Faculty Bibliography

We reviewed the short-term response to and safety of protease inhibitor (PI) therapy in HIV-infected children by performing a retrospective chart review of open-label PI containing combination therapy at two urban pediatric HIV centers. Seventy HIV-infected children received 101 PI containing antiretroviral therapy (ART) combinations. Main outcome measures were follow-up CD4 counts, viral loads, and patient or caregiver reported compliance. During follow-up, treatment with PI ART was associated with a mean maximal increase in CD4+ lymphocyte count of 454 x 10(6)/L and a mean maximal decrease in viral load of 1.76 log units. Of the 32 patients who achieved undetectable viral loads, 28 (87.5%) remained undetectable through a mean follow-up of 8.9 months. Patients who reported good compliance achieved a higher rate of response (92.6%) than those who reported poor compliance (61.5%). Of 14 changes made to a second PI because of treatment failure, 11 (78.6%) resulted in a positive response to the second regimen. Nineteen of 101 courses of PI therapy resulted in significant side effects, including renal complications in 8 of 21 patients treated with indinavir. PI ART was associated with substantial short-term improvement in immunological and virological parameters in this heavily pretreated cohort, with 40% of patients maintaining an undetectable viral load after 9 months of therapy. Patients who failed one PI regimen usually responded to a second regimen. There was a significant rate of side effects from PI treatment

BACKGROUND: The capacity of the immune system of adolescents to generate and repopulate naive and memory cell populations under conditions of normal homeostasis and human immunodeficiency virus (HIV) infection is largely unknown. OBJECTIVE: To assess lymphocyte subsets in HIV-infected and high-risk HIV-negative adolescents. DESIGN: The Reaching for Excellence in Adolescent Care and Health Project of the Adolescent Medicine HIV/AIDS Research Network recruits a cohort of HIV-infected and high-risk HIV-uninfected adolescents, aged 13 to 18 years 364 days, into a study of biomedical and behavioral features of HIV infection as seen in the context of full availability of primary care and HIV-related consultative services. Lymphocyte phenotypes were determined using standard 3-color flow cytometry. SETTING: The Reaching for Excellence in Adolescent Care and Health Project is carried out at 16 clinical sites in 14 urban areas. PARTICIPANTS: T-lymphocyte subsets are reported in 192 HIV-positive and 78 HIV-negative youths. RESULTS: For HIV-positive subjects, the total CD4+ cell count and the percentage of CD4+ cells are decreased when compared with those of the HIV-negative controls (P<.001). The reduction in total CD4+ cells reflects a loss of naive, and memory, CD4+ cells compared with HIV-negative youths. Human immunodeficiency virus-infected adolescents, many of whom have been infected recently (ie, those with CD4+ cell counts > or =0.500 x 10(9)/L [500/microL]), have a significant increase in naive CD8+ cells compared with HIV-negative youths (P<.01). There also is a significant increase in memory CD8+ cells at all strata of total CD4+ cells compared with HIV-negative youths (P<.01). The increase in naive CD8+ cells in those subjects with CD4+ cell counts of 0.500 x 10(9)/L or greater is a unique finding in this cohort. CONCLUSIONS: This study demonstrates high levels of naive CD8+ cells in response to HIV infection in adolescents with CD4+ cell counts of 0.500 X 10(9)/L or greater. The presence of high levels of naive CD8+ cells suggests functioning thymic tissue in some adolescents infected with HIV. Furthermore, the normal level of naive CD4+ cells in adolescents with CD4+ levels of 0.500 x 10(9)/L or greater provides additional support for the concept of a more robust immune system in HIV-infected adolescents compared with HIV-infected adults. These observations suggest that the immune system of HIV-infected adolescents may be capable of better responses to neoantigens and cytotoxic T-lymphocyte responses to HIV than the immune system of infected children or adults. Human immunodeficiency virus-infected adolescents may have an immune system that is capable of reconstitution following highly active antiretroviral therapy

