Recent surveillance suggests that 45% of the 2.7 million people who become HIV infected each year are aged 15–24 years [1,2]. Around the world, 3500 young people (the term ‘young people’ refers to people aged 10–24, ‘adolescents’ refers to those aged 10–19 and ‘youth’ to people aged 15–24) become infected everyday. The majority of HIV in young people is sexually acquired, although in southern Africa there is growing recognition that long-term survivors of perinatal transmission likely make up a growing minority of infected adolescents [3,4].
Young women are particularly vulnerable to sexually acquired HIV; of the 6 million HIV-positive young people in sub-Saharan Africa (SSA), 76% are female . The epidemic in men peaks on average 10 years later than it does in women, making age-disparate relationships particularly risky for young women. Determining reasons for the increased vulnerability of young women was the subject of a recent Joint United Nations Programme on HIV/AIDS (UNAIDS) conference and special issue of AIDS , which concluded that the factors were multifactorial and include human rights violations, harmful social norms, weak community and leadership capacity to tackle these as well as the huge disparities between women and men [7•].
HIV in young people is mitigated through factors operating at an individual level (psychological , biological [9•]), family level (orphaning [10,11], poverty and development factors ), partner level (concurrency [13,14], age-disparate relationships [15•], sex-based violence ) as well as at a broader structural level (access to education [17•], sex inequity and discrimination , poverty  and social unrest). Although changing these contextual factors will be key to preventing HIV among young people in the longer term, in the short-term, specific behavioural, biomedical and structural approaches to prevention among young people are required.
Prevention of HIV in young people is recognized as being central to control of the pandemic overall and as such was one of the key indicator areas outlined by The United Nations General Assembly Special Session on HIV/AIDS (UNGASS) for intervention . Several targets relating to prevention of HIV in young people were set including that by 2005 90% of youth aged 15–24 should have the information, education, services and life-skills needed to reduce their chances of HIV infection (no country achieved this; rates of comprehensive HIV knowledge were less than 40% in both young men and women in 2007)  and that there should be a 25% reduction in new HIV infections in the worst affected countries (six countries have achieved this). Encouragingly, the proportion of young people who first had sex at age less than 15 years appears to be declining .
In this review, we will discuss the findings of recent studies of HIV prevention that are relevant to young people in SSA, specifically addressing issues related to biomedical, behavioural and structural interventions. There will inevitably be some overlap between the approaches outlined here and those outlined for HIV prevention in general. We will also briefly discuss issues related to adolescents living with HIV infection, an increasing number of whom are being recognized.
A recent comprehensive review on this subject (biomedical interventions) was included as part of the 2008 Lancet HIV prevention series [22••]. They have also been discussed in some depth earlier in this issue. Although none of the biomedical interventions is specifically designed for or has been evaluated in youth aged less than 18 years, they are recommended for use in this age group and there are some strategies that may be particularly worth pursuing. For example, contraception is widely available in much of Africa, but in many countries is primarily promoted to married women after the birth of their first baby and is not easily accessed by adolescent girls. Given the particularly high prevalence of HIV among young antenatal clinic attenders (aged 15–19), promotion of contraception to sexually active nulliparous adolescents is likely to be an effective means of preventing mother to child transmission (MTCT) .
In the area of HIV vaccine research, an HIV vaccine would need to be delivered before sexual debut to be most effective. The HIV vaccine community have made strong arguments to include adolescents in trials so that essential information is available to support timely regulatory decisions and prevent delays in adolescents' access to an effective vaccine . Researchers have been conducting studies on acceptability of vaccine use in adolescents in Africa and have been tackling the ethical and legal complexities of enrolling minors in such trials [24–26].
