Improving comprehension for HIV vaccine trial information among adolescents at risk of HIV.

A simplified version of the HIVNET prototype HIV vaccine process was developed for adolescents at risk of HIV by:(1) reducing reading level; (2) reorganizing; (3) adding illustrations; and (4) obtaining focus group feedback. Then adolescents (N = 187) in three cities were randomly assigned to the standard or simplified version. Adolescents receiving the simplified version had significantly higher comprehension scores (80% correct vs. 72% correct), with 37% of items significantly more likely to be answered correctly. They were also significantly more likely to recall study benefits and procedures. Overall, adolescents were less willing to participate in a potential HIV vaccine trial after presentation than prior to presentation. The present study indicates that it would be feasible for adolescents to participate in a vaccine trial, as simplification of vaccine information, combined with illustrations to depict key concepts, resulted in improved scores for adolescents on the comprehension and recall test.

No change in health risk behaviors over time among HIV infected adolescents in care: role of psychological distress.

PURPOSE: To investigate the association of psychological distress and health risk behaviors among HIV infected adolescents. It was hypothesized that higher levels of distress would be associated with increased sexual risk behaviors, and increased use of alcohol and drugs. METHODS: HIV infected adolescents (N = 323) were recruited into an observational study in 15 clinical sites; for the 323 subjects, a total of 1212 visits were used in a repeated measures analysis. Data on depression (using the CES-D), anxiety (manifest anxiety scale), sexual behaviors and alcohol and marijuana use were obtained through computer-assisted self-administered interview. RESULTS: Approximately 65% of the sample was sexually active across all six study visits, with approximately 43% consistently reporting having unprotected sex at last intercourse. Higher levels of depression were associated with frequent alcohol use and with unprotected sex at last intercourse, with depressed adolescents significantly more likely to have had unprotected sex than those who were not depressed. Health anxiety was associated with frequent marijuana use and with recent sexual activity, and physiological anxiety was also associated with recent sexual activity. CONCLUSIONS: Despite the fact that these HIV infected adolescents are all engaged in primary care, overall the sample is maintaining its high-risk sexual behavior. In addition, these adolescents may be self-medicating to deal with health-related anxiety. Health interventions for HIV infected adolescents should examine whether psychological distress is contributing to maintenance health risk behaviors.

Correlation between urine and cervical specimens for the detection of cervical Chlamydia trachomatis and Neisseria gonorrhoeae using ligase chain reaction in a cohort of HIV infected and uninfected adolescents.

PURPOSE: (a) To examine the concordance between ligase chain reaction (LCR) results from urine and cervical samples for Chlamydia trachomatis and Neisseria gonorrhoeae in HIV infected and uninfected adolescent women, and (b) to examine factors that may influence the concordance of LCR results in this population. METHODS: Baseline specimens from 269 of 334 female subjects enrolled in a longitudinal study of HIV infection in adolescents were analyzed for C. trachomatis and N. gonorrhoeae using ligase chain reaction (LCR) assays in a central laboratory. Concordance was measured using kappa coefficient with permutation analyses to calculate the difference between HIV status groups. Discordant LCR results were examined for the co-infection with the other microorganism, bacterial vaginosis, or Trichomonas vaginalis. RESULTS: The prevalence of C. trachomatis detected by LCR in the HIV infected and uninfected groups was 19.3% and 12.2%, respectively (p = .16); the prevalence of N. gonorrhoeae was 7.0% and 2.4%, respectively (p = .16). Urine LCR assay sensitivity to detect cervical C. trachomatis infection was 86% (95% CI: 68%-96%) in the HIV infected group and 100% (95% CI: 69%-100%) in the HIV uninfected group. Urine LCR assay sensitivity to detect cervical N. gonorrhoeae infection was 92% (95% CI: 62%-100%) in the HIV infected group. There were only 2 N. gonorrhoeae infections in the HIV uninfected group, and both were urine LCR positive. Differences in sensitivity between HIV infected and HIV uninfected subjects were not statistically significant. Coinfection with N. gonorrhoeae, bacterial vaginosis or Trichomonas vaginalis was not associated with the concordance of urine and cervical LCR results. CONCLUSION: The relatively high sensitivity of urine LCR testing overall suggests that urine screening may be reasonable for sexually active adolescent females with or without HIV infection in situations in which urine screening may be more acceptable than pelvic examinations.

