Faculty Bibliography

INTRODUCTION: Future HIV vaccine efficacy trials with adolescents will need to ensure that participants comprehend study concepts in order to confer true informed assent. A Hepatitis B vaccine trial with adolescents offers valuable opportunity to test youth understanding of vaccine trial requirements in general. METHODS: Youth reviewed a simplified assent form with study investigators and then completed a comprehension questionnaire. Once enrolled, all youth were tested for HIV and confirmed to be HIV-negative. RESULTS: 123 youth completed the questionnaire (mean age=15 years; 63% male; 70% Hispanic). Overall, only 69 (56%) youth answered all six questions correctly. CONCLUSIONS: Youth enrolled in a Hepatitis B vaccine trial demonstrated variable comprehension of the study design and various methodological concepts, such as treatment group masking.

BACKGROUND: Little is known about the incidence of anal human papillomavirus (HPV) infection and related sequelae, as well as factors associated with these outcomes, among adolescents who are HIV infected versus HIV uninfected but at risk. METHODS: We analyzed the data from a multisite US study, the Reaching for Excellence in Adolescent Care and Health Project. Adolescents aged 12 to 18 years who were behaviorally HIV infected (n = 319) or HIV uninfected but at risk (n = 177) were recruited. Incidence rates for anal HPV, high-risk anal HPV, anogenital warts, and anal dysplasia were calculated using Poisson modeling. Factors associated with these outcomes were examined using Cox proportional hazards modeling. RESULTS: Mean age at entry was 16.8 years; mean (SD) follow-up time for detection of anal HPV was 22.4 (10.8) months. Most participants (76%) were female; 70% were black non-Hispanic. HIV-infected (vs. HIV-uninfected) women had a significantly higher incidence of anal HPV (30 vs. 14 per 100 person-years; P = 0.002), high-risk anal HPV (12 vs. 5.3 per 100 person-years; P = 0.04), and anogenital warts (6.7 vs. 1.6 per 100 person-years; P = 0.002) but not anal dysplasia. Although incidence rates were higher for these outcomes among HIV-infected versus HIV-uninfected men, the differences were not statistically significant. Among women, factors associated with anal HPV and related sequelae differed by HIV status and included biological, behavioral, and HIV-related factors. No factors were associated with outcomes in men. CONCLUSIONS: HIV-infected versus HIV-uninfected adolescent women had higher rates of anal HPV and anogenital warts. Because HIV-infected youth are at increased risk of these outcomes, enhanced HPV prevention efforts such as vaccination are warranted for this group.

Community participation in prevention research has emerged as an important resource for identifying and addressing HIV risk factors and populations that may be more susceptible to these risks. This article focuses on the coalition at the Philadelphia site of Connect to Protect®: Partnerships for Youth Prevention Interventions (C2P), and the partnerships developed to work with an understudied subgroup of young men who have sex with men (YMSM), the House and Ball Community (HBC). The authors describe the coalition's process of identifying HIV risk factors, developing objectives and prevention activities such as increased access to HIV counseling and testing, and building partnerships with the HBC community. Local HIV testing data from C2P affiliated events, additional outcomes, and future directions for the coalition to continue these efforts are presented.

PURPOSE: To understand linkage to care practices at sites providing clinical services to newly diagnosed HIV-positive adolescents. METHODS: Qualitative analysis of detailed interviews conducted with 28 personnel involved in linkage to care at 15 sites providing specialty care to HIV-positive adolescents. RESULTS: We showed that multiple models exist for linkage to care, and that both formal and informal community relationships are important for successful linkage to care. Stigma was seen as a universal issue, enhancing the importance of the balance of confidentiality and social support. Barriers to care, such as mental health issues, substance use, and transportation, are common. CONCLUSIONS: We conclude that the complexity of linkage to care requires thought and planning as HIV testing is expanded to lower-risk populations.

BACKGROUND:: The objectives of this study were to describe the prevalence and risk factors for HPV infection among HIV-infected young women receiving their first quadrivalent HPV (HPV-6, -11, -16, and -18) vaccine dose. METHODS:: We recruited 16- to 23-year-old women from 14 sites for an HPV vaccine trial. At the first visit, they completed a questionnaire and were tested for cervicovaginal HPV DNA (41 types) and HPV serology (4 vaccine types). Factors associated with any HPV, type-specific HPV, and high-risk (cancer-associated) HPV infections were identified using univariate and multivariable logistic regression. RESULTS:: The mean age of participants (N = 99) was 21.4 years, 30.3% were on antiretroviral therapy, 74.7% were positive for >/=1 HPV DNA type, 53.5% for >/=1 high-risk type, 12.1% for HPV-16, and 5.1% for HPV-18. Most were HPV DNA negative and seronegative for HPV-16 (55.6%) and HPV-18 (73.7%); 45.5% were HPV DNA negative and seronegative for both HPV-16 and -18. Three variables were associated with high-risk HPV DNA in multivariable analysis: non-Hispanic black versus Hispanic ethnicity (adjusted odds ratio [AOR]: 7.06, 95% CI: 1.63 to 30.5), HIV viral load >/= 400 versus <400 copies/mL (AOR: 3.47, 95% CI: 1.28 to 9.43), and frequency of vaginal sex in the past 90 days (AOR: 5.82, 95% CI: 1.30 to 26.11 for >/=6 vs 0 times). CONCLUSIONS:: The prevalence of >/=1 HPV type was high in these young women, demonstrating the importance of vaccinating before sexual initiation. However, most women were HPV DNA negative and seronegative for high-risk vaccine-type HPV infection, supporting vaccination of sexually experienced HIV-positive young women.

