SUPPLEMENT ARTICLE
Evidence-Based Programming for Adolescent HIV Prevention and Care: Operational Research to Inform Best Practices Bill G. Kapogiannis, MD,* Ken E. Legins, MPH,† Upjeet Chandan, PhD,† and Sonia Lee, PhD*
Background: Globally, a staggering number of adolescents, approximately 2.1 million, were estimated to be living with HIV in 2012. Unique developmental, psychosocial, and environmental considerations make them particularly vulnerable to HIV acquisition and argue for a comprehensive response to address this burgeoning problem.
Methods: This article explores the current state of the science of HIV prevention, treatment, and care for adolescents and identifies opportunities to address knowledge gaps and improve health outcomes for this age group.
Results: Over the past decade, several important milestones have been achieved in HIV prevention and care among adults, and despite evidence that adherence to care and medications among affected adolescents is significantly compromised, critical research among adolescents and young adults substantially lags behind. Operational research, in particular, is crucial to understanding how to use effective services and interventions for HIV prevention and care safely and effectively for adolescents who are in dire need. Conclusions: Operational research among adolescent populations affected by HIV is critically needed to close the knowledge and investment gaps, and scale-up efforts for HIV prevention, treatment, care, and support for this vulnerable age group. Key Words: operational research, adolescents, HIV (J Acquir Immune Defic Syndr 2014;66:S228–S235)
CRITICAL NEED FOR OPERATIONAL RESEARCH FOR ADOLESCENTS AFFECTED BY HIV Approximately 2.1 million adolescents, aged 10–19 years, were estimated to be living with HIV in 2012.1 The World Health Organization recently provided a staggering estimate that 5 million young people aged 15–24 years are From the *Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; and †UNICEF, New York, NY. The authors have no funding or conflicts of interest to disclose. The comments and views of the authors do not necessarily represent the views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development or those of the Department of Health and Human Services. Correspondence to: Bill G. Kapogiannis, MD, Maternal and Pediatric Infectious Disease Branch, NICHD/NIH, 6100 Executive Boulevard, Room 4B11J, Bethesda, MD 20892-7510 (e-mail: [email protected]). Copyright © 2014 by Lippincott Williams & Wilkins
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currently living with HIV/AIDS on a global basis.2 It is also estimated that 39% of the approximately 2 million new infections that occurred in people aged 15 years or older in the world during 2012 are occurring among young people, with most of them unaware that they are infected. Among 15- to 19-year-old youth in heavily impacted eastern and southern Africa, only 29% of girls and 20% of boys had ever been tested for HIV and received their results.1 Even more concerning is that AIDS-related deaths among 10–19 year olds more than doubled in sub-Saharan Africa during 2005–2012; in contrast, there were overall decreases for such deaths among people of all ages.1 To address the HIV epidemic in adolescents and adolescent health overall, a more focused, efficient, and effective global response to the needs of adolescents is an increasing priority within the global health agenda. A recent review of global prevention science for adolescents, prompted by the observation that many health indicators in later adulthood are rooted in attitudes, behaviors, and lifestyles initiated in early childhood and adolescence, found a substantial number of efficacious interventions aimed at policies and programs addressing multiple levels of risk (eg, individual, peer, family, school, and structural) and targeting different developmental stages of childhood and adolescence.3 However, applying these interventions to adolescents has only recently begun in low-income and middle-income countries. There is a critical need for a more comprehensive response to adolescent health priorities that takes into consideration the health needs and evolving capacities unique to the different developmental stages of adolescents aged 10–19 years. Although many efficacious interventions were identified in the article by Catalano et al,3 the review did not find any controlled trials that assessed long-term outcomes or those that evaluated comparative efficacy of prevention interventions. Furthermore, there seemed to be bias toward support of prevention studies founded on innovation and efficacy principles rather than on replication, generalizability, and effectiveness in realworld settings. More specifically on HIV, a systematic review published in this issue by Napierala Mavegdzenge et al.4 also highlights the lack of practical knowledge on how to reach adolescents, effectively deliver interventions to this age group, and achieve optimal impact on health outcomes. Operational research (OR) efforts are crucially needed to identify and characterize the most effective services and practices suited for implementation within a comprehensive global adolescent HIV prevention and care agenda.
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Definitions of OR In global health, OR has an extremely broad interpretation.5 Therefore, many definitions of OR have been proposed. The World Health Organization defines OR as follows: “The use of systematic research techniques for program decision-making to achieve a specific outcome. OR provides policy-makers and managers with evidence that they can use to improve program operations. It is distinguished from other kinds of research by the following characteristics: 1) It addresses specific problems within specific programs, not general health issues; 2) It addresses those problems that are under control of managers, such as program systems, training, pricing and provision of information; 3) It utilizes systematic data collection procedures, both qualitative and quantitative, to accumulate evidence supporting decision-making; 4) It requires collaboration between managers and researchers in identification of the research problem, development of the study design, implementation of the study and analysis and interpretation of results; and 5) It succeeds only if the study results are used to make program decisions; publications alone is not a valid indicator of success.”5 More succinctly, the United States Institute of Medicine has defined OR as “the use of advanced analytical techniques to achieve better outcomes, definite optimal processes of service delivery, and develop more cost effective systems.”6 Broadly, the goal of OR for adolescent HIV infection is to coordinate and collaborate with HIV prevention, treatment, and care programs and policies by adopting contextappropriate interventions shown to be effective through research and appropriately and widely implementing them in community- and clinic-based settings to improve adolescent HIV outcomes.7 Ultimately, OR on HIV endeavors to accelerate translation of knowledge by linking scientific inquiry to specific program implementation to more rapidly and effectively reduce HIV infections, illness, and AIDSrelated deaths.
ADOLESCENTS AND CURRENT STATE OF THE SCIENCE Adolescence is a critical point on the developmental trajectory.8 Social and psychological pressures encourage adolescents to experiment with drugs and other illicit substances, sexual orientation and preferences, and rebellion against parental expectations. Economic obligations often increase in importance during this period, and in many resource-limited settings (RLS), financial responsibilities are placed upon adolescents because they are expected to take on more adult roles and responsibilities and become contributors within their families and communities. In high HIV-prevalence settings, some adolescents are left orphaned to head households and care for younger siblings, which can have negative impacts on physical and psychological Ó 2014 Lippincott Williams & Wilkins
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well-being, whereas others (orphaned and nonorphaned) take on the role of caregiver for ailing parents and older family members in need of care,9 especially young women and girls.10 Social mores regarding marriage, gender roles, and family also become more prominent during adolescence and begin to shape how adolescents view their reproductive health and their sexual and romantic relationships.11 Adolescence is commonly thought to be the pinnacle of rebellious behavior because of additional pressures placed upon them during this developmental stage, such as peer influences, identity, and self-esteem formation, as well as the incomplete physiological and biological development of impulse control in the frontal cortex.12 In a parallel manner, mental health disorders, such as depression, may manifest themselves during late adolescence,13 also influencing impulsivity, executive functioning, and poor decision making, manifestations that some argue represent more the lack of experiential perspective with novel adult behaviors than are due solely to structural deficits in frontal lobe control.14 The combination of many of these changes and pressures, resulting in risky behaviors,15 place adolescents at an increased risk for contracting HIV by engaging in behaviors such as unprotected sex or through the sharing of nonsterile injecting drug paraphernalia. Indeed, in 2012, young people aged 15–24 years accounted for 39% of new HIV infections in people aged 15 years and older.2 Furthermore, unsafe sex practices because of coercion, transactional sex for survival, intergenerational and age disparate sex, and/or while under the influence of alcohol or drugs are contributing risk factors for contracting HIV in adolescents.11,16,17 There is also a large group of children and adolescents worldwide who contracted HIV perinatally that are tackling additional issues and stressors, such as disclosure, adherence to long-term medication regimens, emergent sexual and reproductive health care needs, and the transition from pediatric to adult, independent medical care.18 As a result of these issues, the building of capacity and the enabling of factors to enhance the dissemination and implementation of interventions to address the HIV epidemic in adolescence, particularly in RLS of highest need, has moved to the forefront. The need to tackle these challenges by examining protective factors, as well as biological, social, and psychological determinants of risk and their impact on HIV-specific outcomes, will become important to the agenda to prioritize OR. In addition to OR efforts in industrialized countries,19–22 efforts to develop OR in RLS should be prioritized because of (1) the greatest burden of HIV borne by such settings, particularly among young people; (2) the established efficacy of HIV prevention23–32 and treatment33,34 interventions, mostly among adults (Fig. 1),23–34 which are covered more in depth elsewhere in this special supplement of the Journal; (3) the poor rates of uptake and challenges to successful implementation of and adherence to many of these interventions among the young people included in these studies27,35–38; and thus, (4) the greatest need for OR efforts related to HIV in younger populations, especially adolescents. Moreover, among the research efforts specifically targeting adolescents, few have measured hard biomedical outcomes, such as HIV incidence, and among those that have only 1, a structural intervention seems to have a significant impact.39 www.jaids.com |
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FIGURE 1. The incremental improvements in efficacy (in percent) (95% confidence interval) at reducing new HIV infections of an array of studies involving biomedical HIV prevention interventions.
