Abstract
Background
A 2015 CDC analysis estimated that 24.7% of sexually active men who have sex with men (MSM) had indications for HIV preexposure prophylaxis (PrEP) based on 2014 US Public Health Service (USPHS) clinical practice guidelines. Given that the USPHS revised these guidelines in 2017, updated estimates of the fraction of MSM indicated for PrEP overall and stratified by demographic factors and geography are needed to scale-up PrEP for MSM in the US.
Methods
We conducted a national web-based study of 4904 MSM aged 15–65 who had ever had sex with another man between July 2017 and January 2019. We estimated the percentage of HIV-negative, sexually active MSM meeting USPHS indications for PrEP by demographic category.
Results
Of 3511 sexually active, HIV-negative MSM, 34.0% (95% CI: 32.4, 35.6) met USPHS indications for PrEP, with percentages consistent across US census region and varying slightly by race/ethnicity (Black: 32.2%, White: 33.7%, Hispanic: 36.4%, Other: 33.6%). Among individuals meeting USPHS PrEP indications, 93.5% reported condomless anal intercourse in the prior 6 months. Among all survey respondents, PrEP eligibility was lowest among non-Hispanic black (18.4%) and younger respondents (15-17: 4.1%; 18-24: 18.1%).
Conclusions
Estimated percentages of MSM meeting indications for PrEP exceeded the previous CDC estimate across race/ethnicity, age, and census regions, with one-third of adult, sexually active, HIV-negative MSM exhibiting indications for PrEP. This study suggests, given current guidelines for PrEP indications, that a different fraction of eligible MSM could be receiving PrEP than previously estimated.
Keywords: Preexposure prophylaxis, eligibility, indications, men who have sex with men
INTRODUCTION
Men who have sex with men (MSM) continue to bear the largest burden of human immunodeficiency virus (HIV) transmission in the United States, accounting for 67% of new HIV diagnoses in 2017.1 In recent years, HIV prevention strategies such as HIV pre-exposure prophylaxis (PrEP) have proven highly effective in preventing HIV transmission among MSM and can be delivered effectively in both clinical and non-clinical settings.2–5 However, determining which MSM are the highest priority for receiving PrEP remains an open question. The new federal Ending the Epidemic strategic initiative has identified geographical and demographic targets to address disparities in HIV incidence and access to HIV prevention tools like PrEP.6
In 2014, the US Public Health Service (USPHS) released clinical practice guidelines for the use of PrEP that included recommended indications for PrEP.7 The 2014 guidelines listed four base indications for MSM: aged 18 or older, HIV-negative, anal intercourse (AI) with a man in the prior 6 months, and not in a monogamous partnership with a recently-tested HIV-negative man. These must be complemented by at least one of the following criteria for MSM to be indicated for PrEP: 1) condomless anal intercourse (CAI) in the prior 6 months; 2) any sexually transmitted infection (STI) diagnosed in the prior 6 months; or 3) is in an ongoing sexual relationship with an HIV-positive partner. In 2017, the USPHS revised their guidelines, with two relevant changes to recommended indications for MSM (Box B1).8 The indication referencing any STI diagnosis in the prior 6 months was revised to specify that the STI diagnosis must be a bacterial STI (gonorrhea, chlamydia, syphilis). Additionally, the indication referencing being in an ongoing relationship with a partner living with HIV was removed from the list of recommended indications, in part reflecting population-level data that showed individuals with undetectable HIV viral loads were unable to transmit HIV to their partners, though the text still suggests that clinicians attempt to evaluate the viral loads of partners living with HIV to determine acquisition risk.
Accurate estimates of the number of MSM exhibiting behavioral indications for PrEP are needed to evaluate progress towards the rollout of PrEP.9 Using the 2014 guidelines, a CDC analysis of National Health and Nutrition Examination Survey (NHANES) data estimated that 24.7% of sexually active, HIV-negative MSM had indications for PrEP, totaling 492,000 MSM (95% Confidence Interval (CI): 212,000 – 772,000).10 However, the authors noted that they were not able to directly correlate their analysis with all guidelines indications, including the HIV status of male sexual partners and the assumption that multiple partners in the past year implied non-monogamy. The accuracy and precision of estimates of MSM with indications for PrEP can be improved with more granular data collection, such as sexual network information.
There are important questions about PrEP eligibility and indications that remain unanswered, including whether certain sub-indications (e.g. recent CAI vs. recent STI diagnosis) are more predictive of having an overall indication for PrEP. Additionally, given existing racial/ethnic and age-based disparities in both HIV incidence and prevalence1,11 as well as PrEP use12–15 among MSM, it is unknown whether these subgroups experience a greater HIV burden or use PrEP less frequently because they exhibit fewer indications. Finally, previous analyses of PrEP indications have used a denominator of HIV-negative, sexually active individuals. USPHS PrEP guidelines state that clinicians should not limit sexual history assessment to selected groups, and sexual activity can vary over time, including for MSM who may reinitiate or increase sexual activity around the time they consider starting PrEP. The possible heterogeneity in behavior and in the interpretation of these guidelines by clinicians, as well as the need to compare the sample composition of other data sources to NHANES, highlight the value of assessing alternate denominators, such as HIV-negative individuals, that might better reflect population-level PrEP need.
