Faculty Bibliography

The responses to HAART in HIV-infected adolescents infected through risk behaviors are not well defined. PACTG 381 collected intensive immunologic and virologic data on youth naive to or with minimal exposure to antiretroviral therapy who began HAART. Subjects were evaluated according to their weeks 16-24 virologic response. Comparisons with a cohort of HIV-uninfected adolescents from the REACH cohort were performed. Cox proportional hazards models were used to identify baseline and week 24 predictors of virologic failure. Only 69 of 120 subjects (58%) achieved virologic suppression by weeks 16-24, whereas 55 of 69 (80%) demonstrated control to week 60. Higher CD4+ naive T cells (CD4+/62L+/RA+: hazard ratio [HR], 2.13; p = 0.018), higher CD8+ activated T cells (CD8+/CD38+/DR+: HR, 1.40, p = 0.028 per 100 cells/mm3) and higher CD8+ naive T cells (CD8+/62L+/RA+: HR, 1.72; p = 0.005) at weeks 16-24 in subjects with early viral success were predictive of subsequent failure. By week 60, total CD4+ T cells remained significantly lower than in uninfected controls. Adolescents beginning HAART achieve moderate rates of viral suppression by weeks 16-24. In those who do achieve early virologic control, suppression to week 60 is high although total CD4+ T cells remain significantly lower than in uninfected controls. Several T cell markers were predictive of subsequent virologic failure in subjects achieving short-term success. Further study is warranted to determine whether these predictors provide any benefit to clinical management

BACKGROUND: Adolescents represent the fastest growing demographic group of new human immunodeficiency virus (HIV) infections in the United States. At present, there is little information available about their response to therapy. METHODS: We studied 120 adolescents infected via high-risk behaviors who began receiving highly active antiretroviral therapy (HAART), to determine their virologic and immunologic response to therapy. RESULTS: Subjects were enrolled at 28 sites of the Pediatric Acquired Immunodeficiency Syndrome Clinical Trials Group. After 16-24 weeks of HAART, 59% of subjects had reproducible undetectable virus loads, according to repeat measurements (virologic success). As enumerated by flow-cytometric analysis, increases in levels of CD4 helper cells (both naive and memory) and decreases in levels of CD8 suppressor cells were observed. Partial restoration of some immunologic parameters for patients who did not achieve virologic success was also observed, but to a more limited extent than for adolescents with virologic success. Adherence to HAART was the only predictor of achieving undetectable virus loads. CONCLUSIONS: Adolescents have the capacity to improve their immunologic status with HAART. Lower than expected success in virologic control is related to lack of adherence, and efforts to improve treatment outcome must stress measures to assure adherence to medication

STIs are one consequence of specific risk-taking behaviors, not sexual orientation. Providers who care for adolescents should be aware of the STIs for which LGBTQ youth are at risk and the necessary screening (see Table 1). Although it is vital to recognize that LGBTQ youth are at risk for STIs, it is important not to view the youth within this narrow perspective. LGBTQ youth, like all adolescents, should be appreciated for their individuality, idealism, and resiliency. Most LGBTQ youth emerge from adolescence as productive and healthy adults. Treating adolescents with understanding and respect and honoring confidentiality are integral to the physical and emotional health of young people dealing with sexual-identity issues. Understanding the process of sexual-identity formation is the first step in gaining knowledge and perspective about young people with sexual-identity issues and helping them reduce their risk for contracting STIs. Physicians caring for adolescents should consult recent comprehensive reviews to improve their understanding of the issues LGBTQ youth may encounter

We characterized the viral dynamics of human immunodeficiency virus (HIV) type 1-infected adolescents receiving highly active antiretroviral therapy regimens (lamivudine [3TC]/zidovudine [ZDV]/efavirenz [EFV], 3TC/ZDV/nelfinavir [NFV], or other regimens) and studied the relationship of viral dynamics with baseline factors and virological responses. Viral decay rates for 115 evaluable subjects were estimated from a viral dynamic model. Viral dynamics in HIV-1-infected individuals aged 12-22 years were similar to those of HIV-1-infected adults and infants. Individuals who received 3TC/ZDV/EFV had a more rapid phase 1 viral decay rate than those who received 3TC/ZDV/NFV or other regimens. Phase 1 viral decay rates were positively correlated with baseline RNA levels and week 1 virus load reductions. Our findings indicate that the 3TC/ZDV/EFV regimen may be more potent than 3TC/ZDV/NFV or other regimens and that early viral dynamics or week 1 virus load reduction measurements may be useful in evaluating the potency of antiretroviral regimens