OBJECTIVE: To examine potential hematologic and immunologic markers for healthy adolescents and for adolescents infected with HIV. DESIGN: The REACH Project (Reaching for Excellence in Adolescent Care and Health) of the Adolescent Medicine HIV/AIDS Research Network (AMHARN) recruits HIV-infected and high-risk HIV-uninfected adolescents, aged at least 13 but less than 19 years. The study evaluates biomedical and behavioral features of HIV infection as observed while under medical care for HIV infection and adolescent health. METHODS: Blood samples were collected from HIV-infected and HIV-uninfected subjects at 16 clinical sites. Cell phenotypes were determined using standard single, dual or three-color flow cytometry. RESULTS: This report includes data at enrollment for 94 HIV-positive adolescents who had never received antiretroviral therapy (ART) (mean age, 17.4 +/- 1.0 years for males and 16.5 +/- 1.3 years for females) and 149 HIV-negative adolescents (mean age, 16.7 +/- 1.2 years for males and 16.6 +/- 1.2 years for females); this is the antiretroviral therapy-naive subset drawn from 294 HIV-positive and 149 HIV-negative adolescents enrolled in the REACH Cohort. The total leukocyte count was significantly reduced in the HIV-positive females in comparison with the HIV-negative females (P < 0.001). There was a reduction in natural killer cells (P < 0.05) in HIV-positive females (mean, 140.6 +/- 104.2 x 10(6) cells/l) in comparison with HIV-negative females (184.3 +/- 142.5 x 10(6) cells/l), whereas no differences were found between the two groups of males. The reduction in the total CD4 cell count in HIV-positive males and females in comparison with the HIV-negative subjects was the consequence of a decrease in both the naive CD4 and memory CD4 components. There was a striking increase in the mean number of CD8 memory cells in HIV-positive compared with HIV-negative adolescents, and a corresponding increase in the percentage of these cells. In contrast, naive CD8 cells were present in increased numbers but their percentage was decreased. CONCLUSIONS: These studies of adolescents provide normative data for high-risk healthy adolescents as well as baseline immunologic data for a cohort of ART-naive HIV-positive adolescents. This comparison suggests that this untreated, recently infected group had relatively intact immunologic parameters

BACKGROUND: Incarcerated and detained youth are at high risk for sexually transmitted diseases (STD), including human immunodeficiency virus (HIV). GOAL OF THE STUDY: To compare the level of sexual activity and substance use-related risk and knowledge regarding HIV/STD among male adolescents with multiple (YMA) versus first admissions (YFA) to a detention facility as a basis for the development of specific intervention strategies. STUDY DESIGN: Sexual and substance use histories, HIV/STD knowledge, and perceived risk were collected through structured interviews of a consecutive sample of detained youth. Human immunodeficiency virus antibody seroprevalence was determined using a blind study of discarded blood. RESULTS: Overall, these youth (N = 486) reported high levels of noninjection drug use, sexual risk activities, and knowledge regarding HIV/STD prevention. Furthermore, most of these youth reported that their risk for HIV infection was low (68%). Eighty-one percent of all youth reported recent (past 6 months) vaginal sex, and 14% reported insertive anal sex. Controlling for age, YMA were more likely to initiate sex at age 13 or younger (OR 1.38; 95% CI, 1.11-1.70), to report eight or more lifetime sex partners (OR 1.36; 95% CI, 1.13-1.63), and to have ever exchanged drugs or money for sex (OR 1.54; 95% CI, 1.08-2.19). However, these youth were less likely to report condom use with their last sex partner (OR 0.74; 95% CI, 0.60-0.93). More than one third (34%) of all youth felt that consistent use of condoms would not provide a high level of protection against HIV. CONCLUSION: Youth with multiple versus first admissions are at higher risk of HIV/STD infections through their lifetime and recent sexual activities. Interventions targeted to this population will need to address the barriers to and facilitators of condom use, strategies to promote positive attitudes toward condoms, and strategies to reduce the high level of alcohol and substance use