Reasons for this scarcity of research include the many challenges faced when attempting to embed an effective research intervention into an already established clinical or programmatic setting. Examples of challenges that may thwart the implementation and programmatic buy-in of OR in RLS may be because of the lack of understanding of research methodology, including potential ethical considerations in working with adolescent populations who have not yet attained their jurisdictionally defined age of majority, ownership of research, appropriate research infrastructure, financial support, training, and oversight.40 Furthermore, research and programmatic efforts to ensure that interventions are not only implemented but also made accessible to vulnerable adolescent populations and sustained throughout the relevant communities need to be prioritized.
PRIORITY SCIENTIFIC OPPORTUNITIES FOR OR With this greater understanding of the HIV epidemic in adolescents and young people, and the many potential factors that drive the disproportionately high rates of infection in this group, an OR framework and agenda should be structured around several priority areas to specifically address the pressing knowledge gaps and opportunities for prevention in adolescents. As it is beyond
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the scope of this review to undertake a comprehensive discussion of all meritorious (eg, biomedical, behavioral, community, and structural level) interventions, which are more comprehensively addressed elsewhere in this supplement by Napierala Mavegdzenge et al.,4 selected areas of priority within the landscape of HIV prevention, treatment, and support for adolescents are highlighted below.
Biomedical Interventions Research in Young People Although there are promising data from numerous biomedical HIV prevention and care interventions among adults, those that included younger populations have identified an Achilles tendon, significant associations between nonadherence and efficacy,27,35,38 despite what participants may have reported in the context of a clinical trial.38 This phenomenon raises important implementation questions about rolling out and scaling up such interventions in the real world, where many providers may be faced with the challenging scenario of providing these agents “off-label” (not in accordance with regulatory agency approval) to a population for which there is little safety information and essentially no data on their effectiveness (the extent to which planned HIV prevention outcomes are achieved as a result Ó 2014 Lippincott Williams & Wilkins
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of using the biomedical HIV prevention agent under ordinary and uncontrolled circumstances). Understanding the effectiveness among adolescents is particularly germane to interventions that require high fidelity and adherence for success, and in whose absence, the risk for the development of untoward effects to the individual and society may be substantial. Such caution is important in the context of considering antiretroviral therapy as a potential widespread prevention intervention among youth; the results from a controlled clinical experiment in adult couples, although highly efficacious (Fig. 1), may be subject to significant biases that threaten their external validity, not only among adult individuals who are not in monogamous relationships but also especially among youth who not only may be less likely to have a steady partner but also be contending with already discussed developmental milestones and issues inherent to those.41 Despite optimism that recent large-scale community level OR in this topic area will shed light on many of the operational challenges to this approach, this work is only planned for adults older than 18 years,42 leaving a tremendous gap for adolescents who are at the high risk of HIV infection and those living with HIV.
HIV Testing and Counseling for Adolescents At the beginning of the continuum of HIV care for adolescents, one of the most feasible intervention areas lies within HIV testing and counseling (HTC) efforts/programs. As mentioned previously, most newly HIV-infected adolescents are completely unaware of their diagnosis—a situation not unique to behaviorally HIV-infected adolescents as many with perinatal HIV infection may not have been disclosed to by their caretakers or have also never been tested.43 In some of the most heavily impacted parts of the world, the proportions of young people aged 15–19 years who undergo testing and receive their result is extremely low, with estimates as low as 29% and 20% among adolescent girls and boys, respectively, in eastern and southern Africa, and even as low as 1% in adolescent girls and boys in south Asia.1 Increasing OR efforts to address structural barriers to HTC for adolescents is important for meaningful impact on increasing HIV testing and ultimately determining the impact on reducing new HIV infections.30 For example, in the United States, the Centers for Disease Control and Prevention has revised recommendations regarding HIV testing of adolescents, emphasizing testing as part of routine medical care, and not just for those in acute-care settings, at high risk for HIV.44 These recent revisions differ from previous recommendations by not requiring specific informed consent for HIV testing and making pretesting counseling unnecessary, both potential barriers to those adolescents seeking testing. As informed consent and counseling have been previously mandated by state law for HIV testing, these Centers for Disease Control and Prevention recommendations have been adopted by most states within the United States, thereby allowing more adolescents to become tested and to learn their HIV status without concerns regarding parental involvement. The United Nations Development Program Commission on HIV and Law outlined a number of structural barriers Ó 2014 Lippincott Williams & Wilkins
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that limit adolescent’s access to HIV services in low- and middle-income countries, including age of consent for HIV testing and medical procedures, and punitive laws aimed at young men who have sex with men, adolescents who inject drugs, and girls in some settings.45 OR offers the opportunity to investigate health and protection service delivery platforms that tailor (adolescent-friendly) interventions for optimized outcomes. More recently, WHO, in collaboration with UNICEF (United Nations Children’s Fund) and other global organizations, developed guidelines on “prioritizing, planning, and providing HIV testing, counseling, treatment, and care services for adolescents”.46 The guidelines recommend that all settings/countries, regardless of epidemic typology, ensure routine testing and counseling for adolescents, with appropriate linkage to prevention, treatment, and care. As the level and quality of evidence is variable and incomplete regarding the impact of HTC services on the HIV epidemic, OR can have an important role in determining how to best implement these recommendations to maximize their effectiveness in reducing HIV acquisition among adolescents. Addressing barriers to HIV testing among adolescents is only a first step and other approaches for scaling up testing need to be continued in resource-limited counties.47 It is notable that recommendations geared toward provision of HTC services through health care settings assume not only that adolescents will access appropriate medical care on a routine basis but also that health care programs will include adolescent-friendly HTC services. These assumptions, however, represent additional priority areas in need of well-designed and supported interventions. For example, in a study at an outpatient clinic in South Africa, researchers investigated whether adults and youth alike would participate in HIV testing efforts. Despite high HIV prevalence among youth in this area, the actual uptake of testing is low.48 Although this study took place in an adult outpatient clinic, not one specifically geared toward serving youth, additional studies that investigated models for HTC service delivery involving adolescents also indicate low uptake.49,50 In RLS especially, where access to and emphasis on routine and regular medical care are often lacking, it is important that OR for implementing targeted HTC services for adolescents, specifically addressing adolescent needs and challenges, be prioritized and developed. OR efforts to prioritize HTC services for adolescents need to be developed in collaboration with not only researchers and local health providers within communityand clinic-based settings but also those key policy makers and stakeholders in HIV/AIDS programs who can influence HIV/ AIDS, health and adolescent policies and funding of these efforts, and offer crucial operational insights to guide OR questions that will optimally inform best practices. Community mobilization efforts are an essential pathway toward encouraging those with decision-making capabilities to invest financial resources in HTC services51 and improve HIV outcomes.29 Community investment in the health and well-being of its adolescents also maintains the on-going quality and adherence to such treatment services.52 But before financial investment can occur, community buy-in www.jaids.com |
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to encourage outreach and engagement of adolescents and their families to participate in OR to optimize HTC programs is a key first step. Overall, improved understanding of the mechanisms behind the social stigma of HIV and community support to disable it will further facilitate the adoption of HTC programs on a routine basis. Maticka-Tyndale and Crouillard-Coyle53 published a systematic review and synthesis of studies evaluating community interventions and emphasized how essential it is for governments and similar bodies to invest in high-quality process and outcome evaluations to identify and promote effective community interventions for young populations.
