Factors Influencing Oral Pre-,Post-,and Doxycycline Post-Exposure Prophylaxis Uptake Among Substance-Using Men Who Have Sex with Men in the Rural Southern US

Abstract

Substance-using men who have sex with men (MSM), especially those in rural areas, face a heightened risk of HIV and sexually transmitted infections (STIs). Despite increased risk, uptake of HIV pre-exposure prophylaxis (PrEP), HIV post-exposure prophylaxis (PEP), and doxycycline post-exposure prophylaxis (Doxy-PEP) remains low among rural MSM. The multi-domain factors influencing past-year use of oral PrEP, PEP, and Doxy-PEP among substance-using MSM in the rural southern US remain unknown. A cross-sectional study of rural substance-using MSM (n = 345) in the Southern US was conducted from February 29 to March 23, 2024. Three series of bivariate and multivariate logistic regression analyses were conducted. Past-year PrEP use was significantly associated with HIV-negative status (adjusted odds ratio [aOR] = 2.55, 95% confidence interval [CI]: 1.12–5.80, p = 0.025), past-year STI diagnosis (aOR = 2.23, 95% CI: 1.19–4.15, p = 0.012), past-year HIV testing (aOR = 3.40, 95% CI: 1.05–10.9, p = 0.040), and past-year STI testing (aOR = 10.09, 95% CI: 2.25–45.37, p = 0.003). Past-year PEP use was significantly associated with past-year STI diagnosis (aOR = 3.70, 95% CI: 1.33–10.32, p = 0.012) and oral sex (aOR = 0.09, 95% CI: 0.01–0.63, p = 0.015). Finally, past-year Doxy-PEP use was significantly associated with past year-STI diagnosis (aOR = 4.44, 95% CI: 2.03–9.71, p < 0.001). Results underscore the need for integrated care across primary care, pharmacy, and substance use treatment settings to improve screening, education, and prescription of HIV/STI preventative biomedical pharmaceuticals for substance-using MSM.

Introduction

In the United States (US), gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV and other sexually transmitted infections (STIs).^1,2 Data show that HIV and STI rates are increasing in rural areas. Approximately 20% of new HIV infections occur in rural areas, with MSM accounting for 77% of these new cases.³ In addition, between 5% and 8% of rural MSM have been diagnosed with an STI in the past year.^4
–6

Condomless anal sex, a well-established risk factor for HIV and STI transmission, is prevalent among rural MSM, with approximately 59%–79% reporting engagement in this behavior within the past year.^4,7

–10 In addition, three biomedical HIV/STI preventive oral pharmaceuticals have been approved in the US, offering effective options for this highly susceptible population. First, HIV pre-exposure prophylaxis (PrEP) is used to prevent HIV before sexual exposure.¹¹ Second, HIV post-exposure prophylaxis (PEP) can prevent HIV if taken within 72 h after sexual exposure.¹² Lastly, doxycycline post-exposure prophylaxis (Doxy-PEP) has been shown to prevent chlamydia, gonorrhea, and syphilis when taken within 72 h after sexual exposure.¹³ Approximately 45%, 5%, and 20% of MSM have ever used PrEP, PEP, and Doxy-PEP, respectively.^14
–16 Moreover, patterns of PrEP use vary across geographic regions in the US. For example, a recent study found that 43% of people on oral PrEP lived in the South, highlighting persistent regional disparities in PrEP access and uptake.¹⁷ Although studies have not examined rural-urban differences in PEP and Doxy-PEP use, there are likely urban-rural disparities similar to those documented in PrEP, where rural MSM are less likely to be aware of PrEP and be prescribed it compared to urban men.^18
–20

Similar demographic and behavioral factors of uptake have been observed across PrEP, PEP, and Doxy-PEP. Demographic factors that have been associated with higher PrEP, PEP, and Doxy-PEP use are race (non-Hispanic White), sexual orientation (gay-identified), education status (higher education), employment status (employed), and health insurance status (has insurance).^15,21,22 Regarding sexual behaviors, those who engage in more condomless anal sex, have multiple sexual partners, use substances during sex, and regularly test themselves for HIV and STIs are more likely to utilize PrEP, PEP, and Doxy-PEP.^15,21,22 While individual-level demographic and behavioral correlates of PrEP, PEP, and Doxy-PEP are well-documented among MSM, existing research has exclusively focused on urban populations. As a result, it is unknown if these similar patterns are seen among rural MSM.

