Abstract
Despite being a population with a high incidence of human immunodeficiency virus (HIV), adolescents and young adults have had limited inclusion in research regarding HIV interventions. One effective method of HIV prevention is pre-exposure prophylaxis (PrEP), which was only approved for adolescents in the United States (U.S.) in 2018. Although PrEP has been available for several years, data demonstrates that few adolescents and young adults vulnerable to HIV have received a prescription. We conducted a systematic review to determine the barriers to acceptance of PrEP for youth 13 to 24 years of age, both domestically and internationally. A literature search was conducted in August 2022 using a set of keywords, yielding 5,710 articles. These articles were screened by three reviewers using prespecified inclusion and exclusion criteria, ultimately narrowing the list down to 13 prevalence studies. From the 3,272 compiled participants, 38 distinct barriers were identified. The top three barriers were lack of knowledge (n=637), fear of family finding out (n=575), and side effects of PrEP (n=449). Of the nine studies that included data on awareness, only 54 percent (n=1435) of participants reported awareness of PrEP. Findings suggest that youth would benefit from intervention measures that raise awareness regarding both HIV risk and the benefits of PrEP use. This type of education would also help combat stigma towards HIV and PrEP that creates an additional barrier for youth.
Background
Although progress has been made in HIV prevention and treatment, the adolescent and young adult population is often overlooked. In the United States (U.S.) alone, 20 percent of new HIV diagnoses in 2020 were in people 13 to 24 years of age.1 Despite this, only six percent of U.S. high school students have ever been tested for HIV, which is an essential first step for people to receive timely care. This implies that the actual number of adolescents and young adults who have HIV is higher than reported. Studies have shown that although the percentage of high schoolers who engage in sexual activity has decreased in the past decade, many youths engage in behaviors that increase their likelihood of contracting HIV. One example of this behavior is the decrease in condom use among sexually active U.S. students from 60 percent in 2011 to 52 percent in 2021.1 Other behaviors include substance use and having multiple partners. This issue is not isolated to the U.S. alone. According to the Centers for Disease Control and Prevention (CDC), there were more than 1.6 million new HIV diagnoses worldwide in 2019, which included 150,000 new diagnoses in children.2 Given that testing rates are lower than desired for adolescents and young adults, it is important to look for additional preventative measures for this population.
One major tool for HIV prevention is pre-exposure prophylaxis (PrEP), which is a medication that protects the high-incidence population from acquiring HIV and can be given as an oral pill or injection. Studies have shown that PrEP reduces the risk of getting HIV from sex by 99 percent, while reducing risk by 74 percent for people who inject drugs.3 Prior to 2012, the drug combination tenofovir disoproxil and emtricitabine was only used to treat people who were already HIV-positive. Once this combination was approved for its current indication as a preventative measure, it still excluded people under the age of 18. It was not until 2018 that the Food and Drug Administration (FDA) approved PrEP pills for use by adolescents who weigh at least 77 pounds and are at risk for acquiring HIV.4 Since then, the injectable PrEP formulation cabotegravir was approved by the FDA in 2021.
Although studies had indicated that PrEP is safe and beneficial for adolescents and young adults to use, 16- to 24-year-olds were the age category that had the lowest PrEP coverage in the U.S. in 2019, with only 16 percent of people who would benefit from PrEP actually receiving a prescription.5 Given that a large number of youth have the indications for PrEP, it would be important to identify the types of barriers to acceptance and use of PrEP among adolescents and young adults. While this population is not the only one to face barriers to PrEP use, there has been a lack of systematic reviews in comparison to more well-researched groups, like adult men who have sex with men (MSM). This systematic review was conducted to discover the most common barriers that impede global youth from starting PrEP using quantitative data from published, peer-reviewed studies. By having a stronger understanding of the actual factors that prevent youth from starting PrEP, we will be able to better inform future HIV prevention efforts.
Methods
:
A systematic review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.6 PubMed, Embase, Web of Science, and Cochrane were searched for the following terms: pre-exposure prophylaxis, emtricitabine, tenofovir disoproxil fumarate drug combination, Truvada, Descovy, young adult, adolescent, emerging adult, young men, young women, boys, girls, youth, barrier, risk, acceptability, feasibility, willingness, perception, awareness, and health attitude. These searches were conducted in August 2022. Institutional Review Board approval was not required as this systematic review did not involve enrollment of human subjects.
The inclusion criteria for the studies were that participants had to be HIV-negative adolescents (ages 13-17) or young adults (ages 18-24) who were surveyed for PrEP acceptability. The studies must also include self-reported barriers experienced by the participants in a quantitative manner. The exclusion criteria for the studies were articles that did not have original data; reviews, case studies, and non-English articles were also excluded.