PURPOSE: To explore factors sexual minority youth believe make them feel safe in a health care setting. METHODS: Participants in three urban programs serving lesbian/gay/bisexual/transgendered and questioning (LGBTQ) youth engaged in a four-stage process to generate, prioritize, and explain their own ideas. In Stage III, 94 youth, aged 14 to 23 years, completed a survey comprised of the 34 highest rated items generated in earlier stages. Using a Likert scale, they answered, 'How important are each of the following ideas in making you feel safe as an LGBTQ youth when you go for health care?' In Stage IV, youth discussed the results in focus groups. The Marginal Homogeneity Test divided the items into priority ranks and the Kruskal-Wallis test explored subgroup differences in item ratings. RESULTS: The 34 items were divided into six ranks. Five items shared the top rank: the clinician maintaining privacy, demonstrating cleanliness, offering respect, being well-educated, and being honest. The second rank was shared by the following: the clinician not talking down to patients, being a good listener, not downplaying patients' fears, being professional, holding a nonjudgmental stance of the LGBTQ lifestyle, and not assuming every LGBTQ youth has HIV. Interspersed among other ranks were items specific to the needs of sexual minority youth: the clinician not assuming LGBTQ sexual behavior was painful or dangerous; the clinician being educated about the gay lifestyle; clinician sensitivity to the needs of same-sex partners; staff sensitivity to the needs of closeted youth; having a choice of an LGBTQ provider; and the clinician not assuming heterosexuality. Youth who had not publicly disclosed their sexuality rated health information being offered in a private place higher (p =.01). CONCLUSIONS: LGBTQ youth value the same clinician characteristics desired by all adolescents: privacy, cleanliness, honesty, respect, competency, and a nonjudgmental stance. They clearly describe what attracts them (e.g., clinicians educated about their lifestyle) and what offends them (e.g., equating their sexuality with HIV). Clinicians need to achieve and convey a higher comfort level in addressing the special needs of sexual minority youth

Flow cytometry analysis of lymphocyte subset markers was performed for a group of sexually active, human immunodeficiency virus (HIV)-negative adolescents over a 2-year period to establish normative data. Data were collected in the REACH Project (Reaching for Excellence in Adolescent Care and Health), a multicenter, longitudinal study of HIV-positive and high-risk HIV-negative adolescents. Two- and three-color flow cytometry data were collected every 6 months for these subjects. We determined the effects of gender, race, and age on the following lymphocyte subset markers: total CD4(+) cells, CD4(+) naive cells, CD4(+) memory cells, all CD8(+) cells, CD8(+) naive cells, CD8(+) memory cells, CD16(+) natural killer cells, and CD19(+) B cells. Gender was the demographic characteristic most frequently associated with differences in lymphocyte subset measures. Females had higher total CD4(+) cell and CD4(+) memory cells counts and lower CD16(+) cell counts than males. Age was associated with higher CD4(+) memory cell counts as well as higher CD8(+) memory cell counts. For CD19(+) cells, there was an interaction between age and gender, with males having significantly lower CD19(+) cell counts with increasing age, whereas there was no age effect for females. Race and/or ethnicity was associated with differences in total CD8(+) cell counts and CD8(+) memory cell counts, although both of these associations involved an interaction with gender

This review paper presents the immunology findings in human immunodeficiency virus (HIV) infected and uninfected youth in the Reaching for Excellence in Adolescent Care and Health (REACH) Project within the context of basic and HIV immunology concepts. Methods employed in the study for specimen collection, management, and laboratory analysis are presented. This paper reviews published analyses of cross-sectional data; longitudinal analyses are underway. These preliminary data extend the work of others in demonstrating the potential for substantial thymic reserve in youth. This finding in HIV infected adolescents has implications for a fuller response to antiretroviral or immune-based therapies compared to that seen in adults. Dysregulation in mucosal immunity may appear before systemic HIV effects are seen and requires attention particularly to screening and treatment of genital co-infections. REACH has demonstrated gender differences in immunologic measures irrespective of HIV infection status

OBJECTIVE: To examine the prevalence of steatorrhea and exocrine pancreatic insufficiency (EPI) and their association with growth and immune status variables in children with perinatally acquired human immunodeficiency virus (HIV) infection. DESIGN: Cross-sectional study. SETTING: Tertiary care HIV subspecialty practice. PARTICIPANTS: Children with perinatally acquired HIV infection. Exclusion criteria included being younger than 1 year and receiving mineral oil as a medication. METHODS: Weight, height, and upper arm anthropometric variables were measured. Spot stool samples were analyzed for steatorrhea using the Sudan III qualitative test and for EPI using fecal elastase-1 enzyme assay. Hormone-stimulated pancreatic function testing and 72-hour stool and dietary fat sample collection were performed when fecal elastase-1 enzyme was in the range of EPI, defined as less than 200 microgram/g. HIV RNA viral load, CD4 status, type of antiretroviral therapy, and biochemical evidence of hepatobiliary disease were measured within 3 months of stool sample collection. z Scores were computed for height, weight, triceps skinfold, and upper arm muscle area. RESULTS: We enrolled 44 patients (23 girls [52%]) with a mean +/- SD age of 7.4 +/- 3.1 years. None had hepatobiliary disease. The prevalence of steatorrhea was 39% (95% confidence interval, 23%-56%). The prevalence of EPI was 0% (95% confidence interval, 0%-9%). There were no associations between steatorrhea and EPI, growth, HIV RNA viral load, CD4 status, or type of antiretroviral therapy. Older children had decreased z scores for height (r = -0.42; P =.006). CONCLUSIONS: The clinical significance of steatorrhea in children with HIV infection is unclear. Furthermore, its evaluation should focus on nonpancreas-based conditions. Continual close monitoring of growth is essential in children with HIV infection