Meeting Minutes - November 9, 2010

Office of AIDS Research Advisory Council
Thirty-first Meeting
November 9, 2010

National Institutes of Health
U.S. Department of Health and Human Services
5635 Fishers Lane Conference Center
Rockville, MD

Members Present: Dr. Sharon L. Hillier (Chair), Dr. Jack Whitescarver (Executive Secretary), Dr. Judith Auerbach, Ms. Dawn Averitt Bridge, Dr. David B. Clifford, Dr. Carrie E. Foote, Dr. Patricia Garcia, Ms. Yvonne M. Green, Dr. Gary W. Harper, Dr. Betsy C. Herold, Dr. Lisa Jacobson, Ms. Catalina Sol, Dr. Ronald Swanstrom, Dr. Irene S. Vernon, Dr. Paul Volberding, and Dr. Judith N. Wasserheit

Ex Officio Members Present: Dr. Emily Erbelding for Dr. Carl Dieffenbach, Dr. Kevin Fenton, and Dr. Christel H. Uittenbogaart

Invited Speakers and Guests: Dr. Lawrence J. D’Angelo, Dr. Patricia M. Flynn, Dr. Donna Futterman, Dr. Sybil G. Hosek, Dr. Marguerita Lightfoot, Dr. Lynne Mofenson, Dr. Sharon Nichols, Dr. Alice Pau, Dr. Ligia Peralta, Dr. Brett J. Rudy, Dr. Monica S. Ruiz, Dr. Craig M. Wilson, and Dr. Gregory D. Zimet

Welcome and Meeting Overview

The National Institutes of Health (NIH) Office of AIDS Research Advisory Council (OARAC) convened its thirty-first meeting at 8:30 a.m. at the Fishers Lane Conference Center in Rockville, Maryland. Dr. Sharon Hillier, Chair, welcomed the OARAC members, invited speakers, and guests.

The topic of the meeting was HIV and AIDS in adolescents. Dr. Hillier noted that today’s presentations would address: the epidemiology of HIV infection among adolescents; the cognitive and biological development of HIV-infected adolescents; behavioral risks/decision-making; prevention and treatment strategies; challenges to engaging and involving adolescents in clinical research; and emerging opportunities and gaps for engaging adolescents in AIDS research.

Dr. Hillier referred participants to the meeting folder for information about the next two OARAC meetings.

The minutes of the March 18, 2010 OARAC meeting were approved as submitted.

Director’s Report

Dr. Jack Whitescarver, Director of the Office of AIDS Research (OAR), welcomed everyone to this meeting of the OARAC. He also welcomed the new OARAC Chair, Dr. Sharon Hillier. She is Professor and Vice-Chair for Faculty Affairs at the University of Pittsburgh and Director of Reproductive Infectious Disease Research at the Magee-Women’s Hospital.

In addition, Dr. Whitescarver welcomed a number of new OARAC members including: Dr. Judith Auerbach, San Francisco AIDS Foundation; Dr. David Clifford, Washington University School of Medicine; Dr. Carrie Foote, Indiana University-Purdue University; Dr. Patricia Garcia, Northwestern University Feinberg School of Medicine; Ms. Yvonne Green, N Street Village, Washington D.C.; Dr. Lisa Jacobson, Johns Hopkins University; Ms. Catalina Sol, La Clinica Del Pueblo, Washington D.C.; Dr. Ronald Swanstrom, University of North Carolina at Chapel Hill; Dr. Irene Vernon, Colorado State University; and Dr. Judith Wasserheit, University of Washington. He also welcomed several new ex officio members including: Dr. James Anderson, who is the newly appointed Director of the NIH Division of Program Coordination Planning and Strategic Initiatives (DPCPSI); Dr. Victoria Davey, Department of Veterans Affairs; and Dr. Kim Lyerly, Duke University, who represents the National Cancer Advisory Board of the National Cancer Institute (NCI).

NIH Personnel Changes

Dr. Whitescarver noted several recent personnel changes at NIH: Dr. Harold Varmus, former Director of NIH and former President of the Memorial Sloan-Kettering Cancer Center, has returned to NIH as the Director of the NCI; and Dr. Lawrence Tabak, former Director of the National Institute of Dental and Craniofacial Research (NIDCR) has been appointed as Principal Deputy Director of NIH.