The collection of detailed sexual network and sexual behavior information to assess indications for PrEP, including subgroup-specific estimates, among MSM can help address some of these knowledge gaps. In this study, we estimated demographic-stratified proportions of MSM with indications for PrEP, following the 2017 update to the clinical provider guidelines, using detailed partner-level sexual behavior data from a web-based cross-sectional study of MSM across the US to closely map onto the PrEP behavioral indications for MSM.
METHODS
Study Design.
The ARTnet study, a sexual network survey of US MSM, recruited from recent participants of the parent American Men’s Internet Study (AMIS).16,17 AMIS participants were recruited online through banner ads on various social media, sex-seeking websites and mobile applications, and gay interest sites. Following completion of AMIS, eligible participants were redirected to the ARTnet consent page, offered participation in the survey, and provided with a small incentive following completion, which they could choose to keep or donate to charitable organizations. ARTnet collected information on participant demographics, use of HIV prevention (PrEP, HIV testing) or treatment (antiretroviral therapy, ART) services, and sexual behaviors and partners.18 A HIPAA-compliant (U.S. Federal Law establishing standards for protection of electronic health care information) online survey platform (SurveyGizmo, Boulder, CO) was used to host the survey and informed consent module. Data were collected in two waves: July 2017 – February 2018, and September 2018 – January 2019. For ARTnet, eligible participants must have been born male, currently identified as a male, be between 15-65 years old, and have ever been sexually active with another man. ARTnet survey responses were linked to a participant’s responses to AMIS, and responses were de-duplicated (by IP and email addresses) both within and across survey waves. The study protocol was approved by the Emory University Institutional Review Board.
PrEP Indication Measures.
To evaluate whether participants met indications for PrEP, detailed sexual behavior and sexual network data regarding recent sexual partners were collected. These data included information about the number of recent partners and, for up to the five most recent partners in the prior year, the following: type of partnership (main, casual, one-time), timing of partnership (start date, date of most recent sexual activity, whether the relationship was ongoing), sexual activity with each partner (anal intercourse, oral intercourse, sexual role, act frequency), and prevention activities (PrEP usage, condom usage, ART usage).
Indication Numerators.
The updated 2017 USPHS guidelines for PrEP list four base indications for PrEP (aged 18 or older, HIV-negative, anal intercourse with a man in the prior 6 months, and not in a monogamous partnership with a recently-tested HIV-negative man) and MSM must meet one of the additional criteria: 1) condomless anal intercourse (CAI) in the prior 6 months; or 2) a bacterial STI diagnosis (gonorrhea, chlamydia, syphilis) in the prior 6 months. The implementation of this in the ARTnet study is summarized in Table 1. MSM categorized as indicated for PrEP in the ARTnet study had to meet the four base indications, implemented as follows:
Aged 18 or older (we excluded this indication for the 15-17 age category)
Reported being HIV-negative
Reported a sexual partnership involving anal intercourse (receptive or insertive) with another man with a date of last sexual activity within the 6 months prior to survey completion
- One of the following:
- Having one ongoing partnership with a partner whose HIV serostatus was reported as either positive or unknown
- Having more than one ongoing partnership
Additionally, to be considered suitable for PrEP, MSM had to have either: 1) reported a partnership, with a last date of sexual activity in the prior 6 months, where the weekly rate of condom-protected CAI acts was less than the reported weekly rate of total CAI acts; or 2) reported being diagnosed with a bacterial STI in the prior 12 months.
Table 1:
Summary of HIV Preexposure Prophylaxis Guidelines for Men who have Sex with Men (MSM) in the 2017 USPHS Clinical Provider Guidelines for PrEP and Implementation in the ARTnet Study
| Numerator: USPHS Guidelines (2017 Update) | Denominator: Sexually active, HIV-negative MSM | |
|---|---|---|
| USPHS Guidelines for PrEP for MSM | • Base Indications: • Aged 18 or older • HIV-negative • Anal intercourse with a man in the past 6 months • Not in a monogamous partnership with a recently tested, HIV-negative man • Additional indications (at least one of the following): • Condomless anal intercourse (CAI) in the past 6 months • Bacterial STI diagnosis in the past 6 months |
• Sexually active with another male in the past 12 months • HIV-negative |
| ARTnet Implementation | • Base Indications: • Aged 18 or older (18-65) • (Note: excluded indication for 15-17-year olds) • HIV-negative • Reported male partner in the past 6 months • One of the following: • One ongoing partner living with HIV or of unknown serostatus • More than one ongoing partner • Additional Indications (at least one of the following): • At least one CAI act in the past 6 months • Bacterial STI diagnosis in the past 12 months |
• Reported partnership with last active end date in the past 12 months • HIV-negative |
Indication Denominators.
To maintain consistency with the previous estimate of MSM with indications for PrEP, the denominators for each category were the number of sexually active, HIV-negative MSM in that category. In the ARTnet study, this number reflected MSM who reported: 1) being HIV-negative; and 2) at least one sexual partnership with a date of last sexual activity in the 12 months prior to survey completion (Table 1). An alternative denominator, comprising MSM who were HIV-negative, is used for analysis and included in Table 3.