Beyond demographic and behavioral characteristics, the Minority Stress Theory²³ provides an important foundation for how distal or external stressors (e.g., discrimination against MSM) and internal stressors (e.g., internalized heterosexism) may reduce the likelihood of PrEP use among MSM.^24

–27 Conversely, resiliency factors, such as community involvement and support, have been shown to enhance PrEP usage.^25,26,28 Despite these associations, the Minority Stress Theory has not yet been applied to explain PEP and Doxy-PEP uptake among MSM. Moreover, research on rural MSM and PrEP has primarily focused on comparing PrEP awareness and uptake between rural and urban populations^18
–20 or qualitatively exploring barriers to access.^8,29

–32 To date, no studies have specifically examined PEP and Doxy-PEP among rural MSM. There is a notable gap in the literature examining how demographic characteristics, sexual behaviors, and minority stress factors influence the use of PrEP, PEP, and Doxy-PEP in rural setting. This is particularly concerning given that rural MSM who engage in substance use face a higher risk of contracting HIV/STIs.^33,34 Research^10,35
–37 has consistently documented high rates of sexualized drug use among rural MSM, underscoring the need for targeted research and intervention efforts.

This study examined which demographic characteristics, sexual behavior, and sexual minority stress factors were associated with the uptake of PrEP, PEP, and Doxy-PEP among rural substance-using MSM.

Methods

Participants

Participants were recruited from Grindr ads and research team members’ participant registries from February 29 to March 23, 2024. Individuals were eligible for the study if they were (1) a man who had oral or anal sex with a man, (2) aged 18 years or older, (3) lived in a rural county in a Southern state, and (4) used alcohol and/or cannabis in the past 12 months. MSM included men who identified with a non-heterosexual sexual orientation label (e.g., gay, bisexual, pansexual) and heterosexually identified men who have sex with men. Transgender women and men were excluded. Rural included living in a county with an Index of Relative Rurality³⁸ score of ≥0.40, which the index developers have classified as the rural/urban cutoff point. Southern states included Alabama, Arkansas, Florida, Georgia, Kentucky, Louisiana, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, and West Virginia.³⁹ We used data quality procedures to detect bots and fraudulent respondents.^40
–42 The total analytical sample is 345. Eligible participants received a $20 electronic gift card. Individuals provided informed consent to participate, and the Texas A&M University institutional review board approved study procedures.

Measures

Past-year PrEP use

Past-year PrEP use was measured with 1 item: “HIV pre-exposure prophylaxis, or HIV PrEP, is a medicine people who are HIV-negative take to reduce their chance of contracting HIV. The HIV PrEP medicines are called Truvada, Descovy, and Apretude. Have you taken HIV PrEP in the past 12 months?” (1 = yes, 0 = no).

Past-year PEP use

Past-year PEP use was measured with 1 item: “HIV post-exposure prophylaxis, or HIV PEP, is a medicine people who may have been exposed to HIV in the last 72 h take to reduce their chance of contracting HIV. Have you taken HIV PEP in the past 12 months?” (1 = yes, 0 = no).

Past-year Doxy-PEP use

Past-year Doxy-PEP use was measured with 1 item: “Doxycycline-PEP, or Doxy-PEP, is a medicine people who may have been exposed to gonorrhea, chlamydia, or syphilis in the last 72 h take to reduce their chance of contracting that STI/STD. Have you taken Doxy-PEP in the past 12 months?” (1 = yes, 0 = no).

Demographic factors

Respondents provided demographic information, including their gender, sexual orientation, ethnicity, race, highest level of education, employment status, annual household income, health insurance coverage, primary care provider coverage, political ideology, HIV status, history of an STI in the past year, current county of residence, childhood residence zip code, and their age. Demographic factors were recoded for analyses based on prior studies:^15,21,22 gender (1 = cisgender, 0 = gender nonbinary), sexual orientation (1 = gay, 0 = other identity label), race/ethnicity (1 = Black, 2 = Hispanic, 3 = another racial/ethnic minority, 0 = Non-Hispanic White), highest education level (1 = bachelor’s degree holder, 0 = not bachelor’s degree holder), employment status (1 = employed full-time, 0 = not employed full-time), annual household income (1 = $80,000 or more, 0 = $79,999 or less), has health insurance (1 = yes, 0 = no), has a primary care provider (1 = yes, 0 = no), political ideology (1 = middle of the road, 2 = overall liberal, 0 = overall conservative), HIV-status (1 = HIV-negative, 0 = HIV-positive), and STI diagnosis in the past year (1 = yes, 0 = no).