Linkage, Engagement, and Retention in Care Among Young People Once adolescents are tested and identified as HIV positive, appropriate efforts to effectively and expediently link them to medical care remains a pervasive challenge, particularly for younger populations. Adherence to care among several thousand youth aged 15–24 years in RLS showed substantial attrition as early as 1 year after enrolling in care.36 The transition from a clinic with adolescent-geared services to an adult-based clinic additionally hampers efforts to provide adequate medical care.54 And further down the continuum of care,55 challenges with engaging adolescents as active participants and advocates of their own care and subsequently retaining them in medical care exacerbate the difficulty in properly treating newly diagnosed, acute HIV infection. A recent article by Hall et al56 estimates that of all persons living with HIV in 2009 in the United States, 82% were aware of their HIV infection, 66% were linked to care (defined as having at least 1 CD4 count or HIV viral load measured within 3 months of diagnosis), 37% were retained in care at 6 months or longer, 33% were prescribed antiretroviral therapy, and 25% had a suppressed viral load. The percentages for all of these categories were even lower in younger age groups, which is especially concerning when you consider that a substantial majority of youth, whether abroad or in the United States, have either never been tested for HIV1 or are unaware they are already infected.57 Such work may be even more critical in low- and middle-income country contexts where adherence rates among adolescents in whom chronic health conditions have been documented at lower levels than among adolescents in the West.58 In low-to middle-income countries, OR priorities need to include efforts to better understand where adolescents fall along the continuum of care by conducting programmatic evaluations of HTC services and ART programs to learn why adolescents fall off at each point of the HIV care continuum and ultimately inform best practices and policies for this vulnerable population. Indeed, a preliminary question that needs to be addressed is how the continuum of care established for adults (Fig. 2A)56 may be used to describe and characterize critical points along the spectrum of care for HIV-infected adolescents and to inform relevant OR efforts in RLS. Efforts now underway to characterize this for American youth have shown that there are substantial differences in outcomes across all domains of the continuum
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(Fig. 2B).19,20,22,36 There is a critical need to understand key implementation considerations for adolescents globally, particularly in RLS for which data at important points along the continuum are absent (Fig. 2B). Better understanding of implementation considerations, like the role youth-friendly clinics, ethical-legal-regulatory challenges, emergent mental health comorbidities, psychosocial instability, and other adolescent-specific issues likely play in favorable adolescent health outcomes, can only be helpful to programmers because they consider how to best refine and implement services to improve focus on adolescents and their outcomes. To address the above knowledge gaps in the adolescent HIV care continuum in RLS, OR efforts evaluating program data are needed to understand not only whether adolescents are accessing HIV testing services but also when and how often adolescents are getting tested. In many RLS, particularly in remote, rural, and periurban areas, there are not enough accessible clinics, let alone adolescent-friendly clinics. Furthermore, if routine testing services are not made available to adolescents, how do those at high risk for HIV become identified?59 Therefore, OR priorities to invest in and understand home-based and community-based (eg, mobile) HTC programs should be encouraged. A pilot study of home-based counseling and testing in South Africa (with adults) showed high rates of both achieving testing uptake and approximately 90% rates of linking newly identified HIV-infected persons and known HIV-infected persons not previously engaged in care into care.60 Similarly, mobile community-based voluntary counseling and testing (as compared with standard clinicbased testing) has been shown to increase testing rates and HIV case detection in 3 study communities in Tanzania, Zimbabwe, and Thailand,61 with indications that in South Africa, mobile testing was a feasible way to engage youth, men, and rural communities in HTC.62 Frequent repeat testing and early diagnosis of HIV through OR efforts need to be prioritized. Additionally, OR is needed to investigate what linkage to care efforts encompasses in resource-limited countries such that accurate estimates of the proportion of adolescents who are aware of their HIV infection that are successfully brought to medical care can be obtained. In the United States, for example, a previous effort to further understand the HIV linkage to care process in adolescents might serve as a starting framework for operational efforts in RLS63: “Three main components of HIV-related linkage to care were identified: the infrastructure and organization of linkage to care, the process of linkage to care, and the content of linkage to care activities.” Under the infrastructure and organization of linkage to care component falls an investigation of models for linkage to care, relationships among networks of testing sites and HIV clinical care sites, community membership, and adolescent friendliness. Under the process of linkage to care components falls readiness for HIV care, crisis management, and patient education and orientation. Third, under the linkage to care content component falls case management, barriers to care, and confidentiality. Throughout all 3 of these components are many rich areas of either programmatic review and/or targeted investigation that lend themselves easily to OR aims. Ó 2014 Lippincott Williams & Wilkins
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FIGURE 2. Proportions of HIV-infected adults succeeding at various steps along the HIV continuum of care in the United States and associated implementation challenges (A) and of HIV-infected adolescents and young adults in the US (green) and in RLS (red) and associated youth-specific implementation challenges (B). ART, antiretroviral therapy.
Further down the care continuum, additional priority areas for OR efforts include what do engagement in care proportions (ie, the percentages of HIV-infected adolescents who initiate clinical care) look like in resource-limited countries and how we can improve these, and of course, similar investigations of retention in care. A systematic review of the literature64 confirmed the limited number of studies investigating the rates of successes and failures of either HIV engagement or retention in care programs for all populations in Africa. Overall, with a greater understanding of all aspects along the continuum of care for adolescents and HIV, including linkage to and engagement and retention in Ó 2014 Lippincott Williams & Wilkins
care of HIV-positive adolescents to medical services, appropriate and effective interventions to address and improve these areas in RLS can be prioritized and implemented.
TRANSLATING SCIENCE INTO EVIDENCE-BASED PRACTICE To effectively reduce the global HIV incidence rate in adolescents, the inclusion of adolescents and young adults in biomedical HIV prevention and care research remains a high priority. Thus, the translation of such findings and interventions from theory and formative research into practice within www.jaids.com |
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high-needs communities remains an OR priority as well. However, the myriad of considerations involving such youth participation and the need for broad community and stakeholder engagement65,66 hinder the pace with which this important work should be accomplished. Nonetheless, researchers in areas highly impacted by HIV in youth continue in their efforts to include adolescents in this important work,67 despite significant ethical, legal, and regulatory challenges in working with these populations.68 Without such efforts, programmers and providers alike will continue to face the unanswered questions of how can they deploy interventions proven efficacious in adults so as to maximize the impact while minimizing costs and potential toxicities to the youth they care for. It is in this context that demonstration projects and bridging safety studies have recently gained popularity in the field.69–71 Bridging studies are a particularly important way to increase youth’s access to key biomedical HIVprevention technologies shown to be effective among adults and to obtain critically needed safety and effectiveness data for this vulnerable population. These safety and preliminary efficacy trials “bridge” to larger scale efficacy trial data among adults based on the notion that biologic efficacy among selected agents should not differ between youth and adults and thus on seeking regulatory licensure with the conduct of small phase I/II clinical trials to demonstrate that a product has a favorable safety profile and preliminary efficacy among youth. An additional advantage to demonstration projects is the crucial feasibility data they can yield about how participants use interventions in the real world, which can be important for refining program design and critically needed areas of investment in infrastructure for scaling up capacity and access to efficacious prevention and care services for vulnerable populations.
