David Ross and colleagues conduct a follow-up survey of the community-based MEMA kwa Vijana (“Good things for young people”) trial in rural Tanzania to assess the long-term behavioral and biological impact of an adolescent sexual health intervention., Background The ability of specific behaviour-change interventions to reduce HIV infection in young people remains questionable. Since January 1999, an adolescent sexual and reproductive health (SRH) intervention has been implemented in ten randomly chosen intervention communities in rural Tanzania, within a community randomised trial (see below; NCT00248469). The intervention consisted of teacher-led, peer-assisted in-school education, youth-friendly health services, community activities, and youth condom promotion and distribution. Process evaluation in 1999–2002 showed high intervention quality and coverage. A 2001/2 intervention impact evaluation showed no impact on the primary outcomes of HIV seroincidence and herpes simplex virus type 2 (HSV-2) seroprevalence but found substantial improvements in SRH knowledge, reported attitudes, and some reported sexual behaviours. It was postulated that the impact on “upstream” knowledge, attitude, and reported behaviour outcomes seen at the 3-year follow-up would, in the longer term, lead to a reduction in HIV and HSV-2 infection rates and other biological outcomes. A further impact evaluation survey in 2007/8 (∼9 years post-intervention) tested this hypothesis. Methods and Findings This is a cross-sectional survey (June 2007 through July 2008) of 13,814 young people aged 15–30 y who had attended trial schools during the first phase of the MEMA kwa Vijana intervention trial (1999–2002). Prevalences of the primary outcomes HIV and HSV-2 were 1.8% and 25.9% in males and 4.0% and 41.4% in females, respectively. The intervention did not significantly reduce risk of HIV (males adjusted prevalence ratio [aPR] 0.91, 95%CI 0.50–1.65; females aPR 1.07, 95%CI 0.68–1.67) or HSV-2 (males aPR 0.94, 95%CI 0.77–1.15; females aPR 0.96, 95%CI 0.87–1.06). The intervention was associated with a reduction in the proportion of males reporting more than four sexual partners in their lifetime (aPR 0.87, 95%CI 0.78–0.97) and an increase in reported condom use at last sex with a non-regular partner among females (aPR 1.34, 95%CI 1.07–1.69). There was a clear and consistent beneficial impact on knowledge, but no significant impact on reported attitudes to sexual risk, reported pregnancies, or other reported sexual behaviours. The study population was likely to have been, on average, at lower risk of HIV and other sexually transmitted infections compared to other rural populations, as only youth who had reached year five of primary school were eligible. Conclusions SRH knowledge can be improved and retained long-term, but this intervention had only a limited effect on reported behaviour and no significant effect on HIV/STI prevalence. Youth interventions integrated within intensive, community-wide risk reduction programmes may be more successful and should be evaluated. Trial Registration ClinicalTrials.gov NCT00248469 Please see later in the article for the Editors' Summary, Editors' Summary Background Every year, about 2.5 million people become infected with the human immunodeficiency virus (HIV), the virus that causes AIDS. HIV is most often spread through unprotected sex with an infected partner, so individuals can reduce their risk of HIV infection by abstaining from sex, by delaying first sex, by having few partners, and by always using a condom. And, because nearly half of new HIV infections occur among youths (15- to 24-year-olds), programs targeted at adolescents that encourage these protective behaviors could have a substantial impact on the HIV epidemic. One such program is the MEMA kwa Vijana (“Good things for young people”) program in rural Tanzania. This program includes in-school sexual and reproductive health (SRH) education for pupils in their last three years of primary education (12- to 15-year-olds) that provides them with the knowledge and skills needed to delay sexual debut and to reduce sexual risk taking. Between 1999 and 2002, the program was trialed in ten randomly chosen rural communities in the Mwanza Region of Tanzania; ten similar communities that did not receive the intervention acted as controls. Since 2004, the program has been scaled up to cover more communities. Why Was This Study Done? Although the quality and coverage of the MEMA kwa Vijana program was good, a 2001/2002 evaluation found no evidence that the intervention had reduced the incidence of HIV (the proportion of the young people in the trial who became HIV positive during the follow-up period) or the