For the initial search, 5,710 articles were found, and 1,663 duplicates were removed. The remaining 4,047 abstracts were screened by three reviewers (Figure 1). The 64 titles and abstracts from this phase that were deemed relevant to the research question were then screened for a full-text review. Articles were included in the systematic review if they fulfilled the inclusion criteria. Of the 64 articles under full-text review, 51 were excluded. At that stage, 36 were excluded because the study did not have quantitative data, five were excluded because the study had participants outside of the age range specified in the inclusion criteria, five were excluded because they provided inadequate outcome measures, and five were excluded because the full text was unavailable. The outcome measures of interest were reported barriers to using PrEP. The 13 articles selected for data extraction were assessed for quality using the Joanna Briggs Institute (JBI) critical appraisal tool.
Figure 1: PRISMA flow diagram
Results
Sample Characteristics
The 13 studies encompassed a total of 3,272 participants who were within the age range of 13 to 24 years old (Table 1). While 66 percent of the participants were from the U.S. (n=2146), 34 percent of participants were international (n=1126), representing China, South Africa, and Kenya. Although some of the studies included youth of any gender and sexuality that fell within the aforementioned age bracket, a few of the articles narrowed their participant criteria to specific demographics. Four articles solely included young MSM, making them the majority of the participants in this systematic review at 66 percent (n=2161). Two articles solely included transgender participants, making them at least seven percent of this review (n=217). An additional article solely focused on sexual and gender minorities (SGM), which is an additional two percent of this review comprised of LGBT+ participants (n=59). Two articles from Kenya and South Africa narrowed their research to female participants, with the latter focusing solely on pregnant youth. One of the articles based in the Southern U.S. narrowed their scope to youth who used substances.
Table 1: Studies included in systematic review
| Study | Global Region | Participant Total (and Age Range) |
|---|---|---|
| Fisher 2017 [7] | U.S. | 150 (14-21 y/o; transgender) |
| Gailloud 2021 [8] | U.S. (NY) | 30 (15-17 y/o) |
| Garrett 2019 [9] | U.S. | 73 (14-24 y/o) |
| Hess 2019 [10] | U.S. (CA) | 14 (19-24 y/o; MSM) |
| Lambert 2021 [11] | U.S. (Southern) | 101 (13-17 y/o substance users) |
| Macapagal 2020 [12] | U.S. | 219 (15-17 y/o; MSM) |
| Macapagal 2021 [13] | U.S. | 59 (14-18 y/o; SGM) |
| Owens 2022 [14] | U.S. | 1433 (13-18 y/o; MSM) |
| Wilson 2016 [15] | U.S. (CA) | 67 (18-24 y/o; YTW) |
| Cui 2021 [16] | Tianjin China | 495 (15-24 y/o; MSM) |
| Shamu 2021 [17] | South Africa | 333 (18-24 y/o) |
| Sila 2020 [18] | Kenya | 111 (15-24 y/o; AGYW) |
| Vazquez 2019 [19] | South Africa | 187 (18-24 y/o; pregnant women) |
Key: MSM = men who have sex with men
SGM = sexual or gender minority
YTW = young transgender women
AGYW = adolescent girls and young women
Barriers Reported
Across the 13 prevalence studies, 38 distinct barriers to PrEP were identified (Figure 2). The top five barriers were lack of knowledge (n=637), fear of family finding out (n=575), side effects of PrEP (n=449), cost of PrEP (n=442), and perceived low HIV risk (n=418). It is important to note that some of the barriers on the frequency list are similar in nature to each other, such as fear of family finding out and confidentiality issues. However, by leaving the barriers as reported in the articles, the nuances in the responses are preserved.
Figure 2: Bar chart showing the frequency of each reported barrier
Awareness of PrEP
Since lack of knowledge was considered the most important barrier, the selected articles were further searched for data on PrEP awareness. From the 13 studies, nine of them include data on participant awareness (Table 2). From the total of 2,664 participants, only 54 percent (n=1435) reported awareness of PrEP.
