Positive status with respect to anti-JC virus antibodies, prior use of immunosuppressants, and increased duration of natalizumab treatment, alone or in combination, were associated with distinct levels of PML risk in natalizumab-treated patients with multiple sclerosis. (Funded by Biogen Idec and Elan Pharmaceuticals.).

ObjectiveThe increased risk of progressive multifocal leukoencephalopathy (PML) with natalizumab treatment is associated with the presence of anti–JC virus (JCV) antibodies. We analyzed whether anti-JCV antibody levels, measured as index, may further define PML risk in seropositive patients.MethodsThe association between serum or plasma anti-JCV antibody levels and PML risk was examined in anti-JCV antibody–positive multiple sclerosis (MS) patients from natalizumab clinical studies and postmarketing sources. For PML and non-PML patients, the probabilities of having an index below and above a range of anti-JCV antibody index thresholds were calculated using all available data and applied to the PML risk stratification algorithm. Longitudinal stability of anti-JCV antibody index was also evaluated.ResultsAnti-JCV antibody index data were available for serum/plasma samples collected >6 months prior to PML diagnosis from 71 natalizumab-treated PML patients and 2,522 non-PML anti-JCV antibody–positive patients. In patients with no prior immunosuppressant use, anti-JCV antibody index distribution was significantly higher in PML patients than in non-PML patients (p < 0.0001). Among patients who were anti-JCV antibody negative at baseline in the AFFIRM and STRATIFY-1 trials, 97% remained consistently negative or below an index threshold of 1.5 over 18 months. Retrospective analyses of pre-PML samples collected longitudinally from PML patients displayed sustained higher anti-JCV antibody index over time.InterpretationAnti-JCV antibody levels in serum/plasma, measured as index, may differentiate PML risk in anti-JCV antibody–positive MS patients with no prior immunosuppressant use. Continued evaluation of anti-JCV antibody index and PML risk is warranted. Ann Neurol 2014;76:802–812

ABSTRACT. Objective. The complexity of highly active antiretroviral therapy (HAART), with multiple medications, formulations, and dosing intervals, makes adherence challenging. Little is known about the adherence of children to HAART. The objective of this study was to identify correlates of adherence to HAART and the relationship between adherence and study outcomes in a pediatric clinical trial.Methods. Pediatric AIDS Clinical Trials Group 377 is a phase I/II randomized trial of 4 HAART regimens in antiretroviral-experienced, clinically stable children aged 4 months to 17 years. The 4 treatment arms include various 3-or 4-drug combinations of d4T, 3TC, nevirapine, ritonavir, and nelfinavir. After informed consent was obtained, 193 children were enrolled between December 1997 and September 1998. Questionnaires were developed to collect subject-or caregiver-reported adherence to study medications and to identify problems associated with medication administration. Every 3 months, the number of doses of each medication missed during the 3 days preceding the study visit was recorded. Full adherence (FA) and non-full adherence were defined as missing no doses and missing at least 1 dose, respectively.Results. Adherence data from study week 48 or the most recent study visit were available for 125 children (week 48 for 109 children). Overall, 70% of children reported FA and 30% reported non-full adherence. Adherence did not differ by treatment arm, age, or the child's knowledge of his or her human immunodeficiency virus infection status. There was a suggestion that adherence was less for white than nonwhite children (40% vs 73% FA) and did not differ between black and Hispanic children. Rates of FA were 82% for d4T, 79% for 3TC, 83% for nevirapine, 84% for ritonavir, and 68% for nelfinavir. Despite the similar rates of FA, difficulties with taking specific medications were reported most frequently for ritonavir and nelfinavir. These included poor taste, patient refusal, and scheduling problems. Adherence was associated with the virologic response: FA was seen in 92% of children with >2 log 10 drop in viral load and in 64% with <2 log 10 drop in viral load.Conclusion. In children, reported adherence predicts the virologic response to HAART therapy and is a useful measure of adherence. Interventions and regimens to increase adherence to HAART should result in an improved outcome. Pediatrics 2002;109(4). URL: http:// www.pediatrics.org/cgi/content/full/109/4/e61; adherence, compliance, HIV, antiretroviral therapy, protease inhibitors.ABBREVIATIONS. HAART, highly active antiretroviral therapy; HIV, human immunodeficiency virus; PACTG, Pediatric AIDS Clinical Trials Group; RT, reverse transcriptase; BID, twice-daily; TID, 3 times a day; FA, full adherence; NFA, non-full adherence.H ighly active combination antiretroviral therapy (HAART) is effective in suppressing human immunodeficiency virus (HIV) replication, preventing opportunistic infections, reducing mortality, and improving the well-being of children and adults with...

No abstract

This study analyzed the content of 125 unique reports published since 1990 that have examined the health and well-being—as well as the interpersonal and contextual experiences—of sexual minority youth of color (SMYoC). One-half of reports sampled only young men, 73% were noncomparative samples of sexual minority youth, and 68% of samples included multiple racial-ethnic groups (i.e., 32% of samples were mono-racial/ethnic). Most reports focused on health-related outcomes (i.e., sexual and mental health, substance use), while substantially fewer attended to normative developmental processes (i.e., identity development) or contextual and interpersonal relationships (i.e., family, school, community, or violence). Few reports intentionally examined how intersecting oppressions and privileges related to sexual orientation and race-ethnicity contributed to outcomes of interest. Findings suggest that research with SMYoC has been framed by a lingering deficit perspective, rather than emphasizing normative developmental processes or cultural strengths. The findings highlight areas for future research focused on minority stress, coping, and resilience of SMYoC.