Audrey Smith Rogers

Delayed onset of pubertal development in children and adolescents with perinatally acquired HIV infection.

Objective: To examine whether greater severity of HIV infection is associated with delayed initiation of pubertal development among perinatally HIV‐infected children, and to compare sexual maturation of perinatally HIV‐infected children with children in the general US population using the National Health and Nutrition Examination Survey III. Methods: In a prospective cohort study, the authors studied 983 HIV‐infected children aged 6 to 18 years, who had Tanner stage assessed on at least two occasions between 1995 and 2000. Analyses were conducted separately for girls and boys to identify factors associated with onset of puberty or adrenarche (progression beyond Tanner stage 1). Results: Among children who were in Tanner stage 1 at their first assessment, 185 of 413 (45%) girls and 144 of 434 (33%) boys entered puberty during the observation period. In multivariate longitudinal regression analyses adjusted for age, race/ethnicity, time interval between study visits, and other clinical factors, girls with severe immunosuppression (CD4% <15) were significantly less likely to enter adrenarche (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.29‐0.83) and puberty (OR, 0.57; 95% CI, 0.33‐0.96) compared with girls who were not immunosuppressed (CD4% ≥25). For boys, those with severe immunosuppression were significantly less likely to enter adrenarche (OR, 0.52; 95% CI, 0.28‐0.96) and tended to be less likely to begin puberty (OR, 0.69; 95% CI, 0.39‐1.22) compared with boys who were not immunosuppressed. Qualitative comparisons suggested that HIV‐infected children may experience delayed puberty and adrenarche compared with similarly aged children in the general US population. Conclusions: Immunosuppression was associated with delayed pubertal onset in perinatally HIV‐infected children. Further studies of perinatally HIV‐infected and uninfected children are needed to better quantify the delay in pubertal onset and to compare the pace of pubertal maturation.

Recruitment and Retention of Adolescent Participants in HIV Research: Findings From the REACH (Reaching for Excellence in Adolescent Care and Health) Project

PURPOSE To evaluate the importance of 13 items in the recruitment and retention of HIV-positive and HIV-negative adolescent participants in a longitudinal study (REACH study). METHODS A confidential, self-administered, visual analog, cross-sectional survey was offered to active participants (November 1999-August 2000) with 438 subjects (86%) participating. Sixty-six percent of the cohort were HIV-positive and 34% were HIV-negative with a mean age of 17 years, and 76% were female. Subjects were asked to recall the importance they placed on 13 items in deciding to join the REACH study (recruitment) and to remain on study (retention). Factors that might explain the judgment placed on the items were analyzed using the nonparametric Wilcoxon Rank-Sum test or the Kruskall-Wallis test. RESULTS The five most important factors for study recruitment were identical to those chosen for retention by participants. The factors were: (a) quality medical care, (b) caring staff, (c) health education, (d) privacy/confidentiality, and (e) altruism. Items judged least important were social activities, compensation, transportation, and food/meals. Subject characteristics (gender, age, HIV status) were not associated with statistically different mean judgment scores at recruitment and retention, although clinical site showed significant variation. Factors that could render subjects vulnerable (health insurance, family finances) were not associated with related items. CONCLUSIONS Adolescents found quality health care and care team characteristics critically important in considering research participation. Attention to privacy and the opportunity to be altruistic were also important. Compensation for participation was not a significant factor for recruitment and retention of this adolescent cohort. This study demonstrates that adolescents apply sound criteria in evaluating research participation and do not appear to be unduly affected by compensation.

The TREAT (therapeutic regimens enhancing adherence in teens) program: theory and preliminary results

The Treatment Regimens Enhancing Adherence in Teens (TREAT) Program is an adolescent-focused multifaceted program based on the Stages of Change Model to promote optimal long-term adherence to highly active antiretroviral therapy (HAART). The program aims to produce and implement a theory-based clinical intervention to promote adherence to HAART among infected youth. It includes a guidance manual for clinicians two videotapes and an information booklet and a set of five audiotapes for each patient. This paper describes the program and presents preliminary data. Preliminary pilot data were collected on its implementation over a 1-year period (1999-2000). The evaluation measures of these preliminary data include the acceptability of the program and movement across stages and acceptance of and adherence to therapy.

Contraceptive choices in HIV infected and HIV at-risk adolescent females

PURPOSE To describe reported contraception use in HIV infected and HIV uninfected but at-risk female adolescents, and determine associations with the reported consistent use of effective contraception methods, including its association with pregnancy. METHODS HIV infected and at-risk female youth, aged 13-18 years, who were sexually active and reporting no intention to become pregnant, were included. Contraception use data from three consecutive visits (approximately 6 months apart) were used. RESULTS Ninety-four percent of HIV infected and 89% of at-risk subjects reported choosing a main contraception method with demonstrated efficacy when used consistently. Approximately 50% chose partner condoms. HIV infected youth were more likely to report 100% partner condom use in the past 3 months (73% vs. 46%; OR 3.3; 95% CI: 1.7-5.6). At-risk youth were 2.5 times more likely than HIV infected subjects to report using nothing (95% CI: 1.1-5.8). Slightly more than half (56%) demonstrated the consistent reporting of effective methods (CREM) of contraception. In multivariate analysis, HIV infection (OR 4.0; 95% CI: 2.2-8.2) and African-American race (OR 2.7; 95% CI: 1.1-6.6) were significantly associated with CREM. Subjects reporting inconsistent or unreliable contraception use had higher 1-year pregnancy rates than CREM subjects (32% vs. 14%; p = .002). CONCLUSIONS Only half of HIV infected and at-risk youth reported using effective contraception consistently, despite its availability. Additionally, regardless of reported contraceptive use, the rates of unplanned pregnancy were unacceptably high.

