Serologic response to hepatitis B vaccine in HIV infected and high-risk HIV uninfected adolescents in the REACH cohort. Reaching for Excellence in Adolescent Care and Health.

PURPOSE: To evaluate hepatitis B (HBV) vaccine response rates in HIV infected and high-risk HIV uninfected youth and examine associations with responsiveness in the HIV infected group. METHODS: Cohorts within the Reaching for Excellence in Adolescent Care and Health (REACH) study population were defined based on receipt of HBV vaccine both retrospectively and prospectively. Sero-responsiveness was determined by HBsAb measurements. Testing was done for HBsAg, HBsAb, and HBcAb. For HBsAb, a value of > 10 International Units per liter was considered a positive response, and the data were collected as either positive or negative from each of the reporting laboratories. Covariates of responsiveness were explored in univariate and multivariate models for each cohort. RESULTS: Sixty-one subjects had received a three-dose vaccination course at the time of entry into REACH. HIV uninfected subjects had significantly higher rates of response by serology compared with HIV infected subjects (70% vs. 41.1%; chi(2) = .05; RR = .586, 95% CI: .36-.96). By the time of an annual visit 43 subjects had received three vaccinations with at least one occurring in the study period. The rates of response were similar for the HIV infected and uninfected groups (37.1% vs. 37.5%) in this cohort. Univariate and multivariate analysis in the prospective HIV infected group (N = 35) found an association between elevated CD8(+)/CD38(+)/HLA-DR(+) T cells and lack of HBV vaccine responsiveness (6.7% vs. 60%; chi(2) = .03; RR = .12, 95% CI: .02- .55). CONCLUSIONS: The poor HBV vaccine response rate in the HIV uninfected high-risk adolescents was unexpected and suggests that HBV vaccination doses have not been optimized for older adolescents. This is the first report of decreased responsiveness in HIV infected subjects being associated with elevated CD8(+)/CD38(+)/HLA(-)DR(+) T cells and suggests that ongoing viral replication and concomitant immune system activation decreases the ability of the immune system in HIV infected subjects to respond to vaccination.

Efficacy of a preventive intervention for youths living with HIV.

OBJECTIVES: HIV transmission behaviors and health practices of HIV-infected youths were examined over a period of 15 months after they received a preventive intervention. METHODS: HIV-infected youths aged 13 to 24 years (n = 310; 27% African American, 37% Latino) were assigned by small cohort to (1) a 2-module ("Stay Healthy" and "Act Safe") intervention totaling 23 sessions or (2) a control condition. Among those in the intervention condition, 73% attended at least 1 session. RESULTS: Subsequent to the "Stay Healthy" module, number of positive lifestyle changes and active coping styles increased more often among females who attended the intervention condition than among those in the control condition. Social support coping also increased significantly among males and females attending the intervention condition compared with those attending the control condition. Following the "Act Safe" module, youths who attended the intervention condition reported 82% fewer unprotected sexual acts, 45% fewer sexual partners, 50% fewer HIV-negative sexual partners, and 31% less substance use, on a weighted index, than those in the control condition. CONCLUSIONS: Prevention programs can effectively reduce risk acts among HIV-infected youths. Alternative formats need to be identified for delivering interventions (e.g., telephone groups, individual sessions).

Serologic examination of hepatitis B infection and immunization in HIV-positive youth and associated risks. The Pediatric AIDS Clinical Trials Group Protocol 220 Team.

