Getting youth PrEPared: adolescent consent laws and implications for the availability of PrEP among youth in countries outside of the United States

Abstract Introduction Youth under the age of 25 are at high risk for HIV infection. While pre‐exposure prophylaxis (PrEP) has the potential to curb new infections within this population, it is unclear how country‐specific laws and policies that govern youth access to sexual and reproductive health (SRH) services impact access to PrEP. The purpose of this review was to analyse laws and policies concerning PrEP implementation and SRH services available to youth in countries with a high HIV incidence. To the best of our knowledge this is the first systematic assessment of country‐level policies that impact the availability of PrEP to adolescent populations. Methods We conducted a review of national policies published on or before 12 June 2018 that could impact adolescents’ access to PrEP, SRH services and ability to consent to medical intervention. Countries were included if: (1) there was a high incidence of HIV; (2) they had active PrEP trials or PrEP was available for distribution; (3) information regarding PrEP guidelines were publicly available. We also included a selected number of countries with lower adolescent HIV incidence. Internet and legal database searches were used to identify policies relevant to adolescent PrEP (e.g. age of consent to HIV testing). Results and Discussion Fifteen countries were selected for inclusion in this review. Countries varied considerably in their respective laws and policies governing adolescents’ access to PrEP, HIV testing and SRH services. Six countries had specific polices around the provision of PrEP to youth under the age of 18. Five countries required people to be 18 years or older to access HIV testing, and six countries had specific laws addressing adolescent consent for‐ and access to‐ contraceptives. Conclusions Adolescents’ access to PrEP without parental consent remains limited or uncertain in many countries where this biomedical intervention is needed. Observational and qualitative studies are needed to determine if and how adolescent consent laws are followed in relation to adolescent PrEP provisions. Intensified efforts to amend laws that limit adolescent access to PrEP and restrict the establishment of national guidelines supporting adolescent PrEP are also needed to address the epidemic in this group.

HIV-related mortality [5]. Because risk behaviours are often highest during adolescence, people who acquire HIV during adolescence have a greater potential of transmitting the virus to others than those who acquire HIV as adults [5,6].
Most adolescent HIV prevention interventions either focus on changing individual behaviours (e.g. condom use) or on addressing structural drivers (e.g. cash transfers conditioned on safer sex practices) to decrease the incidence of behaviourally acquired adolescent HIV [5,7,8]. However, individual-level interventions have had limited success in impacting HIV incidence, and the impact of structural-level interventions tends to be long-term and difficult to assess [5]. Further complicating adolescent HIV prevention efforts is that adolescents have limited access to HIV prevention services due to restrictive age of consent laws for sexual and reproductive health (SRH) services [5,9]. For example, in some counties, adolescents may be able to access HIV testing, but are prohibited from accessing HIV treatment without parental consent. Young people under the age of 25 years are also more likely than their child and adult peers to die from AIDS-related complications [10,11]. While there are a number of programs for children and adults aimed at curtailing the spread of HIV, efficacious interventions for adolescents are sorely needed [5].
Oral pre-exposure prophylaxis (PrEP) for HIV, a tenofovirbased antiretroviral drug, offers a promising solution as it prevents HIV acquisition when taken as prescribed [12]. Following the WHO recommendation that oral PrEP be offered to people at substantial risk of HIV infection as part of combination HIV prevention approaches, several countries expanded their PrEP implementation strategies to include adolescents [13,14]. The WHO recommendations are not-age specific, but rather exclusively focus on risk level and key populations [14]. These recommendations may be difficult for some countries to implement due to restrictive age of consent laws for medical treatment, HIV testing, and other SRH services. As a result, regulatory approvals for PrEP have moved forward at a rapid pace without sufficient consideration of their appropriateness for youth under the age of legal majority [15]. Although there is practical advice on how to implement PrEP at the country level, laws restricting adolescents' ability to independently consent to SRH services may deter adolescents from seeking PrEP and prevent providers from offering confidential SRH services to their adolescent patients [16][17][18]. While PrEP represents a promising biomedical intervention with great potential to help decrease worldwide HIV incidence among adolescents, its full effectiveness will only be realized if it is accessible [19]. To ensure that adolescents have access to PrEP, we must identify and modify policies that contribute to inequitable access to this potentially life-saving intervention.

