ever used PrEP, and 33.3% used PrEP in the last 6 months. Most (60.6%) were interested in non-daily PrEP. Those without health insurance and those with higher incomes were more likely to be interested in non-daily PrEP. Of the 3,232 who used PrEP in the past 6 months, 176 (5.4%) reported non-daily use. Fewer sexual partners, frequent sex planning, and substance use were associated with non-daily use. Common reasons for non-daily use were inconsistent sexual activity (59%) and cost (49%). The most prevalent regimen was event-driven (48.3%); of those, 64.7% used 2-1-1. Of non-daily users, 24.0% used PrEP on a regular schedule but not every day, including only on weekends or days starting with T or S.
Conclusions:
Given substantial interest in non-daily PrEP, and use of non-daily strategies that have not been evaluated in clinical studies, there is a need for U.S. public health authorities to provide guidance on safe and effective non-daily dosing for MSM.
Keywords: event-driven PrEP, episodic PrEP, on-demand PrEP, human immunodeficiency virus (HIV), men who have sex with men (MSM), preexposure prophylaxis (PrEP)
INTRODUCTION
Preexposure prophylaxis (PrEP) is 99% effective in reducing the risk of HIV acquisition when taken daily.1–4 However, uptake has been limited in the U.S.,5 in part because of challenges with daily pill-taking, the high cost of the medication, and other barriers to access.6,7 Event-driven PrEP using a 2-1-1 regimen, with two doses of co-formulated tenofovir disoproxil fumarate and emtricitabine in the 24 hours before sex and single daily doses for the two days after sex, was shown in the IPERGAY study to be highly effective in reducing HIV risk among men who have sex with men (MSM),8–10 offering a potential alternative to daily dosing that could reduce pill burden, drug exposure, and cost.11 Although 2-1-1 PrEP is now endorsed for MSM by the World Health Organization,12 the International Antiviral Society-USA,13 and two local jurisdictions in the U.S.,14–16 the U.S. Centers for Disease Control and Prevention (CDC) continues to recommend only daily PrEP dosing for MSM.17
Despite the lack of guidance from the CDC and U.S. Food and Drug Administration, PrEP users may already be using non-daily dosing; however, data are limited on the prevalence, correlates, and patterns of non-daily PrEP use in the U.S. Self-driven dosing strategies may differ from the 2-1-1 dosing strategy evaluated in clinical research studies, potentially resulting in an increased risk of HIV infection18 and antiretroviral drug resistance.19–21 Given that non-daily PrEP use, including both 2-1-1 and other dosing strategies, may occur when PrEP is obtained outside of healthcare settings, measures of non-daily PrEP use among people recruited from community-based settings may be most reflective of actual patterns of use.
We conducted an online survey of at-risk adults, primarily MSM, in the U.S. to assess interest in and experiences with PrEP, including non-daily dosing. We assessed the prevalence and correlates of interest in and use of non-daily PrEP, reasons for non-daily PrEP use, and patterns of non-daily use, including the extent to which non-daily regimens are consistent with the 2-1-1 strategy that has been shown to be effective in clinical studies.
METHODS
Study Design
We developed a survey to assess experiences with PrEP, including non-daily use, among adults without HIV. The survey was open to U.S. residents who were at least 18 years of age, did not report a history of HIV diagnosis, and could complete a survey in English. Although the survey was open to all sexual orientations and gender identities, we recruited participants from geosocial networking sites that are commonly used by MSM, the only group for whom non-daily PrEP (i.e., 2-1-1) has been shown to be effective.
We piloted the survey during in-depth qualitative interviews with 25 PrEP users recruited from an online social media group for people interested in PrEP and from a community health center in Boston that specializes in care for sexual and gender minorities. We requested open-ended feedback on the survey, which we incorporated into the survey in an iterative fashion. After finalizing the survey, we used online advertisements to recruit a national sample of adults without HIV, including PrEP users and non-PrEP users, from two mobile and online networking sites that are used predominantly by MSM. The survey was distributed in May 2019. Survey responses were anonymous and were not linked to the users’ profiles to help facilitate disclosure of potentially sensitive information. After completing the survey, participants were invited to enter a raffle to receive a $50 gift card via email.
