- Email: [email protected]
HIV research in American youth
JOURNAL OF ADOLESCENT HEALTH 2001;29S:1– 4
THE ADOLESCENT MEDICINE HIV/AIDS RESEARCH NETWORK
HIV Research in American Youth AUDREY SMITH ROGERS, Ph.D., M.P.H.
Most reported new HIV infections are in minority populations; in the group aged 13–19 years, 74% of new infections occur in minority populations [1]. The primary transmission route for reported AIDS cases has always been sexual in adolescent females and became predominantly male-to-male sexual transmission in adolescent males in 1995 after the earlier wave of blood-product transmission began to ebb. Thus, the picture of the current, and estimated to be expanding, adolescent HIV epidemic based on reports to the Centers of Disease Control and Prevention is one that is increasingly female, minority, and sexually transmitted through heterosexual activity in females and homosexual activity in males [2]. HIV infection in American adolescents has not received the attention it merits over the years for a number of reasons. This inattention has been owing primarily to the low number of reported adolescent AIDS cases in comparison to the avalanche of diagnoses in the older age groups. Certainly the numbers of HIV infected youth identified and engaged in care have made the easy dismissal of the problem possible [3]. Accurate knowledge of how many American teens are HIV infected remains elusive. The Multicenter AIDS Cohort Study (MACS) showed that age at seroconversion was a significant predictor of time to AIDS, meaning that, if the extrapolation can be made, the median age at which AIDS would develop in individuals infected at the age of 13 occurs 11.6 years later at age 24.6 years [4]. MACS data also would seem to indicate that it is unlikely that more From the Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, Bethesda Maryland. Address correspondence to: Audrey Smith Rogers, Ph.D., M.P.H., PAMAB/CRMC/NICHD/NIH, 6100 Executive Boulevard, Rm 4B11, MSC 7510, Bethesda MD 20892-7510. E-mail: [email protected]. Manuscript accepted May 4, 2001.
than 10% of the individuals infected at age 13 years would have developed AIDS while they were still teenagers [5]. This conclusion and data from others [6,7] would indicate that the bulk of AIDS diagnoses occurring in later decades results from infection as teens or young adults. Based on this information, if one assumes an annual rate of progression to AIDS in teens of 1% to 3% as was demonstrated in MACS, the size of the HIV infected pool required to generate the 1999 incident AIDS cases in 13–19-year olds would be 10,400 –31,200. In fact, using these parameters, HIV infection estimates in the United States for adolescents, aged 13–19 years, have been within a range of 10,000 to 30,000 for the last 4 years. It appears reasonable to assume then that 20,000 adolescents in this age group are currently infected in the United States. This is no small number: where are these youth? Some would contend that the numbers are overestimates, citing the surveillance data on HIV infection. But those surveillance data, being incomplete and not including the HIV epicenters, can hardly prove such a case. However, countering this skepticism is equally difficult because only circumstantial evidence exists. For example, one-quarter of the mothers participating in the landmark Protocol 076 which demonstrated antiretroviral treatment could decrease the odds of perinatal HIV transmission were young women under age 22 years (Pediatric AIDS Clinical Trials Group, personal communication, 1997). The clinical profile of research volunteers in the Adolescent Medicine HIV/AIDS Research Network (the focus of this supplement) indicates that young women may be preferentially screened through family planning and prenatal clinics. They tended to enter the study earlier in their HIV infection than the young men who have no similar focused screening effort and typically entered after an illness had prompted HIV testing.