CONCLUSIONS Although the HIV epidemic among adolescents and young people affects every country across the globe, one of the greatest priorities for interventions lies within OR in resource-limited countries. Scientists, physicians, policy makers, community stakeholders, advocates, programmatic officials, and adolescents need to work together to close the knowledge and investment gaps and scale-up OR efforts for HIV prevention, treatment, care, and support. Healthy, educated, protected, and empowered adolescents are not only our future but also the means to an AIDS-free generation.
ACKNOWLEDGMENTS The authors thank Dr. Susan Kasedde from UNICEF for her assistance with and critical review of this manuscript. REFERENCES 1. UNICEF. Towards an AIDS-free generation: children and AIDS, sixth stocktaking report. Available at: http://www.childrenandaids.org/. Accessed December 31, 2013. 2. UNAIDS. GLOBAL HIV/AIDS RESPONSE: epidemic update and health sector progress towards universal access. Available at: http://www.unaids.org/ en/media/unaids/contentassets/documents/unaidspublication/2011/20111130_ ua_report_en.pdf and http://www.unaids.org/en/media/unaids/contentassets/
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documents/epidemiology/2013/gr2013/201309_epi_core_en.pdf. Accessed November 17, 2013. Catalano RF, Fagan AA, Gavin LE, et al. Worldwide application of prevention science in adolescent health. Lancet. 2012;379:1653–1664. Napierala Mavedzenge S, Luecke E, Ross DA. Effective approaches for programming to reduce adolescent vulnerability to HIV infection, HIV risk, and HIV-related morbidity and mortality: A systematic review of systematic reviews. J Acquir Immune Defic. 2014;66(suppl 2):S154–S169. UNAIDS. Framework for operations and implementation research in health and disease control programs. Available at: http://www.who.int/ hiv/pub/operational/or_framework.pdf. Accessed November 17, 2013. IOM. Scaling up treatment for the global AIDS pandemic: challenges and opportunities. Available at: http://www.nap.edu/openbook.php? isbn=0309092647. Accessed March 21, 2014. Heidari S, Harries AD, Zachariah R. Facing up to programmatic challenges created by the HIV/AIDS epidemic in sub-Saharan Africa. J Int AIDS Soc. 2011;14(suppl 1):S1. Arnett JJ. Emerging adulthood. A theory of development from the late teens through the twenties. Am Psychol. 2000;55:469–480. Yanagisawa S, Poudel KC, Jimba M. Sibling caregiving among children orphaned by AIDS: synthesis of recent studies for policy implications. Health Policy. 2010;98:121–130. UNAIDS. Caregiving in the Context of HIV/AIDS. Expert Group Meeting on “Equal Sharing of Responsibilities Between Women and Men, Including Care-giving in the Context of HIV/AIDS.” Geneva, Switzerland: United Nations; 2008. Available at: http://www.un.org/womenwatch/daw/egm/ equalsharing/Final%20report%20EGM%2010%20Feb.pdf. Accessed March 23, 2014. Dibua U. Socio-economic and socio-cultural predisposing risk factors to HIV/AIDS: a case study of some locations in eastern Nigeria. Int J Trop Med. 2010;6:2. Anand P, Springer SA, Copenhaver MM, et al. Neurocognitive impairment and HIV risk factors: a reciprocal relationship. AIDS Behav. 2010; 14:1213–1226. Costello EJ, Egger H, Angold A. 10-year research update review: the epidemiology of child and adolescent psychiatric disorders: I. Methods and public health burden. J Am Acad Child Adolesc Psychiatry. 2005;44: 972–986. Romer D. Adolescent risk taking, impulsivity, and brain development: implications for prevention. Dev Psychobiol. 2010;52:263–276. Katz IT, Ybarra ML, Wyatt MA, et al. Socio-cultural and economic antecedents of adolescent sexual decision-making and HIV-risk in rural Uganda. AIDS Care. 2013;25:258–264. Leclerc-Madlala S. Age-disparate and intergenerational sex in southern Africa: the dynamics of hypervulnerability. AIDS. 2008;22(suppl 4):S17–S25. Robbins CL, Zapata L, Kissin DM, et al. Multicity HIV seroprevalence in street youth, Ukraine. Int J STD AIDS. 2010;21:489–496. Kenny J, Mulenga V, Hoskins S, et al. The needs for HIV treatment and care of children, adolescents, pregnant women and older people in lowincome and middle-income countries. AIDS. 2012;26(suppl 2):S105–S116. Philbin M, Tanner A, DuVal A, et al. Factors affecting linkage to care and engagement in care for newly diagnosed HIV-positive adolescents within fifteen adolescent medicine clinics in the United States. AIDS Behav. 2013. In Press. Philbin MM, Tanner AE, Duval A, et al. Linking HIV-positive adolescents to care in 15 different clinics across the United States: creating solutions to address structural barriers for linkage to care. AIDS Care. 2014;26:12–19. Rebeiro P, Althoff KN, Buchacz K, et al. Retention among North American HIV-infected persons in clinical care, 2000-2008. J Acquir Immune Defic Syndr. 2013;62:356–362. Tanner AE, Philbin MM, Duval A, et al. “Youth friendly” clinics: considerations for linking and engaging HIV-infected adolescents into care. AIDS Care. 2014;26(2):199–205. Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010;329:1168–1174. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367: 399–410. Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand
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(the Bangkok Tenofovir Study): a randomised, double-blind, placebocontrolled phase 3 trial. Lancet. 2013;381:2083–2090. Davis KR, Weller SC. The effectiveness of condoms in reducing heterosexual transmission of HIV. Fam Plann Perspect. 1999;31:272–279. 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; 363:2587–2599. Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet. 2007; 369:657–666. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009;361:2209–2220. Rosenberg NE, Westreich D, Barnighausen T, et al. Assessing the effect of HIV counselling and testing on HIV acquisition among South African youth. AIDS. 2013;27:2765–2773. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012;367:423–434. Vlahov D, Robertson AM, Strathdee SA. Prevention of HIV infection among injection drug users in resource-limited settings. Clin Infect Dis. 2010;50(suppl 3):S114–S121. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365:493–505. Wood E, Kerr T, Marshall BD, et al. Longitudinal community plasma HIV-1 RNA concentrations and incidence of HIV-1 among injecting drug users: prospective cohort study. BMJ. 2009;338:b1649. Haberer JE, Baeten JM, Campbell J, et al. Adherence to antiretroviral prophylaxis for HIV prevention: a substudy cohort within a clinical trial of serodiscordant couples in East Africa. PLoS Med. 2013;10:e1001511. Lamb MR, Fayorsey R, Nuwagaba-Birbonwoha H, et al. High attrition before and after ART initiation among youth (15–24 years of age) enrolled in HIV care. AIDS. 2014;28(4):559–568. UNICEF. Opportunity in crisis: preventing HIV from early adolescence to young adulthood. Available at: http://www.unicef.org/publications/ files/Opportunity_in_Crisis-Report_EN_052711.pdf. Accessed November 21, 2013. Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012;367:411–422. Pettifor A, MacPhail C, Nguyen N, et al. Can money prevent the spread of HIV? A review of cash payments for HIV prevention. AIDS Behav. 2012;16:1729–1738. Zachariah R, Reid T, Srinath S, et al. Building leadership capacity and future leaders in operational research in low-income countries: why and how? Int J Tuberc Lung Dis. 2011;15:1426–1435. Cohen MS, Smith MK, Muessig KE, et al. Antiretroviral treatment of HIV-1 prevents transmission of HIV-1: where do we go from here? Lancet. 2013;382:1515–1524. NIH. Study evaluates population-wide testing, early treatment for HIV prevention. Available at: http://www.nih.gov/news/health/sep2013/niaid30.htm. Accessed November 21, 2013. Ferrand RA, Munaiwa L, Matsekete J, et al. Undiagnosed HIV infection among adolescents seeking primary health care in Zimbabwe. Clin Infect Dis. 2010;51:844–851. Branson BM, Handsfield HH, Lampe MA, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006;55:1–17; quiz CE11-14. Strode A, Grant K. Using an evidence-based approach to identify legal strategies that protect and promote the rights of children infected and affected by HIV and AIDS. UNDP Commission on HIV and the law. 2011. Available at: http://www.hivlawcommission.org/index.php/working-papers/ children-and-hiv-using-an-evidence-based-approach-to-identify-legalstrategies-that-protect-and-promote-the-rights-of-children-infected-and-affectedby-hiv-and-aids/download. Accessed March 23, 2014. WHO. HIV, and adolescents: guidance For HIV testing and counselling and care for adolescents living with HIV. Recommendations for a public health approach and considerations for policy-makers and managers. Available at: http://apps.who.int/iris/bitstream/10665/94334/1/9789241506168_ eng.pdf. Accessed March 22, 2014. Branson BM, Viall A, Marum E. Expanding HIV testing: back to the future. J Acquir Immune Defic Syndr. 2013;63(suppl 2):S117–S121.
