We investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children.
Ninety subjects 4 to <25 years of age received two double doses of pH1N1 vaccine. Serum and cells were frozen at baseline, after each vaccination, and at 28 weeks post-immunization. Hemagglutination inhibition (HAI) titers, avidity indices (AI), B-cell subsets, and pH1N1 IgG and IgA antigen secreting cells (ASC) were measured at baseline and after each vaccination. Neutralizing antibodies and pH1N1-specific Th1, Th2 and Tfh cytokines were measured at baseline and post-dose 1.
At entry, 26 (29%) subjects had pH1N1 protective HAI titers (≥1:40). pH1N1-specific HAI, neutralizing titers, AI, IgG ASC, IL-2 and IL-4 increased in response to vaccination (p<0.05), but IgA ASC, IL-5, IL-13, IL-21, IFNγ and B-cell subsets did not change. Subjects with baseline HAI ≥1:40 had significantly greater increases in IgG ASC and AI after immunization compared with those with HAI <1:40. Neutralizing titers and AI after vaccination increased with older age. High pH1N1 HAI responses were associated with increased IgG ASC, IFNγ, IL-2, microneutralizion titers, and AI. Microneutralization titers after vaccination increased with high IgG ASC and IL-2 responses. IgG ASC also increased with high IFNγ responses. CD4% and viral load did not predict the immune responses post-vaccination, but the B-cell distribution did. Notably, vaccine immunogenicity increased with high CD19+CD21+CD27+% resting memory, high CD19+CD10+CD27+% immature activated, low CD19+CD21-CD27-CD20-% tissue-like, low CD19+CD21-CD27-CD20-% transitional and low CD19+CD38+HLADR+% activated B-cell subsets.
HIV-infected children on HAART mount a broad B-cell memory response to pH1N1 vaccine, which was higher for subjects with baseline HAI≥1:40 and increased with age, presumably due to prior exposure to pH1N1 or to other influenza vaccination/infection. The response to the vaccine was dependent on B-cell subset distribution, but not on CD4 counts or viral load.
Background. The safety and immunogenicity of high-dose pandemic H1N1 (pH1N1) vaccination in perinatally human immunodeficiency virus type 1 (HIV-1)–infected children, adolescents, and young adults are unknown.
Methods. Two 30-μg doses of 2009 Novartis pH1N1 monovalent vaccine (Fluvirin) were administered 21–28 days apart to perinatally HIV-1–infected children, adolescents, and young adults. Antibodies were measured by hemagglutination inhibition (HAI) assay at baseline, 21–28 days after first vaccination, 7–13 days after the second vaccination, and 7 months after the first vaccination.
Results. Among the 155 participants, 54 were aged 4–8 years, 51 were aged 9–17 years, and 50 were aged 18–24 years. After 2 doses of Fluvirin, seroresponse (≥4-fold rise in HAI titers) was demonstrated in 79.6%, 84.8%, and 83% of participants in the aforementioned age groups, respectively, and seroprotection (HAI titers ≥40) was shown in 79.6%, 82.6%, and 85.1%, respectively. Of those lacking seroresponse (n = 43) or seroprotection (n = 37) after the first vaccination, 46.5% and 40.5% achieved seroresponse or seroprotection, respectively, after the second vaccination. Among participants who lacked seroprotection at entry, a “complete response” (both seroresponse and seroprotection) after first vaccination was associated with higher baseline log10 HAI titer and non-Hispanic ethnicity. No serious vaccine-related events occurred.
Conclusion. Two doses of double-strength pH1N1 vaccine are safe and immunogenic and may provide improved protection against influenza in perinatally HIV-1–infected children and youth.
Clinical Trials Registration. NCT00992836.
Intensive chemotherapy for pediatric acute myeloid leukemia (AML) incurs the risk of infectious complications, but the benefits of antibiotic prophylaxis remain unclear.
In 103 children treated on the AML02 protocol between October 2002 and October 2008 at St. Jude Children’s Research Hospital, we retrospectively assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia, clinically or microbiologically confirmed infections (including bacteremia), and antibiotic resistance, and on the results of nasal and rectal surveillance cultures. Initially, patients received no prophylaxis or oral cephalosporin (Group A). Then the protocol was amended to give intravenous cefepime alone or intravenous vancomycin plus either oral cephalosporin, oral ciprofloxacin, or intravenous cefepime (Group B).