Published by Elsevier Science Inc., 655 Avenue of the Americas, New York, NY 10010
1054-139X/01/$–see front matter PII S1054-139X(01)00294-4
2
ROGERS
Where are these youth? The answer appears to be that they are not in care because they have not been screened and referred to care. Many, particularly young men, remain unaware of their HIV status and probably even of their risk. Several recent reports attest to the discovery of HIV infected young people when resources have been committed to their identification. The Young Men’s Survey (1994 –1998) conducted HIV serosurveys in seven different American cities among young men aged 15–22 years who reported having sex with other men [8]. The overall rate of sero-positivity among the 3492 young men who consented to testing was 7.2%, and ranged by city from 2.2% to 12.1%. Only 18% knew they were HIV infected before testing and only 15% of those infected were in care. The prevalence of unprotected anal sex during the previous 6 months was 41%. In another study, seven HIV infected young people were identified through contact tracing in a sexual network of 44 persons from a small rural Mississippi town in 1999 [9] after two individuals accepted routine voluntary HIV testing during sexually transmitted infection (STI) evaluation. Another reason that attention to adolescent HIV infection has lagged behind has been the practice of funding pediatric and adult HIV clinical trials networks. Pediatric researchers were focused appropriately on interrupting perinatal transmission; internists frankly did not need to be bothered with the recruitment challenge of adolescents given the queues of compliant adults demanding access and easily filling their research slots. Both specialty groups assumed that adolescents could be managed following the adult treatment guidelines and needed little focused research. The goal, after all, was to arrive at some treatment answers. The most efficient and resource-wise approach compelled investigators to recruit populations with less need than that exhibited by teens from resource-poor neighborhoods, who had little social support and were trying to process a diagnosis of HIV infection. However, the fact remains that information on the manifestation and progression of HIV disease is critical to the development and evaluation of a therapeutic agenda. Without these population-specific data, questions cannot be posed and solutions cannot be tested. Observational data become the foundation on which interventional research is based. In the early part of this decade, adolescent medicine clinicians began to see sexually-infected HIV positive youth in their clinical settings, but none had the resources or numbers to apply for research funding. At that time, the National Institute of Child
JOURNAL OF ADOLESCENT HEALTH Vol. 29, No. 3S
Health and Human Development (NICHD) was supporting a prospective observational study of the other population of HIV infected youth, those with hemophilia who had been infected through the reception of blood products (Hemophilia Growth and Development Study) [10]. That project collected information about growth and development and disease progression but in a youth population coburdened with a chronic disease. In 1993, NICHD in collaboration with adolescent medicine clinicians conducted a survey of selected sites to ascertain the numbers, transmission route, and clinical profile of HIV infected adolescents in care [3]. The data from that survey informed NICHD’s decision to issue a Request for Applications (RFA) for a cooperative agreement to form a network of clinical sites to establish data on youth (13–18 years of age) HIV infected through sexual or drug-taking activity. Other NIH Institutes contributed funding to the network [the National Institutes on Drug Abuse (NIDA), Allergy and Infectious Diseases (NIAID), and Mental Health (NIMH)]. The Health Resources and Services Administration (HRSA) added funding from Ryan White Title IV monies for service infrastructure in support of research. Thus, the Adolescent Medicine HIV/AIDS Research Network (AMHARN) was initiated in the fall of 1994. Its research project, Reaching for Excellence in Adolescent Care and Health (REACH), aimed to describe HIV disease manifestation and progression, to examine the effects of HIV on growth and maturation, to characterize immunologic response and establish normative data, and to explore the influence of co-infections, particularly other STIs among this particular HIV infected adolescent population, using a control group of uninfected adolescents of similar gender and ethnic characteristics, who were engaging in similar risk behaviors. In this supplement, Wilson et al. [11] present an overview of the REACH Project including the study measures and their frequency as well as the final profile of study participants. The structure of AMHARN was unique. The Network was composed of four entities (Basic Science Group, Clinical Science Group, Data and Operations Center, Study Coordinators Group) governed by a Steering Committee, managed by an Executive Committee, counseled by a Community Advisory Board, and periodically evaluated by an external Scientific Advisory Panel that reported to the director of NICHD. The Basic Science Group (BSG) included representatives from the fields of immunology, epi-
September 2001