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.

Natural killer cell enumeration and function in HIV-infected and high-risk uninfected adolescents.

This is the first report of natural killer cell enumeration and function in HIV-infected and high-risk uninfected adolescents. We examined the association of demographic characteristics of this cohort with three outcomes: CD16+ cell absolute count, lytic units per peripheral blood mononuclear cell (PBMC), and lytic units per natural killer (NK) cell. We also examined the association of CD4, CD38, and antiretroviral therapy (ART) use with these outcomes in the subset of HIV-infected adolescents. Adolescents participating in an on-going longitudinal study (the REACH study) were sampled for CD16+ cell count and NK function. This cross-sectional analysis was performed on 412 subjects with NK cell data available. HIV-positive males had higher numbers of CD3-/CD16+/CD56+ NK cells than HIV-positive females. However, for the HIV-negative subjects, we did not observe a gender-related effect for absolute NK cell numbers. Gender, however, was a significant covariate for the analysis, using lytic units per PBMC as the unit of measurement, with males showing higher values than females. Age was not a predictive covariate for any of the three assessments of NK cell number and function examined. Our observations concerning the HIV-positive individuals indicate that reduced CD4+ T cell counts were associated with decreased circulating CD3-/CD16+/CD56+ NK cells. We also observed an association between elevation of CD8+/CD38+/DR+ lymphocytes and lower NK lytic units per PBMC. The results of our multivariate models indicate that there is a reduced number of NK cells and reduced lytic units per PBMC in patients receiving single or multidrug antiretroviral therapy. There are changes in circulating NK cell number and function in HIV-infected adolescents, in comparison with high-risk HIV-negative adolescents. The data suggest that these changes may occur early in the course of HIV disease but that quantitative changes continue to occur with advancing depletion of the CD4+ T cell pool.

Antiretroviral medication adherence among the REACH HIV-infected adolescent cohort in the USA.

Adherence to highly active antiretroviral therapy (HAART) was investigated among HIV-infected adolescents recruited from 13 US cities into the REACH (Reaching for Excellence in Adolescent Care and Health) project, the first large-scale disease progression study of HIV-positive adolescents infected through sexual behaviour or injection drug use. Of 161 subjects, 7% could not correctly identify all their prescribed medications; 11% could identify them but reported never taking at least one medication. The majority (83%) reported taking all of their medications at least some of the time, but only 50% of these subjects reported full adherence. Therefore, only 41% of the sample reported full adherence. A strong association was found between adherence and reduced viral load. A CD4 level of > or = 500 cells/mm3 was also associated with adherence. Higher levels of depression were significantly associated with decreased adherence, and a trend was found for an association between number of medications prescribed and adherence. Strict adherence to HAART is critical for sustained suppression of viral replication allowing for immune recovery and reducing the risk of the selection of antiviral resistance. Adherence appears to be a serious problem among HIV-positive adolescents. Better education, intervention to relieve depression, and efforts to improve ease of medication use are essential.

Marijuana use among HIV-positive and high-risk adolescents: a comparison of self-report through audio computer-assisted self-administered interviewing and urinalysis.