The institutional review board at Harvard Pilgrim Health Care Institute approved this study with a waiver of written informed consent.
Measures
The survey included questions about experiences with PrEP, including awareness of and interest in daily and non-daily PrEP dosing, reasons for non-daily PrEP use, non-daily dosing strategies, and methods of obtaining PrEP pills. Other domains included sociodemographic characteristics (e.g., age, assigned sex at birth, gender identity, race/ethnicity), sources of information about PrEP (e.g., healthcare providers, social media, sex partners), sexual history (e.g., frequency, planning, condom use, diagnoses of hepatitis C virus [HCV] and sexually transmitted infections [STIs]), substance use, and mental health. STI diagnoses included gonorrhea, chlamydia, or syphilis diagnosis in the past 6 months. Substance use included self-reported use of cocaine, heroin, and methamphetamine in the past 6 months. We assessed depression by using the Center for Epidemiologic Studies Depression Scale Revised (CESD; Cronbach’s alpha α = 0.86).22
Our primary outcomes were interest in, and use of, non-daily PrEP in the prior 6 months. Interest in non-daily PrEP was asked of all participants using a multiple-choice item: If available to you and shown to be as safe and effective as daily PrEP, how interested would you be in taking PrEP pills in the following ways? Responses were on a 4-point Likert scale, including “not at all interested,” “slightly interested,” “moderately interested,” and “extremely interested,” for each of the following PrEP dosing strategies: 1) Only around the time of sex (e.g., a few pills before sex and for a few days after), 2) periodically (e.g., for a few weeks at a time such as on vacation), and 3) only on certain days of the week but not every day (e.g., Tuesdays, Thursdays, Saturdays, Sundays). Respondents who indicated they would be slightly to extremely interested in any of these strategies were classified as having any interest in non-daily PrEP use.
For use of non-daily PrEP, respondents who reported using PrEP in the past 6 months were asked: When taking PrEP in the last 6 months, how did you take it? Response options included 1) daily (i.e., took a pill every day, potentially missing a dose on occasion) or 2) less than daily (e.g., only around the time of sex, daily but only for short periods, only on certain days of the week). Respondents could select more than one if they had used PrEP in different ways. Those who indicated less than daily were asked for additional details about their dosing strategies.
Statistical Analyses
We used descriptive statistics to characterize the overall sample of respondents. We then used log-binomial regression to compute unadjusted prevalence ratios (PRs) and corresponding 95% confidence intervals (CIs) for each independent variable in relation to interest in and use of non-daily PrEP. We did not conduct multivariable analyses to adjust for confounding because we were not assessing causal relationships in this cross-sectional study.23 Analyses were conducted in SAS 9.5 (Cary, North Carolina).
RESULTS
Respondent Characteristics
Our study sample included 9,697 respondents. The mean age was 43 years (range 29–56) and two-thirds (68.7%) were non-Hispanic white (Table 1). Most (91.7%) were male, with 7.1% non-binary, 0.7% transgender men, 0.5% transgender women, and 0.1% female; 90.5% were MSM. Respondents were distributed across all regions of the U.S., with the largest proportion in the South (34.0%). Most (89.4%) had health insurance and at least some college education (85.3%), and 24.8% had an annual income of $80,000 or higher. In the prior 6 months, most (84.7%) reported inconsistent condom use, 19.2% reported 10 or more sexual partners, 11.7% reported being diagnosed with an STI, and 1.4% reported a hepatitis C diagnosis. Nearly half of respondents very often or always planned sex in advance (40.7%) or discussed HIV status with partners (48.9%).
Table 1.