demiology, adolescent medicine, virology, and behavioral psychology. The scientific agenda that resulted is weighted quite heavily in two areas of unique relevance to adolescent medicine: immunology including genital mucosal immunology and the interaction between HIV and human papillomavirus (HPV) infections in youth who have other recurrent STI. Review papers in these two areas are included in this supplement; Rudy et al. [12] review the immunology findings and Vermund et al. [13] the STI data. In addition to implementing the extensive common protocol supporting REACH’s own agenda, the Network collaborated on a number of other studies including an evaluation of micronutrients, antioxidants, and evidence of ongoing oxidative damage correlated to dietary intake and their association with HIV disease progression, an examination of the prevalence of genotypic HIV-1 drug-resistant markers in antiretroviral-naive youth to determine the extent of community acquisition of drug-resistant viral strains, an evaluation of chemokine receptor genetic polymorphisms and their associations with HIV disease progression, and HLA Class I and II genotyping of the entire cohort and examination of the associations with HIV disease progression and HIV-1 specific epitope mapping of selected individuals in support of HIV vaccine research. Because REACH’s retention of subjects was unexpectedly high (⬎80%), a survey examining the factors producing this rate has also been conducted. These studies are currently in analysis. The Clinical Science Group (CSG) was initially composed of 12 principal investigators. One site withdrew and four more were added in 1997 for a final network of 15 sites in 13 American cities (the Bronx, Brooklyn, and New York City, Newark, Philadelphia, Baltimore, Washington DC, Atlanta, Birmingham, Memphis, Fort Lauderdale, Miami, New Orleans, Chicago, and Los Angeles). Accrual to the study slowed considerably after the youth in care were recruited and the pipeline emptied. The different sites used various strategies to publicize the study and recruit additional subjects. In an effort to encourage more widespread and targeted HIV counseling and testing among youth, engage them in care and, offer them the opportunity to participate in research, CSG investigators conceived and launched Project ACCESS (Adolescents Connected to Care, Evaluation, and Special Services). An overview of this social marketing project and its preliminary evaluation is presented by Futterman et al. in this supplement [14]. Another challenge encountered by the clinicians and documented in REACH [15] was
HIV RESEARCH IN AMERICAN YOUTH
3
treatment nonadherence. A theory-based program, Project TREAT (Therapeutic Regimens Enhancing Adherence in Teens), was designed in collaboration with Motivational Educational Entertainment, Inc. (MEE). This program was made available to the REACH sites and preliminary pilot data on its utility are included in an overview paper in this supplement [16]. The breadth of the REACH database has supported a series of secondary analyses addressing clinical questions arising in the management of HIV infected youth, ten of which are presented in this supplement. Original papers received the usual internal network reviews but also were reviewed blindly by two Society of Adolescent Medicine members external to the network. We are particularly indebted to these reviewers for this service to us; their names are listed elsewhere in the supplement. These original papers present an interesting array of findings, some testing hypotheses and others generating hypotheses for future study. Murphy et al. [17] examine the risk behaviors in which the REACH youth engaged during the course of their participation in the study; Sturdevant et al. [18] study the characteristics of the sexual partners of adolescent women and their influence on unsafe sexual behavior; D’Angelo et al. [19] evaluate the role of disclosure and the associated support youth received from parents. There is a clear reproductive health agenda for young women: Vermund et al. [20] examine douching practices; Peralta et al. [21] evaluate the comparative use of ligase chain reaction to detect pathogens in urine and cervical samples; Belzer et al. [22] describe the contraceptive choices of the young women in REACH; and Levin et al. [23] depict the incident pregnancy rates in the cohort. Finally clinical issues are addressed: Shiboski et al. [24] discuss the oral manifestations of HIV disease in REACH youth; Schwarz et al. [25] examine selected factors for their influence on the initiation of antiretroviral therapy; and Wilson et al. [26] evaluate seroresponse to Hepatitis B vaccination in this cohort of HIV infected youth. Elsewhere in this supplement is the list of publications to date from the Adolescent Medicine HIV/ AIDS Research Network. Its productivity has been guided by the minds and expertise of its very committed investigators and firmly anchored in the hearts and passion of its devoted clinicians and study coordinators. All of its activity was organized, coordinated, and kept on course by a singularly talented data and operations staff. The enthusiasm and energy of the members of our community advi-
4
ROGERS
JOURNAL OF ADOLESCENT HEALTH Vol. 29, No. 3S
sory board were inspiring, and their thoughtful insights were invaluable. The debt that is owed to both our HIV infected subjects and our control subjects for their commitment to the project, despite long research visits, collection of numerous blood and other samples, and repetitiveness of many of the questionnaires, is immeasurable. They are remarkable young people who, in the case of the control subjects, display high levels of altruism, and in the case of our infected subjects, are confronting more life-affecting issues than any teens deserve to bear. History will not judge this generation of adults well for allowing them to be placed at such risk. This group of people—scientists, clinicians, coordinators, and youth— has established a knowledge base upon which the NICHD’s new initiative is founded, the Adolescent Medicine Trials Network (ATN) for HIV/AIDS Interventions. The ATN begins its work in Spring 2001 and it is expected that it will carry on the tradition so firmly established by the individuals of the Adolescent Medicine HIV/AIDS Research Network.