To respond to the difficulties that community-based providers face in keeping abreast of the rapid changes in HIV-related care, an intensive pediatric HIV mentoring program (Pediatric HIV Miniresidency [MR]) was developed, linking a regional AIDS Education and Training Center (AETC) with an urban children's hospital HIV outpatient care site. The purpose of this study was to evaluate HIV-related knowledge and perceived skills, abilities, and willingness of community-based primary care pediatric providers and providers completing the MR. A convenience sample of community-based primary pediatric practitioners and those participants in the MR program completed a three-part mailed survey. The survey assessed practice characteristics, knowledge of pediatric HIV clinical care, and perceived skills, ability, and willingness (PSAW) to provide HIV-related care. The main outcome measures were overall knowledge and PSAW scores. One hundred nineteen community-based practitioners (NMRs), 20% of those surveyed, completed the instrument, as did 19 of 20 MR participants. NMRs exhibited low knowledge scores in key areas relating to the identification and evaluation of HIV-exposed children. Fewer than half of these respondents correctly answered questions related to HIV antibody incidence in HIV-exposed newborns and recommended diagnostic testing of such infants. Providers completing the MR scored significantly higher on the knowledge survey (15.2 vs. 8.8, p < 0.001), and had higher PSAW scores (45.8 vs. 33.9, p < 0.001). Although the generalizability of our study is limited by the low response rate, community-based physicians completing the survey demonstrated a lack of knowledge we believe necessary to provide pediatric HIV-related care (as defined by Public Health Service practice guidelines). Physicians completing the MR program had substantial HIV-related knowledge and expressed a willingness to provide care to HIV-exposed/infected children. An effective MR program provides a mechanism for developing a network of dedicated community-based physicians who are willing and capable of providing care to HIV-infected or exposed infants and children

OBJECTIVE: To review the short-term response and safety of protease inhibitor therapy in HIV-infected children. DESIGN: Retrospective chart review of open-label protease inhibitor-containing combination therapy. SETTING: Two urban pediatric HIV centers. PATIENTS: Twenty-eight HIV-infected children were prescribed 30 protease inhibitor-containing antiretroviral therapy combinations. The median age at initiation of protease inhibitor antiretroviral therapy was 79 months. Patients had been on previous antiretroviral therapy for a mean of 45.5 months. RESULTS: Of the 28 children who completed at least 1 month of therapy, 26 experienced marked virologic and immunologic improvement (mean maximal decrease in viral load 1.90 log10 copies/ml; SD, 0.8; mean maximal rise in CD4+ lymphocytes of 279 x 10(6)/l; SD, 300 x 10(6)/l). Eleven patients achieved a viral nadir of < 400 copies/ml, and seven sustained this level of viral suppression for a mean of 6 months. Indinavir use was associated with a high incidence of renal side-effects, including two patients who developed interstitial nephritis. Two patients on ritonavir experienced a significant elevation of liver enzymes. CONCLUSIONS: Protease inhibitor therapy was associated with substantial short-term virologic and immunologic improvement in this primarily heavily pretreated cohort, with 25% maintaining a viral load of < 400 copies/ml after 6 months of therapy. There was a significant rate of adverse events. Pharmacokinetic and safety data are needed to guide aggressive antiretroviral therapy in HIV-infected children, and further treatment options are required for those failing or intolerant to the available protease inhibitors

Adolescents infected with the human immunodeficiency virus (HIV) often confront the clinician with difficult medical problems. Besides the host of opportunistic infections, which can affect these patients, side effects from medications can be frequent and, at times, life-threatening. We report a case of aseptic meningitis secondary to trimethoprim-sulfamethoxazole therapy for prophylaxis against Pneumocystis carinii in an HIV-infected adolescent

A child with perinatally acquired HIV infection presented with acute neurologic deterioration. A cerebellar white matter lesion seen on CT and MRI later proved to be progressive multifocal leukoencephalopathy (PML) by histology. Although a recognized disease of HIV-infected adults, PML is certain to be seen with more frequency in HIV-infected children who are surviving longer as a result of improved medical care. Recognition of the clinical and radiographic manifestations is important because of the dismal prognosis