The validity of self-report of drug use has been found to vary widely. Moreover, previous research has focused on samples of adults. In 1996-1998, human immunodeficiency virus (HIV)-infected adolescents and high-risk, noninfected adolescents (n = 182) were recruited at 16 locations in 13 US cities into the Reaching for Excellence in Adolescent Care and Health (REACH) project, to the authors' knowledge, the first national study of disease progression among HIV-positive adolescents who were infected through sexual behavior or injection drug use. Self-report of marijuana use was assessed through audio computer-assisted self-administered interviewing (ACASI). Urines were tested for marijuana at a certified laboratory by using the enzyme-multiplied immunoassay technique. Conditional kappas for 2-, 5-, and 7-day self-reports were 0.57, 0.71, and 0.69, respectively. Maximum sensitivity was obtained from a combination of ACASI and urine drug testing. Contrary to previous studies, the data suggest that if a single evaluative instrument is to be used for prevalence, ACASI is more sensitive than urine drug testing for marijuana overall, but particularly for HIV-infected adolescents.

Seroprevalence and risk factors of hepatitis B, hepatitis C, and human cytomegalovirus among HIV-infected and high-risk uninfected adolescents: findings of the REACH Study. Adolescent Medicine HIV/AIDS Research Network.

BACKGROUND AND OBJECTIVES: In adolescents and young adults, multiple studies have identified sexual activity and behaviors as significant risk factors for acquiring both human cytomegalovirus (HCMV) and hepatitis B virus (HBV). However, there are no reports on the prevalence or risk factors for infection of these viruses and hepatitis C virus (HCV) in an adolescent population with sexually acquired HIV. GOALS: To examine the seroprevalence and risk factors of HBV, HCV, and HCMV infection in a population of HIV-infected male and female adolescents and in an age- and risk behavior-matched HIV-uninfected cohort. STUDY DESIGN: A cross-sectional analysis of HBV, HCV, and HCMV infections in a cohort of HIV-infected and HIV-uninfected adolescents. RESULTS: Adolescent males infected with HIV were more likely to have evidence of HBV and HCMV infection than HIV-uninfected males (23.7% versus 0%, respectively, for HBV, P = 0.008; 79.7% versus 50%, respectively, for HCMV, P = 0.004). HIV-infected females were more likely to have evidence of HCMV infection (78.5% versus 61.4%, P = 0.003) than HIV-uninfected females. No significant difference was found for HBV infection in the two groups of females. The rate of HCV infection (1.6%) was too small to make comparisons between the groups. To determine whether the differences in infection rates for HBV and HCMV could be explained by factors other than HIV status, a variety of possible risk factors were examined using univariate and multivariate analyses. A significant risk factor for HBV and HCMV infections for males was a homosexual or bisexual orientation. For females, a risk factor for HBV infection was having more than 10 lifetime sexual partners; for HCMV infection, HIV infection was the only risk factor. In addition, in the HIV-infected cohort, 15% of females and 36% of males who were seropositive for HBV had evidence of active HBV infection. CONCLUSIONS: These results emphasize the need for continued development of primary and secondary prevention programs and clinical screening and treatment for HBV and HCMV in adolescents.

Neurologic status of human immunodeficiency virus 1-infected infants and their controls: a prospective study from birth to 2 years. Mothers and Infants Cohort Study.

OBJECTIVE: To determine the timing, extent, severity, and persistence of neurologic abnormalities in children with perinatally acquired human immunodeficiency virus 1 (HIV-1) infection compared with similar uninfected children of HIV-1-infected women and control children. METHODS: Serial neurologic examinations and head circumference measurements were performed on a cohort of HIV-1-infected children born to HIV-1-infected women, seroreverting children born to HIV-1-infected women, and control children born to uninfected women. Examination data from 32 HIV-1-infected children, 99 reverters, and 116 control children were summarized by eight neurologic domains. Data were analyzed by longitudinal analysis. RESULTS: Reverter children were not different from control children in neurologic function for any of the eight domains or head circumference. HIV-1-infected children had significantly more neurologic problems than the control and reverter children for seven of the eight domains. The HIV-1-infected children were further classified by whether they had acquired immunodeficiency syndrome (AIDS)-defining clinical conditions (other than lymphoid interstitial pneumonitis) in the first 24 months of life (the AIDS-opportunistic infection group) or did not (the infected-other group). Neurologic abnormalities were early, severe, pervasive, and persistent in the AIDS-opportunistic infection group, and nearly all in this group had head circumference measurements below the 10th percentile. The infected-other group had no statistically significant differences from the uninfected children, although individual children in the infected-other group had some abnormalities. CONCLUSIONS: In utero exposure to HIV-1 without infection seems to have no negative impact on neurologic function in children in the first 2 years of life. Among children with perinatally acquired HIV-1 infection, the most severe and pervasive neurologic problems occur in those children who have early serious HIV-1 clinical disease. Most children without serious AIDS-defining clinical conditions in the first 2 years of life are also free from serious neurologic problems during that period.