Table 3:
Estimated Number of ARTnet Respondents Meeting Indications for PrEP by Race/Ethnicity, Geography, and Age
| Meet Indications for PrEP |
||||||||
|---|---|---|---|---|---|---|---|---|
| Category | Sexually Active, HIV-Negative Denominator* | HIV-Negative Denominator | Meets USPHS Base Indications** | USPHS Base + Recent CAI | USPHS Base + Recent STI*** | Total Meeting Indications for PrEP (Sexually Active, HIV-Negative Denominator) | Total Meeting Indications for PrEP (HIV-Negative Denominator) | Total Meeting Indications for PrEP (All Respondents) |
| N (%) | N (%) | N (Row Percents) | N (Row Percents) | N (Row Percents) | N (Row Percent) | N (Row Percent) | N (Percent of all respondents) | |
| All | 3511 | 3726 | 1751 (49.9, 47.0) | 1116 (31.8, 30.0) | 295 (8.4, 7.9) | 1194 (34.0) | 1194 (32.0) | 1194 (24.3) |
| Race/Ethnicity | ||||||||
| Non-Hispanic White | 2581 | 2743 | 1284 (49.7, 46.8) | 822 (31.8, 30.0) | 204 (7.9, 7.4) | 871 (33.7) | 871 (31.8) | 871 (24.7) |
| Non-Hispanic Black | 152 | 171 | 72 (47.4, 42.1) | 39 (25.7, 22.8) | 17 (11.2, 9.9) | 49 (32.2) | 49 (28.7) | 49 (18.4) |
| Hispanic | 473 | 487 | 244 (51.6, 50.1) | 160 (33.8, 32.9) | 45 (9.5, 9.2) | 172 (36.4) | 172 (35.3) | 172 (25.4) |
| Other Race/Ethnicity | 305 | 325 | 151 (49.5, 46.5) | 95 (31.1, 29.2) | 29 (9.5, 8.9) | 102 (33.4) | 102 (31.4) | 102 (23.2) |
| US Census Region | ||||||||
| Northeast | 652 | 687 | 333 (51.1, 48.6) | 192 (29.4, 27.9) | 55 (8.4, 8.0) | 214 (32.8) | 214 (31.1) | 214 (24.3) |
| Midwest | 693 | 742 | 340 (49.1, 45.8) | 245 (35.4, 33.0) | 45 (6.5, 6.1) | 252 (36.4) | 252 (34.0) | 252 (25.4) |
| South | 1272 | 1348 | 626 (49.2, 46.4) | 389 (30.6, 28.9) | 104 (8.2, 7.7) | 418 (32.9) | 418 (31.0) | 418 (23.5) |
| West | 894 | 949 | 452 (50.6, 47.6) | 290 (32.4, 30.6) | 91 (10.2, 9.6) | 310 (34.7) | 310 (32.7) | 310 (24.9) |
| Age Category | ||||||||
| 15-17**** | 25 | 27 | 7 (28.0, 25.9) | 6 (24.0, 22.2) | 2 (8.0, 7.4) | 6 (24.0) | 6 (22.2) | 6 (4.1) |
| 18-24 | 764 | 784 | 305 (39.9, 38.9) | 200 (26.2, 25.5) | 56 (7.3, 7.1) | 213 (27.9) | 213 (27.2) | 213 (18.1) |
| 25-34 | 1025 | 1074 | 458 (44.7, 42.6) | 302 (29.5, 28.1) | 96 (9.4, 8.9) | 331 (32.3) | 331 (30.8) | 331 (26.1) |
| 35-44 | 545 | 576 | 288 (52.8, 50.0) | 191 (35.0, 33.2) | 59 (10.8, 10.2) | 205 (37.6) | 205 (35.6) | 205 (29.5) |
| 45-54 | 604 | 647 | 374 (61.9, 57.8) | 238 (39.4, 36.8) | 51 (8.4, 7.9) | 252 (41.7) | 252 (38.9) | 252 (30.3) |
| 55-65 | 548 | 618 | 319 (58.2, 51.6) | 179 (32.7, 29.0) | 31 (5.7, 5.0) | 187 (34.1) | 187 (30.3) | 187 (23.8) |
Row percent values reflect two denominators: 1) HIV-negative respondents; 2) HIV-negative respondents who were sexually active with a man in the past 12 months
Denominator: 1) HIV-negative; and 2) Sexually active with a man in the past 12 months
USPHS Base Indications: 1) Aged 18+; 2) HIV-negative; 3) Sexually active with a man in the past 6 months; 4) Not in a monogamous partnership with a HIV-negative man
USPHS Guidelines for STI diagnoses are based on the past 6 months (ARTnet based on 12 months)
Base indications for 15-17-year olds exclude 18+ USPHS guideline
Recent CAI: Condomless anal intercourse with another man in the past 6 months
Recent STI: Bacterial STI diagnosis in the past 12 months
Statistical Analysis.
Descriptive analyses of persons with indications for PrEP by demographic category are presented using percentages and standard errors. The numerators for these analyses reflected the number of individuals, within each category, who met all USPHS indications for PrEP for MSM, and the denominators for each category reflected the number of sexually active, HIV-negative MSM. Data analyses were performed in R 3.6.0.
