Adolescence is a period of major transitions, particularly in terms of sexual and reproductive health needs. Interventions that are appropriate for older adolescents may not be relevant or appropriate for younger adolescents. In addition to sexual orientation and gender, interventions should be tailored to the specific populations targeted, taking into account, for example, whether youth are attending school, whether they are married, and other variables. Although we set out to disaggregate the results based on criteria, such as age, marital status, and whether the adolescent was still in formal education, the data were not usually reported by such subgroups in the review articles included in this report.
Certain types of interventions in this review have considerable amounts of evidence and/or evidence of high quality, whereas other interventions have very little evidence in terms of their effectiveness on HIV-related outcomes and/or only have evidence of relatively low quality. In some cases, this may be because of the limited effectiveness having been found within the initial intervention studies and thus little impetus to conduct additional and higher quality research. However, in other instances, this may not be a reflection of the potential of the intervention but rather the barriers to conducting high-quality interventions, in terms of logistics and/or resources. Such studies are particularly problematic among adolescents, for several reasons. First, the incidence of HIV among young adolescents is generally relatively low so population-based studies need to be very large. Studies of adolescents below the age of 18 years (or even older in some countries) are also complicated by additional parental informed consent requirements, especially if they include collection of biological specimens. Finally, if an intervention type is relatively new, sufficient studies may not have yet been conducted to have resulted in the publication of a systematic review. This review was not able to distinguish between these various possibilities but rather was designed to present the current state of the published evidence.
A major constraint on this review was that, with the exception of a few intervention types, there was a dearth of systematic review data on how best to enable adolescents to access the intervention types that were identified as having proven effective among adults. There is a clear need for more rigorous research in this area.
This review provides an important summary of the existing evidence on the effectiveness of a wide range of different types of interventions. We employed a systematic review of systematic reviews methodology24,33,81 to consolidate and summarize the data on the effectiveness of a total of 20 intervention types, to identify key characteristics of effective interventions, and to explore the evidence from systematic reviews of how adolescents can best access those interventions with proven effectiveness. This approach allowed us to rigorously and systematically review a large number of intervention types in 1 document using a standard transparent methodology. We developed criteria for assessing the strength of the available evidence on effectiveness, which was systematically applied to each intervention type and used to develop author recommendations for what intervention types are most promising to consider for adolescent HIV programming in terms of their evidence of effectiveness. Methodological limitations are inherent in this strategy. In using only review articles rather than primary data, we relied on the data and focus presented by the review authors. There is likely to have been heterogeneity of interventions, outcomes, and study designs. Furthermore, the reports of the studies had already been summarized; so, the information will have been less detailed than in the primary study reports, resulting in the potential for exclusion of more nuanced descriptions of characteristics of interventions important to their effectiveness or lack thereof. In addition, by only searching for review articles, we may have missed effective interventions that have been evaluated but have not yet been included in a published systematic review. Nonetheless, systematic review of systematic reviews is a useful strategy that has been proposed by the UK Health Development Agency81 and employed in numerous previous peer-reviewed articles.24,33 We reviewed a very large number of interventions, and a systematic review of systematic reviews was employed for practical reasons and also because, for most intervention types, high-quality reviews could be identified that adequately summarized the available data. Our review did highlight an absence of systematic reviews of some intervention types, which is likely to reflect the lack of published primary data, at least up to the recent past.
Another methodological limitation is that we limited our search to just 2 databases, PubMed and Cochrane; therefore, there is the possibility that we did not identify all high-quality systematic reviews. However, with the large volume of citations included in these databases, we feel it is unlikely that we overlooked any high-quality reviews that would have substantively altered the results presented here. We also did not systematically search the gray literature. After reviewing our results, expert consultants in adolescent HIV research and programming were asked to inform us of any other review articles of relevance, and these were included when they met the inclusion criteria. We also summarized unpublished systematic reviews conducted for the World Health Organization related to recent global or regional HIV guidelines and referred to these guidelines where available. For interventions specifically designed to target adolescents and young adults, we systematically reviewed all review articles that met our criteria for inclusion, but for the interventions primarily designed for adults, we selected the most recent, high-quality systematic reviews for inclusion that adequately summarized the available data from all the citations identified. In doing so, we may have overlooked important reviews that were published less recently.