11. Wilson CM, Houser J, Partlow C, et al. The REACH (Reaching for Excellence in Adolescent Care and Health) Project: Study design, methods, and population profile. J Adolesc Health 2001;29(Suppl):8 –18.
The views expressed in this paper are those of the author alone and do not necessarily reflect the opinions of the agency for which she works.
18. Sturdevant MS, Belzer M, Weissman G, et al. The relationship of unsafe sexual behavior and the characteristics of sexual partners of HIV infected and HIV uninfected adolescent females. J Adolesc Health 2001;29(Suppl):64 –71.
References 1. Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report 2000;12(1):15. 2. Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report 2000;12(1):20 –1. 3. Rogers AS, Futterman D, Levin L, D’Angelo L. A profile of human immunodeficiency-infected adolescents receiving health care services at selected sites in the United States. J Adolesc Health 1996;19:401– 8. 4. Munoz A, Sabin CA, Phillips AN. The incubation period of AIDS. AIDS 1997;11(Suppl A):S69 –S76. 5. Yong FHL, Taylor JMC, Bryant JL, et al. Dependence of the hazard of AIDS on markers. AIDS 1997;11:217–28. 6. Rosenberg PS, Goedert JJ, Biggar RJ. Effect of age at seroconversion on the natural AIDS incubation distribution. AIDS 1994;8:803–10. 7. Carre N, Deveau C, Belanger F, et al. Effect of age and exposure group on the onset of AIDS in heterosexual and homosexual HIV-infected patients. AIDS 1994;8:797– 802. 8. Valleroy LA, MacKellar DA, Karon J, et al. HIV prevalence and associated risks in young men who have sex with men. JAMA 2000;284:198 –204. 9. Centers for Disease Control and Prevention. Cluster of HIVinfected adolescents and young adults- Mississippi, 1999. MMWR 2000;49:861– 4. 10. Hilgartner MW, Donfield SM, Willoughby A, et al. Hemophilia growth and development study: Design, methods, and entry data. Am J Pediatr Hematol/Oncol 1993;15:208 –18.
12. Rudy BJ, Crowley-Nowick PA, Douglas SD. Immunology and the REACH study: HIV immunology and preliminary findings. J Adolesc Health 2001;29(Suppl):39 – 48. 13. Vermund SH, Wilson CM, Rogers AS, Partlow C, Moscicki AB. Sexually transmitted infections among HIV infected and HIV uninfected high-risk youth in the REACH Project. J Adolesc Health 2001;29(Suppl):49 –56. 14. Futterman DC, Peralta L, Rudy BJ, et al. The ACCESS (Adolescents Connected to Care, Evaluation, and Special Services) Project: Social marketing to promote HIV testing to adolescents, methods and first year results from a six city campaign. J Adolesc Health 2001;29(Suppl):19 –29. 15. Murphy DA, Wilson CM, Durako SJ, et al. Antiretroviral medication adherence among REACH HIV-infected adolescent cohort in the USA. AIDS Care 2001;13:27– 40. 16. Rogers AS, Miller S, Murphy DA, Tanney M, Fortune T. The TREAT (Therapeutic Regimens Enhancing Adherence in Teens) Program: Theory and preliminary results. J Adolesc Health 2001;29(Suppl):30 – 8. 17. Murphy DA, Durako SJ, Moscicki AB, et al. No change in health risk behaviors over time among HIV infected adolescents in care: Role of psychological distress. J Adolesc Health 2001;29(Suppl):57– 63.