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.

Sexually Transmitted Infections Among HIV Infected and HIV Uninfected High-Risk Youth in the REACH Study

Abstract Overview: This review presents the findings of published research in the Reaching for Excellence in Adolescent Care and Health (REACH) Project on sexually transmitted infections (STIs) within the context of the projects scientific agenda. Methods employed in the study for specimen collection, management, and laboratory analysis are presented. This review presents published analyses of cross-sectional data; longitudinal analyses are underway. In addition, baseline prevalence data on selected STIs and sexual risk profiles of the subjects in REACH are presented. High STI rates were evident in both human immunodeficiency virus (HIV) infected and uninfected youth of both genders regardless of sexual orientation. High infection rates at baseline suggest that prevention-oriented programs for risk reduction among adolescents should focus on both HIV infected and at-risk, uninfected youth.

Guidelines for adolescent participation in research: current realities and possible resolutions.

morbidity in adolescents from drug abuse, preventable injury, violence, and unprotected sexual activity continues to increase. Moreover, with AIDS this generation of adolescents is threatened by an epidemic of potentially devastating proportions. This epidemic requires that the origins of risk-taking behaviors be understood in appropriate developmental and behavioral terms and that every opportunity be seized to learn what programs are effective in adolescent risk reduction and health mainte-

Inclusion of Adolescents in Preventive HIV Vaccine Trials : Public Health Policy and Research Design at a Crossroads

PURPOSE To report a case of surgically induced necrotizing scleritis (SINS) as a complication of conjunctival autograft after pterygium excision. METHODS A 52-year-old man had undergone nasal pterygium excision with conjunctival autograft in the right eye at another facility. He was treated for suspected infective scleritis before presentation. RESULTS The sclera, at the site of prior pterygium excision, showed significant thinning with uveal show. There was active inflammation adjacent to the site of thinning. Systemic studies and the examination were noncontributory. The patient was suspected of having SINS and received pulsed injections of methylprednisolone 1000 mg/d for 3 days. The patient also underwent an emergency scleral patch graft with amniotic membrane graft. Over the next 2 weeks, the scleral graft showed vascularization and was taken well. CONCLUSIONS SINS may develop after pterygium surgery with conjunctival autograft. Evidence of connective tissue disease may or may not be found on clinical examination and on laboratory studies. Early diagnosis, prompt immunosuppression, and scleral patch grafting prevents progression and further devastating complications.

Incident pregnancy rates in HIV infected and HIV uninfected at-risk adolescents.

PURPOSE To compare pregnancy incidence between HIV infected and HIV uninfected adolescents over a 3-year period and to characterize factors that differentiate pregnant from nonpregnant HIV infected females. METHODS Female adolescents enrolled in Reaching for Excellence in Adolescent Care and Health (REACH), a national cohort study, and nonpregnant at baseline comprised the sample (n = 345). Subject information on pregnancy, risk behavior, and psychosocial characteristics was obtained through interview, chart review, physical examination and laboratory data collected every 3 months. Incident pregnancy rate was analyzed using Cox proportional hazards modeling; the predictors of incident pregnancy were evaluated using repeated measures analysis. RESULTS Ninety-four pregnancies were identified over 3 years. No significant difference in pregnancy incidence was detected between HIV infected and uninfected females (20.6 and 28.4 per 100 person-years, respectively, p = .16). However, for adolescents with living children at entry, HIV infected females were significantly less likely to become pregnant than HIV uninfected (HR = .45; p = .03). Among HIV infected adolescents, significant predictors of incident pregnancy were older age (p = .01) and not using hormonal contraception (p = .00), whereas increased spiritual hope and passive problem-solving capacity were protective against pregnancy (p = .02, and.05, respectively). Multivariate analysis revealed pregnancy prior to study entry to be predictive for (OR = 3.0; 95% CI: 1.2-7.7), and increased spiritual hope to be protective (OR = .4; 95% CI: .2-.9) against incident pregnancy in HIV infected females without the hormonal contraceptive variable in the model. CONCLUSIONS The pregnancy rate is high in this study population. Further research is needed into its determinants and attenuating factors, particularly the role of spiritual elements, to design better contraceptive services and reproduction-related education targeting high-risk youth.

The role of cytochrome P450 in developmental pharmacology.

Numerous sources of human heterogeneity affect biotransformation of compounds. Cytochrome P450, the primary oxidative pathway of drug metabolism, is the dominant phase I oxidative system metabolizing, to some degree, most of the drugs used clinically in humans. The P450 pathway is a major site of drug-drug, drug-diet, and drug-disease/condition interactions. Functional variability in this system can have pronounced consequences in suboptimal therapeutic response or enhanced toxicity. Methods for cataloguing specific P450 enzymes are being developed and their identification will promote rational drug development, more efficient clinical trial evaluation, and improved therapeutic approaches to patients requiring special consideration. These methods will facilitate the study of the impact of pubertal development on function in this system.