There were 334 infectious episodes. Group A had a significantly greater frequency of documented infections and bacteremia (both P < .0001) (including gram-positive and gram-negative bacteremia, P = .0003 and .001, respectively) than Group B, especially viridans streptococcal bacteremia (P = .001). The incidence of febrile neutropenia without documented infection was not different between the two groups. Five cases of bacteremia with vancomycin-resistant enterococci (VRE) occurred in group B (vs. none in Group A), without related mortality. Two of these cases were preceded by positive VRE rectal surveillance cultures.
Outpatient intravenous antibiotic prophylaxis is feasible in children with AML and reduces the frequency of documented infection but not of febrile neutropenia. Despite emergence of VRE bacteremia, the benefits favor antibiotic prophylaxis. Creative approaches to shorten the duration of prophylaxis and thereby minimize resistance should be explored.
acute myeloid leukemia; antibiotics; children; infection; prophylaxis
Sickle cell disease (SCD) patients are at high risk of contracting pneumococcal infection. To address this risk, they receive pneumococcal vaccines, and antibiotic prophylaxis and treatment. To assess the impact of SCD and these interventions on pneumococcal genetic architecture, we examined the genomes of over 300 pneumococcal isolates from SCD patients over 20 years. Modern SCD strains retained invasive capacity but shifted away from the serotypes used in vaccines. These strains had specific genetic changes related to antibiotic resistance, capsule biosynthesis, metabolism and metal transport. A murine SCD model coupled with Tn-seq mutagenesis identified 60 non-capsular pneumococcal genes under differential selective pressure in SCD, which correlated with aspects of SCD pathophysiology. Further, virulence determinants in the SCD context were distinct from the general population and protective capacity of potential antigens was lost over time in SCD. This highlights the importance of understanding bacterial pathogenesis in the context of high-risk individuals.
Limited information exists regarding the use of posaconazole for treating systemic fungal infections in children, adolescent, and young adult patients with cancer. At St. Jude Children’s Research Hospital, the recommended posaconazole dose in patients less than 34 kg is 18–24 mg/kg daily given in 4 divided doses. For patients 13 years and older or those weighing 34 kg or more, the recommended dose is 800 mg daily given orally in four divided doses.
This study was conducted to determine if the current posaconazole dosing guidelines achieved target posaconazole plasma concentrations of ≥ 0.7 μg/mL.
We examined data from patients who received treatment-dose posaconazole with at least one posaconazole plasma concentration measurement.
Data from 33 patients who received posaconazole for the treatment of fungal infections were analyzed. The median age of patients was 11.5 years (range 0.5–23.2 years). Twenty-one patients out of 33 (63.6%) had posaconazole concentrations of ≥ 0.7 μg/mL (median 1.4 μg/mL; range 0.7–2.98 μg/mL) at the first measurement. The median posaconazole dosage referenced to total body weight in these patients was 20 mg/kg per day. Patients with concentrations < 0.7 μg/mL (median 0.4 μg/mL; range 0.025–0.69 μg/mL) received lower posaconazole dosages when referenced to body weight (median 12.9 mg/kg per day; p = 0.02). Of the 12 patients with concentrations < 0.7 μg/mL, seven (58.3%) were 13 years of age or older.
The current dosing approach for posaconazole yielded therapeutic plasma concentrations more frequently in patients < 13 than those > 13 years of age. This difference may be related to the practice of capping adolescent and young adult doses at the suggested maximum adult daily dose. Therefore, we recommend weight-based dosing in all pediatric, adolescent and young adult cancer patients with routine therapeutic drug monitoring in all patients to ensure adequate concentrations.
posaconazole; pediatric; fungal infection; therapeutic drug monitoring
Tenofovir (TDF) is associated with phosphaturia and elevated 1,25 dihydroxy vitamin D (1,25-OH(2)D). Fibroblast growth factor 23 (FGF23) causes phosphaturia and increases in response to elevated 1,25-OH(2)D. Vitamin D binding protein (VDBP) binds to 1,25-OH(2)D, decreasing its biologic activity, and is elevated in persons with higher plasma tenofovir concentrations. We compared FGF23 and VDBP before and after vitamin D3 (VITD) supplementation in youth treated with combination antiretroviral therapy (cART) containing or not containing TDF.