19. D’Angelo LJ, Abdalian SE, Sarr M, et al. Disclosure of serostatus by HIV infected youth: The experience in the REACH study. J Adolesc Health 2001;29(Suppl):72–9. 20. Vermund SH, Sarr M, Murphy DA, et al. Douching practices among HIV infected and uninfected adolescents in the United States. J Adolesc Health 2001;29(Suppl):80 – 6. 21. Peralta L, Durako SJ, Ma Y, Adolescent Medicine HIV/AIDS Research Network. Correlation between urine and cervical specimens for the detection of cervical Chlamydia trachomatis and Neisseria gonorrhoeae using ligase chain reaction in a cohort of HIV infected and uninfected adolescents. J Adolesc Health 2001;29(Suppl):87–92. 22. Belzer M, Rogers AS, Camarca M, et al. Contraceptive choices in HIV infected and HIV at-risk adolescent females. J Adolesc Health 2001;29(Suppl):93–100. 23. Levin L, Henry-Reid L, Murphy DA, et al. Incident pregnancy rates in HIV infected and HIV uninfected at-risk adolescents. J Adolesc Health 2001;29(Suppl):101– 8. 24. Shiboski CH, Wilson CM, Greenspan D, et al. HIV-related oral manifestations among adolescents in a multicenter cohort study. J Adolesc Health 2001;29(Suppl):109 –14. 25. Schwarz DF, Henry-Reid L, Houser J, Ma Y, Adolescent Medicine HIV/AIDS Research Network. The association of perceived health, clinical status, and initiation of HAART (highly active antiretroviral therapy) in adolescents. J Adolesc Health 2001;29(Suppl):115–22. 26. Wilson CM, Ellenberg JH, Sawyer MK, et al. Serologic response to hepatitis B vaccine in HIV infected and high-risk HIV uninfected adolescents in the REACH cohort. J Adolesc Health 2001;29(Suppl):123–9.
THE ADOLESCENT MEDICINE HIV/AIDS RESEARCH NETWORK
HIV Research in American Youth AUDREY SMITH ROGERS, Ph.D., M.P.H.
Most reported new HIV infections are in minority populations; in the group aged 13–19 years, 74% of new infections occur in minority populations [1]. The primary transmission route for reported AIDS cases has always been sexual in adolescent females and became predominantly male-to-male sexual transmission in adolescent males in 1995 after the earlier wave of blood-product transmission began to ebb. Thus, the picture of the current, and estimated to be expanding, adolescent HIV epidemic based on reports to the Centers of Disease Control and Prevention is one that is increasingly female, minority, and sexually transmitted through heterosexual activity in females and homosexual activity in males [2]. HIV infection in American adolescents has not received the attention it merits over the years for a number of reasons. This inattention has been owing primarily to the low number of reported adolescent AIDS cases in comparison to the avalanche of diagnoses in the older age groups. Certainly the numbers of HIV infected youth identified and engaged in care have made the easy dismissal of the problem possible [3]. Accurate knowledge of how many American teens are HIV infected remains elusive. The Multicenter AIDS Cohort Study (MACS) showed that age at seroconversion was a significant predictor of time to AIDS, meaning that, if the extrapolation can be made, the median age at which AIDS would develop in individuals infected at the age of 13 occurs 11.6 years later at age 24.6 years [4]. MACS data also would seem to indicate that it is unlikely that more From the Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, Bethesda Maryland. Address correspondence to: Audrey Smith Rogers, Ph.D., M.P.H., PAMAB/CRMC/NICHD/NIH, 6100 Executive Boulevard, Rm 4B11, MSC 7510, Bethesda MD 20892-7510. E-mail: [email protected]. Manuscript accepted May 4, 2001.