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48. Ramirez-Avila L, Nixon K, Noubary F, et al. Routine HIV testing in adolescents and young adults presenting to an outpatient clinic in Durban, South Africa. PLoS One. 2012;7:e45507. 49. MacPhail C, Pettifor A, Moyo W, et al. Factors associated with HIV testing among sexually active South African youth aged 15-24 years. AIDS Care. 2009;21:456–467. 50. Sherr L, Lopman B, Kakowa M, et al. Voluntary counselling and testing: uptake, impact on sexual behaviour, and HIV incidence in a rural Zimbabwean cohort. AIDS. 2007;21:851–860. 51. Gupta GR, Parkhurst JO, Ogden JA, et al. Structural approaches to HIV prevention. Lancet. 2008;372:764–775. 52. Schwartlander B, Stover J, Hallett T, et al. Towards an improved investment approach for an effective response to HIV/AIDS. Lancet. 2011;377: 2031–2041. 53. Maticka-Tyndale E, Brouillard-Coylea C. The effectiveness of community interventions targeting HIV and AIDS prevention at young people in developing countries. World Health Organ Tech Rep Ser. 2006;938: 243–285; discussion 317–241. 54. COPA. Transitioning HIV-infected youth into adult health care. Pediatrics. 2013;132:192–197. 55. Gardner EM, McLees MP, Steiner JF, et al. The spectrum of engagement in HIV care and its relevance to test-and-treat strategies for prevention of HIV infection. Clin Infect Dis. 2011;52:793–800. 56. Hall HI, Frazier EL, Rhodes P, et al. Differences in human immunodeficiency virus care and treatment among subpopulations in the United States. JAMA Intern Med. 2013;173:1337–1344. 57. Barnes W, D’Angelo L, Yamazaki M, et al. Identification of HIVinfected 12- to 24-year-old men and women in 15 US cities through venue-based testing. Arch Pediatr Adolesc Med. 2010;164:273–276. 58. Vreeman RC, Wiehe SE, Pearce EC, et al. A systematic review of pediatric adherence to antiretroviral therapy in low- and middle-income countries. Pediatr Infect Dis J. 2008;27:686–691. 59. Ferrand RA, Weiss HA, Nathoo K, et al. A primary care level algorithm for identifying HIV-infected adolescents in populations at high risk through mother-to-child transmission. Trop Med Int Health. 2011;16:349–355. 60. van Rooyen H, Barnabas RV, Baeten JM, et al. High HIV testing uptake and linkage to care in a novel program of home-based HIV counseling and testing with facilitated referral in KwaZulu-Natal, South Africa. J Acquir Immune Defic Syndr. 2013;64:e1–8. 61. Sweat M, Morin S, Celentano D, et al. Community-based intervention to increase HIV testing and case detection in people aged 16-32 years in Tanzania, Zimbabwe, and Thailand (NIMH project accept, HPTN 043): a randomised study. Lancet Infect Dis. 2011;11:525–532. 62. van Rooyen H, McGrath N, Chirowodza A, et al. Mobile VCT: reaching men and young people in urban and rural South African pilot studies (NIMH project accept, HPTN 043). AIDS Behav. 2013;17:2946–2953. 63. Fortenberry JD, Martinez J, Rudy BJ, et al. Linkage to care for HIVpositive adolescents: a multisite study of the adolescent medicine trials units of the adolescent trials network. J Adolesc Health. 2012;51:551–556. 64. Rosen S, Fox MP. Retention in HIV care between testing and treatment in sub-Saharan Africa: a systematic review. PLoS Med. 2011;8:e1001056. 65. Kapogiannis BG, Handelsman E, Ruiz MS, et al. Introduction: paving the way for biomedical HIV prevention interventions in youth. J Acquir Immune Defic Syndr. 2010;54(suppl 1):S1–S4. 66. Kapogiannis BG, Lee SS. Rolling up our sleeves now to reap the benefits later: preparing the community for an adolescent HIV vaccine. Curr Opin HIV AIDS. 2007;2:375–384. 67. Pettifor A, Bekker LG, Hosek S, et al. Preventing HIV among young people: research priorities for the future. J Acquir Immune Defic Syndr. 2013;63(suppl 2):S155–S160. 68. Nelson RM, Lewis LL, Struble K, et al. Ethical and regulatory considerations for the inclusion of adolescents in HIV biomedical prevention research. J Acquir Immune Defic Syndr. 2010;54(suppl 1):S18–S24. 69. CDC. Division of HIV/AIDS prevention annual report 2012: maximizing impact. Available at: http://www.cdc.gov/hiv/pdf/policies_DHAP_ AnnualReport_2012.pdf. Accessed November 21, 2013. 70. Hosek S. Project PrEPare. Available at: http://www.projectprepare.net/. Accessed November 21, 2013. 71. Pace JE, Siberry GK, Hazra R, et al. Preexposure prophylaxis for adolescents and young adults at risk for HIV infection: is an ounce of prevention worth a pound of cure? Clin Infect Dis. 2013;56:1149–1155.
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Evidence-Based Programming for Adolescent HIV Prevention and Care: Operational Research to Inform Best Practices Bill G. Kapogiannis, MD,* Ken E. Legins, MPH,† Upjeet Chandan, PhD,† and Sonia Lee, PhD*
Background: Globally, a staggering number of adolescents, approximately 2.1 million, were estimated to be living with HIV in 2012. Unique developmental, psychosocial, and environmental considerations make them particularly vulnerable to HIV acquisition and argue for a comprehensive response to address this burgeoning problem.
Methods: This article explores the current state of the science of HIV prevention, treatment, and care for adolescents and identifies opportunities to address knowledge gaps and improve health outcomes for this age group.