A randomized controlled trial in HIV+ youth ages 18–25 years enrolled participants based on cART treatment with TDF (TDF, N=118) or without TDF (no-TDF, N=85) and randomized within those groups to VITD (50,000 IU every four weeks) or placebo (PL). We measured FGF23 and VDBP and calculated free 1,25-OH(2)D at baseline and week 12, and compared changes by TDF treatment and VITD randomized group.
At baseline, serum FGF23 concentration showed a quadratic relationship with 1,25-OH(2)D most pronounced in the TDF group. At week 12, total and free 1,25-OH(2)D increased in the VITD but not PL groups, independent of TDF use. FGF23 increased in the TDF group receiving VITD, but there was no FGF23 change in the no-TDF group receiving VITD or the PL groups. The adjusted mean change in FGF23 from baseline to week 12 was +7.7 pg/mL in the TDF/VITD group, compared to −1.7 (no-TDF/VITD, p=0.010); −1.3 (TDF/PL, p=0.006); and +1.1 (no-TDF/PL, p=0.035).
These results suggest that TDF-containing cART may alter the FGF23 response to vitamin D supplementation in HIV-infected youth.
With the emergence of pandemic influenza A (pH1N1) in 2009, children and youth infected with human immunodeficiency virus (HIV) were vulnerable because of immunologic impairment and the greater virulence of this infection in young persons.
A multicenter study of the immunogenicity of 3 licensed influenza A (H1N1) monovalent vaccines (1 live attenuated and 2 inactivated) was conducted in children and youth with perinatal HIV infection, most of whom were receiving ≥3 antiretroviral drugs, had CD4% ≥15, and plasma HIV RNA levels <400 copies/mL. Serum hemagglutinin inhibition assay (HAI) antibody levels were measured and correlated with baseline demographic and clinical variables.
One hundred forty-nine subjects were enrolled at 26 sites in the United States and Puerto Rico. Over 40% had baseline HAI titers ≥40. For subjects aged 6 months to <10 years, 79% and 68%, respectively, achieved a ≥40- and ≥4-fold rise in HAI titers after the second dose of vaccine. Three weeks after a single immunization with an inactivated vaccine, similar immunogenicity results were achieved in youth aged 10–24 years. With multivariable analysis, only Hispanic ethnicity and CD4% ≥15 were associated with achieving both HAI titer ≥40- and ≥4-fold rise in titer.
Although licensed pH1N1 vaccines produced HAI titers that were considered to be protective in the majority of HIV-infected children and youth, the proportion with titers ≥40- and ≥4-fold rise in titer was lower than expected for children without HIV infection. Vaccine immunogenicity was lower in HIV-infected children and youth with evidence of immune suppression.
HIV-infected youth are at risk of hepatitis B (HBV) infection and should be vaccinated. Previous reports suggest reduced response to standard HBV vaccine regimens.
HIV-infected youth, age 12 to <25 years, were randomly assigned to one of three treatment arms: Arm 1: Engerix B®, 20 mcg HBsAg; Arm 2: Engerix B®, 40 mcg; and Arm 3: Twinrix®, 20mcg HBsAg combined with 720 ELU hepatitis A antigen. Vaccines were administered at weeks 0, 4 and 24.
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 (IQR: 305 to 668); 13% were < 200 cells/mm3. Among Engerix B®, 20 mcg recipients, 60.4% responded to vaccine (HBsAb ≥ 10 IU/mL at week 28). Improved vaccine response was seen in recipients of Engerix B®, 40 mcg, (73.2%, vs. Arm 1, p=0.04) and Twinrix® (75.4%, vs. Arm 1, p=0.02). In multivariate analysis, only baseline CD4+ T-cell count and study arm were independent predictors of vaccine response.
In HIV-infected youth, a three dose vaccination regimen with Engerix B®, 40 mcg, or Twinrix® and higher baseline CD4+ T-cell counts were independently associated with improved vaccine response.