This seroprevalence report examines serologic evidence of hepatitis B immunization or infection and associated demographic/behavioral factors in adolescent (aged 12-20) subjects enrolled in a nontherapeutic clinical trial at 43 Pediatric AIDS Clinical Trials Group (PACTG) clinical centers. Subjects (n = 94) infected with the human immunodeficiency virus (HIV) through sexual activity were categorized as hepatitis B virus (HBV)-immunized, HBV-infected, or nonimmune by hepatitis B serology performed on specimens collected within the subject's first 48 weeks on study (1993-1995). Sixteen percent of the 94 serologically classified subjects were immunized; 19% HBV-infected; 65% nonimmune. Of the three risk factor scores examined (sociodemographic, sexual, and substance abuse), substance use alone demonstrated a significant difference among groups (despite virtually no reported injecting drug behavior), with the sexual risk score exhibiting marginally significant differences. Logistic regression analysis (restricted to nonimmunized subjects) showed that male-male sexual activity raised the odds of HBV infection by a factor of 5.14 (95% confidence interval [CI]: 1.45-18. 23) relative to heterosexual activity; and that for every one point increase on the substance abuse risk scale the odds of infection increased 5% (95% CI: 0.99-1.10). The HBV infection rate in PACTG 220 HIV-positive females is twice United States population-based rates; the rate in PACTG 220 HIV-positive males is nearly seven times higher. Past immunization efforts in this population appear to have been based on sexual activity volume without regard to injecting-drug use in sex partners.

Relationship of CD4+ T cell counts and HIV type 1 viral loads in untreated, infected adolescents. Adolescent Medicine HIV/AIDS Research Network.

The REACH Project (Reaching for Excellence in Adolescent Care and Health) of the Adolescent Medicine HIV/AIDS Research Network was designed as a study of an adolescent cohort composed of HIV-1-infected and -uninfected subjects. The goal of the analysis presented was to examine the relationship of CD4+ T cell counts and HIV-1 plasma viral loads in adolescents. The CD4+ T cell counts of 84 HIV+ subjects who were 13 to 19 years of age were measured at the clinical sites, using ACTG standardized techniques. HIV-1 viral loads in frozen plasma were determined by the NASBA/NucliSens assay at a central laboratory. Past and current treatment with antiretroviral drugs was determined by medical record abstraction and interview data. The slope of the line generated by regressing log10 HIV-1 RNA (copies/ml) versus CD4+ T cell counts of REACH subjects who are antiretroviral drug naive was negative and significantly different than zero. A negative association has also been reported for antiretroviral drug-naive, adult males in the Pittsburgh Men's Study, a component of MACS (Pitt-MACS) (Mellors J, et al.: Science 1996;272:1167). These data show that in adolescents, as in adults, HIV-1 RNA concentrations are correlated with corresponding absolute CD4+ T cell count. The slopes of the lines generated with data from each cohort were different (p = 0.003). In addition to age, there are sex and racial differences in the makeup of the two cohorts. Any or all of these differences may affect the slopes of the lines.

Promoting early detection of human immunodeficiency virus infection among adolescents.

While a significant and increasing number of adolescents are infected with the human immununodeficiency virus (HIV), few youth are identified as seropositive and even fewer are linked to medical care and social services. If more youth were identified, transmission to sexual partners and offspring would be reduced and individuals could benefit from treatment. Prior to initiating wide-scale early detection for HIV, we must (1) examine alternative strategies of conducting pretest and posttest counseling; (2) address barriers to prevention and testing within the HIV system of care; and (3) mount community-level intervention campaigns that address youth at high risk of infection.

HIV and AIDS in adolescents.

HIV infection in adolescents continues to challenge health care providers, policy makers, and advocates for youth. Primary care providers working with parents of adolescents and at-risk youth are in a unique position to identify or help develop HIV prevention and care programs that address many needs. Effective interventions are those that move beyond moralism to realism and a willingness to engage youth and their families. Youth at high risk for HIV should be identified and engaged in primary care as soon as possible. HIV-infected youth need intensive individual and group interventions to keep themselves healthy and reduce transmission to others. Incumbent on all providers is to make adolescents' services visible, flexible, affordable, confidential, culturally appropriate, and available for all youth.

Adolescents and HIV.

AIDS: Worldwide, the rate of new HIV infections is highest among people between the ages of 15 and 24, with 25 percent of all new infections in the U.S. occurring among people aged 13 to 21. The Institute of Medicine released a report in 1996 which highlighted the interaction between behavioral, biological, and socioeconomic factors that increase adolescents' vulnerability to both HIV infection and other sexually transmitted diseases (STDs). Many normal behaviors of young people are associated with high risk behaviors that can lead to HIV infection, and many young people, such as those who are homeless or are drug users, are at an especially high risk. Biological and sociological factors that can lead to increased risk of infection are discussed, as is the need for adolescent-specific intervention programs. Information on the epidemiology of HIV infection is presented.^ieng

Treatment issues for HIV-positive adolescents.