Conflict of Interest Statements

Dr. Whitescarver asked Council members to review and sign the conflict of interest statement provided to them. He reminded the Council members of the importance of this process.

Budget Update

Dr. Whitescarver stated that Fiscal Year (FY) 2011 Appropriations bill has not been completed by Congress; and therefore NIH is operating under a continuing resolution through December 3, 2010 at the FY 2010 funding level. He referred participants to the meeting folder for information on the AIDS research portion of the Fiscal Year (FY) 2011 President’s budget request to Congress that would include an approximate 3.2 percent increase over the FY 2010 level.

President’s National HIV/AIDS Strategy

Dr. Whitescarver reported that the OAR has been working with other Department of Health and Human Services (HHS) agencies to develop the HHS Operational Plan to the President’s National HIV/AIDS Strategy. The goals of the strategy are: 1) reducing the incidence of HIV; 2) increasing access to care and improving outcomes; and 3) reducing health disparities. He noted that the plan places significant focus on HIV/AIDS services and programs than on research. He stated that the OARAC will discuss the role of NIH in the Strategy once the Operational Plan has been sent to President Obama.

International AIDS Society Conference

Dr. Whitescarver reported that OAR sponsored a series of highly successful satellite meetings and scholarship programs in conjunction with the International AIDS Society (IAS) conference that was held in Vienna in July 2010. This included: a workshop on viral reservoirs leading to a cure; a satellite meeting on AIDS and Aging; and a grantsmanship workshop. He noted that he will be serving on the Conference Coordinating Committee for the next International AIDS Conference, which will be held in Washington, D.C. in 2012. Dr. Whitescarver commented that OAR is working closely with the White House, State Department, the United States Agency for International Development (USAID), and the U.S. Food and Drug Administration (FDA) to coordinate the next steps in follow-up to the CAPRISA 004 microbicide clinical study results that were reported at the IAS conference. This study was sponsored by USAID, with infrastructure and training support from NIH.

International Initiatives

Dr. Whitescarver noted that the OAR continues to sponsor several ongoing bilateral HIV/AIDS collaborative initiatives with India, Russia, China, and several Caribbean countries. These initiatives provide critical support to increase research collaborations between U.S. and international scientists building on the unique scientific strengths and capabilities of researchers in these nations.

Social and Behavioral HIV Prevention Research Think Tank

Dr. Whitescarver reported that OAR convened a comprehensive “think tank” on social and behavioral HIV prevention research on September 26-28. The think tank was co-chaired by Dr. Judith Auerbach and Dr. Thomas Coates and organized with assistance from Dr. Ellen Stover from NIMH. The meeting brought together a stellar group of experts from across the government and around the world to identify new research priorities to move the science forward in this critical scientific area and address the current AIDS epidemic. Dr. Whitescarver noted that he plans to organize a trans-NIH group to assist the OAR in implementing the recommendations that were developed at this highly successful meeting.

Meeting Overview

Dr. Whitescarver noted that OARAC meetings play a critical role in encouraging in depth discussions on selected topics that are current and reflect the changing AIDS epidemic. He stated that the discussions provide guidance to OAR and NIH in priority setting and strategic planning. He noted that the last meeting, on March 2010, was devoted to the topic of AIDS and aging. Today’s meeting will address another important at-risk population - adolescents. He pointed out that adolescents continue to represent an important population at risk for and acquiring HIV infection. Recent data from the Centers for Disease Control and Prevention (CDC) show increasing rates of new HIV infections among men-who-have–sex-with-men (MSM) aged 13-24, especially among Black/African Americans and women aged 13-19 years old. This meeting is designed to provide additional insight on the complex factors that facilitate HIV transmission and risk behaviors among adolescents. Dr. Whitescarver stated that he is looking to OARAC to assist in identifying the most important scientific opportunities, gaps, and priorities in this area of research.