Sexual behavioral factors

Behavioral factors were informed by the clinical guideline indications.^11
–13 Respondents were asked to report if they had engaged in any of the following behaviors in the past year: been tested for HIV, been tested for STIs, had oral sex with a man, had condomless anal sex with a man whose HIV status they did not know or were unsure about, received or given drugs to a man in exchange for sex (drug-related transactional sex), and used alcohol or other substances/drugs immediately before or during sex with a man (sexualized drug use). All variables were 1 = yes and 0 = no.

Sexual minority stress factors

Five sexual minority stress factors were assessed. First, respondents completed the Sexual and Gender Minority Adverse Childhood Experiences Scale⁴³ (α = 0.77), which included 7 items rated on a 5-point frequency scale (0 = never, 4 = always). A cumulative sum was added from 0 to 7 (0 = no exposure, 7 = exposure to all 7 adverse childhood experiences). Second, respondents completed the Sexual Orientation Microaggression Inventory Short-Form⁴⁴ (α = 0.84), consisting of 8 items rated on a 5-point frequency scale (0 = not at all, 4 = about every day). A cumulative sum was added from 0 to 8 (0 = no exposure, 8 = exposure to all 8 sexual minority stressors). Third, respondents completed the Internalized Homophobia Scale-Revised⁴⁵ (α = 0.87), responding to 5 items on a 5-point agreement scale (1 = strongly disagree, 5 = strongly agree) with a mean score calculated on all 5 items. Fourth, respondents completed the Gay Community Participation Scale⁴⁶ (α = 0.86), responding to 7 items on a 5-point frequency scale (0 = never, 4 = always). A cumulative sum was added from 0 to 7 (0 = participation in zero activities, 7 = participating in all 7 activities). Finally, respondents completed the Connectedness to the LGBT Community Scale—Connectedness or Closeness subscale⁴⁷ (α = 0.80), answering 3 items on a 4-point agreement scale (1 = strongly disagree, 4 = strongly agree), and a mean score was calculated on all 4 items.

Analysis

Data were analyzed using SPSS (version 29). Three separate bivariate analyses were conducted to examine the associations between demographic, sexual behavioral, and sexual minority stress independent variables and each of the three dependent variables of PrEP, PEP, and Doxy-PEP use. Point-biserial correlations (r_pb ) were used for continuous independent variables, and chi-square tests (χ² ) were used for categorical independent variables. Variables with a p value (p) of ≤0.10 were included in the three separate multiple logistic regression models. Adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) are reported. p < 0.05 was considered statistically significant in the regression models.

Results

Demographic characteristics

Table 1 presents the demographic characteristics of the sample. Most participants identified as gay (58.6%) or bisexual (29.6%), were non-Hispanic White (60.3%), were not bachelor’s degree holders (67.8%), were employed full-time (55.1%), had an annual household income of less than $60,000 (76.8%), had health insurance (80.0%) and a primary care provider (65.2%), and were politically liberal (41.7%). The mean (M) age was 36.47 years old (standard deviation [SD] = 11.90). The average Index of Relative Rurality score was 0.46 (SD = 0.05), while the average childhood Index of Relative Rurality was 0.42 (SD = 0.10). Over three-quarters of men were HIV-negative (82.3%), and nearly one-quarter (24.1%) were diagnosed with an STI in the past year. Substance use in the past 12 months (not shown in tables) was common, with high reported prevalence of alcohol (88.1%) and cannabis (77.1%), followed by poppers (56.5%), methamphetamine (34.8%), cocaine (20.6%), pain relivers (18.6%), sedatives or depressants (18.6%), stimulants (17.1%), gamma-hydroxybutyrate (GHB) or gamma-butyrolactone (GBL), (15.9%), methylenedioxymethamphetamine (MDMA) (15.9%), and ketamine (7.2%).

Table 1.