Results: Over the past decade, several important milestones have been achieved in HIV prevention and care among adults, and despite evidence that adherence to care and medications among affected adolescents is significantly compromised, critical research among adolescents and young adults substantially lags behind. Operational research, in particular, is crucial to understanding how to use effective services and interventions for HIV prevention and care safely and effectively for adolescents who are in dire need. Conclusions: Operational research among adolescent populations affected by HIV is critically needed to close the knowledge and investment gaps, and scale-up efforts for HIV prevention, treatment, care, and support for this vulnerable age group. Key Words: operational research, adolescents, HIV (J Acquir Immune Defic Syndr 2014;66:S228–S235)
CRITICAL NEED FOR OPERATIONAL RESEARCH FOR ADOLESCENTS AFFECTED BY HIV Approximately 2.1 million adolescents, aged 10–19 years, were estimated to be living with HIV in 2012.1 The World Health Organization recently provided a staggering estimate that 5 million young people aged 15–24 years are From the *Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; and †UNICEF, New York, NY. The authors have no funding or conflicts of interest to disclose. The comments and views of the authors do not necessarily represent the views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development or those of the Department of Health and Human Services. Correspondence to: Bill G. Kapogiannis, MD, Maternal and Pediatric Infectious Disease Branch, NICHD/NIH, 6100 Executive Boulevard, Room 4B11J, Bethesda, MD 20892-7510 (e-mail: [email protected]). Copyright © 2014 by Lippincott Williams & Wilkins
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currently living with HIV/AIDS on a global basis.2 It is also estimated that 39% of the approximately 2 million new infections that occurred in people aged 15 years or older in the world during 2012 are occurring among young people, with most of them unaware that they are infected. Among 15- to 19-year-old youth in heavily impacted eastern and southern Africa, only 29% of girls and 20% of boys had ever been tested for HIV and received their results.1 Even more concerning is that AIDS-related deaths among 10–19 year olds more than doubled in sub-Saharan Africa during 2005–2012; in contrast, there were overall decreases for such deaths among people of all ages.1 To address the HIV epidemic in adolescents and adolescent health overall, a more focused, efficient, and effective global response to the needs of adolescents is an increasing priority within the global health agenda. A recent review of global prevention science for adolescents, prompted by the observation that many health indicators in later adulthood are rooted in attitudes, behaviors, and lifestyles initiated in early childhood and adolescence, found a substantial number of efficacious interventions aimed at policies and programs addressing multiple levels of risk (eg, individual, peer, family, school, and structural) and targeting different developmental stages of childhood and adolescence.3 However, applying these interventions to adolescents has only recently begun in low-income and middle-income countries. There is a critical need for a more comprehensive response to adolescent health priorities that takes into consideration the health needs and evolving capacities unique to the different developmental stages of adolescents aged 10–19 years. Although many efficacious interventions were identified in the article by Catalano et al,3 the review did not find any controlled trials that assessed long-term outcomes or those that evaluated comparative efficacy of prevention interventions. Furthermore, there seemed to be bias toward support of prevention studies founded on innovation and efficacy principles rather than on replication, generalizability, and effectiveness in realworld settings. More specifically on HIV, a systematic review published in this issue by Napierala Mavegdzenge et al.4 also highlights the lack of practical knowledge on how to reach adolescents, effectively deliver interventions to this age group, and achieve optimal impact on health outcomes. Operational research (OR) efforts are crucially needed to identify and characterize the most effective services and practices suited for implementation within a comprehensive global adolescent HIV prevention and care agenda.
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Definitions of OR In global health, OR has an extremely broad interpretation.5 Therefore, many definitions of OR have been proposed. The World Health Organization defines OR as follows: “The use of systematic research techniques for program decision-making to achieve a specific outcome. OR provides policy-makers and managers with evidence that they can use to improve program operations. It is distinguished from other kinds of research by the following characteristics: 1) It addresses specific problems within specific programs, not general health issues; 2) It addresses those problems that are under control of managers, such as program systems, training, pricing and provision of information; 3) It utilizes systematic data collection procedures, both qualitative and quantitative, to accumulate evidence supporting decision-making; 4) It requires collaboration between managers and researchers in identification of the research problem, development of the study design, implementation of the study and analysis and interpretation of results; and 5) It succeeds only if the study results are used to make program decisions; publications alone is not a valid indicator of success.”5 More succinctly, the United States Institute of Medicine has defined OR as “the use of advanced analytical techniques to achieve better outcomes, definite optimal processes of service delivery, and develop more cost effective systems.”6 Broadly, the goal of OR for adolescent HIV infection is to coordinate and collaborate with HIV prevention, treatment, and care programs and policies by adopting contextappropriate interventions shown to be effective through research and appropriately and widely implementing them in community- and clinic-based settings to improve adolescent HIV outcomes.7 Ultimately, OR on HIV endeavors to accelerate translation of knowledge by linking scientific inquiry to specific program implementation to more rapidly and effectively reduce HIV infections, illness, and AIDSrelated deaths.
ADOLESCENTS AND CURRENT STATE OF THE SCIENCE Adolescence is a critical point on the developmental trajectory.8 Social and psychological pressures encourage adolescents to experiment with drugs and other illicit substances, sexual orientation and preferences, and rebellion against parental expectations. Economic obligations often increase in importance during this period, and in many resource-limited settings (RLS), financial responsibilities are placed upon adolescents because they are expected to take on more adult roles and responsibilities and become contributors within their families and communities. In high HIV-prevalence settings, some adolescents are left orphaned to head households and care for younger siblings, which can have negative impacts on physical and psychological Ó 2014 Lippincott Williams & Wilkins
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well-being, whereas others (orphaned and nonorphaned) take on the role of caregiver for ailing parents and older family members in need of care,9 especially young women and girls.10 Social mores regarding marriage, gender roles, and family also become more prominent during adolescence and begin to shape how adolescents view their reproductive health and their sexual and romantic relationships.11 Adolescence is commonly thought to be the pinnacle of rebellious behavior because of additional pressures placed upon them during this developmental stage, such as peer influences, identity, and self-esteem formation, as well as the incomplete physiological and biological development of impulse control in the frontal cortex.12 In a parallel manner, mental health disorders, such as depression, may manifest themselves during late adolescence,13 also influencing impulsivity, executive functioning, and poor decision making, manifestations that some argue represent more the lack of experiential perspective with novel adult behaviors than are due solely to structural deficits in frontal lobe control.14 The combination of many of these changes and pressures, resulting in risky behaviors,15 place adolescents at an increased risk for contracting HIV by engaging in behaviors such as unprotected sex or through the sharing of nonsterile injecting drug paraphernalia. Indeed, in 2012, young people aged 15–24 years accounted for 39% of new HIV infections in people aged 15 years and older.2 Furthermore, unsafe sex practices because of coercion, transactional sex for survival, intergenerational and age disparate sex, and/or while under the influence of alcohol or drugs are contributing risk factors for contracting HIV in adolescents.11,16,17 There is also a large group of children and adolescents worldwide who contracted HIV perinatally that are tackling additional issues and stressors, such as disclosure, adherence to long-term medication regimens, emergent sexual and reproductive health care needs, and the transition from pediatric to adult, independent medical care.18 As a result of these issues, the building of capacity and the enabling of factors to enhance the dissemination and implementation of interventions to address the HIV epidemic in adolescence, particularly in RLS of highest need, has moved to the forefront. The need to tackle these challenges by examining protective factors, as well as biological, social, and psychological determinants of risk and their impact on HIV-specific outcomes, will become important to the agenda to prioritize OR. In addition to OR efforts in industrialized countries,19–22 efforts to develop OR in RLS should be prioritized because of (1) the greatest burden of HIV borne by such settings, particularly among young people; (2) the established efficacy of HIV prevention23–32 and treatment33,34 interventions, mostly among adults (Fig. 1),23–34 which are covered more in depth elsewhere in this special supplement of the Journal; (3) the poor rates of uptake and challenges to successful implementation of and adherence to many of these interventions among the young people included in these studies27,35–38; and thus, (4) the greatest need for OR efforts related to HIV in younger populations, especially adolescents. Moreover, among the research efforts specifically targeting adolescents, few have measured hard biomedical outcomes, such as HIV incidence, and among those that have only 1, a structural intervention seems to have a significant impact.39 www.jaids.com |
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FIGURE 1. The incremental improvements in efficacy (in percent) (95% confidence interval) at reducing new HIV infections of an array of studies involving biomedical HIV prevention interventions.