BACKGROUND: HIV-infected youth are at risk of hepatitis B infection and should be vaccinated. Previous reports suggest reduced response to standard hepatitis B vaccine regimens. METHODS: HIV-infected youth, aged 12 to younger than 25 years, were randomly assigned to one of three treatment arms: Arm 1: Engerix B, 20 mug HBsAg; Arm 2: Engerix B (GlaxoSmithKline, Rixensart, Belgium), 40 mug; and Arm 3: Twinrix (GlaxoSmithKline, Rixensart, Belgium), 20 mug HBsAg combined with 720 ELU hepatitis A antigen. Vaccines were administered at Weeks 0, 4, and 24. RESULTS: Characteristics of evaluable patients (n = 336) at entry were similar in the study arms. At enrollment, median CD4+ T-cell count was 460 cells/mm3 (interquartile range, 305-668); 13% were less than 200 cells/mm3. Among Engerix B, 20-mug recipients, 60.4% responded to vaccine (HBsAb 10 IU/mL or greater at Week 28). Improved vaccine response was seen in recipients of Engerix B, 40 mug (73.2% versus Arm 1, P = 0.04) and Twinrix (75.4% versus Arm 1, P = 0.02). In multivariate analysis, only baseline CD4+ T-cell count and study arm were independent predictors of vaccine response. CONCLUSIONS: In HIV-infected youth, a three-dose vaccination regimen with Engerix B, 40 mug, or Twinrix and higher baseline CD4+ T-cell counts were independently associated with improved vaccine response

OBJECTIVES: The present study aimed to describe the experiences of youth with behaviorally acquired HIV who transitioned to adult care, to identify difficulties encountered, and to explore areas for improvement. METHODS: Semi-structured interviews were conducted with 10 young adults ranging from 24 to 29 years old. Themes were derived from coding participant interviews. RESULTS: Participants experienced adolescent care providers as an important source of support, felt anxiety about transition, provided recommendations for improving the process, and described significant changes associated with adult HIV care. CONCLUSIONS: Findings support the development of a clear and structured transition process to address patients' fears and worries through early communication, planning, and coordination for adult healthcare, highlighting the need for future research in this area

BACKGROUND: Multiple studies have shown excellent response rates after hepatitis B immunization in youth; however, one previous study conducted in urban youth demonstrated poor responses. METHODS: Urban youth, ages 12 to 17 years, at participating Adolescent Medicine Trials Network for HIV/AIDS Interventions Clinical/Research sites were randomized to receive either 2 doses of Recombivax HB (10 microg hepatitis B surface antigen) or Twinrix (20 microg hepatitis B surface antigen and 720 EL.U hepatitis A antigen) at 0 and 24 weeks. Safety data were collected and antibody measures performed at 0, 28, and 76 weeks. RESULTS: A total of 123 subjects were enrolled and 102 had week 28 serum samples available for antibody measure. A positive response (serum antibody > or =10 mIU/mL) to hepatitis B antigen was documented in 41 of 47 (87.2%; 95% confidence interval [CI] 74.3%-95.2%) Recombivax HB recipients and in 52 of 55 (94.6%; 95% CI, 84.9%-98.9%) Twinrix recipients (P = 0.295). In an adjusted analysis, those identified as Hispanic ethnicity (N = 86) were more likely to have a positive response (odds ratio 7.38, 95% CI, 1.56-34.95; P = 0.0018); whereas those who identified as not heterosexual (N = 9) were less likely to respond (odds ratio = 0.12, 95% CI, 0.02-0.74). The majority of youth in the Twinrix arm were hepatitis A antibody positive at baseline (26/51; 51%); however, 24 of 25 hepatitis A antibody negative youth responded to the hepatitis A component. Both vaccines were safe. CONCLUSIONS: Response rate to 2 doses of Recombivax HB in urban youth is lower than previous studies suggest. The factors associated with diminished response are not known.

Abstract Adherence to antiretroviral regimens continues to be a significant problem in HIV-infected individuals facing a lifetime of therapy. Youth who were infected through perinatal transmission enter into adolescence often with a history of multiple medication regimens. Thus, adherence can be a particularly important issue in these young people, as medication options can often be limited. This was a cross-sectional, observational study to determine the prevalence of personal barriers to adherence and to identify associations among the following barriers in subjects 12 to 24 years old: mental health barriers, self-efficacy and outcome expectancy, and structural barriers. Among the 368 study participants, 274 (74.5%) were adherent and 94 (25.5%) were nonadherent to highly active antiretroviral therapy (HAART). No significant differences were found between adherent and nonadherent subjects according to mental health disorders. Adherence was associated with some but not all structural barriers. Both self-efficacy and outcome expectancy were significantly higher in adherent versus nonadherent subjects (p < 0.0001). In subjects with low self-efficacy and outcome expectancy, adherence differed according to the presence or absence of either mental health or structural barriers, similar to findings in behaviorally- infected adolescents. Interventions that address the breadth and clustering of adherence barriers in adolescents are needed to have the maximum chance for positive effects