| Current review
This review explores attributes of prevailing laws and policies that may impact access to adolescent PrEP in a sample of countries with higher adolescent HIV incidence and a select sample of countries with lower adolescent HIV incidence. Laws include age of consent to sexual intercourse, medical treatment, contraceptives and HIV testing. We also include a review of PrEP national guidelines and adolescent PrEP directives. For this purpose, three sources of information have been triangulated including a review of policies, a review of current country-specific guidelines, and an analysis of country surveillance and programme monitoring data.

| Inclusion criteria
We used the following inclusion criteria to select countries: (1) the country had a high incidence of HIV; (2) the country had either active PrEP trials or PrEP was available for distribution; and (3) information regarding PrEP guidelines were publicly available. Our search for policies related to adolescents' access to PrEP focused largely on countries with the highest burden of adolescent HIV and a select sample of Western countries where PrEP is available. Western countries were selected to explore how countries that have a comparatively low incidence of adolescent HIV, but have a well-resourced healthcare infrastructure, may address PrEP access among adolescents. We used the WHO and the United Nations' definition of adolescence, which is classified as the period in human growth and development that occurs after childhood and before adulthood from ages 10 to 19 years [20]. Considering that the availability of PrEP in many countries remains limited and the uptake among members of key populations has been slow, we used a broad definition of "policy" to enable us to include all national laws and documents that may govern adolescent PrEP provisions including laws on adolescents' consent to SRH services and independence in obtaining PrEP.

| Search strategy
We conducted an Internet search for national policies related to adolescent PrEP use, its availability, and adolescents' ability to consent to medical treatment in the identified countries using the following key words: ["Pre-exposure prophylaxis OR PrEP"] AND ["Policy" OR "Strategies" OR "Guidelines"] AND ["Adolescent" OR "Youth" OR "Child" OR "Teen"]. We specifically targeted reports by the WHO, the President's Emergency Plan for AIDS Relief, and PrEPwatch.org, a website that tracks the global availability of PrEP and ongoing medication trials [21]. We searched the official websites of the government or agencies responsible for regulating medical interventions (including prevention, testing and/or screening, and treatment) to identify policies related to PrEP and adolescents' rights to SRH services. We also searched for policies on the following legal and advocacy databases: GlobaLex, Foreign Law Guide and Global Advocacy for HIV Prevention. For each country, we focused on the most recent policies and guidelines available. Our policy search was conducted from inception until 12 June 2018.

| Data extraction
Countries were divided equally among the four coders (TT, KTB, TDR and JCS). We extracted information regarding age of majority, national guidelines and policies for adolescent PrEP, age of consent to SRH services (i.e. contraceptives and HIV testing), medical treatment and diagnostic laws, and PrEP availability. These data were documented in tabular form in Microsoft Excel for analyses. The research team met to discuss findings and exchange information, and adjusted search strategies as necessary.

| RESULTS AND DISCUSSION
We identified 15 countries for this review. The majority of the countries identified are in Eastern and Southern Africa, and South Asia. Table 1 summarizes the age of consent laws for sexual intercourse, medical treatment, SRH services and HIV testing.

| Age of consent to sexual intercourse
Age of consent to sexual intercourse is 18 years in seven countries (47%) with some countries' consent laws differing

| Age of consent to access contraceptives
Although the majority of countries in this review have national healthcare directives for access to contraceptive services, only six countries (40%) have specific laws addressing adolescent consent for-and access to-contraceptives. For example, Ukrainian law requires legal guardian or parental consent for anyone aged 14 to 18 years to access SRH services, while Indonesian law restricts access to contraceptives to anyone who is not married.  Table 2 provides an overview of PrEP national guidelines and adolescent PrEP directives within each country. Ten countries (66%) have national guidelines for PrEP to assist providers with patient care. Of these, six countries (60%) include specifications for people under the age of 18 years. For example, in the Ukraine, PrEP can be provided to people 14 years and older who are at risk for HIV. In Australia, guidelines do not list a specific age limit for PrEP; rather, guidelines offer considerations for side effects, health benefits and risk of HIV infection when providing PrEP to adolescents. In South Africa and the UK, national guidelines recommend that PrEP be offered to adolescents who are members of key populations (e.g. young MSM and young women).

