Challenges to Conducting HIV Preventative Vaccine Trials With Adolescents

Abstract

It is estimated that 10.3 million people aged 15-24 are living with HIV infection/AIDS worldwide, with 7000 new infections occurring each day. Many of these infections occur during the adolescent years. These rates of infection make adolescents an important target for research in primary prevention. Currently, preparations are under way by the National Institutes of Health-supported HIV networks--the Adolescent Trials Network, the Pediatric AIDS Clinical Trials Group, and the HIV Vaccines Trials Network--for phase 1/2 HIV vaccine trials involving adolescents in the United States. Identifying the challenges to conducting HIV vaccine trials with this population is a crucial component of these preparations. Challenges to HIV vaccine trials with adolescents were identified by reviewing previous vaccine research for adolescents and HIV infection in adolescents and speaking with experts in HIV/AIDS and adolescent medicine. Adolescents (typically those younger than 18 years of age) are minors and fall under ethical and regulatory safeguards for their participation in clinical research including parental permission. Adolescents may not appropriately perceive personal risk, posing challenges for informed consent as well as prevention counseling during a trial. Safety and immunogenicity studies of adolescents are likely to be required by the US Food and Drug Administration before vaccine approval for this population. Early identification and subsequent follow-up of high-risk adolescents are problematic. Vaccine-induced seropositivity may present potential barriers to military service, employment, marriage, and acquiring health insurance. The age at optimal immunization, particularly for girls in some countries, may be during preadolescence. The successful completion of HIV vaccine trials with adolescents must address these challenges both in the United States and internationally. This report addresses relevant background information, identifies the issues surrounding HIV vaccine trials with adolescents, discusses what progress has been made, and addresses plans and implications for the implementation of these trials.

Ethical and practical challenges in implementing informed consent in HIV/AIDS clinical trials in developing or resource-limited countries

“…Adolescents should agree to participate in the vaccine trial if they are capable of assenting (Jaspan et al, 2008;Mc Clure et al, 2008;Slack et al, 2007). The adolescent's right to autonomy should be respected, while post-consent testing should provide verification of adolescents' understanding of concrete elements of the research (Slack et al, 2007).…”

“…The adolescent's right to autonomy should be respected, while post-consent testing should provide verification of adolescents' understanding of concrete elements of the research (Slack et al, 2007). Adolescents who agree to enrol in the research trial should receive comprehensive prevention counselling, tailored to their developmental age (Mc Clure et al, 2008). The information sheets for informed consent for adolescents and their parents/legal guardians should address age-specific concerns to ensure truly informed consent (Bekker et al, 2005).…”

“…Thus, parental concerns to post-study vaccine-induced seropositivity, as well as to the stigma and fear of such an HIV-positive diagnosis should be addressed (Mc Clure et al, 2008). Agreement to participate to Phase I/II trials of safety and immunogenicity should be given by potential study participants and their parents only after thorough evaluation of information available from previous trials among adults and only if the research does not place them at greater than minimal risk (Jaspan et al, 2008;Mc Clure et al, 2008). Reasonable safety data should be available after trial completion in an adult cohort (Bekker et al, 2005;Jaspan et al, 2008;Mc Clure et al, 2008;Slack, et al, 2007).…”

“…Agreement to participate to Phase I/II trials of safety and immunogenicity should be given by potential study participants and their parents only after thorough evaluation of information available from previous trials among adults and only if the research does not place them at greater than minimal risk (Jaspan et al, 2008;Mc Clure et al, 2008). Reasonable safety data should be available after trial completion in an adult cohort (Bekker et al, 2005;Jaspan et al, 2008;Mc Clure et al, 2008;Slack, et al, 2007). Protocols should be designed in close consultation with local community leaders and community attitudes, adolescent consultants and experts (Mc Clure et al, 2008), as well as with regulatory authorities (Jaspan et al, 2008).…”

Out of the Black Box: Treatment of Resistant Depression in Adolescents and the Antidepressant Controversy

“…Recruiting and retaining adolescents is especially challenging (McClure et al 2004). To ensure adequate sample size, pediatric clinical trials are often conducted at multiple sites.…”