HIV; Hepatitis B Vaccination; Adolescents; Engerix B; Twinrix
Tenofovir disoproxil fumarate (TDF) causes bone, endocrine, and renal changes by an unknown mechanism(s). Data are limited on tenofovir pharmacokinetics and these effects. Using baseline data from a multicenter study of HIV-infected youth on stable treatment with regimens containing TDF (n = 118) or lacking TDF (n = 85), we measured cross-sectional associations of TDF use with markers of renal function, vitamin D-calcium-parathyroid hormone balance, phosphate metabolism (tubular reabsorption of phosphate and fibroblast growth factor 23 [FGF23]), and bone turnover. Pharmacokinetic-pharmacodynamic associations with plasma tenofovir and intracellular tenofovir diphosphate concentrations were explored among those receiving TDF. The mean age was 20.9 (standard deviation [SD], 2.0) years; 63% were male; and 52% were African American. Compared to the no-TDF group, the TDF group showed lower mean estimated glomerular filtration rates and tubular reabsorption of phosphate, as well as higher parathyroid hormone and 1,25-dihydroxy vitamin D [1,25-OH(2)D] levels. The highest quintile of plasma tenofovir concentrations was associated with higher vitamin D binding protein, lower free 1,25-OH(2)D, higher 25-OH vitamin D, and higher serum calcium. The highest quintile of intracellular tenofovir diphosphate concentration was associated with lower FGF23. Higher plasma tenofovir concentrations were associated with higher vitamin D binding protein and lower free 1,25-OH(2)D, suggesting a functional vitamin D deficiency explaining TDF-associated increased parathyroid hormone. The finding of lower FGF23 accompanying higher intracellular tenofovir diphosphate suggests that different mechanisms mediate TDF-associated changes in phosphate handling. Separate pharmacokinetic properties may be associated with distinct TDF toxicities: tenofovir with parathyroid hormone and altered calcium balance and tenofovir diphosphate with hypophosphatemia and FGF23 regulation.
(The clinical trial registration number for this study is NCT00490412 and is available online at http://clinicaltrials.gov/ct2/show/NCT00490412.)
HIV-infected individuals have poor responses to inactivated influenza vaccines. To evaluate the potential role of regulatory T (Treg) and B cells (Breg), we analyzed their correlation with humoral and cell-mediated immune (CMI) responses to pandemic influenza (pH1N1) monovalent vaccine in HIV-infected children and youth. Seventy-four HIV-infected, 4- to 25-y old participants in a 2-dose pH1N1 vaccine study had circulating and pH1N1-stimulated Treg and Breg measured by flow cytometry at baseline, post-dose 1 and post-dose 2. Concomitantly, CMI was measured by ELISPOT and flow cytometry; and antibodies by hemagglutination inhibition (HAI). At baseline, most of the participants had pH1N1-specific IFNγ ELISPOT responses, whose magnitude positively correlated with the baseline pH1N1, but not with seasonal H1N1 HAI titers. pH1N1-specific IFNγ ELISPOT responses did not change post-dose 1 and significantly decreased post-dose 2. In contrast, circulating CD4+CD25+% and CD4+FOXP3+% Treg increased after vaccination. The decrease in IFNγ ELISPOT results was marginally associated with higher pH1N1-specific CD19+FOXP3+ and CD4+TGFβ+% Breg and Treg, respectively. In contrast, increases in HAI titers post-dose 1 were associated with significantly higher circulating CD19+CD25+% post-dose 1, whereas increases in IFNγ ELISPOT results post-dose 1 were associated with higher circulating CD4+/C8+CD25+FOXP3+%. In conclusion, in HIV-infected children and youth, influenza-specific Treg and Breg may contribute to poor responses to vaccination. However, robust humoral and CMI responses to vaccination may result in increased circulating Treg and/or Breg, establishing a feed-back mechanism.
HIV infection; influenza vaccine; cell-mediated immunity; regulatory T cells; regulatory B cells
Concern has been raised about possible increased mortality associated with the use of cefepime. There are limited data available on the pragmatic use of beta-lactam antibiotics, especially in children.
This retrospective study included 532 pediatric oncology patients. The outcomes of patients treated with cefepime for suspected serious bacterial infections were compared to those of patients treated with ceftazidime. Primary outcomes included 30- and 90-day all-cause mortality.