UPDATE ON OARAC WORKING GROUPS FOR TREATMENT AND PREVENTION GUIDELINES

Dr. Alice Pau, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, and Executive Secretary for the Adult and Adolescent Guidelines Working Group, and Dr. Lynne Mofenson, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and Co-chair of the Perinatal and Pediatric Treatment Guidelines Working Group, provided an overview of the recent updates of the Treatment and Prevention Guidelines.

Dr. Mofenson reported that the Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States were updated in May 2010. The revisions included: boxed recommendations with ratings for strength and quality of evidence; specific descriptions of the criteria used to categorize recommendations for use of drugs in pregnancy; and a caution on the use of lopinavir-ritonavir in newborns (especially preterm). The revisions also included an update based on a recent international perinatal clinical trial on breastfeeding by HIV-infected women, which is not recommended in the United States. The updates also included new data on the feeding of premasticated food to infants and the risk of HIV transmission. A planned mid-2011 update will include information on new antiretrovirals for use during pregnancy, as well as an expansion of the table on antiretroviral (ARV) drug use in pregnancy. The update also will include several new sections on acute HIV infection during pregnancy, HIV-2 infection during pregnancy, and pregnancy in perinatally-infected females. Dr. Mofenson stated that the Working Group is seeking new members with expertise in women’s health.

Dr. Mofenson reported that the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection were also updated in August 2010. The revisions included: boxed recommendations with ratings for strength and quality of evidence; flagging of recommendations based on data from research in adults; expansion of the Pediatric Antiretroviral Drug Supplement; and modification of toxicity management hyperlinks in table format. The update also included revisions to recommendations on: viral diagnostic testing of infants at high risk of infection at birth; CD4 criteria for when to start antiretroviral therapy (ART) in children older than one year of age; initiation of protease inhibitor (PI)-based therapy in children less than three years of age who were exposed to single-dose nevirapine; and use of darunavir/ritonavir and nelfinavir. A planned mid-2011 update is expected to include revisions to the “What to Start” section, as well as updates on pediatric information for various drugs. Dr. Mofenson stated that the Working Group is seeking new members with relevant expertise. Dr. Mofenson stated that the Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-Exposed and HIV-Infected Children were last published in 2009. Dr. Mofenson reviewed changes in Working Group membership and stated that revisions to these Guidelines are planned for later next year.

Dr. Pau reported that the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents were last updated in 2009. Revisions are expected in 2011 in a new, easily searchable, HTML format. The Working Group will meet in March 2011 to address the development and implementation of these treatment guidelines. Dr. Pau reported that the Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents were last updated in 2009. She noted that the next revisions are expected in early 2011 and will be available on the AIDSinfo website along with all of the other guidelines. The revisions will harmonize the style, content, and rating system with the adult ARV guidelines. The revisions will address when to start ART in individuals with opportunistic infections; the management of immune reconstitution inflammatory syndrome (IRIS); and major changes to sections on HIV coinfections including tuberculosis (TB), human papillomavirus (HPV), hepatitis B virus (HBV), and hepatitis C virus (HCV).

SUMMARY OF THE FORUM FOR COLLABORATIVE HIV RESEARCH WORKSHOP ON INCLUSION OF ADOLESCENTS IN HIV BIOMEDICAL PREVENTION CLINICAL TRIALS

Dr. Monica Ruiz, Assistant Research Professor, George Washington University School of Public Health and Health Services, summarized the recent Forum for Collaborative HIV Research (FCHR) Workshop on the Inclusion of Adolescents in HIV Biomedical Prevention Trials. She stated that although adolescents are biologically and behaviorally at increased risk of HIV infection, few clinical trials on biomedical HIV prevention strategies include adolescents. She noted that the development and eventual use of these prevention modalities in adolescent populations requires an understanding of the unique psychosocial and biomedical changes that occur during adolescence and the impact of these changes on product safety, efficacy, and ultimately effectiveness.