Characteristics of the Sample (N = 345)

	N	%	M	SD
Demographic characteristics
Gender identity
Cisgender man	320	92.8
Gender nonbinary man	25	7.2
Sexual orientation
Gay	202	58.6
Bisexual	102	29.6
Pansexual	16	4.6
Queer	10	2.9
Unsure or questioning	7	2.0
Straight or heterosexual	2	0.6
Another option	6	1.7
Age
Race/Ethnicity
American Indian or Alaskan Native	8	2.3
Asian or Asian American	6	1.7
Non-Hispanic Black or African American	49	14.2
Hispanic or Latin American	54	15.7
Middle Eastern or Arab American	1	0.3
Non-Hispanic White	208	60.3
Multiracial	17	4.9
Another option	2	0.6
Highest level of education
No high school diploma or GED	14	4.1
High school diploma or GED	69	20.0
Some college, no degree	104	30.1
Associate’s or technical degree	47	13.6
Bachelor’s degree	75	21.7
Master’s degree	28	8.1
Doctoral or professional degree	8	2.3
Employment status
Employed full-time	190	55.1
Not employed full-time	155	44.9
Annual household income
Under $20,000	113	32.8
$20,000 to 39,999	86	24.9
$40,000 to 59,999	66	19.1
$60,000 to 79,999	39	11.3
$80,000 to 99,999	15	4.3
$100,000 or more	26	7.5
Has health insurance
Yes	276	80.0
No	69	20.0
Has primary care provider
Yes	225	65.2
No	120	34.8
Political ideology
Overall conservative	74	21.4
Middle of the road	127	36.8
Overall liberal	144	41.7
HIV status
HIV-negative, meaning that I do not have HIV	284	82.3
HIV-positive, meaning that I do have HIV	61	17.7
Past year STI diagnosis
Yes	83	24.1
No	262	75.9
State of residence
Alabama	33	9.6
Arkansas	21	6.1
Florida	19	5.5
Georgia	23	6.7
Kentucky	23	6.7
Louisiana	8	2.3
Mississippi	18	5.2
North Carolina	17	4.9
Oklahoma	26	7.5
South Carolina	12	3.5
Tennessee	17	4.9
Texas	85	24.6
Virginia	27	7.8
West Virginia	16	4.6
Current index of relative rurality			0.46	0.05
Childhood index of relative rurality			0.42	0.10
Sexual behavioral characteristics
Past-year HIV PrEP use
Yes	87	25.2
No	258	74.8
Past-year HIV PEP use
Yes	18	5.2
No	327	94.8
Past-year Doxy-PEP use
Yes	37	10.7
No	308	89.3
Past-year HIV tested
Yes	268	77.7
No	77	22.3
Past-year STI tested
Yes	268	77.7
No	77	22.3
Past-year oral sex with man
Yes	338	98.0
No	7	2.0
Past-year condomless anal sex with man with HIV-unknown status
Yes	203	58.8
No	142	41.2
Past-year sexualized drug use
Yes	197	81.1
No	46	18.9
Past-year drug-related transactional sex
Yes	275	79.7
No	70	20.3
Sexual minority
Sexual and gender minority adverse childhood experiences scale			4.31	2.03
Sexual orientation microaggression inventory short-form			4.52	2.61
Internalized homophobia scale-revised			2.36	1.01
Gay community participation scale			4.24	2.36
Connectedness to the LGBT community scale—connectedness or closeness subscale			2.30	0.79

Sexual behavioral characteristics

Table 1 shows the sexual behaviors of the sample. Over three-quarters of men were tested for HIV (77.7%) and STIs in the past year (77.7%). Nearly all reported having oral sex with a man in the past year (98.0%), and over half had condomless anal sex with a man whose HIV status was unknown. Although less than one-fifth engaged in drug-related transactional sex in the past year (20.3%), over three-quarters engaged in sexualized drug use in the past year (79.7%). About one-quarter of men used PrEP in the past year (25.2%), while 5.2% and 10.7% used PEP and Doxy-PEP in the past year, respectively.

Sexual minority stress characteristics

Table 1 displays the sexual minority stress characteristics of the sample. On average, participants experienced four sexual minority-related adverse childhood experiences before the age of 18 (M = 4.31, SD = 2.03, 0–7 scale). Overall, participants reported experiencing four sexual minority-related microaggressions in the past year (M = 4.52, SD = 2.61, 0–8 scale). Respondents reported relatively low levels of internalized heterosexism (M = 2.36, SD = 1.01, 1–5 scale). On average, most respondents disagreed with the notion that they felt connected to the sexual and gender minority community (M = 2.30, SD = 0.79, 1–4 scale) and reported participating in four sexual and gender minority-related community activities (M = 4.23, SD = 2.36, 0–7 scale).