The demographic and clinical characteristics of 337 patients treated with ceftazidime were similar to those of 195 patients receiving cefepime. Thirty-day and 90-day all cause mortality rates were comparable (30-day OR for cefepime: 3.48, 95% CI 0.31 to 38.84, P=0.3; 90-day OR: 0.99, 95% CI 0.29 to 3.42, P=1.0]. There were also no differences in infection-related mortality rates, secondary infections, or adverse drug events. Deaths occurring within 30 days of hospitalization were judged to be attributable to infection, but not the result of treatment failure or adverse drug events. Deaths occurring between 30 and 90 days were associated with progressive or new malignancy. Secondary infection was significantly associated with mortality.
The use of cefepime in pediatric oncology patients is not associated with increased mortality when compared to ceftazidime, however the small number of deaths in this study limits the strength of this conclusion. Previous associations between antimicrobial therapy and increased all-cause mortality may have been confounded by patients' demographic characteristics and co-morbid conditions. All-cause mortality may be an insensitive outcome for studies examining the efficacy and safety of these agents.
cefepime; ceftazidime; pediatric; oncology; drug safety
Current HIV guidelines recommend monitoring CD4 counts every 3–4 months. In the era of highly active antiretroviral therapy (HAART) and HIV PCR, this retrospective study reexamines the required frequency of the CD4 assay. Predictor variables, including age, previous CD4 count, HIV viral load (VL), time interval since last VL and CD4 count (TINT), and antiretroviral history, were abstracted. A recursive partitioning-based regression tree analysis was used to determine if the absolute current CD4 count was above or below the age appropriate Pneumocystis jiroveci pneumonia (PCP) prophylaxis cutoff. We analyzed concurrently obtained VLs and CD4 count including 601 results from 43 HIV-infected children aged 1–<6 years (Group I) and 1,364 results from 93 children/adolescents 6–<23 years (Group II). Using 75% of observations to build a predictive model (learning dataset), the ability to correctly predict the range of the outcome variable in the remaining 25% of observations (training dataset) was 93% in Group I and 97% in Group II. Predictor variables included age, recent VL and CD4 count, and TINT. A total of 1,000 repeats of this model building using randomly selected observations showed a correct predictive ability of 89.6% [standard error (SE) 2.3%] in Group I and 95.6% (SE 1%) in Group II. The ability of a classification tree to determine if the current CD4 count is above or below the age-specific cutoff for PCP prophylaxis is very good and allows less frequent CD4 assays. The principles underlying this modeling-based approach have broad applicability and cost saving implications.
Serum 25-hydroxyvitamin D [25(OH)D] is often deficient (<12 ng/ml) or insufficient (<20 ng/ml) in youth living with human immunodeficiency virus type 1 infection (YLH). Based on evidence from multiple genome-wide association studies, we hypothesized that genetic factors associated with 25(OH)D deficiency should be readily detectable in YLH even when controlling for other known factors, including use of the antiretroviral drug efavirenz (EFV). Genotyping by bi-directional sequencing targeted 15 single nucleotide polymorphisms (SNPs) at the GC/DBP locus, with a focus on coding and regulatory variants, as well as those repeatedly reported in the literature. Three intronic SNPs (rs222016, rs222020, and rs222029) in a conserved haplotype block had unequivocal association signals (false discovery rate ≤ 0.006). In particular, the minor allele G for rs222020 was highly unfavorable among 192 YLH (99 African–Americans and 93 others), as gauged by relatively low likelihood for 25(OH)D sufficiency at enrollment (odds ratio = 0.31, p = 9.0 × 10-4). In a reduced multivariable model, race, season, latitude, body mass index, exposure to EFV, and rs222020-G were independent factors that collectively accounted for 38% of variance in the log10-transformed 25(OH)D concentration (p < 0.0001). Interaction terms were evident for rs222020-G × season (p < 0.001), latitude × season (especially fall and winter; p < 0.01), and race × EFV use (p = 0.024). Overall, variance in serum 25(OH)D is substantially attributable to multiple factors, but the exact contribution of genetic and non-genetic factors can be obscured by partial overlaps and frequent interactions.
antiretroviral; genetics; HIV-1; race; youth; vitamin D
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/mm3 per year) than those without detectable NNRTI-R (median: +149 cells/mm3 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.
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.
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.
123 youth completed the questionnaire (mean age=15 years; 63% male; 70% Hispanic). Overall, only 69 (56%) youth answered all six questions correctly.