Characteristics of respondents. (N=9697)
| Demographics | N(%) or M(SD) |
|---|---|
| Age M(SD) | 42.6 (13.5) |
| Gender | |
| Male | 8893 (91.7) |
| Female | 7 (0.1) |
| Transgender woman | 45 (0.5) |
| Transgender man | 68 (0.7) |
| Non-binary gender | 684 (7.1) |
| Men who have sex with men | 8778 (90.5) |
| Race/ Ethnicity | |
| White | 6327 (68.8) |
| Black | 709 (7.7) |
| Hispanic | 1057 (11.5) |
| Other | 1108 (12.0) |
| U.S. Regions | |
| South | 3068 (34.0) |
| West | 2360 (26.2) |
| Northeast | 1755 (19.5) |
| Midwest | 1821 (20.2) |
| Puerto Rico | 18 (0.2) |
| Education | |
| Less than high school | 93 (1.0) |
| High school | 960 (10.4) |
| Some college | 2344 (25.5) |
| College graduate/ Graduate School | 5800 (59.8) |
| Income (USD) | |
| Less than 20,000 | 1745 (19.2) |
| 20,000–39,999 | 2032 (22.3) |
| 40,000–59,999 | 1764 (19.4) |
| 60,000–79,999 | 1304 (14.3) |
| 80,000+ | 2261 (24.83) |
| Health Insurance | |
| Private | 5916 (66.8) |
| Medicaid | 668 (7.5) |
| Medicare | 869 (9.8) |
| None | 933 (10.5) |
| Other | 469 (5.3) |
| Depressive Symptoms (CESD) M(SD) | 9.9 (6.9) |
| PrEP awareness and use | |
| Heard of PrEP | 8826 (91.0) |
| Interest in Non-Daily PrEP Use | 5876 (60.6) |
| Used PrEP in last 6 months | 3232 (33.3) |
| Non-Daily PrEP Use | 176 (5.5) |
| Sexual behaviors and health (last 6 months) | |
| Sex planned in advance | |
| Never | 649 (8.7) |
| Rarely | 1382 (18.4) |
| Sometimes | 2412 (32.1) |
| Very Often | 2084 (27.8) |
| Always | 980 (13.0) |
| Discussed HIV status | |
| Never | 1202 (16.0) |
| Rarely | 1043 (13.9) |
| Sometimes | 1582 (21.1) |
| Very Often | 1572 (20.9) |
| Always | 2104 (28.1) |
| Used condoms | |
| Never | 2458 (32.8) |
| Rarely | 1339 (17.8) |
| Sometimes | 1637 (21.8) |
| Very Often | 922 (12.3) |
| Always | 1144 (15.3) |
| STI diagnosis | 1138 (11.7) |
| Hepatitis C diagnosis | 121 (1.2) |
| Number of sexual partners M(SD) | 8 (40.6) |
| 0–1 | 3460 (35.7) |
| 2–9 | 4373 (45.1) |
| 10+ | 1864 (19.2) |
| Substance use | |
| Amphetamine | 756 (9.7) |
| Cocaine | 594 (7.6) |
| Heroin | 85 (1.1) |
CESD, The Center for Epidemiologic Studies Depression Scale Revised; PrEP, preexposure prophylaxis; HIV, human immunodeficiency virus; STI, sexually transmitted infection.
Nearly all respondents (91.0%) had heard of PrEP, 40.1% had ever used PrEP, and 33.3% had used PrEP in the last 6 months. Almost two-thirds (60.6%) were interested in non-daily PrEP. Of the 3,232 who used PrEP in the past 6 months, 93.4% reported receiving PrEP from a healthcare provider; less common sources of PrEP were the internet, research studies, friends, and sexual partners. Nearly all respondents (98.7%) reported being prescribed TDF/FTC. Of the 2,054 (23.4%) who had heard of non-daily PrEP use, 72.3% reported having heard of taking PrEP only around the time of sex. Of recent PrEP users, 176 (5.4%) reported non-daily use.
Factors Associated with Interest in Non-Daily PrEP
Factors associated with interest in non-daily PrEP are shown in Table 2. Interest in non-daily PrEP was more common among respondents who were uninsured compared to those with health insurance (PR = 1.21; 95% CI = 1.08, 1.35) and among respondents with a graduate degree compared to those without a graduate degree (PR = 1.16; 95% CI = 1.08, 1.24). Interest in non-daily PrEP was less common among those aged ≤30 years compared to those >30 years (PR = 0.90; 95% CI = 0.83, 0.97) and among respondents with annual income <$80,000 vs. ≥$80,000 (PR = 0.91; 95% CI = 0.85, 0.98).
Table 2.