RESULTS
Table 2 presents descriptive statistics of the 4904 de-duplicated, unique individuals completing the ARTnet survey. ARTnet participants were mainly non-Hispanic white (71.8%), over one-third (36.3%) were from the South, and about half (49.9%) were aged 18-34. In total, more than two-thirds (71.6%) of respondents reported both being HIV-negative and having had anal intercourse with a male partner in the past year. This fraction was notably lower among non-Hispanic black respondents (57.1%), but similar across geographic regions. Very few adolescent MSM reported being sexually active and HIV-negative (17.2%), while more than three-quarters of MSM aged 25-34 (80.8%) and 35-44 (78.5%) reported being sexually active and HIV-negative.
Table 2:
Number of HIV-Negative and Sexually Active ARTnet Respondents by Race/Ethnicity, Geography, and Age
| Category | ARTnet Respondents | HIV-Negative | Sexually active with a man in the past 12 months | Sexually Active, HIV-Negative Denominator* |
|---|---|---|---|---|
| N (Column %) | N (Row %) | N (Row %) | N (Row %) | |
| All | 4904 (100.0) | 3726 (76.0) | 4596 (93.7) | 3511 (71.6) |
| Non-Hispanic White | 3523 (71.8) | 2743 (77.9) | 3297 (93.6) | 2581 (73.3) |
| Non-Hispanic Black | 266 (5.4) | 171 (64.3) | 239 (89.8) | 152 (57.1) |
| Hispanic | 676 (13.8) | 487 (72.0) | 652 (96.4) | 473 (70.0) |
| Other Race/Ethnicity | 439 (9.0) | 325 (74.0) | 408 (92.9) | 305 (69.5) |
| Northeast | 882 (18.0) | 687 (77.9) | 841 (95.4) | 652 (73.9) |
| Midwest | 994 (20.3) | 742 (74.6) | 922 (92.8) | 693 (69.7) |
| South | 1782 (36.3) | 1348 (75.6) | 1672 (93.8) | 1272 (71.4) |
| West | 1246 (25.4) | 949 (76.2) | 1161 (93.2) | 894 (71.7) |
| 15-17**** | 145 (3.0) | 27 (18.6) | 133 (91.7) | 25 (17.2) |
| 18-24 | 1179 (24.0) | 784 (66.5) | 1136 (96.4) | 764 (64.8) |
| 25-34 | 1268 (25.9) | 1074 (84.7) | 1202 (94.8) | 1025 (80.8) |
| 35-44 | 694 (14.2) | 576 (83.0) | 657 (94.7) | 545 (78.5) |
| 45-54 | 833 (17.0) | 647 (77.7) | 775 (93.0) | 604 (72.5) |
| 55-65 | 785 (16.0) | 618 (78.7) | 693 (88.3) | 548 (69.8) |
Denominator: 1) HIV-negative; and 2) Sexually active with a man in the past 12 months
PrEP indication estimates across race/ethnicity, age, and census regions usually exceeded the previous CDC estimate (Table 3).10 In total, one-third (34.0%, 95% Confidence Interval (CI): 32.4%, 35.6%) of adult, sexually active, HIV-negative MSM completing the ARTnet study met USPHS guidelines for indications for PrEP. An age-adjusted estimate, directly standardized to MSM population estimates19, of MSM meeting indications for PrEP was 35.4% (not shown). In contrast, 24.0% (CI: 9.4%, 45.6%) of sexually active, HIV-negative 15-17-year-old MSM met all indications except for age. A slightly greater percentage of non-Hispanic white respondents (33.7%, CI: 31.9%, 35.6%) had indications for PrEP than non-Hispanic black (32.2%, CI: 24.9%, 40.3%) respondents, with a higher figure among Hispanic (36.4%, CI: 32.0%, 40.9) respondents. PrEP indications did not differ greatly by geographic region, with the highest values in the Midwest (36.4%, CI: 32.8%, 40.1%) and lowest values in the Northeast (32.8%, CI: 29.2%, 36.6%) and South (32.9%, CI: 30.3%, 35.5%). PrEP indications followed a parabolic shape with age, with 27.9%, 41.7%, and 34.1% of MSM aged 18-24, 45-54, 55-65, respectively, meeting indications. The proportions of respondents meeting each individual indication for PrEP are presented in Supplementary Table 1.
Of those meeting all indications for PrEP (four base indications and either recent STI diagnosis or recent CAI), recent CAI (79-100% of those meeting indications for PrEP) was far more common as an indication than a recent STI diagnosis (17-35% of those meeting indications for PrEP). Nearly one-third of MSM (31.8%) meeting the base indications for PrEP did not report recent CAI or a recent STI diagnosis and were not considered to meet all indications for PrEP. Among all ARTnet respondents, the overall percentage of MSM with indications for PrEP was 24.3%, with values lowest among non-Hispanic black (18.4%) and younger respondents (15-17: 4.1%; 18-24: 18.1%). PrEP indication proportion estimates were slightly lesser when using the alternative denominator of all HIV-negative respondents.
