Faculty Bibliography

Adolescents and youth aged 15-24 are one of the populations most impacted by the global HIV epidemic with an estimated 50% of new infections occurring in this age group. They are thus one of the prime populations for targeting behavioral and biomedical preventions. However, the dynamics of the HIV epidemic in youth vary widely by geographic region and risk behavior profiles. There are also biological and neurodevelopmental considerations that must be considered in the development, testing, and ultimate dissemination of HIV prevention interventions. These concepts are broadly discussed here

Preventing HIV infection in adolescents and young adults will require a multimodal targeted approach, including individual-directed behavioral risk reduction, community-level structural change, and biomedical interventions to prevent sexual transmission. Trials testing biomedical interventions to prevent HIV transmission will require special attention in this population due to the unique psychosocial and physiologic characteristics that differentiate them from older populations. For example, microbicide research will need to consider acceptability, dosing requirements, and coinfection rates that are unique to this population. Preexposure prophylaxis studies also will need to consider potential unique psychosocial issues such as sexual disinhibition and acceptability as well as unique pharmacokinetic parameters of antiretroviral agents. Vaccine trials also face unique issues with this population, including attitudes toward vaccines, risks related to false-positive HIV tests related to vaccine, and different immune responses based on more robust immunity. In this article, we will discuss issues around implementing each of these biomedical prevention modalities in trials among adolescents and young adults to help to guide future successful research targeting this population

Understanding the multiple forms of stigma experienced by young HIV-positive African American men who have sex with men and how they relate to sexual risk behaviors is essential to design effective HIV prevention programs. This study of 40 African American young MSM found that 90% of those surveyed experienced sexual minority stigma, 88% experienced HIV stigma, and 78% experienced dual stigma. Sexual minority stigma was characterized by experiences of social avoidance, and HIV stigma, by shame. Individuals with high HIV stigma were significantly more likely to engage in unprotected sex while high or intoxicated. Associations between stigma and sexual practices were examined; youth endorsing higher levels of sexual minority stigma engaged in less insertive anal intercourse. Individuals endorsing more HIV stigma reported more receptive anal intercourse. These findings support the development of stigma-informed secondary prevention interventions for African American HIV-positive young MSM

Adherence continues to be a major barrier to successful treatment with highly active antiretroviral therapy (HAART) for HIV-infected individuals. HIV-infected adolescents and young adults face a lifetime of treatment with HAART. Often, individuals who struggle with adherence to HAART face multiple barriers that would therefore impact on the success of any single modality intervention. Thus, we conducted a cross-sectional, observational study to determine the prevalence of personal barriers to adherence and to identify associations between these barriers in HIV-infected subjects, 12 to 24. We studied the following personal barriers to adherence: mental health barriers, high/low self-efficacy and outcome expectancy, and the presence of specific structural barriers. There were 396 subjects infected after age 9 recruited from sites from the Adolescent Trials Network for HIV/AIDS Interventions or the Pediatric AIDS Clinical Trials Group. Of the 396 subjects, 148 (37.4%) self-identified as nonadherent. No significant differences were found between adherent and nonadherent subjects for the presence of mental health disorders. Adherence was significantly associated with all but one structural barrier. Both self-efficacy and outcome expectancy were higher among adherent versus nonadherent subjects (p < 0.0001). Grouping subjects according to low self-efficacy and outcome expectancy for adherence, adherence differed according to the presence or absence of mental health disorders and structural barriers (p < 0.0001). Our data suggest that adolescents have significant rates of non-adherence and face multiple personal barriers. Adherence interventions must address multiple barriers to have the maximum chance for positive effects.

This was a proof-of-principle study to evaluate the impact of short cycle therapy (SCT; 4 days on/3 days off) in adolescents and young adults with good viral suppression on a protease inhibitor-based antiretroviral regimen. Subjects were recruited by the Adolescent Trials Network for HIV/AIDS Interventions and the Pediatric AIDS Clinical Trials Group. Subjects were infected either through perinatal/early childhood transmission or later via risk behaviors. All subjects were required to have at least 6 months of documented viral suppression below 400 copies/ml plus a preentry value below 200 copies/ml and an entry CD4+ T cell count above 350 cells/mm3. Of the 32 subjects enrolled, 12 (37.5%) had confirmed viral load rebound >400 copies, with 18 subjects (56%) coming off for any reason. The majority of subjects resuppressed when placed back onto continuous therapy using the same agents. Although no difference was found in virologic rebound rates between the early and later transmission groups, those infected early in life had higher rates of coming off SCT for any reason. There was no impact of SCT on the CD4+ T cell counts in those who remained on study or those who came off SCT for any reason. Subjects demonstrated good adherence to the SCT regimen. This study suggests that further evaluation of SCT may be warranted in some groups of adolescents and young adults infected with HIV