Factors associated with interest in and use of non-daily PrEP.
| Interest in Non-Daily PrEP (N=9697) | Use of Non-Daily PrEP (N=3232) |
|||||
|---|---|---|---|---|---|---|
| Variable | PR | (95% CI) | P | PR | (95% CI) | P |
| Age <= 30 (ref = >30 years) | 0.90 | (0.83, 0.97) | 0.008 | 1.07 | (0.75, 1.52) | 0.69 |
| Race non-White (ref= White) | 0.93 | (0.87, 1.00) | 0.06 | 1.16 | (0.86, 1.57) | 0.32 |
| U.S. Regiona (ref= South) | ||||||
| West | 0.98 | (0.91, 1.07) | 0.77 | 1.82 | (1.22, 2.71) | 0.003 |
| Midwest | 1.01 | (0.92, 1.09) | 0.88 | 1.41 | (0.88, 2.25) | 0.15 |
| Northeast | 1.06 | (0.98, 1.16) | 0.14 | 1.60 | (1.03, 2.49) | 0.03 |
| Graduate education (ref= < graduate) | 1.16 | (1.08, 1.24) | <.0001 | 1.22 | (0.91, 1.64) | 0.18 |
| Income <80,000 (ref= 80,000+) | 0.91 | (0.85, 0.98) | 0.01 | 0.76 | (0.57, 1.03) | 0.07 |
| Uninsured (ref= insured) | 1.21 | (1.08, 1.35) | <.001 | 0.84 | (0.45, 1.56) | 0.58 |
| Depression (CESD) | 0.99 | (0.98, 0.99) | 0.002 | 1.02 | (1.00, 1.04) | 0.03 |
| Sexual behaviors and health (past 6 mo.) | ||||||
| Sex planned in advance (ref=Always) | ||||||
| Never | 1.18 | (1.04, 1.35) | 0.01 | 0.52 | (0.25, 1.11) | 0.09 |
| Rarely | 1.01 | (0.90, 1.14) | 0.78 | 0.39 | (0.22, 0.68) | <.001 |
| Sometimes | 0.96 | (0.86, 1.07) | 0.49 | 0.59 | (0.39, 0.91) | 0.01 |
| Very Often | 0.96 | (0.86, 1.08) | 0.53 | 0.52 | (0.33, 0.81) | 0.003 |
| Discussed HIV status (ref=Always) | ||||||
| Never | 1.13 | (1.03, 1.24) | 0.009 | 1.1 | (0.62, 1.94) | 0.74 |
| Rarely | 0.91 | (0.81, 1.01) | 0.08 | 1.04 | (0.63, 1.73) | 0.86 |
| Sometimes | 0.86 | (0.78, 0.95) | 0.004 | 0.99 | (0.64, 1.53) | 0.97 |
| Very Often | 0.93 | (0.84, 1.020 | 0.13 | 1.06 | (0.70, 1.61) | 0.76 |
| Used condoms (ref= Always) | ||||||
| Never | 1.17 | (1.06, 1.29) | 0.002 | 0.95 | (0.53, 1.69) | 0.85 |
| Rarely | 1.04 | (0.93, 1.17) | 0.45 | 0.63 | (0.33, 1.19) | 0.16 |
| Sometimes | 0.85 | (0.75, 0.95) | 0.006 | 0.89 | (0.48, 1.65) | 0.72 |
| Very Often | 0.91 | (0.80, 1.04) | 0.19 | 0.72 | (0.35, 1.49) | 0.38 |
| STI diagnosis (ref=no diagnosis) | 1.05 | (0.96, 1.14) | 0.28 | 0.75 | (0.52, 1.09) | 0.12 |
| Hepatitis C diagnosis (ref=nodiagnosis) | 0.97 | (0.75, 1.27) | 0.84 | 0.97 | (0.25, 3.76) | 0.96 |
| Number of sexual partners
(ref=0–1 sex partners) |
||||||
| 2–9 sexual partners | 0.89 | (0.83, 0.96) | 0.002 | 0.65 | (0.45, 0.95) | 0.024 |
| 10+ sexual partners | 1.12 | (1.04, 1.22) | 0.004 | 0.56 | (0.38, 0.84) | 0.005 |
| Substance use (ref=none) | 0.95 | (0.86, 1.04) | 0.30 | 1.99 | (1.45, 2.75) | <.0001 |
PrEP, preexposure prophylaxis; HIV, human immunodeficiency virus; STI, sexually transmitted infection; PR, prevalence ratio; CI, confidence interval. Substance use included heroin, cocaine, or amphetamine. CESD, The Center for Epidemiologic Studies Depression Scale Revised. Analyses of interest in non-daily PrEP included the full sample, whereas analyses of use of non-daily PrEP included the subset who reported PrEP use in the past 6 months. a Puerto Rico was excluded from the analysis because of small sample size.