| Discussion
Currently, indications for PrEP including initial and follow-up prescribing and testing recommendations are the same for adolescents and adults [22]. However, adolescents' access to PrEP is dependent upon several external factors including parental consent and involvement, confidentiality, and access to healthcare providers who are knowledgeable and trained to prescribe PrEP [23,24]. Even in countries where adolescents can independently consent to PrEP, providers may be reluctant to prescribe due to concerns about medication adherence, ability to understand the risks and benefits of PrEP, and risk compensation [25]. Additional concerns that potentially limit adolescents' access to PrEP include stigma, psychological burden and potential adverse health effects such as decreased bone mineral density [13,22,26].
Despite these concerns, PrEP represents a promising biomedical intervention for addressing the global adolescent HIV epidemic. With the onset of regulatory approval of adolescent PrEP in the United States, understanding the laws which govern access and adherence to PrEP is a necessary and critical next step [27]. To the best of our knowledge, this is the first review of laws and national guidelines on adolescent PrEP in countries with some of the highest rates of adolescent HIV. Our review included a cross-section of age of consent laws that affect adolescent PrEP delivery services including consent to HIV testing, SRH services and general medical treatment. Study findings indicate a need for: (1) the amendment of age of consent laws that also require parental consent to ensure that safeguards (e.g. providers protecting adolescents' confidentiality) are delineated [25], (2) the amendment of laws to support prophylaxis, not as medical treatment for HIV, but as prevention of HIV, and (3) consistency in age of consent laws that differentiate between gender and/or sexual orientation and ability to consent.
Most countries in this review have written national guidelines for implementing PrEP. Many of these guidelines include directives for key populations such as at-risk adolescents. However, age of consent laws requiring parental consent for HIV testing and medical treatment undermine these directives. Adolescents may be unwilling to disclose their sexual activity to their parents because of fear, sexual stigma and discomfort [28]. Requiring parental consent may also dissuade adolescents from seeking basic SRH services and raises concerns about physician-patient confidentiality [21,29]. In fact, recent findings from ATN 113, a clinical trial to explore the safety, acceptability and feasibility of PrEP among adolescents aged 15-17 years, showed that requirements for parental/ guardian consents may inhibit access and uptake of PrEP due to unwanted disclosure of sexual activity and sexual orientation [30]. Alternatives to parental consent, such as waivers to consent and provider reporting mandates, especially for adolescents who may be engaging in consensual but underage sexual activity, are needed to ensure adolescent PrEP uptake.
Across laws and national guidelines, classification of PrEP as biomedical HIV prevention rather than HIV treatment is inconsistent. This inconsistency has implications for provider prescribing behaviours due to ethical and legal differences between HIV prevention and treatment options, challenges identifying appropriate PrEP-eligible patients and cost barriers for youth under 18 years [15,31,32]. In the United States, for example, all states allow some adolescents to consent to receive testing or treatment for sexual transmitted infections (STI) [21]; however, states vary with regard to whether adolescents are able to consent to HIV-related services, as some states have yet to classify HIV as an STI. Moreover, only eight states allow adolescents to consent to preventive or prophylactic services [21]. In countries where adolescent consent is determined by provider discretion, with the exception of the United Kingdom (England) and France, there is no evidence of legal guidance for providers to systematically assess an adolescent's ability to consent or determine parental autonomy [33]. Although there has been an increase in professional guidance for providers to assess an adolescent's ability to consent to clinical care and PrEP, it remains unclear if this guidance has led to an increase in adolescent PrEP provisions [26,34,35]. Nevertheless, new language should be added to current minor consent laws with consideration of the multilevel vulnerabilities (e.g. disclosure of sexual activity to parents or guardians; or report of underage consensual sexual activity as a criminal offense) that adolescents face in accessing SRH services. Additional global guidance is needed to standardize the classification of PrEP as HIV prevention, and to advocate for the amendment of laws governing age of consent to SRH services that do not reflect the healthcare needs of adolescents who are vulnerable to HIV.
Our review identified age of consent laws that differ by an adolescent's age, gender and sexual orientation and laws that criminalize same-sex sexual activity. Discordant age of consent laws that criminalize consensual sexual activity among adolescents drives HIV risks and are barriers to accessing SRH services, including PrEP [28,36]. Reporting mandates for providers and other sexual health practitioners hinders their ability to provide confidential SRH services to adolescents, creates mistrust and fear in adolescents towards the medical system, and may further impede adolescents from seeking care when they are in criminalized consensual relationships with other adolescents [16,37,38]. For example, in Mozambique, age of consent for HIV testing is lower than age of consent to sexual activity. Meaning, a younger adolescent may consent to HIV testing, but in doing so will disclose their sexual activity to a provider who will need to report this activity to law enforcement. Furthermore, decriminalizing same-sex sexual activity is a recognized important step to addressing sexual stigma and other challenges to accessing adolescent PrEP [28]. For women, younger age of consent laws for sexual intercourse perpetuate age-disparate or intergenerational relationships which increase HIV risk [39,40]. Given that much of the adolescent HIV incidence exists within young MSM and young women, differential laws based on sexual orientation and gender limit access to basic HIV prevention services and care. Global efforts to increase support for adolescents seeking PrEP must also be accompanied by efforts to decriminalize same-sex sexual activity, challenge and seek to change social norms that support age discordant relationships, and increase community-level interventions that address the root causes of these relationships and norms.