Past-year PrEP use

As shown in Table 2, past-year PrEP use was significantly correlated with having a bachelor’s degree (χ² = 5.72, p = 0.017), having health insurance (χ² = 3.94, p = 0.047), and having a primary care provider (χ² = 4.62, p = 0.032). Additional correlates included being HIV-negative (χ² = 3.06, p = 0.080), being diagnosed with an STI in the past year (χ² = 12.26, p < 0.001), receiving past-year HIV (χ² = 21.07, p < 0.001) and STI testing (χ² = 26.89, p < 0.001), engaging in past-year condomless anal sex (χ² = 6.11, p = 0.013), and engaging in sexualized drug use in the past year (χ² = 4.21, p = 0.040). Exposure to sexual minority microaggressions (r_pb = 0.10, p = 0.060) and higher levels of community participation (r_pb = 0.11, p = 0.041) were significantly correlated with past-year PrEP use. Table 3 presents the results of the multiple logistic regression analyses. The overall model was significant, χ²(11) = 72.24, p < 0.001; Nagelkerke R ² = 0.279. Men who were HIV-negative (aOR = 2.55, 95% CI: 1.12–5.80, p = 0.025) and those diagnosed with an STI in the past year (aOR = 2.23, 95% CI: 1.19–4.15, p = 0.012) were more than twice as likely to use PrEP compared with HIV-positive and STI-negative men. In addition, past-year HIV testing (aOR = 3.40, 95% CI: 1.05–10.9, p = 0.040) and STI testing (aOR = 10.09, 95% CI: 2.25–45.37, p = 0.003) were both significantly associated with past-year PrEP use.

Table 2.

Bivariate Analyses

	PrEP	PEP	Doxy-PEP
	χ²	χ²	χ²
Demographic factors
Cisgender man (ref: gender nonbinary male)	0.02	0.42	0.78
Gay sexual orientation label (ref: other label than gay)	2.33	0.07	1.39
Race/ethnicity (Black, Hispanic, Another racial/ethnic minority, ref: Non-Hispanic White)	6.16	1.91	5.60
Bachelor’s degree holder (ref: non-bachelor’s degree holder)	5.72 ^*	0.01	0.11
Employed (ref: not employed)	0.99	0.43	1.43
Annual household income ($80,000 or more, ref: $79,999 or less)	0.06	0.01	1.66
Has health insurance (ref: no)	3.94 ^*	0.94	0.03
Has a primary care provider (ref: no)	4.62 ^*	1.32	0.10
Political ideology (Middle of the road, Overall liberal, ref: Overall conservative)	4.27	1.54	3.05
HIV-negative status (ref: HIV-positive status)	3.06^ms	1.92	11.57 ^**
STI diagnosis past year (ref: no)	12.26 ^***	7.00 ^**	32.94 ^***
Current Index of Relative Rurality^a	−.07	0.08	−0.01
Childhood Index of Relative Rurality^a	.02	0.10^ms	0.02
Age^a	−0.06	0.03	−0.02
Sexual behavioral factors
HIV tested past year (ref: no)	21.07 ^***	1.38	0.01
STI tested past year (ref: no)	26.89 ^***	3.08^ms	4.83 ^*
Oral sex with man past year (ref: no)	1.18	7.88 ^**	0.10
Condomless anal sex with man with HIV-unsure status past year (ref: no)	6.11 ^*	1.40	8.47 ^**
Drug-related transactional sex past year (ref: no)	0.67	2.00	5.65 ^*
Sexualized drug use past year (ref: no)	4.21 ^*	2.55	5.68 ^*
Sexual minority stress factors
Sexual and gender minority adverse childhood experiences scale^a	0.06	0.03	0.04
Sexual orientation microaggression inventory short-form^a	0.10^ms	0.07	0.02
Revised internalized homophobia scale^a	−0.02	.09 ^ms	0.01
Gay community participation scale^a	0.11 ^*	−0.01	0.12 ^*
Connectedness to the LGBT community scale^a	006	−0.06	0.05

Bold represents statistically significant finding of p ≤ 0.10.

p < 0.05; ^** p < 0.01; ^*** p < 0.001; ms p < 0.10.

represents the point biserial correlation coefficient (r_pb ).