We limited the review to the impact of interventions on biological HIV-related outcomes. Where such evidence was not available, or did not strongly support the intervention type, we looked beyond our 3 key outcomes to capture data on reported behavior change. For interventions that target adolescents, we also incorporated data on the impact on knowledge and reported attitudes. Some interventions may have effects on other outcomes, which are not directly HIV related but may be potential structural or other indirect determinants of HIV acquisition risk, such as poverty or employment, which we will not have captured yet may be extremely important. For example, cash transfers conditioned on adolescent girls remaining in, or returning to, school may have important effects on educational attainment, earning potential, desirability as a potential spouse, subsequent mothering skills, other health outcomes for themselves and their future families, and so on.
We developed a methodology to assess the strength of evidence available for each intervention type and to generate recommendations. It is relatively simple to use, can be applied across multiple intervention types, and indicates the weights assigned to the evidence on each intervention type. However, this methodology has limitations. First, although an experimental study is considered the strongest form of evidence, for ethical or other reasons, the comparison arm in an experimental study may not always have been the complete absence of any intervention but rather the current standard of care. In such cases, the measured effectiveness would likely be less than if the intervention had been evaluated against no intervention. Second, this methodology does not explicitly take account of geographical representativeness of the existing studies or their likely generalizability. Lastly, the methodology does not take account of the fact that different interventions will need different strengths of evidence to justify implementation based on their feasibility, cost, potential size of benefit, risk of harm, acceptability, and other social or health benefits.4 Evaluation of these factors was beyond the scope of this review and will need to be done as a separate exercise before decisions are made about the relative priority to be given to each intervention type.
Also worth noting is that this review attempted to examine individual intervention types but did not look at combinations of interventions. Integrated programs with multiple, linked synergistic interventions may be more effective than any single intervention. Programs such as MEMA kwa Vijana in Tanzania82–84 and Regai Dzive Shiri in Zimbabwe85,86 are examples of combination interventions targeting adolescents, and several large rigorous evaluations of combination HIV interventions are currently in progress, such as the Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART) trial in Zambia and South Africa, which includes young adults, but not adolescents.87
From our systematic review of systematic reviews, we identified a number of interventions that showed strong promise of effectiveness (Tables 5 and 6). Of the interventions designed specifically for adolescents, there was high-quality evidence which indicated that, if they include identified key characteristics, in-school interventions and interventions in geographically defined communities can have a positive impact on a number of important HIV outcomes. Based on these results, it is recommended that these interventions should be considered for wide-scale implementation. Additionally, there is promising evidence that some cash transfer interventions can positively affect HIV outcomes in adolescents, though additional results from a number of ongoing trials and careful consideration of cost-effectiveness and sustainability are required before these can be recommended for scale-up. As health services are a gateway to a number of other effective interventions, including antiretroviral therapy, PMTCT, treatment as prevention strategies, STI treatment, and provision of condoms, resources should be allocated toward the development and implementation of interventions to increase health service use among adolescents and young people, including making them more adolescent friendly. Few other interventions in this category can be recommended for scale-up, due to weak evidence of effectiveness, evidence for an impact on self-reported behavior only, or there having been too few rigorous intervention studies.2,12,22,27,34–39,43,44,79
A number of interventions designed primarily for adults have high-quality evidence of potential efficacy: VMMC, ARVs for PMTCT, HIV testing and counseling, HIV treatment, condom use, and provision of sterile injecting equipment to PWID. There was also evidence of potential efficacy for oral PrEP among heterosexual couples and MSM and behavior change interventions among PWID and MSM. These should be priority interventions, which should be included in all HIV prevention programming for adolescents. A key public health question is “What does it take to reach adolescents more effectively with these high-impact interventions?” However, with only a few notable exceptions, there was a dearth of rigorous reviews of their current uptake by adolescents relative to older age groups and of what should be done differently to enable adolescents to access these interventions at least as much as adults. While there may have been primary studies addressing this question, the lack of systematic reviews indicates that inadequate attention has been paid to adolescent access to effective HIV prevention, treatment, and care strategies. We recommend that the generation of such evidence through operations research, and age and sex disaggregation of programmatic and research study coverage and utilization data, be an urgent research priority, with rigorous studies focusing on those interventions of proven efficacy identified here.
The authors thank Susan Kasedde, Ken Legins, Craig McClure, Rachel Yates, Chewe Luo, and Upjeet Chandan of UNICEF for advice and critical review of an earlier draft of this report. The authors also thank participants of the April 2013 meeting at UNICEF Headquarters in New York and of the July 2013 UNICEF meeting in London for their comments and suggestions. The authors thank Harriet Hallas and Claudia DaSilva of the Infectious Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, for administrative support.
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