| CONCLUSIONS
This study provides a review of age of consent laws and PrEP initiatives based on a comprehensive internet and legal database search; however, we did not review case law or grey literature that were not available in English. This review did not examine sociocultural drivers of policy such as religion or HIV stigma, nor did we examine the structure of various healthcare delivery systems. Analysis of these factors is beyond the scope of this review and should be considered for future research as they may influence laws and guidelines on PrEP. Lastly, this review reports age of consent laws as written. We are not able to determine how these laws are implemented, how closely providers follow these laws, or if they truly impact access to SRH services including PrEP provisions for adolescents. These limitations lead to some uncertainty about adolescent PrEP implementation in light of current age of consent laws. The degree to which youth have access to PrEP remains unclear in many countries where this biomedical intervention is needed. Given that adolescent HIV is acquired chiefly through sexual transmission, scaling up PrEP among adolescent populations could significantly curb new infections within this population. This review identifies a number of ambiguities in current laws that may influence the provision of PrEP to youth, and a need for further consideration of adolescent-specific PrEP issues. Adolescents at substantial risk of HIV are excluded from services for multiple reasons including their age, lack of information on SRH services, discriminatory attitudes of service providers, gender inequality and sexual orientation criminalization. Intensified efforts to modify national and sub-national laws related to adolescent informed consent are needed to ensure that policy constraints associated with adolescent PrEP are minimized. It is imperative that policy makers, policy implementers, providers and advocates meaningfully engage youth in devising strategies to address the structural (e.g. policy and national guidelines) challenges of implementing adolescent PrEP programmes. More support for providers is needed in order to facilitate trustful and empathetic relationships with their adolescent patients [34]. These relationships are particularly important in countries where there is a risk of criminalization due to sexual orientation or where providers are tasked with assessing an adolescent's decision-making capacity for care [34]. Adolescent PrEP providers should ensure confidentiality and continually seek feedback from their adolescent patients on how services and provider-patient interactions might be improved. PrEP services for youth should endeavour to be youth-friendly, supportive and include services such as tailored adherence support and flexible visit schedules. Future research is needed to better determine whether: adolescent age of consent laws for sexual intercourse, SRH services, and medical treatment truly influence clinical practice; these laws are associated with the establishment and implementation of PrEP national guidelines; and if these laws influence the provision of PrEP to PrEP-eligible adolescents. The authors have no conflicts to disclose.

A U T H O R S ' C O N T R I B U T I O N S
TT conceived and designed the study, conducted data collection and analysis, wrote sections of the paper, and reviewed and approved the final draft of the manuscript. KTB conducted data collection, drafted the introduction and implication sections, and reviewed and approved the final draft of the manuscript. TR conducted data collection, drafted the methods section, edited the manuscript and reviewed and approved the final draft of the manuscript. JCS conducted data collection, edited the manuscript, and reviewed and approved the final draft of the manuscript.

A C K N O W L E D G E M E N T S
We thank Lucie Olejnikova, JD, MLS, Head of Foreign and International Law at Yale Law School library, for her assistance with our policy search, identifying sources, and refining our search strategy. We also thank Trace Kershaw, PhD, Yale School of Public Health, for his review of our manuscript. Dr. Taggart was supported by funding from the Center for Interdisciplinary Research on AIDS award number P30MH062294 and the UCLA HIV/AIDS, Substance Abuse, and Trauma Training Program (HA-STTP) award number R25DA035692. Dr. Bond was supported by funding from the REIDS Scholar Program Yale School of Public Health award number R25MH087217. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.