Dr. Ruiz stated that NIH and FCHR convened the workshop on June 17-19, 2009, in Washington D.C. The goals of the international Workshop were to: 1) examine and discuss the feasibility, desirability, timing of, and barriers to the enrollment of adolescents in clinical trials to test new HIV biomedical prevention technologies; 2) open a dialogue and develop recommendations for inclusion of adolescents in such trials; and 3) inform drug development and licensure processes that would be employed during the pursuit of efficacy data in adult trials, ideally allowing labeling indications for youth concurrent with those of adults. Dr. Ruiz stated that Workshop participants represented academia, industry, HIV-affected communities, and various branches of the U.S. Government. Participants provided medical, behavioral, ethical, legal, and regulatory expertise to discussions on the ramifications of including or not including adolescents in biomedical prevention trials.

Dr. Ruiz summarized the Workshop recommendations, including the need to: collect adolescent-specific data in biomedical HIV prevention clinical trials; address behavioral and social concerns associated with adolescent participation in those trials; and involve the community in determining whether young adolescents should participate in clinical studies. She noted that a report on the Workshop and the specific recommendations are available in the Journal of Acquired Immune Deficiency Syndromes (JAIDS); 54, S12-S17.

EPIDEMIOLOGY OF HIV INFECTION AMONG ADOLESCENTS

Dr. Bret Rudy, Associate Professor and Vice Chair, New York University Langone Medical Center, described the HIV epidemic among adolescents in the United States and internationally. He presented statistics from the Joint United Nations Programme on HIV/AIDS (UNAIDS) that highlight the magnitude of the HIV epidemic in 15 to 25 year olds. He also noted the prominent role of new HIV infections among adolescents in the ongoing epidemic.

Dr. Rudy described data to show that the overall HIV epidemic can be viewed as many smaller HIV epidemics that vary in risk factors and demographics, depending on the population affected. He noted that the MSM population is driving the epidemics in North America, Latin America, Central Europe, Western Europe, and Oceania, while intravenous drug use is driving the epidemic in Eastern Europe and parts of Asia.

Dr. Rudy described the differences in the HIV epidemic in the United States across racial/ethnic groups, age, gender, and sexual identity. He noted the high rates of HIV infection among young MSM, adolescent females, African Americans, and Latino populations.

Dr. Rudy provided a summary of two research initiatives that are developing new ways of partnering with the community to identify HIV-infected youth and link them to care. The Men’s Sexual Health Project offers HIV information and testing in youth-oriented venues. In addition, the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) is conducting the “Connect to Protect” protocol that is designed to evaluate venue-based HIV testing of young men and women, including adolescents, at 15 clinical sites located within high risk communities.

Dr. Rudy identified the need for more research on: barriers for young adults to HIV testing and linkage to care; the increasing reports of antiretroviral-resistant strains of HIV in young people; metabolic complications of long-term HIV infection and treatment in adolescents; and high risk behaviors among several groups of youth.

COGNITIVE DEVELOPMENT OF HIV-INFECTED ADOLESCENTS

Dr. Sharon Nichols, Professor, University of California, San Diego, discussed the effects of HIV disease on neurological and cognitive functioning in adolescents. She stated that adolescents with perinatally-acquired HIV are at risk for central nervous system (CNS) impairments, especially expressive language impairments. She noted that ART appears to reduce the risk of CNS impairments. Dr. Nichols also described the impact of cognitive impairments on medication adherence, judgment and risk behaviors, as well as academic and day-to-day functioning.

Dr. Nichols suggested that research on HIV and the CNS in adolescents with perinatally-acquired HIV should include comparisons with carefully matched control populations. She also described several new studies on imaging and other biomarkers that may yield clues to the mechanisms of how HIV infection impacts the CNS.

Dr. Nichols stated that few studies have examined the effects of HIV infection on the CNS in adolescents who became infected as a result of high risk behaviors. She described an ongoing ATN study entitled, “Neurocognitive Assessments of Youth Initiating ART”. This study will evaluate whether early initiation of ART in HIV-infected individuals 18 to 24 years of age is neuro-protective. The study also will test for cognitive and behavioral functioning.

Dr. Nichols identified several research questions relevant to HIV and the CNS in adolescents including: the vulnerability of the developing adolescent brain to HIV infection and long-term ART; how the timing of ARV initiation affects neurocognition; early HIV infection events that predispose to later neurocognitive impairment; and the need to identify biomarkers for neurocognitive impairment. She commented that additional research is needed in this area in order to better diagnose and treat neurocognitive complications associated with HIV disease and ART.