AIDS: This second part of a series on HIV treatment in adolescents aged 13 to 21 highlights the clinical challenges posed by physical and psychosocial development. Special challenges involve helping adolescents adjust to their HIV status and take their medications correctly. A description is provided of the REACH study (Reaching for Excellence in Adolescent Care and Health), which involves 300 HIV-positive and 150 HIV-negative volunteers aged 12 to 19. The study looks at disease progression and manifestations, effects of puberty on treatment, interactions between HIV and other sexually transmitted diseases, and social and mental health. Major issues faced by HIV-positive adolescents are discussed, including receiving a diagnosis and coping with the disease. Guidelines are given for providing adolescent-centered healthcare. Tables illustrate transmission categories, testing methods for other sexually transmitted diseases, immunizations, and suggested adherence methods.^ieng

The REACH Project of the Adolescent Medicine HIV/AIDS Research Network: design, methods, and selected characteristics of participants.

PURPOSE: To describe the Reaching for Excellence in Adolescent Care and Health (REACH) Project of the Adolescent Medicine Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) Research Network, a unique collaborative effort to conceive and implement a research design intended to examine HIV pathogenesis, pubertal hormonal variation, and the effects of sexually transmitted disease comorbidity in HIV-infected youth to improve their health care. METHODS: This multidisciplinary team has drawn on basic science and clinical experience to produce a study design with relevant and feasible study aims and testable hypotheses. Particular attention has been paid to centralized training and quality control practices. Standardized measurements include direct and computer interviews, physical examination, laboratory analysis, and medical chart abstraction. The protocol has been approved by local institutional review boards. RESULTS: A highly standardized and quality control monitored protocol has been implemented at 16 sites throughout the United States collecting historical, observational, and laboratory data in a group of HIV-infected adolescents and HIV-negative controls. Preliminary data collected on subjects are consistent with published reports of the sociodemographic and clinical characteristics of the HIV epidemic in sexually active youth, thus supporting the integrity of the protocol development process. The study population is, for the most part, in older adolescence, predominantly minority and female, and with publicly financed or no health insurance. CONCLUSIONS: The REACH Project is positioned to address questions about the clinical course, immunologic profile, and viral dynamics in HIV-positive youth, and thus is able to inform drug development and management strategies for this understudied population.

REP: health care for youth.

AIDS: Dr. Donna Futterman, Director of the Adolescent AIDS Program at Montefiore Hospital, discusses the Risk Evaluation Program (REP), part of their overall program for adolescents. REP, the largest program in New York City, offers medical treatment to people ages 13 to 24, a research program, and training and outreach activities. Many of the patients are referred through a prenatal testing system. Confidentiality and anonymity are sensitive areas, particularly for teenagers, who have the highest rates of STDs of any population. About 94 percent of the clients are teenagers of color, many of whom distrust medications and present adherence problems. Dr. Futterman is working toward overcoming teens' reluctance of being tested since early treatment is beneficial.^ieng

Lesbian and Gay Youth: Care and Counseling.

Adolescents face many barriers in accessing appropriate primary care. Among the most underserved are lesbian, gay, and bisexual youth who are often neglected by traditional systems of care. This is a reference guide that provides background knowledge, substantive references, and detailed information on the stressors, health needs, experiences, and developmental challenges facing lesbian and gay youth. The first part focuses on experiences and needs of lesbian and gay adolescents-health challenges, identity development, their experiences, vulnerabilities, and risks, and confidentiality and legal issues that are of concern. The second part deals with primary care and disease prevention objectives in this group of adolescents-most frequent health concerns, issues of transgendered youth, special populations, primary interventions and anticipatory guidance, medical assessment, treatment, and prevention, and mental health concerns, assessment, and treatment. The third part presents an overview of HIV infection in all adolescents, with a focus on issues of concern for lesbians and gay males. It covers issues of HIV counseling, testing, and prevention as well as clinical care and prevention. Several appendices offer additional resources for primary care needs of lesbian and gay adolescents, resources for parents and youth, recommended reading for providers, adolescent HIV counseling and testing protocols and clinical care protocols.