Youth enrolled in a Hepatitis B vaccine trial demonstrated variable comprehension of the study design and various methodological concepts, such as treatment group masking.
In this randomized, double-blind, placebo-controlled trial of human immunodeficiency virus–infected youths aged 18–25, vitamin D3, 50000 IU once monthly for 3 months decreased parathyroid hormone in participants treated with tenofovir-containing antiretroviral regimens but not in those participants whose regimens did not contain tenofovir.
Background. The study goal was to determine the effect of vitamin D (VITD) supplementation on tubular reabsorption of phosphate (TRP), parathyroid hormone (PTH), bone alkaline phosphatase (BAP), and C-telopeptide (CTX) in youth infected with human immunodeficiency virus (HIV) receiving and not receiving combination antiretroviral therapy (cART) containing tenofovir disoproxil fumarate (TDF).
Methods. This randomized, double-blind, placebo-controlled multicenter trial enrolled HIV-infected youth 18–25 years based on stable treatment with cART containing TDF (n = 118) or no TDF (noTDF; n = 85), and randomized within those groups to vitamin D3, 50 000 IU (n = 102) or placebo (n = 101), administered at 0, 4, and 8 weeks. Outcomes included change in TRP, PTH, BAP, and CTX from baseline to week 12 by TDF/noTDF; and VITD/placebo.
Results. At baseline, VITD and placebo groups were similar except those on TDF had lower TRP and higher PTH and CTX. At week 12, 95% in the VITD group had sufficient serum 25-hydroxy vitamin D (25-OHD; ≥20 ng/mL), increased from 48% at baseline, without change in placebo (P < .001). PTH decreased in the TDF group receiving VITD (P = .031) but not in the noTDF group receiving VITD, or either placebo group. The decrease in PTH with VITD in those on TDF occurred with insufficient and sufficient baseline 25-OHD (mean PTH change, −7.9 and −6.2 pg/mL; P = .031 and .053, respectively).
Conclusions. In youth on TDF, vitamin D3 supplementation decreased PTH, regardless of baseline 25-OHD concentration.
Clinical Trials Registration. NCT00490412.
Although health disparity research has investigated social structural, cultural, or psychological factors, the interrelations among these factors deserve greater attention.
This study aims to examine cancer screening emotions and their relations to screening fatalism as determinants of breast cancer screening among women from diverse socioeconomic and ethnic backgrounds.
An integrative conceptual framework was used to test the multivariate relations among socioeconomic status, age, screening fatalism, screening emotions, and clinical breast exam compliance among 281 Latino and Anglo women, using multi-group structural equation causal modeling.
Screening emotions and screening fatalism had a negative, direct influence on clinical breast exam compliance for both ethnic groups. Still, ethnicity moderated the indirect effect of screening fatalism on clinical breast exam compliance through screening emotions.
Integrative conceptual frameworks and multivariate methods may shed light on the complex relations among factors influencing health behaviors relevant to disparities. Future research and intervention must recognize this complexity when working with diverse populations.
Emotions; Culture; Fatalism; Breast cancer screening; Health disparities
Examine psychological functioning and beliefs about medicine in adolescents with HIV-1 on HAART in a community-based directly observed therapy (DOT) pilot feasibility study.
Youth with behaviorally-acquired HIV (n=20; 65% female; median age 21 years) with adherence problems, received once-daily DOT. Youth were assessed at baseline, week 12 (post-DOT) and week 24 (follow-up).
Baseline to week 12 comparisons: 55% of youth reported clinical depressive symptoms compared to 27% at week 12 with sustained improvements at week 24. Substance use: Borderline clinical range (Tscore=68), with clinical but statistically non-significant improvement (Tscore=61). Hopelessness scores reflected optimism for the future. Coping strategies showed significantly decreased Cognitive Avoidance (p=0.02), Emotional Discharge (p=0.004), and Acceptance/Resignation (“nothing I can do,” p=0.004); Positive Reappraisal and Seeking Support emerged. Aside from depressive symptoms, week 12 improvements were not sustained at week 24. DOT adherence was predicted by higher baseline depression (p=0.05), Beliefs About Medicine (p=0.006) and Perceived Threat of illness scores (p=0.03).