BIOLOGICAL DEVELOPMENT OF ADOLESCENTS WITH HIV DISEASE

Dr. Patricia Flynn, Professor of Pediatrics and Preventive Medicine, University of Tennessee Health Science Center, and the Arthur Ashe Chair of Pediatric AIDS Research at St. Jude Children’s Research Hospital, described the growth and development of HIV-infected adolescents. She noted that there are several international and domestic clinical studies that demonstrate lower height and weight scores (a measure of body mass index [BMI]) in children with perinatally-acquired HIV compared with HIV-uninfected peers. She stated that the slowest growth was associated with higher viral loads and that ART was associated with slight increases in growth rate and BMI, especially in children with low levels of viral loads. Dr. Flynn also described several studies reporting delayed onset of puberty in children with perinatally-acquired HIV.

Dr. Flynn described several developmental abnormalities caused by HIV and/or ART in several organ systems in HIV-infected children and adolescents. She presented an overview of several studies that showed increased occurrence of lipodystrophy or fat redistribution syndrome; dyslipidemia; glucose metabolism deficits; cardiovascular risk; and renal dysfunction in HIV-infected children and adolescents compared with HIV-uninfected children and adolescents.

Dr. Flynn discussed a study that showed gender differences in cardiovascular risk factors in adolescents with behaviorally-acquired HIV infection. She stated that several ATN clinical studies would be reporting data on this topic in the coming year.

Dr. Flynn noted that improvements in survival, growth, and development gained with ART must be balanced against its adverse effects. She commented that research needs to consider that genetics and lifestyle factors, such as obesity, diet, and exercise, may play a role in the long-term outcome in HIV-infected children and adolescents. She noted that optimal clinical management has not been determined for many of the HIV-associated complications observed in adolescents.

DISCUSSION

OARAC members, speakers, and guests discussed the heterogeneity of important clinical data collected in broad age populations (e.g., 14 to 29 year olds) and the need for data on narrower age ranges. They also noted the need for: additional research on young adolescents; creative strategies to enroll and retain young adolescents in clinical studies; family involvement in research on adolescents; and inclusion of pre-adolescents in clinical trials. OARAC members also noted the need for additional research on biological development in HIV-infected adolescents; long-term outcomes in HIV-infected adolescents; and the efficacy of microbicides for HIV prevention in HIV-infected youth. There also was discussion on the role of circumcision for HIV prevention in young MSM.

BEHAVIORAL RISKS/DECISION MAKING AMONG ADOLESCENTS AND RISK FOR HIV DISEASE

Dr. Sybil Hosek, Professor, John Stroger Hospital of Cooke County, provided an overview of the norms of adolescent sexual activity and described HIV risk behaviors in adolescents. She stated that adolescents today are considerably more likely to engage in a broader repertoire of sexual activities including anal and oral sex. She noted that sexual concurrency, which is characterized by maintaining sexual partnerships that overlap in time, is common among adolescents, and it increases the risks for sexually transmitted infections (STI) including HIV.

Dr. Hosek discussed HIV risk and cognitive development in adolescents. She described how egocentrism, feelings of invulnerability, and the incomplete transition to formal operational thought contribute to increased risk for HIV transmission and acquisition.

Dr. Hosek described adolescent psychological development and HIV risk behaviors. She noted that a healthy identity formation in adolescents can reduce HIV risk behaviors. She stated that the incidence of mental health problems increases during adolescence, and it is associated with an increase in HIV risk behaviors.

Dr. Hosek also described social development and HIV risk behaviors in adolescents. She commented that adolescents with peer groups who engage in HIV risk behaviors are more likely to engage in the same behaviors, while having socially responsible peers can reduce risk behaviors. She also described the association between substance abuse and HIV risk behaviors.

Dr. Hosek summarized several factors that are important for HIV prevention including: providing clear messages about modes of HIV transmission and condom use; identifying the range of social, cultural, economic, and political forces that impact risk/protection; openness in discussion of sexuality; delineating the role of substance use and psychological factors in increasing sexual risk; involving the family and community in the design and conduct of prevention clinical studies; determining historical, psychological, and structural factors that influence sexual risk/protection; and utilizing interactive HIV prevention programs.