MSM PrEP indication percentages and confidence intervals, presented in two-way stratifications by race/ethnicity and age category, are displayed visually in Figure 1. Among MSM aged 18 or older, nearly all two-way categories (22/25, 88%) had estimated percentages of MSM with indications for PrEP greater than the previously published 24.7% value (red line). MSM in the youngest age category (15-17 years) had the smallest fraction of respondents meeting indications for PrEP, although confidence bounds were wide due to smaller sample sizes, while Hispanic MSM (olive green bars) consistently had greater fractions of respondents meeting indications for PrEP. Across the whole sample (blue bars), PrEP indications increased with age before decreasing in the oldest age category, with lower confidence bounds surpassing the 24.7% value for the four oldest age categories.
Figure 1:
Indications for PrEP, Stratified by Age and Race/Ethnicity, among Sexually Active, HIV-Negative MSM in the United States
DISCUSSION
This study sought to estimate demographic-stratified proportions of MSM with indications for PrEP based on the updated 2017 USPHS guidelines. We found that, across nearly all stratifications of race/ethnicity, the estimated percentage of MSM meeting indications for PrEP exceeded the previous CDC estimate. This percentage was relatively consistent across US census regions and varied only slightly by race/ethnicity, while increasing parabolically with age. When considering all survey respondents in the denominator, younger and non-Hispanic black respondents were least likely to meet indications for PrEP. The vast majority of MSM meeting indications for PrEP reported recent CAI, compared to a much smaller proportion reporting a recent STI diagnosis, and nearly all surveyed MSM reported a male AI partner in the past 6 months.
This study suggests, given current guidelines for PrEP indications, that the fraction of eligible MSM receiving PrEP may differ from previous estimates. We found that more than one-third of sexually active, HIV-negative MSM surveyed met all indications for PrEP. This finding is 37.7% higher than previously estimated among sexually active, HIV-negative men10, which could result in more than 180,000 additional MSM being considered eligible for PrEP. This adjustment would increase the size of MSM with indications for PrEP and, thus, could decrease the estimated percent of PrEP-indicated MSM who are receiving PrEP. The increased proportion with indications for PrEP observed in this study correlates with recent estimates of increasing PrEP eligibility.20 Accurately measuring PrEP need is necessary to assess whether PrEP uptake approaches the levels required to have population-level impact on both HIV21 and STI22 incidence.
There is a need to understand whether reduced PrEP uptake can be attributed to certain subgroups meeting fewer indications for PrEP. In a previous study, black men and women accounted for more than 40% of persons with PrEP indications23, but disparities in PrEP uptake have been observed in multiple settings, particularly in the US South12 and among racial/ethnic minority populations13–15, despite a general trend of increasing PrEP prescription.24 Among sexually active, HIV-negative MSM in this study, non-Hispanic black MSM did not differ greatly from other racial/ethnic groups in terms of meeting PrEP indications, but a smaller percentage (18.4%) of all surveyed non-Hispanic black respondents met indications for PrEP compared to non-Hispanic white (24.7%) or other racial/ethnic groups. In this study, this appeared to be driven by a smaller percentage of black respondents reporting either a recent male sex partner or recent CAI, as well as by higher HIV prevalence (thus reducing the number of HIV-negative MSM who could be eligible for PrEP) among non-Hispanic black respondents (24.1%, data not shown), consistent with racial/ethnic disparities in new HIV diagnoses in national surveillance data.1
One hypothesis to explain these racial disparities in HIV prevalence is the prevalence pool hypothesis, where high incidence and prevalence are sustained by race/ethnicity-based assortative mixing. This same hypothesis, although insufficient to explain long-term dynamics sustaining HIV prevalence disparities25, also explains why there is great need for black MSM to be aware of and benefit from access to PrEP. Black MSM may be at increased risk for HIV acquisition compared to other MSM, but this study found that current PrEP guidelines do not identify them to a greater extent than other MSM. This complements recent studies pointing to a misalignment of patient-perceived HIV risk and PrEP guidelines26, as well as a NHBS analysis that highlighted racial/ethnic disparities in PrEP use among insured and uninsured MSM likely eligible for PrEP who discussed PrEP with a health care provider.20 To observe the predicted population-level impact21 and cost-effectiveness of targeting PrEP to MSM27, further research into racial/ethnic disparities in PrEP implementation is needed to determine whether additional guidelines should be considered to better indicate minority MSM at highest risk for HIV acquisition. Interventions focusing on increasing initiation into, adherence to, and retention in PrEP care could reduce incidence and the magnitude of the disparity.28
In addition to the race-based differences observed in this study, there were significant differences in PrEP indications by age. A larger percentage of older MSM demonstrated more indications for PrEP, tracking with parabolic age-based increases in the proportion of MSM reporting recent CAI or not being in a monogamous partnership with a HIV-negative partner. A very small proportion of all 15-17-year-old MSM exhibited sufficient indications for PrEP, but, when considering sexually active, HIV-negative MSM aged 15-17 (albeit a small denominator), this proportion was much closer to the overall estimate. In this study, similar to what was observed among black MSM, this was driven by a very small number of younger MSM reporting being HIV-negative, while around 80% had unknown HIV status (data not shown). Given the high proportion of young MSM who are not aware of their status, a push to increase HIV testing should be of primary importance to point young MSM to HIV prevention or care. Additionally, recent mathematical modeling work focusing on adolescent sexual minority males (ASMM) has shown the potential for PrEP implementation to reduce population-level HIV incidence, particularly when targeting highest-risk ASMM based on sexual history29, and efficiently reach young black ASMM.30 The CDC guidelines for PrEP indications presently exclude 15-17 year old MSM, but these findings indicate that this group may exhibit sufficient behavioral indications that may put them at risk for HIV acquisition and make them good candidates for PrEP.