Unlike biomedical interventions, numerous behavioural interventions, specifically targeting young people have been developed and evaluated. Relatively few have been rigorously evaluated in developing country settings and even fewer have included HIV as endpoints. In 2004, UNAIDS commissioned systematic reviews to provide policy makers with evidence on the effectiveness of HIV prevention for young people in developing countries . There was good behavioural evidence that school-based interventions can reduce reported sexual risk taking; however, behavioural outcomes are likely to be subject to social desirability bias and this bias is likely to be differential between arms . At the time of the review, there was only one trial of a school-based intervention from Africa with biomarker endpoints identified, the MEMA kwa Vijana trial from Mwanza Tanzania [29–31]. This trial showed some impact of the school, clinic and community-based intervention on knowledge, attitudes and sexual behaviour, particularly among young men, but no impact of the intervention on biological outcomes, including HIV, herpes simplex virus-2 (HSV-2), other sexually transmitted infections (STIs) or pregnancy . A follow-up survey conducted 5 years after the main trial found that although some knowledge, attitude and behavioural change persisted, there was no evidence of long-term impact on biological endpoints.
In addition to school-based interventions, the UNAIDS review included systematic reviews to asses the impact of training healthcare workers to make clinics more ‘youth friendly’ , community-based HIV prevention interventions  and HIV prevention mass media interventions . There is evidence that healthcare interventions increase clinic accessibility and that mass media interventions do, if carefully designed and appropriately delivered, improve knowledge and impact social norms and condom use. However, at the time of the review, there were relatively few data to support or argue against the implementation of broader, more community-based approaches, which aim to change societal norms in order to support individual behaviour change . Overall, few trials of adolescent HIV prevention interventions with objective biomedical endpoints were identified and one of the key recommendations of the review was that more rigorous research should be funded and conducted.
Since these systematic reviews were published, three more HIV prevention trials among young people in Africa with objective endpoints have been reported. Jewkes et al.  have reported the results of a community-randomized trial of the Stepping Stones intervention among young people in South Africa [36,37]. The intervention, described as a sex-transformative HIV prevention intervention, consisted of 13 participatory 3-h sessions and three peer group meetings and included sessions on communication, various aspects of sexual health and relationships and on sex-based violence. The intervention had an impact on knowledge, behaviour [including reducing reported intimate partner violence (IPV)] and attitudes and a borderline effect on HSV-2 prevalence.
The Regai Dzive Shiri trial from Zimbabwe tested a multicomponent community-based intervention delivered to in-school and out-of-school youth, parents and clinic staff and was theoretically based on social learning theory and the stages of change model. The intervention aimed to achieve change in societal norms within communities. The effect of intervention delivery was assessed after 4 years. There was an impact of the intervention on knowledge, self-efficacy and attitudes, as well as on reported pregnancy among young women and all pregnancies in unmarried women but had no effect on the primary endpoints of HIV and HSV-2 [38,39].
In addition, a trial from Kenya looked at the effect of a short intervention aimed at young women by drawing attention to the HIV prevalence of older partners compared to younger ones  resulted in a 61% decrease in reported pregnancy with adult partners (corroborating evidence of these self-reports was sought where possible), suggesting a reduction in cross-generational sex.
These behavioural interventions all had an impact on knowledge and attitudes, which are important endpoints in their own right. Two interventions reported a reduction in reported pregnancy, one a borderline effect on HSV-2 and on IPV, again both important endpoints. None of the interventions was effective in reducing rates of HIV per se. All interventions were carefully designed and delivered; all included in-school youth who are a captive audience and easiest to access. All interventions except the one in Kenya made some attempt to include the wider community in order to address societal norms more broadly, perhaps most comprehensively addressed and demonstrated in the Regai Dzive Shiri trial from Zimbabwe in which effects were found across the community and not just in intervention recipients. It seems likely that changing societal norms will be a key element to success, although there is no direct evidence to support this at present. These interventions that were all aimed at youth of school-going age, by definition excluded the somewhat older men that young women have sex with [15•]. There is no evidence from the long-term follow-up of the Mwanza trial, however, that the reduction in risky behaviour reported by school-going boys in 2001 has translated into reduced risk for young girls in the community 5 years later. Direct comparison between trials about what worked and what did not, however, is difficult. The trials used different intervention designs, delivery modes and impact evaluation techniques. It seems likely, however, that as outlined in the recent review by Coates et al. of behavioural approaches to HIV prevention [41••], we need to do more and use multilevel behavioural approaches, which use strategies working across many levels of influence and brought to scale to bring about sufficient and sustained behaviour change to impact the epidemic.