Effect of perinatally acquired human immunodeficiency virus infection on neurodevelopment in children during the first two years of life.

OBJECTIVE: To determine the timing, extent, and magnitude of neurodevelopmental problems in children with perinatal HIV infection compared to similar uninfected children of HIV-infected women and controls. METHODS: Neurodevelopmental assessments during the first 24 months of life for 21 HIV-infected children born to HIV-infected mothers, 65 seroreverted children born to HIV-infected mothers, and 95 non-HIV-infected children born to non-HIV-infected mothers were analyzed. Neurodevelopment was assessed by using the Bayley Scales of Infant Development beginning at 3 months of age. Kent Scoring Adaptation was also utilized. A two-stage Hierarchical Linear Model was used for analysis of neurodevelopmental scores. RESULTS: In the initial comparison of these three groups, infected children had significantly lower scores on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) than the other two groups. The HIV-infected children were further classified into HIV-infected without Centers for Disease Control-defined AIDS, those with lymphoid interstitial pneumonitis (LIP) only as their AIDS-defining illness, and children with an AIDS-defining diagnosis other than LIP in the first 24 months. The children with LIP-only AIDS and the infected children without AIDS on average were not significantly different from the seroreverters or the controls on MDI or PDI, while the children with non-LIP AIDS had significantly lower scores after 3 months of age. Analysis of the Kent scores indicated that the decrement in the non-LIP AIDS children was seen in all five functional domains. CONCLUSION: Children with serious HIV symptomatology appear to be at very high risk for serious developmental impairments, HIV-infected children not highly symptomatic have relatively normal neurodevelopment, and uninfected children of HIV-infected mothers do not appear to be adversely affected by the mother's HIV infection.

Risk of leukemia after treatment with pituitary growth hormone.

OBJECTIVE: To determine whether pituitary-derived human growth hormone treatment increases the subsequent risk of developing leukemia and lymphoma. DESIGN: Cohort study. SETTING: United States. PARTICIPANTS: A total of 6284 recipients of pituitary-derived human growth hormone distributed by the National Hormone and Pituitary Program between 1963 and 1985. MAIN OUTCOME MEASURES: Leukemia and lymphoma. RESULTS: Three cases of leukemia occurred in 59,736 patient-years of follow-up from the start of growth hormone therapy to case ascertainment at interview; this number was not significantly higher (P = .23) than the 1.66 cases expected in the US age-, race-, and gender-matched general population. Three additional cases, found in an extended follow-up that provided 83,917 person-years of risk, yielded a minimum rate of leukemia that was significantly increased (six cases found, 2.26 expected; P = .028). The relative risk of leukemia in pituitary growth hormone recipients compared with the general population was 1.8 (90% confidence interval [CI], 0.82 to 7.5) for the defined follow-up and 2.6 (90% CI, 1.2 to 5.2) for the extended follow-up. Five of the six subjects who developed leukemia had antecedent cranial tumors (four craniopharyngioma, one astrocytoma) as the cause of growth hormone deficiency, and four had received radiotherapy. There was no increase in leukemia in patients with idiopathic growth hormone deficiency. The association of leukemia and craniopharyngioma was significant (P < .001). There was no excess of lymphoma in the cohort. CONCLUSIONS: This cohort of growth hormone recipients had a significantly increased rate of leukemia compared with the age-, race-, and gender-matched general population. However, the upper bound CI of the relative risk in our population (5.2) is well below the other estimates (7.6). Compared with the general population, our study population had more possible risk factors for leukemia (radiation, tumor) that may have contributed to the excess observed. The clustering of cases of leukemia in craniopharyngioma patients should be further evaluated.

Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group.

BACKGROUND: Acute non-A, non-B hepatitis after blood transfusion often progresses to chronic hepatitis and sometimes culminates in cirrhosis or even hepatocellular carcinoma. However, the frequency of these sequelae and their effects on mortality are not known. METHODS: We traced patients with transfusion-related non-A, non-B hepatitis who had been identified in five major prospective studies conducted in the United States between 1967 and 1980. We matched each patient with two control subjects (identified as the first and second controls) who received transfusions but who did not have hepatitis. The mortality rates in the three groups were determined with use of data from the National Death Index and Social Security Death Tapes. Cause-specific mortality was determined by reviewing death certificates. RESULTS: Vital status was established for over 94 percent of the 568 patients who had had non-A, non-B hepatitis and the two control groups (526 first controls and 458 second controls). After an average follow-up of 18 years, the estimate by life-table analysis of mortality from all causes was 51 percent for those with transfusion-associated non-A, non-B hepatitis, as compared with 52 percent for the first controls and 50 percent for the second controls. The survival curves for the three groups were virtually the same. Mortality related to liver disease was 3.3, 1.1, and 2.0 percent, respectively, among the three groups (P = 0.033 for the comparison of the group with non-A, non-B hepatitis with the combined control group). Seventy-one percent of the deaths related to liver disease occurred among patients with chronic alcoholism. CONCLUSIONS: In this long-term follow-up study, there was no increase in mortality from all causes after transfusion-associated non-A, non-B hepatitis, although there was a small but statistically significant increase in the number of deaths related to liver disease.

A collaborative study of differences in the survival rates of black patients and white patients with cancer.

In 1983, the National Cancer Institute began a social-epidemiologic study of possible behavioral and biologic determinants of black/white racial disparities in cancer survival. The design, methodology, underlying hypotheses, and patient accrual of this study are discussed. Survival differences in four organ sites are investigated: cancers of the uterine corpus, breast, bladder, and colon. The first three sites were chosen because of significant observed black/white differentials in survival. Although racial disparities in survival from colon cancer are less prominent, this site was included because it is a leading cause of deaths attributable to cancer, because regional variations have been observed in black/white survival disparities, and because colon data permit cross-gender comparisons. Data collection centers for the study included the Georgia Center for Cancer Statistics, the Louisiana Tumor Registry, and the California Tumor Registry. Probability samples of patients newly diagnosed with these cancers were drawn from the areas served by these registries. Diagnostic years of eligibility were 1985 to 1986 for breast and colon cancer, and 1985 to 1987 for bladder and uterine corpus cancer. Data were collected by personal interview, medical records abstract, physician records, and pathology review. Analyses focus on seven main explanatory hypotheses.

Creutzfeldt-Jakob disease in pituitary growth hormone recipients in the United States.

To assess the magnitude of Creutzfeldt-Jakob disease (CJD) occurrence among recipients of pituitary-derived human growth hormone (HGH), we conducted an epidemiologic follow-up of 6284 recipients of HGH distributed through the National Hormone and Pituitary Program. Seven neuropathologically confirmed cases of CJD have occurred in this population to date: six patients with clinical CJD presented with ataxia and imbalance, rather than with altered mentation, which is the most common initial manifestation in sporadic CJD, and one patient died in the preclinical incubation state of the disease. All seven cases occurred among the nearly 700 HGH recipients who started therapy before 1970. Since only 10% of the cohort has been followed up for the 15-year average incubation interval from midpoint of HGH treatment to onset of symptoms, the great majority of potentially exposed patients have not yet attained the requisite incubation period for expression of CJD. The median duration of HGH therapy of 100 months in the CJD cases was significantly longer than 41 months for all patients starting treatment before 1970; thus, the duration of pituitary HGH therapy is a major risk factor for CJD.