Table 3.

Multiple Logistic Regression of Past Year-PrEP Use

	aOR	95% CI	p
Bachelor’s degree holder (ref: non-bachelor’s degree holder)	1.74	0.97–3.11	0.063
Has health insurance (ref: no)	1.58	0.71–3.50	0.260
Has a primary care provider (ref: no)	1.54	0.82–2.91	0.182
HIV-negative status (ref: HIV-positive status)^*	2.55	1.12–5.80	0.025
STI diagnosis past year (ref: no)^*	2.23	1.19–4.15	0.012
HIV tested past year (ref: no)^*	3.40	1.05–10.94	0.040
STI tested past year (ref: no)**	10.09	2.25–45.37	0.003
Condomless anal sex with man with HIV-unsure status past year (ref: no)	1.80	0.99–3.27	0.055
Sexualized drug use past year (ref: no)	0.94	0.42–2.12	0.883
Sexual Orientation Microaggression Inventory Short-Form	1.07	0.96–1.20	0.243
Gay Community Participation Scale	1.05	0.93–1.19	.436

Bold represents statistically significant finding of p < 0.05.

p < 0.05; ^** p < 0.01.

Past-year PEP use

Past-year PEP use was significantly correlated with a past-year STI diagnosis (χ² = 7.00, p = 0.008), childhood Index of Relative Rurality (r_pb = .10, p = 0.066), past-year STI testing (χ² = 3.08, p = 0.079), past-year oral sex with a man (χ² = 7.88, p = 0.005), and internalized heterosexism (r_pb = 0.09, p = 0.089) (see Table 2). Table 4 shows the results of the multiple logistic regression analyses. The model was statistically significant, χ² (5) = 20.24, p = 0.001; Nagelkerke R ² = .169. Men who were diagnosed with an STI in the past year were nearly four times more likely to use PEP (aOR = 3.70, 95% CI: 1.33–10.32, p = 0.012). However, those who had oral sex with a man in the past year had significantly lower odds of using PEP (aOR = 0.09, 95% CI: 0.01–0.63, p = 0.015).

Table 4.

Multiple Logistic Regression of Past-Year PEP Use

	aOR	95% CI	p
STI diagnosis past year (ref: no)^*	3.70	1.33–10.32	0.012
Childhood Index of Relative Rurality	28.63	0.25–67.90	0.128
STI tested past year (ref: no)	4.77	0.56–40.44	0.152
Oral sex with man past year (ref: no)^*	0.09	0.01–0.63	0.015
Revised Internalized Homophobia Scale	1.55	0.93–2.58	0.091

Bold represents statistically significant finding of p < 0.05.

p < 0.05.

Past-year Doxy-PEP use

Table 2 presents the demographics and behavioral correlations of using Doxy-PEP in the past year. Past-year Doxy-PEP use was significantly correlated with being HIV-negative (χ² = 11.57, p = 0.001), having been diagnosed with an STI in the past year (χ² = 32.94, p < 0.001), STI testing in the past year (χ² = 4.83, p = 0.028), condomless anal sex in the past year (χ² = 8.47, p = 0.004), engaging in drug-related transactional sex in the past year (χ² = 5.65, p = 0.017), engaging in sexualized drug use in the past year (χ² = 5.68, p = 0.017), and engagement with the sexual minority community (r_pb = 0.12, p = 0.032). Table 5 displays the multiple logistic regression results. The model was statistically significant, χ² (7) = 41.70, p < 0.001; Nagelkerke R ² = 0.230. Men who were diagnosed with an STI in the past year were over four times more likely to report past-year Doxy-PEP (aOR = 4.44, 95% CI: 2.03–9.71, p < 0.001).

Table 5.

Multiple Logistic Regression of Past-Year Doxy-PEP Use

	aOR	95% CI	p
HIV-negative status (ref: HIV-positive status)	0.47	0.20–1.09	0.078
STI diagnosis past year (ref: no)^***	4.44	2.03–9.71	<0.001
STI tested past year (ref: no)	2.20	0.61–7.94	0.230
Condomless anal sex with man with HIV-unsure status past year (ref: no)	1.41	0.53–3.73	0.488
Drug-related transactional sex past year (ref: no)	1.58	0.67–3.74	0.297
Sexualized drug use past year (ref: no)	2.28	0.49–10.61	0.294
Gay Community Participation Scale	1.13	0.94–1.34	0.187

Bold represents statistically significant finding of p < 0.05.