These estimates may differ from the previous CDC estimate for several reasons. First, the previous CDC NHANES-based analysis may have been less able to measure certain indications such as respondent HIV status and the HIV status of male sexual partners and assumed that reporting multiple prior-year partners meant that respondents were not monogamous.10 ARTnet collected detailed sexual behavior data on several past-year partners, allowing this analysis to more closely adhere to the partner-based indications (such as partner HIV status) in the PrEP guidelines. Although the denominator methodology was similar across analyses, the numerator for the previous analysis defined the numerator for PrEP indications as MSM with at least 2 CAI partners in the past year and either CAI or a STI diagnosis in the prior 12 months. We also report PrEP indications using two other denominators, all respondents and HIV-negative respondents. The PrEP guidelines include a recommended indication of “without acute or established HIV infection.” The previous estimate implemented this by including all MSM “not known to be HIV-positive”, whereas this analysis implemented this indication as “reporting being HIV-negative.” The guidelines also state that providers should establish the HIV status of potentially eligible recipients prior to PrEP initiation. Thus, we feel that the exclusion of status-unknown participants in this analysis may more closely represent the clinical implementation and assessment of PrEP eligibility, despite differences from the previous methodology.
A second, external explanation for the increase in percentages between analyses may be an increase in risky behavior among US MSM, as an analysis of sexual behavior trends of 2013-2016 identified significant increases in both CAI and STI diagnoses and, despite recent increases, suboptimal uptake of recommended HIV and STI testing, particularly among the youngest MSM.16 Estimating the percentage of MSM with indications for PrEP regularly is critical to stay up-to-date with changing sexual risk behavior. Third, the sampling frame for these analyses also differed, with the 24.7% figure drawn from a weighted, nationally representative survey and the ARTnet survey representing an online convenience sample that may be more sexually active (see limitations).
Regular assessments of indications for PrEP, whether through online surveys or other methods, can provide useful data for implementation and intervention development to address low PrEP uptake and estimate coverage when combined with information about changing sexual behavior, PrEP prescriptions, and PrEP uptake (numerators).12,15,24,31–33 Similarly, recent analyses among British MSM34,35 and US women36 have estimated the number and percentage of individuals with indications for PrEP, using their findings to inform recruitment targets for PrEP trials and identify factors associated with PrEP eligibility. Finally, a European study similar to this analysis used participant-reported online survey data on HIV testing and sexual behaviors to estimate eligibility, finding that 40.7% of surveyed European MSM met indications in the 2014 USPHS PrEP Guidelines.37 This highlighted that estimates of MSM with indications for PrEP can provide realistic inputs for cost-effectiveness analyses of PrEP and cost estimates for appropriate PrEP delivery. Frequent, rigorous measurement of indications for PrEP at the population level can thus aid in PrEP implementation and evaluation efforts.
Limitations.
There are limitations to this analysis. Unlike the NHANES-based analysis, this represents a convenience sample of MSM recruited online. Despite efforts to recruit from a diverse range of websites and social networking platforms, these data may not be generalizable to all US MSM or to all MSM online, including possible under-representation of black and other racial/ethnic minority MSM, a more sexually active population, and demographics varying between survey years.16,38 The demographic-stratified estimates presented in this analysis may address some of the potential selection bias associated with those covariates. A similar European eligibility analysis had similar limitations, comprising a higher-risk group of MSM39 (including more MSM living with HIV40) that could lead to potential overestimation of PrEP eligibility. Although these online studies might more be inclusive than traditional venue-based sampling, these results should be seen as a complement to other studies, including National HIV Behavioral Surveillance.17 Second, the influence of social desirability and recall biases on participated-reported data is a concern in all studies, including those online, making it possible that MSM might under-report risk behaviors and over-report prevention behaviors that could lead to underestimation of MSM meeting indications for PrEP. Participant-reported data on partner information, including serostatus, relies on disclosure of information or participant perceptions, which could both be subject to error. Finally, ARTnet only measured STI diagnoses in the past 12 months, rather than the past 6 month timeframe included as part of the guidelines.
Conclusions.
This analysis of an online convenience sample of MSM in the US found that more sexually active MSM are potentially indicated for and, thus, a smaller fraction of indicated MSM may be receiving PrEP than previously estimated, although this may be offset by increasing PrEP uptake. Online sexual behavior surveys of sexually active MSM can help produce regular demographic- or geography-specific estimates of people meeting indications for PrEP that can complement other data collection methods, support service planning, and monitor trends in sexual behaviors and PrEP indications.
Supplementary Material
Acknowledgments
Funding
This work was supported by National Institutes of Health grants R21 MH112449 and R01 AI138783, and a grant from the MAC AIDS Fund.
Footnotes
Conflicts of Interest
The authors declare no conflicts of interest.