than 10% of the individuals infected at age 13 years would have developed AIDS while they were still teenagers [5]. This conclusion and data from others [6,7] would indicate that the bulk of AIDS diagnoses occurring in later decades results from infection as teens or young adults. Based on this information, if one assumes an annual rate of progression to AIDS in teens of 1% to 3% as was demonstrated in MACS, the size of the HIV infected pool required to generate the 1999 incident AIDS cases in 13–19-year olds would be 10,400 –31,200. In fact, using these parameters, HIV infection estimates in the United States for adolescents, aged 13–19 years, have been within a range of 10,000 to 30,000 for the last 4 years. It appears reasonable to assume then that 20,000 adolescents in this age group are currently infected in the United States. This is no small number: where are these youth? Some would contend that the numbers are overestimates, citing the surveillance data on HIV infection. But those surveillance data, being incomplete and not including the HIV epicenters, can hardly prove such a case. However, countering this skepticism is equally difficult because only circumstantial evidence exists. For example, one-quarter of the mothers participating in the landmark Protocol 076 which demonstrated antiretroviral treatment could decrease the odds of perinatal HIV transmission were young women under age 22 years (Pediatric AIDS Clinical Trials Group, personal communication, 1997). The clinical profile of research volunteers in the Adolescent Medicine HIV/AIDS Research Network (the focus of this supplement) indicates that young women may be preferentially screened through family planning and prenatal clinics. They tended to enter the study earlier in their HIV infection than the young men who have no similar focused screening effort and typically entered after an illness had prompted HIV testing.
Published by Elsevier Science Inc., 655 Avenue of the Americas, New York, NY 10010
1054-139X/01/$–see front matter PII S1054-139X(01)00294-4
2
ROGERS
Where are these youth? The answer appears to be that they are not in care because they have not been screened and referred to care. Many, particularly young men, remain unaware of their HIV status and probably even of their risk. Several recent reports attest to the discovery of HIV infected young people when resources have been committed to their identification. The Young Men’s Survey (1994 –1998) conducted HIV serosurveys in seven different American cities among young men aged 15–22 years who reported having sex with other men [8]. The overall rate of sero-positivity among the 3492 young men who consented to testing was 7.2%, and ranged by city from 2.2% to 12.1%. Only 18% knew they were HIV infected before testing and only 15% of those infected were in care. The prevalence of unprotected anal sex during the previous 6 months was 41%. In another study, seven HIV infected young people were identified through contact tracing in a sexual network of 44 persons from a small rural Mississippi town in 1999 [9] after two individuals accepted routine voluntary HIV testing during sexually transmitted infection (STI) evaluation. Another reason that attention to adolescent HIV infection has lagged behind has been the practice of funding pediatric and adult HIV clinical trials networks. Pediatric researchers were focused appropriately on interrupting perinatal transmission; internists frankly did not need to be bothered with the recruitment challenge of adolescents given the queues of compliant adults demanding access and easily filling their research slots. Both specialty groups assumed that adolescents could be managed following the adult treatment guidelines and needed little focused research. The goal, after all, was to arrive at some treatment answers. The most efficient and resource-wise approach compelled investigators to recruit populations with less need than that exhibited by teens from resource-poor neighborhoods, who had little social support and were trying to process a diagnosis of HIV infection. However, the fact remains that information on the manifestation and progression of HIV disease is critical to the development and evaluation of a therapeutic agenda. Without these population-specific data, questions cannot be posed and solutions cannot be tested. Observational data become the foundation on which interventional research is based. In the early part of this decade, adolescent medicine clinicians began to see sexually-infected HIV positive youth in their clinical settings, but none had the resources or numbers to apply for research funding. At that time, the National Institute of Child
JOURNAL OF ADOLESCENT HEALTH Vol. 29, No. 3S