Interest in non-daily PrEP was more common among those who never planned sex in advance compared to those who always planned sex in advance (PR = 1.18; 95% CI = 1.04, 1.35), respondents who never discussed their HIV status with sexual partners compared to those who always discussed HIV status (PR = 1.13; 95% CI = 1.03, 1.24), among those who never used condoms compared to those who always used condoms (PR = 1.17; 95% CI = 1.06, 1.29), and among those who reported having 10 or more sexual partners in the last 6 months compared to those with 0–1 partners (PR = 1.12; 95% CI = 1.04, 1.22). Interest in non-daily PrEP was less common among those who sometimes used condoms compared to those who always used condoms (PR = 0.85; 95% CI = 0.75, 0.95), those with 2–9 sexual partners in the last 6 months compared to those with 0–1 partners (PR = 0.89; 95% CI = 0.83, 0.96), and those with higher CESD scores (PR = 0.99; 95% CI = 0.98, 0.99). Race/ethnicity, U.S. region, STI diagnosis, HCV diagnosis, and substance use were not associated with interest in non-daily PrEP.
Factors Associated with Use of Non-Daily PrEP
Among the 176 respondents who reported non-daily PrEP use, common reasons for non-daily use were not being consistently sexually active (59%), concerns about the cost of PrEP (49%), concerns about potential long-term side effects (39%), not engaging in sex perceived as high-risk for HIV (37%), having heard that non-daily use offers the same protections as daily use (28%), and planning sex in advance (25%).
Among the 3,232 respondents who reported using PrEP in the past 6 months, non-daily PrEP use was more common among those who resided in the West (PR = 1.82; 95% CI = 1.22, 2.71; Table 2) and Northeast (PR = 1.60; 95% CI = 1.03, 2.49) compared with those in the South, those with higher CESD scores (PR = 1.02; 95% CI = 1 .00, 1.04) and those who reported substance use in the past 6 months (PR = 1.99; 95% CI = 1.45, 2.75). Non-daily PrEP use was less common among respondents who reported rarely (PR = 0.39; 95% CI = 0.22, 0.68), sometimes (PR = 0.59; 95% CI = 0.39, 0.91), or very often (PR = 0.52; 95% CI = 0.33, 0.81) planning sex in advance compared to those who always planned sex in advance. Non-daily PrEP use was also less common among those who reported 2–9 sexual partners (PR = 0.65; 95% CI = 0.45, 0.95) or 10 or more sexual partners (PR = 0.56; 95% CI = 0.38, 0.84) compared with those with 0–1 partners in the last 6 months. Age, race/ethnicity, education, income, insurance status, discussing HIV status, condom use, STI diagnosis, and HCV diagnosis were not associated with non-daily PrEP use.
Patterns of Non-Daily PrEP Use
Of the 176 respondents who reported non-daily PrEP use, several regimens were identified and are shown in Table 3. The most commonly reported regimen was “only around the time of sex” (i.e., event-driven; 48.3%), with two-thirds (64.7%) of this group reporting the 2-1-1 strategy. Less commonly reported event-driven regimens included one pill the day before sex and one pill the day after sex, and a single pill on the day of sex. A quarter (24.0%) reported using PrEP “on a regular schedule but not every day,” with common examples including only on weekends or only on days of the week that start with T or S (i.e., Tuesdays, Thursdays, Saturdays, and Sundays). One in five (19.3%) reported any episodic PrEP use (e.g. for a few weeks at a time, such as on vacation).
Table 3.