Several emergency department (ED)-based HIV screening programs have been described. However, the majority of these programs have been aimed at adults and older adolescents, and few have taken place in a dedicated pediatric ED. Given that many adolescents seek care in hospital EDs, and that the ED may be an adolescent's only contact with the health care system, we decided to implement an HIV-counseling and testing program in the ED of an urban children's hospital. The program included a dedicated health educator who provided sexual health counseling in a 30-minute session as well as optional HIV testing and test results to patients aged 14-24 years, and arranged necessary follow-up care for adolescents who tested positive for HIV. We collected aggregate data on the number of youth counseled, tested, and followed up. A total of 1287 patients were approached for potential counseling and testing during the first 3 years of the project. Of these, 643 (50.0%) agreed to meet with the health educator and were counseled. Three hundred eighteen (49.5%) of these patients agreed to HIV testing. One hundred eighty-seven (58.8%) patients returned for follow-up. Two patients (0.6%) whose previous HIV status was unknown tested positive for HIV; both of these patients were successfully linked to care. Fifty-six health care providers (17.3% of ED providers) were surveyed about their opinions of the program; although 93% were supportive of the program, several respondents were concerned about the appropriateness of HIV testing in the ED setting. This project suggests that, if appropriate resources are available, a dedicated HIV counseling and testing program can be successfully implemented in a busy, urban, pediatric ED. Providing access to these services to high-risk adolescents has the potential to significantly impact their health.

Treatment failure and drug resistance create obstacles to long-term management of HIV-1 infection. Nearly 60% of infected persons fail their first highly active antiretroviral therapy (HAART) regimen, partially because of nonadherence, requiring a switch to a second regimen to prevent drug resistance. Among HIV-infected youth, a group with rising infection rates, treatment switch is often delayed; virologic and immunologic consequences of this delay are unknown. We conducted a retrospective, longitudinal study of drug resistance outcomes of initial HAART in U.S. youth enrolled between 1999-2001 in a multicenter, observational study and experiencing delayed switch in their first nonsuppressive treatment regimen for up to 3 years. HIV-1 genotyping was performed on plasma samples collected longitudinally, and changes in drug resistance mutations, CD4+ T cell numbers and viral replication capacity were assessed. Forty-four percent (n = 18) of youth in the parent study experiencing virologic nonsuppression were maintained on their initial HAART regimen for a median of 144 weeks. Drug resistance was detected in 61% (11/18) of subjects during the study. Subjects on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens developed more (8/10) drug resistance mutations than those on protease-inhibitor (PI) regimens (2/7) (p = 0.058). Subjects developing NNRTI-resistance (NNRTI-R), showed a trend toward lower CD4+ T cell gains (median: -6 cells/mm(3) per year) than those without detectable NNRTI-R (median: +149 cells/mm(3) per year) (p = 0.16). HIV-1-infected youth maintained on initial nonsuppressive NNRTI-based HAART regimens are more likely to develop drug-resistant viremia than with PI-based HAART. This finding may have implications for initial treatment regimens and transmission risk in HIV-infected youth, a group with rising infection rates

This study examined trauma history and posttraumatic stress in a sample of 30 adolescents and young adults with HIV/AIDS, recruited from December 14, 2004 through May 3, 2005. Overall, participants reported a mean of 5.63 traumatic events, with 93% of the sample reporting that receiving a diagnosis of HIV was experienced as traumatic. Of these, 13.3% met criteria for posttraumatic stress disorder in response to HIV diagnosis, while an additional 20% showed significant post-traumatic stress symptoms. Even greater rates of posttraumatic stress were reported in response to other trauma, with 47% of youth surveyed reporting symptoms of posttraumatic stress in response to such traumatic events as being a victim of a personal attack, sexual abuse, or being abandoned by a caregiver. These findings may inform professionals about the potential impact of the HIV diagnosis on adolescents and young adults, particularly as this may impact participation in medical care and need for mental health support

The PACTG 381 cohort included 120 adolescents infected via high-risk behaviors and treated with at least two NRTIs plus either a protease inhibitor or an efavirenz-containing HAART regimen. After 24 weeks of therapy, only 69 of 118 (59%) evaluable subjects had undetectable viral loads. We now present findings of the study after 3 years of follow-up. Virologic, immunologic, and treatment information were collected from subjects every 12 weeks beyond the first 24 weeks of therapy through 156 weeks. Of the 120 subjects starting HAART, 44 (37%) stayed on study treatment for the 3 years of observation. Twenty-nine (24%) subjects reached and maintained undetectable viral loads. Poorer adherence (p = 0.016), higher baseline viral load (p = 0.010), and CD8 naive counts (p = 0.034) predicted virologic failure. Immunologic measurements improved from entry to the end of follow-up in the subjects with undetectable viral loads. CD4 counts at the end of study were not significantly different from HIV-uninfected youth, but CD4%, CD8 counts and percent, and CD8 activation markers remained significantly different. Adolescents infected with HIV via high-risk behaviors have less than optimal responses to HAART therapy with only 24% achieving and maintaining undetectable viral loads over 3 years. Immunologic improvement was demonstrated and CD4 counts in subjects with virologic control reached levels in HIV-uninfected adolescents. Interventions, especially those focused on adherence, are necessary to improve HAART outcomes in adolescents