Youth with behaviorally-acquired HIV and adherence problems who participated in a community-based DOT intervention reported clinically improved depressive symptoms, and temporarily reduced substance use and negative coping strategies. Depressive symptoms, Beliefs About Medicine and viewing HIV as a threat predicted better DOT adherence.
HIV; adolescent; psychological functioning; directly observed therapy (DOT); adherence
Tenofovir (TFV) is effective in preventing simian immunodeficiency virus (SIV) transmission in a macaque model, is available as the oral agent tenofovir disoproxil fumarate (TDF), and may be useful in the prevention of mother-to-child transmission of human immunodeficiency virus (HIV). We conducted a trial of TDF and TDF-emtricitabine (FTC) in HIV-infected pregnant women and their infants. Women received a single dose of either 600 mg TDF, 900 mg TDF, or 900 mg TDF-600 mg FTC at labor onset or prior to a cesarean section. Infants received no drug or a single dose of TDF at 4 mg/kg of body weight or of TDF at 4 mg/kg plus FTC at 3 mg/kg as soon as possible after birth. All regimens were safe and well tolerated. Maternal areas under the serum concentration-time curve (AUC) and concentrations at the end of sampling after 24 h (C24) were similar between the two doses of TDF; the maximum concentrations of the drugs in serum (Cmax) and cord blood concentrations were higher in women delivering via cesarean section than in those who delivered vaginally (P = 0.04 and 0.046, respectively). The median ratio of the TFV concentration in cord blood to that in the maternal plasma at delivery was 0.73 (range, 0.26 to 1.95). Without TDF administration, infants had a median TFV concentration of 12 ng/ml 12 h after birth. Following administration of a single dose of TDF at 4 mg/kg, infant TFV concentrations fell below the targeted level, 50 ng/ml, by 24 h postdose. In HIV-infected pregnant women and their infants, 600 mg of TDF is acceptable as a single dose during labor. Low concentrations at birth support infant dosing as soon after birth as possible. Rapidly decreasing TFV levels in infants suggest that multiple or higher doses of TDF will be necessary to maintain concentrations that are effective for viral suppression.
Multiple studies have shown excellent response rates after hepatitis B immunization in youth; however, one previous study conducted in urban youth demonstrated poor responses.
Urban youth, ages 12-17 years, at participating Adolescent Medicine Trials Network for HIV/AIDS Interventions Clinical/Research (ATN) sites were randomized to receive either two doses of Recombivax HB (10mcg hepatitis B surface antigen) or Twinrix (20mcg 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.
123 subjects were enrolled and 102 had week 28 serum samples available for antibody measure. A positive response (serum antibody ≥ 10mIU/mL) to hepatitis B antigen was documented in 41/47 (87.2%; 95% confidence interval (CI) 74.3%-95.2%) Recombivax HB recipients and in 52/55 (94.6%; 95% CI 84.9%-98.9%) Twinrix recipients (p=.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% confidence interval 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, 24/25 hepatitis A antibody negative youth responded to the hepatitis A component. Both vaccines were safe.
Response rate to two doses of Recombivax HB in urban youth is lower than previous studies suggest. The factors associated with diminished response are not known.
Adolescents; hepatitis B; Vaccination; Immunogenicity
The aim of this research was to examine the relation of perceptions of healthcare mistreatment and related emotions to continuity of cancer screening care among women who reported healthcare mistreatment. The structure of relations among cultural beliefs about healthcare professionals, perceptions of mistreatment, mistreatment-related emotions, and continuity of screening was investigated. Participants included 313 Anglo and Latino American women of varying demographic characteristics from Southern California who were recruited using multistage stratified sampling. Structural equation modeling confirmed the relation of perceptions of mistreatment to continuity of care for both Anglo and Latino American women, with ethnicity moderating this association. For Anglo Americans, greater perceptions of mistreatment were negatively related to continuity of screening. However, for Latinas the relation was indirect, through mistreatment-related anger. While greater perceptions of mistreatment were associated with higher levels of anger for both ethnic groups, anger was negatively related to continuity of care for Latino but not for Anglo women. Furthermore, cultural beliefs about professionals were indirectly related to continuity of screening through perceptions of mistreatment and/or mistreatment-related anger. These findings highlight the importance of the role of cultural and psychological factors in research and interventions aimed at improving patient-professional relations with culturally diverse women.