Table 2: PrEP awareness of participants across studies
| Study | Global Region | Participant Total (and Age Range) | Awareness |
|---|---|---|---|
| Gailloud 2021 | U.S. (NY) | 30 (15-17 y/o) | 47% (n=14) |
| Garrett 2019 | U.S. | 73 (14-24 y/o) | 25% (n=18) |
| Lambert 2021 | U.S. (Southern) | 101 (13-17 y/o substance users) | 31% (n=31) |
| Macapagal 2020 | U.S. | 219 (15-17 y/o; MSM) | 55% (n=120) |
| Macapagal 2021 | U.S. | 59 (14-18 y/o; SGM) | 83% (n=49) |
| Owens 2022 | U.S. | 1433 (13-18 y/o; MSM) | 73% (n=1046) |
| Wilson 2016 | U.S. (CA) | 67 (18-24 y/o; YTW) | 42% (n=28) |
| Cui 2021 | Tianjin China | 495 (15-24 y/o) | 26% (n=129) |
| Vazquez 2019 | South Africa | 187 (18-24 y/o; pregnant women) | 0% (n=0) |
Risk of Bias
The 13 included manuscripts were all prevalence studies with a wide range of sample sizes. Five of the studies had less than 100 participants, whereas one study had over 1,000 participants. With this distribution, the majority of the participants were from the U.S. Risk of bias was assessed using the JBI critical appraisal tool for prevalence studies, which indicated a uniform low level of risk of bias across all papers. Eleven studies utilized anonymous questionnaires, which made the verification of information more difficult. Two studies utilized in-depth interviews alongside a codebook, which explains the limited sample size of 30 and 14 participants each, as it required more resources. One study used both surveys and focus groups, the latter causing a limitation in answer clarity and leaving room for social desirability bias. In terms of recruitment, five studies used advertisements, social media campaigns, and registries, with a few engaging racially and ethnically diverse LGBT+ minorities. Four studies directly approached potential participants who were part of local health programs and clinics. One study did snowball sampling at gay bars, gay bath houses, and social media, while another did multistage sampling via household surveys in low income communities. Overall, these different recruitment methods yielded distinct and comprehensive coverage across studies for this systematic review.
Discussion
These data indicate that the biggest barriers to PrEP for adolescents and young adults are related to lack of education and issues with confidentiality. While the material logistics of taking PrEP are also documented as barriers, including side effects, cost, adherence to daily dosage, and accessibility, there is a noticeably larger number of participants who reported lack of knowledge and fear of their family finding out as barriers. Given that so many youths engage in behaviors that make them vulnerable to HIV, it is important to be able to link them to preventative care like PrEP that can potentially reduce the number of new HIV diagnoses among 13- to 24-year-olds. Understanding that lack of knowledge is the most frequently reported barrier, future intervention efforts can focus on developing efficient awareness campaigns to broaden PrEP education among youth instead of solely addressing accessibility issues. According to the data in this review, approximately half of the participants were aware of PrEP at all. Without an initial awareness of PrEP, youth who would greatly benefit from it will not receive a prescription even if the medication is made to be cheaper and more accessible in clinics. In addition to expanding knowledge regarding PrEP itself, there should also be an effort to educate youth about HIV in general. This will help youth better understand perceived HIV risk, since knowledge of PrEP alone may not be useful if the individual does not realize that they are behaviorally vulnerable to HIV and can benefit from PrEP use. Education may also help combat other barriers like confidentiality because it can reduce the stigma that surrounds PrEP use and HIV.
There are limitations to this study, including the small sample sizes found in some of the included reports. Another limitation is that the participant pool reflects the U.S. more than other nations, so it may be more challenging to generalize the findings globally. Finally, with the exclusion of qualitative data, potentially insightful articles could not be used, limiting the amount of information available for barriers to PrEP adoption in young people. Future research should focus on continuing to gather quantitative data on adolescents and young adults given that this population is both high-incidence and understudied. Additional global prevalence studies may provide a better understanding of any differences in barriers between U.S. and international youth.
Declarations
Ethics approval and consent to participate: This systematic review did not involve the enrollment of human subjects, so ethical approval from the Institutional Review Board was not required.
Consent for publication: Informed consent is not applicable as human subjects were not enrolled.
Availability of data and materials: The data that support the findings of this study are available on Figshare and are accessible through the following URL: https://figshare.com/s/e4fee25f72022453db6e.
Competing interests: All authors declare that they have no competing interests.
Funding: Not applicable
Authors’ contributions: HU developed the research strategy, screened articles, extracted data, and wrote the manuscript. JC guided the development of the research and was a major editor of the manuscript. All authors read and approved the final manuscript.
Acknowledgements: We would like to thank the research staff at Donald and Barbara Zucker School of Medicine at Hofstra/Northwell who helped bring this project to fruition. We would also like to thank Hanwen Yang and Katherine Carroll for their work as additional reviewers.
HELEN UREÑA 