A profile of human immunodeficiency virus-infected adolescents receiving health care services at selected sites in the United States.

OBJECTIVE: To determine the demographic/clinical profile of human immunodeficiency virus (HIV)-infected adolescents in care at selected sites. METHODS: We mailed surveys requesting prevalence data from physicians in government-funded HIV research and care programs on HIV-infected youth (10-21 years) receiving care. RESULTS: A total of 49% responses yielded information on 978 subjects. Vertical, blood, and sexual were predominant transmission modes. Three-quarters were of an ethnic/racial minority; 50% were female. The earliest median CD4 count was 0.467 x 10(9)/liter (467/microliter). Percent asymptomatic varied by transmission: vertical (16%), blood products (40%), male-male sexual (67%) and female-male sexual (M:73%) (F:74%). Clinical indicated Pneumocystis carinii pneumonia prophylaxis was differentially prescribed: vertical (96%), blood (89%), and sexually (male-male-47%) (female-male: M: 36% and F: 56%). Of these youth 78% are not represented in national AIDS case data. CONCLUSIONS: Examination of numerator data from selected sites indicates three transmission-driven adolescent HIV epidemics with different characteristics. Minority youth are disproportionately represented; many vertically infected infants are surviving to adolescence; sexual activity is a significant transmission avenue. HIV-infected youth appear to enter care with considerable immunosuppression. Clinical profiles and treatment patterns appear to differ by transmission mode. Further study is needed on adolescent HIV disease progression and determinants of access to care and treatment.

Tuberculosis infection in human immunodeficiency virus-positive adolescents and young adults: a New York City cohort.

OBJECTIVES: Adolescents with human immunodeficiency virus (HIV) infection are at increased risk for tuberculosis (TB), underscoring the importance of early identification of TB infection. The goals of this study were to assess the factors associated with the completion of evaluations for TB in a cohort of HIV-positive adolescents and young adults and to describe the prevalence of Mycobacterium tuberculosis infection and adherence to antituberculous treatment regimens. METHODS: A retrospective chart review was done for all HIV-positive adolescents and young adults, ages 13 to 21 years (n = 49), seen in a comprehensive care program from January 1991 through December 1992. Data collected included CD4 cell count, HIV clinical status, living situation, substance use history, and the completion of an annual evaluation for TB infection. The evaluation consisted of a tuberculin skin test (Mantoux test), using an intraepidermal injection of 0.1 mL of 5 tuberculin units of purified protein derivative (PPD) and a simultaneous Merieux multitest anergy panel. Chi-square analysis was used to assess the association between the completion of the evaluation for TB and both living status and substance use. RESULTS: Thirty-one (63%) of 49 patients completed evaluations for TB. Of the 31 completed evaluations, 18 were assessed by clinic staff on site, and 13 were assessed by other medical or trained nonmedical observers through community networking efforts. Neither homelessness nor illicit substance use were factors in the completion of the evaluation. Six (19%) of the 31 patients had positive PPD skin test results. Three had medical histories and chest radiographs suggesting active TB, and all were hospitalized for at least 2 weeks. Two had positive cultures for M tuberculosis, although the third also responded clinically to antituberculous therapy. All three were otherwise asymptomatic for HIV infection, with only moderately depressed CD4 cell counts. All three were homeless and used crack cocaine. After the initial treatment as inpatients, none completed treatment within the prescribed time period. CONCLUSIONS: The completions of the evaluations for TB were greatly facilitated by community networking, but innovative strategies to enhance both screening and treatment programs, such as training youth service providers in the community to read PPD skin tests, expansion of directly observed therapy services, and youth-centered programs for housing and substance use, need further development. The high prevalence of TB in the cohort underscores the need for providers to increase efforts to identify cases of TB infection among adolescents and young adults and to incorporate HIV risk assessment, counseling, and testing into their practices routinely.