Health and Human Development (NICHD) was supporting a prospective observational study of the other population of HIV infected youth, those with hemophilia who had been infected through the reception of blood products (Hemophilia Growth and Development Study) [10]. That project collected information about growth and development and disease progression but in a youth population coburdened with a chronic disease. In 1993, NICHD in collaboration with adolescent medicine clinicians conducted a survey of selected sites to ascertain the numbers, transmission route, and clinical profile of HIV infected adolescents in care [3]. The data from that survey informed NICHD’s decision to issue a Request for Applications (RFA) for a cooperative agreement to form a network of clinical sites to establish data on youth (13–18 years of age) HIV infected through sexual or drug-taking activity. Other NIH Institutes contributed funding to the network [the National Institutes on Drug Abuse (NIDA), Allergy and Infectious Diseases (NIAID), and Mental Health (NIMH)]. The Health Resources and Services Administration (HRSA) added funding from Ryan White Title IV monies for service infrastructure in support of research. Thus, the Adolescent Medicine HIV/AIDS Research Network (AMHARN) was initiated in the fall of 1994. Its research project, Reaching for Excellence in Adolescent Care and Health (REACH), aimed to describe HIV disease manifestation and progression, to examine the effects of HIV on growth and maturation, to characterize immunologic response and establish normative data, and to explore the influence of co-infections, particularly other STIs among this particular HIV infected adolescent population, using a control group of uninfected adolescents of similar gender and ethnic characteristics, who were engaging in similar risk behaviors. In this supplement, Wilson et al. [11] present an overview of the REACH Project including the study measures and their frequency as well as the final profile of study participants. The structure of AMHARN was unique. The Network was composed of four entities (Basic Science Group, Clinical Science Group, Data and Operations Center, Study Coordinators Group) governed by a Steering Committee, managed by an Executive Committee, counseled by a Community Advisory Board, and periodically evaluated by an external Scientific Advisory Panel that reported to the director of NICHD. The Basic Science Group (BSG) included representatives from the fields of immunology, epi-
September 2001
demiology, adolescent medicine, virology, and behavioral psychology. The scientific agenda that resulted is weighted quite heavily in two areas of unique relevance to adolescent medicine: immunology including genital mucosal immunology and the interaction between HIV and human papillomavirus (HPV) infections in youth who have other recurrent STI. Review papers in these two areas are included in this supplement; Rudy et al. [12] review the immunology findings and Vermund et al. [13] the STI data. In addition to implementing the extensive common protocol supporting REACH’s own agenda, the Network collaborated on a number of other studies including an evaluation of micronutrients, antioxidants, and evidence of ongoing oxidative damage correlated to dietary intake and their association with HIV disease progression, an examination of the prevalence of genotypic HIV-1 drug-resistant markers in antiretroviral-naive youth to determine the extent of community acquisition of drug-resistant viral strains, an evaluation of chemokine receptor genetic polymorphisms and their associations with HIV disease progression, and HLA Class I and II genotyping of the entire cohort and examination of the associations with HIV disease progression and HIV-1 specific epitope mapping of selected individuals in support of HIV vaccine research. Because REACH’s retention of subjects was unexpectedly high (⬎80%), a survey examining the factors producing this rate has also been conducted. These studies are currently in analysis. The Clinical Science Group (CSG) was initially composed of 12 principal investigators. One site withdrew and four more were added in 1997 for a final network of 15 sites in 13 American cities (the Bronx, Brooklyn, and New York City, Newark, Philadelphia, Baltimore, Washington DC, Atlanta, Birmingham, Memphis, Fort Lauderdale, Miami, New Orleans, Chicago, and Los Angeles). Accrual to the study slowed considerably after the youth in care were recruited and the pipeline emptied. The different sites used various strategies to publicize the study and recruit additional subjects. In an effort to encourage more widespread and targeted HIV counseling and testing among youth, engage them in care and, offer them the opportunity to participate in research, CSG investigators conceived and launched Project ACCESS (Adolescents Connected to Care, Evaluation, and Special Services). An overview of this social marketing project and its preliminary evaluation is presented by Futterman et al. in this supplement [14]. Another challenge encountered by the clinicians and documented in REACH [15] was