PREVENTION PROGRAMS TARGETED FOR ADOLESCENTS

Dr. Marguerita Lightfoot, Associate Professor, Center for AIDS Prevention Studies, University of California, San Francisco, described the use of technology to engage at-risk adolescents in HIV prevention programs. She stated that current electronic communication technology can be used to deliver brief, sustainable, feasible, and easily accessible HIV prevention interventions to large numbers of adolescents.

Dr. Lightfoot compared the use of technology to deliver interventions to small group counseling formats. She stated that small groups are useful and successful, but also are expensive, require extensive staff training, and reach small numbers of youth. She noted that adolescents may be more comfortable accessing interventions delivered through the technologies they use and enjoy such as social media. She noted most adolescents, regardless of whether they have a computer at home, access the internet regularly. Dr. Lightfoot discussed the need to adapt existing, successful prevention interventions for internet delivery to reach a larger audience.

Dr. Lightfoot described Project Light, an HIV prevention program that uses small group counseling in parallel with culturally-tailored computer sessions to reach at-risk youth. The program was tested at a continuation school attended by predominately African American and Latino adolescents of low socioeconomic status. She stated that completion rates for the computer intervention were much higher than for the small group intervention. She commented that risk behaviors decreased significantly among youth who participated in the computerized intervention. Dr. Lightfoot stated that Project Light is now being tested in a large randomized controlled trial.

Dr. Lightfoot also described Street Smart, an HIV prevention intervention for runaway and homeless youth distributed as a Diffusion of Effective Behavioral Intervention (DEBI) by the CDC. Dr. Lightfoot and colleagues have developed an interactive Internet website designed to establish the peer norms and peer environment that support positive changes and healthy sexual behaviors in youth who have completed the initial Street Smart intervention.

Dr. Lightfoot described other forms of technology that may be suitable for reaching youth, including texting, smart phones, and social networking media. She concluded that today’s electronic communication technology is an acceptable way to reach and engage youth; allows delivery of interventions with fidelity; reduces staff training; allows targeting to different subpopulations of youth; and permits a less guarded response by youth than is possible to obtain in face-to-face interactions.

DISCUSSION

OARAC members, speakers, and guests discussed the use of electronic communication technologies for dissemination of HIV prevention strategies in adolescents; the accessibility of these technologies in the United States and internationally; and the need to offer follow-up personal counseling opportunities. They also addressed: the importance of HIV education in schools; inclusion of racial/ethnic minorities in epidemiologic data on HIV infection in adolescents; the importance of multilingual prevention interventions; and the potential impact of racism and homophobia on HIV risk behaviors in adolescents.

The OARAC members and speakers also discussed: the effects of ART regimens on organ system comorbidities; the need for additional research on the biological determinants of vulnerability to HIV infection, organ system disorders, and responses to treatment; HIV testing in adolescents, including identification of behaviorally-acquired and perinatally-acquired infection; and potential differences in risk-taking behaviors and rates of disease progression among perinatally-infected and behaviorally-infected adolescents.

TREATMENT AND CARE OF ADOLESCENTS WITH HIV DISEASE

Dr. Lawrence D’Angelo, Chief of the Division of Adolescent and Young Adult Medicine, Children’s National Medical Center described the challenges to treatment and care of HIV-infected adolescents. He summarized U.S. treatment guidelines and noted that while early, aggressive treatment appears to be beneficial to long-term HIV outcomes, the effects of long-term ART are not known. He also described variations in ARV pharmacokinetics in adolescents from different racial/ethnic populations.

Dr. D’Angelo outlined the challenges to treatment adherence in HIV-infected adolescents. He also discussed possible strategies to improve adherence, including group/individual interventions, electronic memory tools, and directly observed therapy.

Dr. D’Angelo described research on disclosure of HIV serostatus by adolescents. He noted that adolescents are unlikely to disclose their HIV infection to parents and sexual partners. He described potential consequences of non-disclosure including: non-adherence to therapy; continued risky drug use or sexual behaviors; failure to seek/receive appropriate treatment and healthcare; impaired mental health/psychosocial functions; and secondary transmission of HIV infection.