REFERENCES
- 1.Centers for Disease Control and Prevention. HIV Surveillance Report, 2017; Vol. 29; 2018. [Google Scholar]
- 2.Volk JE, Marcus JL, Phengrasamy T, et al. No New HIV Infections With Increasing Use of HIV Preexposure Prophylaxis in a Clinical Practice Setting. Clin Infect Dis. 2015;61(10):1601–1603. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Marcus JL, Volk JE, Pinder J, et al. Successful Implementation of HIV Preexposure Prophylaxis: Lessons Learned From Three Clinical Settings. Curr HIV/AIDS Rep. 2016;13(2):116–124. [DOI] [PubMed] [Google Scholar]
- 4.Grant RM, Lama JR, Anderson PL, et al. Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men. N Engl J Med. 2010;363(27):2587–2599. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Marcus JL, Hurley LB, Hare CB, et al. Preexposure Prophylaxis for HIV Prevention in a Large Integrated Health Care System. JAIDS J Acquir Immune Defic Syndr. 2016;73(5):540–546. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Fauci AS, Redfield RR, Sigounas G, Weahkee MD, Giroir BP. Ending the HIV Epidemic. JAMA. 2019;321(9):844. [DOI] [PubMed] [Google Scholar]
- 7.US Public Health Service. Preexposure Prophylaxis for the Prevention of HIV Infection in the United States - 2014: A Clinical Practice Guideline.; 2014. [Google Scholar]
- 8.US Public Health Service. Preexposure Prophylaxis for the Prevention of HIV Infection in the United States - 2017 Update: A Clinical Practice Guideline.; 2018. [Google Scholar]
- 9.Rosenberg ES, Marcus JL. Progress and pitfalls in measuring HIV preexposure prophylaxis coverage in the United States. Ann Epidemiol. 2018;28(12):830–832. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Smith DK, Van Handel M, Wolitski RJ, et al. Vital Signs: Estimated Percentages and Numbers of Adults with Indications for Preexposure Prophylaxis to Prevent HIV Acquisition — United States, 2015. MMWR Morb Mortal Wkly Rep. 2015;64(46):1291–1295. [DOI] [PubMed] [Google Scholar]
- 11.Centers for Disease Control and Prevention. HIV Infection Risk, Prevention, and Testing Behaviors Among Men Who Have Sex With Men—National HIV Behavioral Surveillance, 23 U.S. Cities, 2017.; 2019. [Google Scholar]
- 12.Siegler AJ, Mouhanna F, Giler RM, et al. The prevalence of pre-exposure prophylaxis use and the pre-exposure prophylaxis–to-need ratio in the fourth quarter of 2017, United States. Ann Epidemiol. 2018;28(12):841–849. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Rolle C-P, Rosenberg ES, Siegler AJ, et al. Challenges in Translating PrEP Interest Into Uptake in an Observational Study of Young Black MSM. JAIDS J Acquir Immune Defic Syndr. 2017;76(3):250–258. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Marcus JL, Hurley LB, Hare CB, Silverberg MJ, Volk JE. Disparities in Uptake of HIV Preexposure Prophylaxis in a Large Integrated Health Care System. Am J Public Health. 2016;106(10):e2–3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Huang YA, Zhu W, Smith DK, Harris N, Hoover KW. HIV Preexposure Prophylaxis, by Race and Ethnicity — United States, 2014–2016. MMWR Morb Mortal Wkly Rep. 2018;67(41):1147–1150. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Sanchez TH, Zlotorzynska M, Sineath RC, Kahle E, Tregear S, Sullivan PS. National Trends in Sexual Behavior, Substance Use and HIV Testing Among United States Men Who have Sex with Men Recruited Online, 2013 Through 2017. AIDS Behav. 2018;22(8):2413–2425. [DOI] [PubMed] [Google Scholar]
- 17.Zlotorzynska M, Sullivan P, Sanchez T. The Annual American Men’s Internet Survey of Behaviors of Men Who Have Sex With Men in the United States: 2016 Key Indicators Report. JMIR Public Heal Surveill. 2019;5(1):e11313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Jenness SM, Weiss KM, Prasad P, Zlotorzynska M, Sanchez T. Bacterial Sexually Transmitted Infection Screening Rates by Symptomatic Status Among Men Who Have Sex With Men in the United States. Sex Transm Dis. 2019;46(1):25–30. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Jones J, Grey JA, Purcell DW, Bernstein KT, Sullivan PS, Rosenberg ES. Estimating Prevalent Diagnoses and Rates of New Diagnoses of HIV at the State Level by Age Group Among Men who Have Sex With Men in the United States. Open Forum Infect Dis. 2018;5(6):ofy124. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Kanny D, Jeffries WL, Chapin-Bardales J, et al. Racial/Ethnic Disparities in HIV Preexposure Prophylaxis Among Men Who Have Sex with Men - 23 Urban Areas, 2017. MMWR Morb Mortal Wkly Rep. 2019;68(37):801–806. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Jenness SM, Goodreau SM, Rosenberg E, et al. Impact of the Centers for Disease Control’s HIV preexposure prophylaxis guidelines for men who have sex with men in the United States. J Inf Dis. 2016;214(12):1800–1807. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Jenness SM, Weiss KM, Goodreau SM, et al. Incidence of Gonorrhea and Chlamydia Following HIV Preexposure Prophylaxis among Men Who Have Sex with Men: A Modeling Study. Clin Infect Dis. 2017;65(5):712–718. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Smith DK, Van Handel M, Grey J. Estimates of adults with indications for HIV pre-exposure prophylaxis by jurisdiction, transmission risk group, and race/ethnicity, United States, 2015. Ann Epidemiol. 2018;28(12):850–857.e9. [DOI] [PubMed] [Google Scholar]