perceived mistreatment; emotions; culture; cancer screening; health disparities
To illustrate the implementation of a bottom-up approach to the study of culture in health disparities, this article describes the development of a cultural cancer screening scale (CCSS) using mixed methodologies. The aim was to identify cultural factors relevant to breast and cervical cancer screening, develop an instrument to assess them and examine its preliminary psychometric properties among Latin American (Latino) and non-Latino White (Anglo) women in Southern California. Seventy-eight Latino and Anglo women participated in semi-structured interviews, which were content coded based on Triandis' methods for the analysis of subjective culture. Based on the emerging cultural elements, items relevant to cancer screening were developed and pilot tested with 161 participants. After the instrument was refined, 314 Latino and Anglo women from various socioeconomic backgrounds completed the CCSS and data were factor analyzed resulting in five cultural factors: cancer screening fatalism, negative beliefs about health professionals, catastrophic disease expectations, symptomatic deterrents and sociocultural deterrents. The instrument demonstrated measurement equivalence, adequate reliability and predictive validity. The research and the CCSS are discussed in terms of implications for the study of culture in relation to health disparities and the development of evidence-based interventions with culturally diverse populations and their health professionals.
Adherence to medications is critical to optimizing HIV care and is a major challenge in youth. The utility of directly observed therapy (DOT) to improve adherence in youth with HIV remains undefined and prompted this pilot study. Four U.S. sites were selected for this 24-week cooperative group study to assess feasibility and to identify the logistics of providing DOT to HIV-infected youth with demonstrated adherence problems. Once-a-day DOT was provided by DOT facilitators at the participant's choice of a community-based location and DOT tapered over 12 weeks to self-administered therapy based on ongoing adherence assessments. Twenty participants, median age 21 years and median CD4 227 cells/μl, were enrolled. Participants chose their homes for 82% of DOT visits. Compliance with recommended DOT visits was (median) 91%, 91%, and 83% at weeks 4, 8, and 12, respectively. Six participants completed >90% of the study-specified DOT visits and successfully progressed to self-administered therapy (DOT success); only half sustained >90% medication adherence 12 weeks after discontinuing DOT. Participants considered DOT successes were more likely to have higher baseline depression scores (p = 0.046). Via exit surveys participants reported that meeting with the facilitator was easy, DOT increased their motivation to take medications, they felt sad when DOT ended, and 100% would recommend DOT to a friend. In conclusion, this study shows that while community-based DOT is safe, feasible, and as per participant feedback, acceptable to youth, DOT is not for all and the benefits appear short-lived. Depressed youth appear to be one subgroup that would benefit from this intervention. Study findings should help inform the design of larger community-based DOT intervention studies in youth.
The world is facing a novel H1N1 pandemic. A pandemic scare with a similar virus in 1976 resulted in the vaccination of nearly 45 million persons. We hypothesized that prior receipt of the 1976 “swine flu” vaccine would enhance immune responses to the 2009 novel H1N1 strain.
A prospective, volunteer sample of employees 55 years of age and older at a children’s cancer hospital in August of 2009 was assessed for antibody responses to the 2009 pandemic H1N1 influenza virus and the 2008-2009 seasonal H1N1 influenza virus.
Antibody responses by hemagglutination-inhibition assay were high against both the seasonal (89.7% had a titer considered seroprotective) and pandemic (88.8% had a seroprotective titer) H1N1 viruses. These antibodies were effective at neutralizing the seasonal H1N1 virus in 68.1% of participants (titer ≥ 40), but only 18.1% had detectable neutralizing titers against the pandemic H1N1. Of 116 participants, 46 (39.7%) received the 1976 “swine flu” vaccine. Receipt of this vaccine significantly enhanced neutralization responses as 8 of 46 (17.4%) vaccine recipients had titers ≥ 160 compared to only 3 of 70 (4.3%) who did not receive the vaccine (P = 0.018 by chi-squared test).
In this cohort, persons 55 years and older had evidence of robust immunity to the 2008-2009 seasonal H1N1 virus. These antibodies were cross-reactive but non-neutralizing against the 2009 pandemic H1N1 strain. Receipt of a vaccine to a related virus significantly enhanced the neutralization capacity of these responses, suggesting homologous vaccination against the 2009 pandemic H1N1 would have a similar effect.