***

p < 0.001.

Discussion

HIV rates in rural parts of the US are increasing, with rural MSM representing more than three-quarters of new cases in these areas. Substance-using MSM represent a key population for PrEP, PEP, and Doxy-PEP.⁴⁸ Existing research has either largely focused on comparing awareness and uptake between rural and urban MSM^18
–20 or qualitatively exploring facilitators and barriers to use among rural men.^8,29

–32 There is extant literature on the factors that contribute to rural MSM using HIV/STI preventive pharmaceuticals, especially among substance-using rural MSM. This study is one of the first to examine multi-domain factors associated with PrEP, PEP, and Doxy-PEP use within the rural MSM community. Results from this study can inform future research and interventions aiming to reduce HIV and STI health disparities among rural MSM.

Around 25% of rural substance-using MSM reported using PrEP in the past year, a prevalence consistent with prior research.^18
–20 In contrast, fewer participants used PEP, which corroborates prior national studies.^49,50 About 10% of our sample used Doxy-PEP, also aligning with previous research.^16,21 Future research is warranted to directly compare the uptake of PEP and Doxy-PEP between rural and urban MSM to better determine to what extent geographic disparities may exist. Moreover, disseminating PrEP, PEP, and Doxy-PEP information are key activities of the Ending the HIV Epidemic Plan.⁵¹ Because rural MSM use Grindr and other sexual networking apps,⁵² health officials and the platforms themselves could approve and disseminate PrEP, PEP, and Doxy-PEP via these apps. Prior research had found that MSM generally find PrEP-related messaging and other sexual health promotion social marketing campaigns on Grindr as acceptable.^53
–55 Future research could assess if social marketing campaigns are influencing rural MSM’s knowledge, attitudes, and behaviors surrounding PrEP, PEP, and Doxy-PEP.

Substance-using MSM diagnosed with an STI in the past year were more likely to use PrEP, PEP, and Doxy-PEP, aligning with previous research.^56
–58 This pattern suggests that clinicians are adhering to prescribing guidelines, as a prior STI diagnosis is an indication for these medications.^11
–13 The Andersen Model of Health Service Utilization provides a useful framework for understanding this finding, specifically the need factor.⁵⁹ This includes both perceived need (an individual’s subjective judgment about their health) and evaluated need (objective judgment about their health). Evaluated need is often operationalized as clinical or self-reported diagnoses, symptomology, or medication indications, such as prior STI diagnosis.⁶⁰ However, only 18% of primary care providers inquire about recent STI history or symptoms among their MSM patients,⁶¹ highlighting the importance of comprehensive sexual health assessments, including STI history, in primary care setting. Recent research has also investigated the role other clinical or self-reported diagnoses have on PrEP uptake, particularly veterans with a substance use disorder (SUD).^62
–64 Future studies are warranted to explore how SUD diagnoses may influence PrEP, PEP, and Doxy-PEP among rural MSM populations.

Past-year HIV and STI testing were significantly associated with past-year PrEP use, as concordant with the literature. HIV/STI testing might serve as a proxy for engagement with broader health care, with participants likely accessing testing services through primary care, health departments, and HIV/AIDS service organizations.⁶⁵ Although these are common locations for HIV/STI testing, the Ending the HIV Epidemic⁵¹ and National HIV/AIDS Strategy⁶⁶ highlight the need for integrated preventative models to enhance PrEP screenings and referrals for hard-to-reach at-risk populations, such as substance-using MSM. For example, the National HIV Behavioral Surveillance⁶⁷ showed only 11% of MSM who inject drugs used PrEP, compared with 40% in a community study of substance-using MSM in the South.⁶⁸ These findings highlight a missed opportunity for HIV/STI testing and PrEP referrals in substance use treatment settings. Currently only 29% of outpatient substance use treatment facilities offer HIV testing,⁶⁹ and 7% of outpatient mental and behavioral health settings⁷⁰ provide both HIV and STI testing. Staff in substance use treatment facilities identified organizational barriers to HIV testing and PrEP services, such as limited or no leadership engagement, incompatibility with current workflow, insufficient resources, and low prioritization.⁷¹ Future implementation research is necessary to determine and evaluate implementation strategies that promote integrated HIV/STI testing and PrEP referrals in substance use treatment facilities.