Structural factors have been defined as physical, social, cultural, organizational, community, economic, legal or policy aspects of the environment that impede or facilitate HIV prevention efforts [42••,43,44]. In developing country settings, structural factors that increase the risk of HIV transmission and help explain the epidemiology of infection have been grouped into three broad categories: economic underdevelopment and poverty; migration and mobility; and sex inequalities . As part of the 2008 Lancet prevention series, there was a particular focus on structural interventions and a special edition of AIDS in 2000 also explored the role of structural interventions for HIV prevention [43,44]; the role of economic empowerment in young women has also been reviewed recently .
Although the number of rigorously evaluated structural interventions for HIV prevention is few, it is growing. Structural interventions targeted at adolescents specifically are even more limited; however, a number of interventions have included adolescents and young people. A recent intervention that addressed both sex inequality and poverty was the Intervention with Microfinance for AIDS and Gender Equity (IMAGE) study. It was a cluster-randomized trial that assessed the effect of a structural intervention combining group-based microfinance with a sex and HIV training curriculum on HIV risk behaviour and IPV. Over a 2-year period, there were improvements in economic wellbeing and multiple dimensions of empowerment among programme participants and levels of IPV were reduced by 55% [46,47]. In the young female participants (age 14–35 years), participants also had higher levels of HIV-related communication, were more likely to have accessed HIV testing and less likely to have had unprotected sex at last intercourse with a nonspousal partner [48•]. Other HIV prevention interventions addressing young women's economic vulnerability are underway. One such intervention called Shaping the Health of Adolescents in Zimbabwe (SHAZ) is a study to evaluate the effectiveness of a combined intervention to reduce economic vulnerability and HIV risk in young women in Zimbabwe and Tanzania . Both IMAGE and SHAZ combine interventions to reduce young women's economic vulnerability with HIV prevention skills; thus, in a sense these interventions are multilevel. It is not possible to determine whether the economic components alone would be sufficient to reduce HIV risk.
In another recent trial of an economic intervention to reduce costs of education for youth with the aim of keeping them in school longer and thereby reduce their risk of HIV infection, 328 schools in western Kenya were randomized to provide free school uniforms. Among girls in schools who received free uniforms, there was close to a 10% decrease in teen childbearing 2 years later . Interventions that aim to reduce structural barriers to education to decrease HIV infection have received more attention of late and there are randomized trials planned to further explore their effect [17•].
Other notable examples of structural interventions, although not youth-specific, include the 100% condom use policy in Thailand and Uganda's national-level social mobilization and policy efforts to achieve a reduction in HIV incidence [42••].
Although structural factors are often considered distal to HIV risk or difficult to intervene upon, it has increasingly been noted in research on drivers of HIV infection, particularly in youth that sexual behaviours alone do not explain the epidemics observed in SSA and that structural and biological factors must also be key .
As already outlined, adolescence is a period of particular vulnerability for a host of biological, behavioural, social and structural reasons. Finding a way to protect young people until they are physically and emotionally mature, as well as sufficiently skilled to protect themselves, is the challenge for HIV prevention in this age group. Not only do we need multilevel approaches to behavioural interventions, but we also need to integrate structural, behavioural and biomedical approaches to ensure they are mutually supportive and reinforcing. Young people are highly mobile, particularly young women, who often move when they marry. HIV prevention needs to scale up, so it is present everywhere and the messaging and service remain consistent wherever they live.