Dr. D’Angelo outlined the increasing problem of ARV resistance in HIV-infected adolescents. He stated that the most important antecedent to the development of resistance is poor adherence to an ARV regimen. He also described the complexity and timing requirements of a successful transition of HIV-infected adolescents and young adults from a child-centered to an adult-oriented healthcare system.

Dr. D’Angelo also described the resources needed to surmount the challenges to treatment and care for adolescents including: continued acknowledgement of the unique health needs of HIV-infected youth; committed networks of caregivers; linkages of diagnosis, treatment and care; and availability and access to psychosocial programs. He noted the importance of additional research on the clinical needs of adolescents.

ENGAGING YOUTH IN AIDS CLINICAL RESEARCH

Dr. Gregory Zimet, Professor, Indiana University School of Medicine, described the challenges to engaging adolescents in HIV prevention clinical research. He stated that adolescents are a natural target group for biomedical prevention programs and should be included in clinical trials. He commented that adolescents, a vulnerable population, require greater attention to minimize potential harm.

Dr. Zimet noted that additional understanding is needed regarding the need for the inclusion of parents and families in the recruitment of adolescents in biomedical clinical research. He addressed the unique challenges related to the potential disclosure of the adolescent’s sexual behaviors to his/her parent(s), particularly for young MSM.

Dr. Zimet described risk compensation, whereby an intervention that reduces risk will result in increased risk behaviors. He also discussed the link between risk compensation and “preventive misconception.” The latter occurs when a study participant: 1) overestimates the probability of being assigned to the experimental intervention; and 2) assumes that the intervention will be effective. Dr. Zimet stated that there is little evidence of risk compensation in HIV prevention trials of circumcision and pre-exposure prophylaxis in adults, despite the occurrence of preventive misconception.

Dr. Zimet discussed the need for more research on preventive misconception and risk compensation in adolescents. He stated that researchers have an ethical responsibility to minimize the potential for risk compensation in this population. He described the following approaches to reducing risk compensation by: reduction of behavioral risk; modification of the informed consent process; and providing supplemental materials outside of the informed consent process to directly address preventive misconception.

Dr. Zimet underscored the need for further research in these areas in order to better engage adolescents in AIDS clinical studies.

ETHICAL AND REGULATORY ISSUES FOR INVOLVING ADOLESCENTS IN AIDS CLINICAL RESEARCH

Dr. Legia Peralta, Associate Professor of Pediatrics, University of Maryland Medical Center, described several ethical and regulatory issues when adolescents are involved in AIDS clinical research. She discussed engagement of racial/ethnic minority youth in AIDS clinical trials. She stated that factors that may influence an adolescent’s willingness or eligibility to participate in a clinical trial include: substance abuse; mental health issues; sexuality; stigma; homelessness; unemployment; mistrust of researchers and clinical trials; HIV-associated cognitive issues; and biological developmental factors. She discussed the need for representation of youth, especially from racial/ethnic minority groups, on community advisory boards. She noted that youth are willing to participate in research when they understand the informed consent process. Dr. Peralta stated that monetary payments and other incentives increase the willingness of adolescents to participate in clinical research. She noted that higher monetary payments do not appear to blind respondents to the study risks.

Dr. Peralta discussed special regulatory issues associated with participation of adolescents in AIDS clinical studies. She described potential conflicts between research protocols and clinical practice and between cultural norms and research regulatory policies. She stated that community participation in the design and conduct of research is essential.

Dr. Peralta discussed the need for more research on the retention of adolescents in clinical trials. She stated that research on adults has identified factors associated with loss to follow-up including: HIV-seronegative status; age; and increasing duration of clinical trials. She stated that higher retention rates among HIV-infected individuals were associated with previous participation in clinical trials, linkage to care, and access to ART.

Dr. Peralta stated that research using the Internet represents an innovative communication technology to attract young clinical trial participants, although special considerations are needed in regards to screening of potential study participants, the informed consent process, incentives, and retention.