This study found that oral sex was associated with past-year PEP use among rural substance-using MSM. While oral sex poses little to no risk of HIV transmission,⁷² MSM often view oral sex as a harm-reduction strategy, and this often precedes other sexual risk behaviors such as condomless anal sex.^73,74 Despite this, PEP accessibility is particularly challenging in rural areas, where MSM are more likely to reside in PrEP deserts²⁰ and often lack HIV/AIDS service organizations.^75,76 Further influencing this issue, many primary care providers are unfamiliar with PEP and report wanting more training, with only 24%–30% having prescribed it.^77,78 Education for rural providers is crucial, along with pharmacy-initiated PEP legislation, which allows pharmacists to prescribe PEP.⁷⁹ To date, 12 states⁷⁹ have passed such legislation, leaving a policy framework for other state legislators to adopt or adapt. However, rural pharmacies are less likely to stock it,⁸⁰ emphasizing the need for community pharmacies to carry PEP for emergencies like they do for other post-exposure prophylaxis pharmaceuticals.

Study limitations must be acknowledged. The cross-sectional design restricts the ability to determine causality or temporal changes. The sample is not representative, limiting generalizability of findings. Social desirability and recall bias may be introduced, which could affect the over- or under-reporting of responses. The study examined past year use rather than lifetime use, which may not fully capture long-term patterns of engagement with these medications. Given these limitations of the study design, future research could use more objective and national data, such as health insurance claim databases and other administrative databases (e.g., electronic medical or health records), to examine the trends and demographic, behavioral, clinical, and other factors associated with PrEP, PEP, and Doxy-PEP use among rural populations.¹⁷

In addition, the models explained 17%–28% of the variance. Future research could explore other motivations, facilitators, and barriers to accessing these medications. One barrier warranting further investigation among rural MSM and rural health care providers is cost. Indeed, prior research has noted the cost of PrEP along with other associated expenses (e.g., copays, required testing) are significant barriers to rural MSM using PrEP and other sexual health services.^31,32 Similarly, health care providers have reported concerns about patient costs and reimbursement issues as the most reported barrier to prescribing PrEP, PEP, and Doxy-PEP.^77,81,82 Moreover, only a handful of PrEP studies investigate financial implementation strategies, highlighting the need for future work to identify sustainable, cost-effective care and access models.^83,84 Despite these limitations, this study offers the first data on the proportion and factors of HIV/STI preventive medicine uptake among rural substance-using MSM and makes intervention and research suggestions to improve uptake.

Given the role substance use plays in amplifying HIV/STI risk, and because HIV/STI rates are increasing among rural MSM, preventative strategies like PrEP, PEP, and Doxy-PEP can be important sexual health harm-reduction tools for these rural men who use substances.⁴⁸ This study explored the prevalence and correlates of PrEP, PEP, and Doxy-PEP uptake among rural substance-using MSM. Past-year PrEP, PEP, and Doxy-PEP uptake among rural substance-using MSM is suboptimal. Results underscore the need to implement integrated care in primary care, pharmacy, and substance use treatment settings to better screen, educate, and prescribe substance-using MSM these biomedical pharmaceuticals.

Footnotes

Acknowledgments

Thank the participants for their time in this study.

Authors’ Contributions

V.T.: Writing—original draft. B.N.M.: Conceptualization, methodology, writing—original draft. Writing—review and editing. C.O.: Conceptualization, methodology, formal analysis, investigation, writing—original draft, writing—review and editing.

Availability of Data and Material

The data are available from the corresponding author, CO, upon reasonable request and institutional review board approval.

Code Availability

The data are available from the corresponding author, CO, upon reasonable request and institutional review board approval.

Ethical Approval

This study was performed in line with the principles of the Declaration of Helsinki. The Texas A&M University institutional review board approved the study protocols (STUDY2023-0070, February 22, 2024).

Consent for Publish

Respondents provided electronic written informed consent to have their data published in-aggregate.

Consent to Participate

Respondents provided electronic written informed consent prior to participating.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This research was supported by an internal grant from the Texas A&M University Health Science Center.

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