With the exception of circumcision and vaccines, biomedical interventions require the ‘operator’ to be skilled to some degree in their usage and, if coitally dependent, to adhere to consistent usage, a challenge for many prevention technologies . For adolescents, even more so than for adults, effective usage will likely depend on coupling these biomedical interventions with some kind of educational/behavioural and possibly structural intervention to enhance their knowledge and skills and motivations to use them.
HIV infection in adolescence
There is now increasing evidence that around one third of infants vertically infected with HIV progress slowly and that their median life expectancy may be as high as 14–16 years without antiretroviral therapy [53,54]. Increasingly, these long-term survivors are presenting for care . In countries with early onset severe epidemics, there is a substantial but largely hidden epidemic among these young people . These HIV-infected adolescents require care and support as well as secondary prevention and adherence interventions. In addition, scale up antiretroviral therapy among the fast progressors (who would have previously died in early childhood) increases the burden of adolescent HIV still further .
Specific considerations for HIV-related research in adolescents
There are some specific issues that need to be considered for HIV prevention research in adolescents.
In addition to the ethical challenges previously mentioned, which effect prevention research more generally, an additional challenge specific to research among adolescents is the need to ensure that these vulnerable young people are adequately protected, while ensuring that research that is relevant and appropriate to their needs is conducted. In some African countries, it is not possible to conduct any research on minors, regardless of their maturity or life experiences, without first obtaining parental/caregiver consent. Although motivated by the best of intentions, this restriction will inevitably mean that adolescents who feel unable to involve their parents/guardians in questions about their sexual health, by definition likely to be those who are most vulnerable and who perhaps could benefit the most from prevention intervention research, will be unable to participate in research projects, potentially limiting the scope of research and its relevance to those most at risk.
Outcome measures for HIV prevention trials
As a general rule, evidence of prevention intervention effectiveness needs to be assessed using objective outcomes that are not subject to social desirability or other biases. However, even in SSA, there are relatively few settings in which it is feasible to conduct prevention trials with HIV endpoints. Even when HIV incidence is horrendously high, as it is among young women from southern Africa, trials with HIV endpoints need to enrol large numbers and include lengthy follow-up, which makes them complex and expensive to conduct. There is no good surrogate for HIV. STIs, such as HSV-2, and pregnancy are more common than HIV making them potentially easier to detect among smaller sample sizes and as such they are often used as proxies for HIV. Although these proxies are imperfect as they do not mirror risk of HIV acquisition exactly, they are at least objective, externally valid outcome measures, which can be used to assess sexual risk taking. Clearly, the outcome measures need to reflect the context in which the intervention is being delivered and the specific behaviours or other factors being targeted by the intervention. Assessing the wider societal impact of these interventions, although important in terms of disentangling intervention effects, adds to their cost and complexity.
As a consequence of the difficulties of using biomarker endpoints, many HIV prevention studies on adolescents choose instead to rely on changes in reported sexual behaviour to assess intervention effectiveness. Measurement of self-reported sexual behaviour is subject to social desirability bias, particularly so for young people. This is reflected in the many studies among young people in Africa, in which there is a mismatch between self-reports and externally validated measures of sexual behaviour (biomarkers, including HIV, STIs and pregnancy) [57–60]. In addition, there are few culturally appropriate and validated scales of other proximate determinants of HIV infection such as mental health, self-esteem, self-efficacy and so on. There is a growing research literature on studies aimed at improving the validity of measurement in developing country settings, which investigators need to take into account when designing their studies.
To conclude, young people in Africa, particularly the young women, continue to bear the brunt of the HIV epidemic. Adolescents need to continue to be an important focus for HIV prevention programming and research. It is increasingly clear that multilevel approaches to prevention will be required to reduce rates of HIV in this age group. It is imperative that adolescents are not excluded from the opportunity to take part in prevention research.
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 339).
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