prevalence (the proportion of the young people in the trial who were HIV positive at the end of the follow-up period) of herpes simplex virus 2 (HSV-2, another sexually transmitted virus). However, the evaluation found improvements in SRH knowledge, in reported sexual attitudes, and in some reported sexual behaviors. Evaluations of other HIV prevention programs in other developing countries have also failed to provide strong evidence that such programs decrease the risk of HIV infection or other biological outcomes such as the frequency of other sexually transmitted infections or pregnancies, even when SRH knowledge improves. One possibility is that it takes some time for improved SRH knowledge to be reflected in true changes in sexual behavior and in HIV prevalence. In this follow-up study, therefore, researchers investigate the long-term impact of the MEMA kwa Vijana program on HIV and HSV-2 prevalence and ask whether the improvement in knowledge, reported attitudes and sexual risk behaviours seen at the 3-year follow up has persisted. What Did the Researchers Do and Find? In 2007/8, the researchers surveyed nearly 14,000 young people who had attended the trial schools between 1999 and 2002. Each participant had their HIV and HSV-2 status determined and answered questions (for example, “can HIV be caught by sexual intercourse (making love) with someone,” and “if a girl accepts a gift from a boy, must she agree to have sexual intercourse (make love) with him?”) to provide three composite sexual knowledge scores and one composite attitude score. 1.8% of the male and 4.0% of the female participants were HIV positive; 25.9% and 41.4% of the male and female participants, respectively, were HSV-2 positive. The prevalences were similar among the young people whose trial communities had been randomly allocated to receive the MEMA kwa Vijana Program and those whose communities had not received it, indicating that the MEMA kwa Vijana intervention program had not reduced the risk of HIV or HSV-2. The intervention program was associated, however, with a reduction in the proportion of men reporting more than four sexual partners in their lifetime and with an increase in reported condom use at last sex with a non-regular partner among women. Finally, although the intervention had still increased SRH knowledge, it now had had no impact on reported attitudes to sexual risk, reported pregnancies, or other reported risky sexual behaviors beyond what might have happened due to chance. What Do These Findings Mean? These findings indicate that, in the MEMA kwa Vijana trial, SRH knowledge improved and that this improved knowledge was retained for many years. Disappointingly, however, this intervention program had only a limited effect on reported sexual behaviors and no effect on HIV and HSV-2 prevalence at the 9-year follow-up. Although these findings may not be generalizable to other adolescent populations, they suggest that intervention programs that target only adolescents might not be particularly effective. Young people might find it hard to put their improved skills and knowledge into action when challenged, for example, by widespread community attitudes such as acceptance of older male–younger female relationships. Thus, the researchers suggest that the integration of youth HIV prevention programs within risk reduction programs that tackle sexual norms and expectations in all age groups might be a more successful approach and should be evaluated. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000287. This study is further discussed in a PLoS Medicine Perspective by Rachel Jewkes More information about the MEMA kwa Vijana program is available at their Web site Information is available from the Programme for Research and Capacity Building in Sexual and Reproductive Health and HIV in Developing Countries on recent and ongoing research on HIV infection and other STIs Information is available from the World Health Organization on HIV and on the health of young people Information on HIV is available from UNAIDS Information on HIV in children and adolescents is available from UNICEF Information on HIV prevention interventions in the education sector is available from UNESCO Information on HIV infection and AIDS is available from the US National Institute of Allergy and Infectious Diseases The US Centers for Disease Control and Prevention provide information on HIV/AIDS and on HIV/AIDS among youth (in English and Spanish) HIV InSitehas comprehensive information on all aspects of HIV/AIDS, including links to information on the prevention of HIV/AIDS Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on HIV and AIDS prevention and AIDS and sex education (in English and Spanish)