- 24.Wu H, Mendoza MCB, Huang YA, Hayes T, Smith DK, Hoover KW. Uptake of HIV Preexposure Prophylaxis Among Commercially Insured Persons—United States, 2010–2014. Clin Infect Dis. 2017;64(2):144–149. [DOI] [PubMed] [Google Scholar]
- 25.Goodreau SM, Rosenberg ES, Jenness SM, et al. Sources of racial disparities in HIV prevalence in men who have sex with men in Atlanta, GA, USA: a modelling study. Lancet HIV. 2017;4(7):e311–e320. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Lockard A, Rosenberg ES, Sullivan PS, et al. Contrasting Self-Perceived Need and Guideline-Based Indication for HIV Pre-Exposure Prophylaxis Among Young, Black Men Who Have Sex with Men Offered Pre-Exposure Prophylaxis in Atlanta, Georgia. AIDS Patient Care STDS. 2019;33(3):112–119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Desai K, Sansom SL, Ackers ML, et al. Modeling the impact of HIV chemoprophylaxis strategies among men who have sex with men in the United States: HIV infections prevented and cost-effectiveness. AIDS. 2008;22(14):1829–1839. [DOI] [PubMed] [Google Scholar]
- 28.Jenness SM, Maloney KM, Smith DK, et al. Addressing Gaps in HIV Preexposure Prophylaxis Care to Reduce Racial Disparities in HIV Incidence in the United States. Am J Epidemiol. 2019;188(4):743–752. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Goodreau SM, Hamilton DT, Jenness SM, et al. Targeting Human Immunodeficiency Virus Pre-Exposure Prophylaxis to Adolescent Sexual Minority Males in Higher Prevalence Areas of the United States: A Modeling Study. J Adolesc Heal. 2018;62(3):311–319. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Hamilton DT, Goodreau SM, Jenness SM, et al. Potential Impact of HIV Preexposure Prophylaxis Among Black and White Adolescent Sexual Minority Males. Am J Public Health. 2018;108(S4):S284–S291. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Flash C, Landovitz R, Mera Giler R, et al. Two years of Truvada for pre-exposure prophylaxis utilization in the US. J Int AIDS Soc. 2014;17(4 Suppl 3):19730. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Sullivan PS, Giler RM, Mouhanna F, et al. Trends in the use of oral emtricitabine/tenofovir disoproxil fumarate for pre-exposure prophylaxis against HIV infection, United States, 2012–2017. Ann Epidemiol. 2018;28(12):833–840. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Finlayson T, Cha S, Xia M, et al. Changes in HIV Preexposure Prophylaxis Awareness and Use Among Men Who Have Sex with Men — 20 Urban Areas, 2014 and 2017. MMWR Morb Mortal Wkly Rep. 2019;68(27):597–603. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Miltz AR, Cambiano V, Lampe FC, et al. Eligibility for PrEP among MSM attending GUM clinics in the UK. Sex Transm Infect. 2017;93(8):571–571. [DOI] [PubMed] [Google Scholar]
- 35.Mitchell HD, Desai S, Mohammed H, et al. Preparing for PrEP: Estimating the size of the population eligible for HIV pre-exposure prophylaxis among men who have sex with men in England. Sex Transm Infect. 2019;95(7):484–487. [DOI] [PubMed] [Google Scholar]
- 36.Patel AS, Goparaju L, Sales JM, et al. Brief Report: PrEP Eligibility Among At-Risk Women in the Southern United States: Associated Factors, Awareness, and Acceptability. JAIDS J Acquir Immune Defic Syndr. 2019;80(5):527–532. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Kenyon CR, Osbak K. How many MSM in Europe could benefit from PrEP – a 9 billion Euro question? Int J STD AIDS. 2015;26(13):988–990. [DOI] [PubMed] [Google Scholar]
- 38.Sullivan PS, Khosropour CM, Luisi N, et al. Bias in Online Recruitment and Retention of Racial and Ethnic Minority Men Who Have Sex With Men. J Med Internet Res. 2011;13(2):e38. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Marcus U, Hickson F, Weatherburn P, Schmidt AJ. Estimating the size of the MSM populations for 38 European countries by calculating the survey-surveillance discrepancies (SSD) between self-reported new HIV diagnoses from the European MSM internet survey (EMIS) and surveillance-reported HIV diagnoses am. BMC Public Health. 2013;13(1):919. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Marcus U, Hickson F, Weatherburn P, Schmidt AJ, EMIS Network. Prevalence of HIV among MSM in Europe: comparison of self-reported diagnoses from a large scale internet survey and existing national estimates. BMC Public Health. 2012;12(1):978. [DOI] [PMC free article] [PubMed] [Google Scholar]
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