Reasons for this scarcity of research include the many challenges faced when attempting to embed an effective research intervention into an already established clinical or programmatic setting. Examples of challenges that may thwart the implementation and programmatic buy-in of OR in RLS may be because of the lack of understanding of research methodology, including potential ethical considerations in working with adolescent populations who have not yet attained their jurisdictionally defined age of majority, ownership of research, appropriate research infrastructure, financial support, training, and oversight.40 Furthermore, research and programmatic efforts to ensure that interventions are not only implemented but also made accessible to vulnerable adolescent populations and sustained throughout the relevant communities need to be prioritized.
PRIORITY SCIENTIFIC OPPORTUNITIES FOR OR With this greater understanding of the HIV epidemic in adolescents and young people, and the many potential factors that drive the disproportionately high rates of infection in this group, an OR framework and agenda should be structured around several priority areas to specifically address the pressing knowledge gaps and opportunities for prevention in adolescents. As it is beyond
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the scope of this review to undertake a comprehensive discussion of all meritorious (eg, biomedical, behavioral, community, and structural level) interventions, which are more comprehensively addressed elsewhere in this supplement by Napierala Mavegdzenge et al.,4 selected areas of priority within the landscape of HIV prevention, treatment, and support for adolescents are highlighted below.
Biomedical Interventions Research in Young People Although there are promising data from numerous biomedical HIV prevention and care interventions among adults, those that included younger populations have identified an Achilles tendon, significant associations between nonadherence and efficacy,27,35,38 despite what participants may have reported in the context of a clinical trial.38 This phenomenon raises important implementation questions about rolling out and scaling up such interventions in the real world, where many providers may be faced with the challenging scenario of providing these agents “off-label” (not in accordance with regulatory agency approval) to a population for which there is little safety information and essentially no data on their effectiveness (the extent to which planned HIV prevention outcomes are achieved as a result Ó 2014 Lippincott Williams & Wilkins
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of using the biomedical HIV prevention agent under ordinary and uncontrolled circumstances). Understanding the effectiveness among adolescents is particularly germane to interventions that require high fidelity and adherence for success, and in whose absence, the risk for the development of untoward effects to the individual and society may be substantial. Such caution is important in the context of considering antiretroviral therapy as a potential widespread prevention intervention among youth; the results from a controlled clinical experiment in adult couples, although highly efficacious (Fig. 1), may be subject to significant biases that threaten their external validity, not only among adult individuals who are not in monogamous relationships but also especially among youth who not only may be less likely to have a steady partner but also be contending with already discussed developmental milestones and issues inherent to those.41 Despite optimism that recent large-scale community level OR in this topic area will shed light on many of the operational challenges to this approach, this work is only planned for adults older than 18 years,42 leaving a tremendous gap for adolescents who are at the high risk of HIV infection and those living with HIV.
HIV Testing and Counseling for Adolescents At the beginning of the continuum of HIV care for adolescents, one of the most feasible intervention areas lies within HIV testing and counseling (HTC) efforts/programs. As mentioned previously, most newly HIV-infected adolescents are completely unaware of their diagnosis—a situation not unique to behaviorally HIV-infected adolescents as many with perinatal HIV infection may not have been disclosed to by their caretakers or have also never been tested.43 In some of the most heavily impacted parts of the world, the proportions of young people aged 15–19 years who undergo testing and receive their result is extremely low, with estimates as low as 29% and 20% among adolescent girls and boys, respectively, in eastern and southern Africa, and even as low as 1% in adolescent girls and boys in south Asia.1 Increasing OR efforts to address structural barriers to HTC for adolescents is important for meaningful impact on increasing HIV testing and ultimately determining the impact on reducing new HIV infections.30 For example, in the United States, the Centers for Disease Control and Prevention has revised recommendations regarding HIV testing of adolescents, emphasizing testing as part of routine medical care, and not just for those in acute-care settings, at high risk for HIV.44 These recent revisions differ from previous recommendations by not requiring specific informed consent for HIV testing and making pretesting counseling unnecessary, both potential barriers to those adolescents seeking testing. As informed consent and counseling have been previously mandated by state law for HIV testing, these Centers for Disease Control and Prevention recommendations have been adopted by most states within the United States, thereby allowing more adolescents to become tested and to learn their HIV status without concerns regarding parental involvement. The United Nations Development Program Commission on HIV and Law outlined a number of structural barriers Ó 2014 Lippincott Williams & Wilkins
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that limit adolescent’s access to HIV services in low- and middle-income countries, including age of consent for HIV testing and medical procedures, and punitive laws aimed at young men who have sex with men, adolescents who inject drugs, and girls in some settings.45 OR offers the opportunity to investigate health and protection service delivery platforms that tailor (adolescent-friendly) interventions for optimized outcomes. More recently, WHO, in collaboration with UNICEF (United Nations Children’s Fund) and other global organizations, developed guidelines on “prioritizing, planning, and providing HIV testing, counseling, treatment, and care services for adolescents”.46 The guidelines recommend that all settings/countries, regardless of epidemic typology, ensure routine testing and counseling for adolescents, with appropriate linkage to prevention, treatment, and care. As the level and quality of evidence is variable and incomplete regarding the impact of HTC services on the HIV epidemic, OR can have an important role in determining how to best implement these recommendations to maximize their effectiveness in reducing HIV acquisition among adolescents. Addressing barriers to HIV testing among adolescents is only a first step and other approaches for scaling up testing need to be continued in resource-limited counties.47 It is notable that recommendations geared toward provision of HTC services through health care settings assume not only that adolescents will access appropriate medical care on a routine basis but also that health care programs will include adolescent-friendly HTC services. These assumptions, however, represent additional priority areas in need of well-designed and supported interventions. For example, in a study at an outpatient clinic in South Africa, researchers investigated whether adults and youth alike would participate in HIV testing efforts. Despite high HIV prevalence among youth in this area, the actual uptake of testing is low.48 Although this study took place in an adult outpatient clinic, not one specifically geared toward serving youth, additional studies that investigated models for HTC service delivery involving adolescents also indicate low uptake.49,50 In RLS especially, where access to and emphasis on routine and regular medical care are often lacking, it is important that OR for implementing targeted HTC services for adolescents, specifically addressing adolescent needs and challenges, be prioritized and developed. OR efforts to prioritize HTC services for adolescents need to be developed in collaboration with not only researchers and local health providers within communityand clinic-based settings but also those key policy makers and stakeholders in HIV/AIDS programs who can influence HIV/ AIDS, health and adolescent policies and funding of these efforts, and offer crucial operational insights to guide OR questions that will optimally inform best practices. Community mobilization efforts are an essential pathway toward encouraging those with decision-making capabilities to invest financial resources in HTC services51 and improve HIV outcomes.29 Community investment in the health and well-being of its adolescents also maintains the on-going quality and adherence to such treatment services.52 But before financial investment can occur, community buy-in www.jaids.com |
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to encourage outreach and engagement of adolescents and their families to participate in OR to optimize HTC programs is a key first step. Overall, improved understanding of the mechanisms behind the social stigma of HIV and community support to disable it will further facilitate the adoption of HTC programs on a routine basis. Maticka-Tyndale and Crouillard-Coyle53 published a systematic review and synthesis of studies evaluating community interventions and emphasized how essential it is for governments and similar bodies to invest in high-quality process and outcome evaluations to identify and promote effective community interventions for young populations.