DISCUSSION

OARAC members, speakers, and guests discussed the need for more research to identify the optimal treatment regimens for HIV-infected adolescents who were infected perinatally compared to behaviorally infected. They also discussed the need for public-private partnerships for conducting research using Internet or video game interventions.

INTERNATIONAL PERSPECTIVE ON ADOLESCENTS AND HIV/AIDS RESEARCH

Dr. Donna Futterman, Director of the Adolescent AIDS Program and Professor of Clinical Pediatrics, Albert Einstein College of Medicine of Yeshiva University, presented the most recent statistics of AIDS among adolescents worldwide. She described gender disparities, stating that in the hardest impacted regions of the world, Africa and Southeast Asia, about two-thirds of the HIV infections among youth are in females. In most other parts of the world, she noted that the majority of HIV infections are among male youth.

Dr. Futterman discussed several factors that increase the vulnerability of youth to HIV acquisition and transmission. She stated that biological factors of vulnerability include: the immature cervix; lack of male circumcision; and a high prevalence of other STIs in some populations. She stated that there are economic, social, behavioral, and legal barriers that can prevent young people from obtaining prevention interventions, being tested, and receiving treatment.

Dr. Futterman differentiated between the generalized HIV epidemic and epidemics in areas of concentrated HIV prevalence. She stated that in the generalized epidemic, the leading risk factor for young people is sexual transmission. She stated that in areas of a concentrated epidemic, the most at-risk populations include: intravenous drug users; young MSM; commercial and transactional sex workers; and youth in juvenile detention centers.

Dr. Futterman described adolescent-specific issues related to biomedical HIV prevention interventions. She also discussed the need to engage HIV-infected adolescents in care, as well as the need to scale up proven interventions. She stated that youth-friendly care must address three major issues: coping with HIV infection; accessing treatment; and preventing transmission to others.

Dr. Futterman noted that additional research is needed on scalable, usable, and realistic solutions that can impact the HIV epidemic. She noted a need for a continuum of effort, from research to implementation, which applies the best of what is already known and adapts successful interventions for youth. She also described the need for structural interventions for youth.

DISCUSSION

OARAC members, speakers, and guests discussed developmental, social, and behavioral aspects of HIV research in adolescents. They addressed the need for: a definition of adolescence that considers biology and behavior as well as age; more research on the effects of gender, culture, and sexuality norms on the HIV epidemic in adolescents; enrollment of more adolescents and younger age groups, MSM, and youth from racial and ethnic populations in behavioral/social research studies; and interdisciplinary research that links behavior and biology. OARAC members also commented on the need for access to HIV prevention interventions in high-risk venues and the potential use of Internet interventions in schools, domestic violence centers, homeless shelters, and juvenile detention facilities.

The need to engage parents and the community in the design and conduct of clinical trials for adolescents was noted as critical. OARAC members also discussed: parental consent for adolescents in AIDS clinical studies; the conduct of parallel HIV intervention research in adolescents and their parents; and the challenges to possible implementation of community-level ART for HIV prevention. Dr. Whitescarver concluded the discussion session noting that research on HIV and AIDS in adolescents is identified as a research priority as noted in the Fiscal Year (FY) 2011 Trans-NIH Plan for HIV-Related Research and the FY 2011 trans-NIH AIDS budget, and he thanked OARAC for the useful discussions.

PUBLIC COMMENTS

Ms. Carole Treston, Executive Director, AIDS Alliance for Children, Youth, and Families, described a recent summit held in conjunction with the White House Office of National AIDS Policy to examine the impact of HIV disease on youth. She noted that youth are not mini-adults, but are a unique category with many subcategories. She stated that care and research systems, including implementation research systems, must have the flexibility to take youth concerns into account.

CLOSING COMMENTS

Dr. Hillier thanked the OARAC members, speakers, and guests for their participation. The meeting was adjourned at 4:25 p.m. on November 9, 2010.

Signed:

/Jack Whitescarver, Ph.D./
Jack Whitescarver, Ph.D., Executive Secretary

Sharon L. Hillier, Ph.D./
Sharon L. Hillier, Ph.D., Chair