Patterns of non-daily PrEP use (N=176).
| Non-daily PrEP regimen | N (%) | Examples |
|---|---|---|
| Only around the time of sex | 85 (48.3) | Two doses of PrEP in the 24 hours before sex and single doses for the two days after sex (i.e., 2-1-1) |
| One pill day before sex and one pill day after sex | ||
| One pill day of sex | ||
| On a regular schedule but not daily | 42 (23.9) | T and S (Tuesdays, Thursdays, Saturdays, Sundays) |
| Every other day | ||
| Fridays and Saturdays | ||
| Only for a few weeks at a time | 34 (19.3) | — |
| Other non-daily regimen | 14 (7.9) | Daily when expecting sexual activity, otherwise every other day |
| Take pills whenever I remember | ||
| Daily except when I have college classes |
PrEP, preexposure prophylaxis. Follow-up questions on dosing regimens were not asked of those who reported using PrEP only for a few weeks at a time.
DISCUSSION
In this large, recent online sample of primarily MSM using geosocial networking sites in the U.S., we found that nearly two-thirds were interested in non-daily PrEP, but that only 5% of recent PrEP users reported non-daily dosing. Lack of health insurance, greater educational attainment, and higher income were associated with interest in non-daily PrEP, while fewer sexual partners, sex planning, and substance use were associated with use of non-daily PrEP. The most common reasons for non-daily PrEP use were inconsistent sexual activity and concerns about the cost of PrEP. Although many respondents used 2-1-1 dosing, various other regimens were reported, including some that have not undergone rigorous study and may not be prevention-effective. There was a low prevalence of non-daily PrEP use in our sample, and even lower for 2-1-1 dosing, but non-daily PrEP use could increase substantially as awareness increases and guidelines change. Our study highlights the need for U.S. public health authorities to provide clear guidance, similar to that issued by the World Health Organization and the International Antiviral Society-USA, on safe and effective non-daily dosing options for MSM.
Consistent with prior studies identifying cost as a barrier to PrEP initiation, adherence, and persistence in the U.S.,6,24 we found that lack of health insurance was associated with greater interest in non-daily PrEP, and that cost was a commonly cited reason for non-daily PrEP use. Although individuals who are insured are more likely to use PrEP services than those who are uninsured,25 cost-related barriers to PrEP use remain even in insured populations. Deductibles, copayments, coinsurance, and prior authorization requirements can create financial and logistical barriers to PrEP,26 with higher copayments associated with reduced adherence.24 We also found that higher incomes and greater education were associated with interest in non-daily PrEP, which may reflect the lower likelihood of eligibility for patient assistance programs in this group, as well as greater knowledge of the findings from IPERGAY and other PrEP studies. In addition to reducing uptake overall, cost-related barriers to PrEP may be one of the factors driving the stark racial and ethnic inequities that have been observed in PrEP uptake.24,27 Although we did not observe an association between race/ethnicity and non-daily PrEP use, our findings suggest that non-daily PrEP use could help mitigate cost-related barriers to PrEP.
Several non-daily PrEP regimens were identified in our study, the most common being event-driven PrEP dosing, including the 2-1-1 regimen evaluated in the IPERGAY study. Although 2-1-1 is the only non-daily regimen that has been shown to be effective in clinical research studies,8–10 other commonly reported non-daily regimens may also be effective in preventing HIV acquisition. For example, some respondents reported using PrEP only on days of the week that start with T and S, a regimen that may be prevention-effective among MSM based on post-hoc analyses suggesting that drug levels consistent with four PrEP pills per week are associated with 96% efficacy among MSM.1,2 In contrast, some respondents reported using regimens that may not be prevention-effective, such as a single pill around the time of sex. Our results suggest that new guidance from CDC on 2-1-1 dosing for MSM, along with existing endorsements from the World Health Organization and two local health departments in the U.S., is needed to help ensure safe and effective non-daily dosing among PrEP users.