Linkage, Engagement, and Retention in Care Among Young People Once adolescents are tested and identified as HIV positive, appropriate efforts to effectively and expediently link them to medical care remains a pervasive challenge, particularly for younger populations. Adherence to care among several thousand youth aged 15–24 years in RLS showed substantial attrition as early as 1 year after enrolling in care.36 The transition from a clinic with adolescent-geared services to an adult-based clinic additionally hampers efforts to provide adequate medical care.54 And further down the continuum of care,55 challenges with engaging adolescents as active participants and advocates of their own care and subsequently retaining them in medical care exacerbate the difficulty in properly treating newly diagnosed, acute HIV infection. A recent article by Hall et al56 estimates that of all persons living with HIV in 2009 in the United States, 82% were aware of their HIV infection, 66% were linked to care (defined as having at least 1 CD4 count or HIV viral load measured within 3 months of diagnosis), 37% were retained in care at 6 months or longer, 33% were prescribed antiretroviral therapy, and 25% had a suppressed viral load. The percentages for all of these categories were even lower in younger age groups, which is especially concerning when you consider that a substantial majority of youth, whether abroad or in the United States, have either never been tested for HIV1 or are unaware they are already infected.57 Such work may be even more critical in low- and middle-income country contexts where adherence rates among adolescents in whom chronic health conditions have been documented at lower levels than among adolescents in the West.58 In low-to middle-income countries, OR priorities need to include efforts to better understand where adolescents fall along the continuum of care by conducting programmatic evaluations of HTC services and ART programs to learn why adolescents fall off at each point of the HIV care continuum and ultimately inform best practices and policies for this vulnerable population. Indeed, a preliminary question that needs to be addressed is how the continuum of care established for adults (Fig. 2A)56 may be used to describe and characterize critical points along the spectrum of care for HIV-infected adolescents and to inform relevant OR efforts in RLS. Efforts now underway to characterize this for American youth have shown that there are substantial differences in outcomes across all domains of the continuum
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(Fig. 2B).19,20,22,36 There is a critical need to understand key implementation considerations for adolescents globally, particularly in RLS for which data at important points along the continuum are absent (Fig. 2B). Better understanding of implementation considerations, like the role youth-friendly clinics, ethical-legal-regulatory challenges, emergent mental health comorbidities, psychosocial instability, and other adolescent-specific issues likely play in favorable adolescent health outcomes, can only be helpful to programmers because they consider how to best refine and implement services to improve focus on adolescents and their outcomes. To address the above knowledge gaps in the adolescent HIV care continuum in RLS, OR efforts evaluating program data are needed to understand not only whether adolescents are accessing HIV testing services but also when and how often adolescents are getting tested. In many RLS, particularly in remote, rural, and periurban areas, there are not enough accessible clinics, let alone adolescent-friendly clinics. Furthermore, if routine testing services are not made available to adolescents, how do those at high risk for HIV become identified?59 Therefore, OR priorities to invest in and understand home-based and community-based (eg, mobile) HTC programs should be encouraged. A pilot study of home-based counseling and testing in South Africa (with adults) showed high rates of both achieving testing uptake and approximately 90% rates of linking newly identified HIV-infected persons and known HIV-infected persons not previously engaged in care into care.60 Similarly, mobile community-based voluntary counseling and testing (as compared with standard clinicbased testing) has been shown to increase testing rates and HIV case detection in 3 study communities in Tanzania, Zimbabwe, and Thailand,61 with indications that in South Africa, mobile testing was a feasible way to engage youth, men, and rural communities in HTC.62 Frequent repeat testing and early diagnosis of HIV through OR efforts need to be prioritized. Additionally, OR is needed to investigate what linkage to care efforts encompasses in resource-limited countries such that accurate estimates of the proportion of adolescents who are aware of their HIV infection that are successfully brought to medical care can be obtained. In the United States, for example, a previous effort to further understand the HIV linkage to care process in adolescents might serve as a starting framework for operational efforts in RLS63: “Three main components of HIV-related linkage to care were identified: the infrastructure and organization of linkage to care, the process of linkage to care, and the content of linkage to care activities.” Under the infrastructure and organization of linkage to care component falls an investigation of models for linkage to care, relationships among networks of testing sites and HIV clinical care sites, community membership, and adolescent friendliness. Under the process of linkage to care components falls readiness for HIV care, crisis management, and patient education and orientation. Third, under the linkage to care content component falls case management, barriers to care, and confidentiality. Throughout all 3 of these components are many rich areas of either programmatic review and/or targeted investigation that lend themselves easily to OR aims. Ó 2014 Lippincott Williams & Wilkins
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FIGURE 2. Proportions of HIV-infected adults succeeding at various steps along the HIV continuum of care in the United States and associated implementation challenges (A) and of HIV-infected adolescents and young adults in the US (green) and in RLS (red) and associated youth-specific implementation challenges (B). ART, antiretroviral therapy.
Further down the care continuum, additional priority areas for OR efforts include what do engagement in care proportions (ie, the percentages of HIV-infected adolescents who initiate clinical care) look like in resource-limited countries and how we can improve these, and of course, similar investigations of retention in care. A systematic review of the literature64 confirmed the limited number of studies investigating the rates of successes and failures of either HIV engagement or retention in care programs for all populations in Africa. Overall, with a greater understanding of all aspects along the continuum of care for adolescents and HIV, including linkage to and engagement and retention in Ó 2014 Lippincott Williams & Wilkins
care of HIV-positive adolescents to medical services, appropriate and effective interventions to address and improve these areas in RLS can be prioritized and implemented.
TRANSLATING SCIENCE INTO EVIDENCE-BASED PRACTICE To effectively reduce the global HIV incidence rate in adolescents, the inclusion of adolescents and young adults in biomedical HIV prevention and care research remains a high priority. Thus, the translation of such findings and interventions from theory and formative research into practice within www.jaids.com |
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high-needs communities remains an OR priority as well. However, the myriad of considerations involving such youth participation and the need for broad community and stakeholder engagement65,66 hinder the pace with which this important work should be accomplished. Nonetheless, researchers in areas highly impacted by HIV in youth continue in their efforts to include adolescents in this important work,67 despite significant ethical, legal, and regulatory challenges in working with these populations.68 Without such efforts, programmers and providers alike will continue to face the unanswered questions of how can they deploy interventions proven efficacious in adults so as to maximize the impact while minimizing costs and potential toxicities to the youth they care for. It is in this context that demonstration projects and bridging safety studies have recently gained popularity in the field.69–71 Bridging studies are a particularly important way to increase youth’s access to key biomedical HIVprevention technologies shown to be effective among adults and to obtain critically needed safety and effectiveness data for this vulnerable population. These safety and preliminary efficacy trials “bridge” to larger scale efficacy trial data among adults based on the notion that biologic efficacy among selected agents should not differ between youth and adults and thus on seeking regulatory licensure with the conduct of small phase I/II clinical trials to demonstrate that a product has a favorable safety profile and preliminary efficacy among youth. An additional advantage to demonstration projects is the crucial feasibility data they can yield about how participants use interventions in the real world, which can be important for refining program design and critically needed areas of investment in infrastructure for scaling up capacity and access to efficacious prevention and care services for vulnerable populations.
CONCLUSIONS Although the HIV epidemic among adolescents and young people affects every country across the globe, one of the greatest priorities for interventions lies within OR in resource-limited countries. Scientists, physicians, policy makers, community stakeholders, advocates, programmatic officials, and adolescents need to work together to close the knowledge and investment gaps and scale-up OR efforts for HIV prevention, treatment, care, and support. Healthy, educated, protected, and empowered adolescents are not only our future but also the means to an AIDS-free generation.
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