HIV RESEARCH IN AMERICAN YOUTH
3
treatment nonadherence. A theory-based program, Project TREAT (Therapeutic Regimens Enhancing Adherence in Teens), was designed in collaboration with Motivational Educational Entertainment, Inc. (MEE). This program was made available to the REACH sites and preliminary pilot data on its utility are included in an overview paper in this supplement [16]. The breadth of the REACH database has supported a series of secondary analyses addressing clinical questions arising in the management of HIV infected youth, ten of which are presented in this supplement. Original papers received the usual internal network reviews but also were reviewed blindly by two Society of Adolescent Medicine members external to the network. We are particularly indebted to these reviewers for this service to us; their names are listed elsewhere in the supplement. These original papers present an interesting array of findings, some testing hypotheses and others generating hypotheses for future study. Murphy et al. [17] examine the risk behaviors in which the REACH youth engaged during the course of their participation in the study; Sturdevant et al. [18] study the characteristics of the sexual partners of adolescent women and their influence on unsafe sexual behavior; D’Angelo et al. [19] evaluate the role of disclosure and the associated support youth received from parents. There is a clear reproductive health agenda for young women: Vermund et al. [20] examine douching practices; Peralta et al. [21] evaluate the comparative use of ligase chain reaction to detect pathogens in urine and cervical samples; Belzer et al. [22] describe the contraceptive choices of the young women in REACH; and Levin et al. [23] depict the incident pregnancy rates in the cohort. Finally clinical issues are addressed: Shiboski et al. [24] discuss the oral manifestations of HIV disease in REACH youth; Schwarz et al. [25] examine selected factors for their influence on the initiation of antiretroviral therapy; and Wilson et al. [26] evaluate seroresponse to Hepatitis B vaccination in this cohort of HIV infected youth. Elsewhere in this supplement is the list of publications to date from the Adolescent Medicine HIV/ AIDS Research Network. Its productivity has been guided by the minds and expertise of its very committed investigators and firmly anchored in the hearts and passion of its devoted clinicians and study coordinators. All of its activity was organized, coordinated, and kept on course by a singularly talented data and operations staff. The enthusiasm and energy of the members of our community advi-
4
ROGERS
JOURNAL OF ADOLESCENT HEALTH Vol. 29, No. 3S
sory board were inspiring, and their thoughtful insights were invaluable. The debt that is owed to both our HIV infected subjects and our control subjects for their commitment to the project, despite long research visits, collection of numerous blood and other samples, and repetitiveness of many of the questionnaires, is immeasurable. They are remarkable young people who, in the case of the control subjects, display high levels of altruism, and in the case of our infected subjects, are confronting more life-affecting issues than any teens deserve to bear. History will not judge this generation of adults well for allowing them to be placed at such risk. This group of people—scientists, clinicians, coordinators, and youth— has established a knowledge base upon which the NICHD’s new initiative is founded, the Adolescent Medicine Trials Network (ATN) for HIV/AIDS Interventions. The ATN begins its work in Spring 2001 and it is expected that it will carry on the tradition so firmly established by the individuals of the Adolescent Medicine HIV/AIDS Research Network.
11. Wilson CM, Houser J, Partlow C, et al. The REACH (Reaching for Excellence in Adolescent Care and Health) Project: Study design, methods, and population profile. J Adolesc Health 2001;29(Suppl):8 –18.
The views expressed in this paper are those of the author alone and do not necessarily reflect the opinions of the agency for which she works.
18. Sturdevant MS, Belzer M, Weissman G, et al. The relationship of unsafe sexual behavior and the characteristics of sexual partners of HIV infected and HIV uninfected adolescent females. J Adolesc Health 2001;29(Suppl):64 –71.
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