We found that inconsistent sexual activity and sex planning were associated with non-daily PrEP use, consistent with prior studies in which MSM who had less frequent sexual activity or planned sex more often were more likely to opt for non-daily PrEP.28,29 Our study highlights the subset of PrEP users in the U.S. who are most likely to benefit from the availability of a non-daily dosing option. Our findings are also consistent with qualitative studies in which MSM have reported a preference for non-daily dosing when it is congruent with their patterns of sexual activity. For instance, some people might find taking PrEP only around travel/vacation, when there is an anticipated increase in sexual activity, to be a preferred strategy compared with daily dosing.30 In contrast to our findings on non-daily use, we found that people who never planned sex were more likely to be interested in non-daily PrEP than those who always planned sex, suggesting that interest in non-daily PrEP is not necessarily a marker of who will find non-daily dosing feasible.
Non-daily PrEP use was more common among respondents who reported recent substance use, and may reflect either intentional non-daily PrEP use or lower adherence to daily PrEP. Prior studies have found that cocaine use is associated with lower adherence to daily PrEP and higher rates of disengagement from PrEP care among MSM,24,31 and that marijuana use is associated with PrEP discontinuation among young Black MSM.32 Qualitative studies have revealed that the use of methamphetamine among MSM is related to disruption in daily routines, creating a barrier to daily use of PrEP.33 PrEP users who use substances and have frequent unplanned exposures may benefit from additional support with daily dosing, while non-daily PrEP may be feasible alternative for PrEP users who use substances and have infrequent or planned sex. Further research is needed to understand how non-daily PrEP dosing can be optimally integrated into the lives of people who use substances.
Several limitations must be considered in interpreting these results. First, we used convenience sampling to recruit respondents through online and mobile geosocial networking sites and were unable to assess the extent to which individuals who completed the study differed from those who were eligible but did not respond. Second, the majority of the study population was non-Hispanic White and MSM, with relatively high incomes and educational attainment. Our sample was also older in age than young MSM at the highest risk of HIV. Thus, our sample is not generalizable to all populations impacted by HIV infection in the United States. However, 31–36% of MSM in the U.S. report using geosocial networking sites, suggesting that our results may reflect a substantial proportion of HIV-negative MSM in the U.S.34,35 Third, our study was cross-sectional, and was therefore not designed to determine the causal relationship between demographic or behavioral characteristics and interest in or use of non-daily PrEP. However, the associations we identified may generate hypotheses for future longitudinal studies. Finally, some non-daily PrEP use may have reflected low adherence to daily PrEP. However, we minimized this possibility by including language in the survey that allowed for missed doses as part of the definition of daily PrEP use.
Our study also had several strengths. First, we conducted qualitative interviews to inform survey design and piloted the survey with participants, incorporating feedback in an iterative fashion before finalizing the survey for distribution. Second, the study’s large sample size allowed us to gain a deeper understanding of non-daily PrEP users, including reasons for and patterns of non-daily use. Finally, the anonymity of the online survey may have reduced social desirability bias compared with other data collection strategies, facilitating reporting of potentially sensitive information about sexual behavior, PrEP use, and substance use.
In this large online sample of primarily MSM, we found high interest in non-daily PrEP use, and that 5% of recent PrEP users reported non-daily dosing. Our study suggests that a non-daily PrEP option could increase PrEP uptake in the U.S., with the potential to reduce cost-related barriers to PrEP, particularly for people who have infrequent sexual activity and tend to plan sex in advance. Given the use of non-daily strategies that have not been evaluated in clinical studies, there is an urgent need for U.S. public health authorities to provide clear guidance on safe and effective non-daily dosing options for MSM.
ACKNOWLEDGMENTS
Conflicts of interest: Julia Marcus has consulted for Kaiser Permanente Northern California on a research grant from Gilead Sciences. Douglas Krakower has conducted research with project support from Gilead Sciences; has received honoraria for authoring or presenting continuing medical education content for Medscape, MED-IQ, and DKBMed; and has received royalties for authoring content for Up-to-Date, Inc. Kenneth Mayer has received unrestricted research grants from Gilead Sciences and Janssen, and has been on Scientific Advisory Boards for Gilead and Merck and royalties for authoring content for Up-to-Date. All other authors declare no conflicts. Source of funding: This work was supported by the National Institute of Allergy and Infectious Diseases [K01 AI122853 to JLM] and the Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute.
Footnotes
PRESENTATION: Parts of this work will be presented at the Conference on Retroviruses and Opportunistic Infections in Boston, MA, on March 9, 2020.
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