Background: Women, particularly women of color, remain underrepresented in antiretroviral (ARV) clinical trials. To evaluate sex-based differences in darunavir/ritonavir-based therapy, the Gender, Race And Clinical Experience (GRACE) study was designed to enroll and retain a high proportion of women representative of the racial/ethnic demographics of women with HIV/AIDS in the United States. The recruitment and retention strategies used in GRACE are described in this article. Methods: Recruitment and retention strategies targeting women included selecting study sites that focused on women, involving community consultants, site-specific enrollment plans, access to other ARV drugs, study branding, site and patient toolkits, targeted public relations, site grants for patient support, and subsidized child care and transportation. Results: The recruitment strategies were successful; 287 (67%) women were enrolled, primarily women of color (black, n = 191 [67%], Hispanic, n = 60 [21%]). Despite the focus on retention, a greater proportion of women (32.8%) discontinued compared with men (23.2%). Conclusions: The successes of GRACE in enrolling a representative population of women were rooted in pretrial preparation, engagement of community advisors, enrollment quotas, choice of study sites and site support. Lessons learned from GRACE may be applied to future study design. Further focus on factors that influence discontinuation is warranted.
Objectives:Increasing life expectancy of HIV-1–infected patients raises interest in how trial results apply to
older patients. This post-hoc analysis evaluated potential differences in efficacy and safety in older (≥50 years) versus
younger (<50 years) patients in the ECHO and THRIVE trials over 96 weeks.Methods:HIV-infected, treatment-naÏve adults were randomized to receive rilpivirine (RPV) or efavirenz (EFV), plus a
background regimen. Virologic response rates (FDA snapshot analysis; HIV-1 RNA <50 copies/mL) were assessed at
Week 96. Total-body bone mineral density was evaluated at baseline and Week 96 by dual-energy X-ray absorptiometry
scans. Serum concentrations of 25-hydroxy vitamin D (ECHO trial only) were also measured at baseline, Week 24 and
Week 48.Results:1368 patients were treated. At Week 96, virologic response rates were similar between older (77%) and younger
(76%) RPV-treated patients and numerically higher in older (84%) versus younger (76%) EFV-treated patients. No
clinically relevant age-related differences were observed in immunologic responses. Small differences were noted in older
versus younger patients in adverse events (higher rates of depression, insomnia, and rash in older EFV-treated patients),
laboratory abnormalities (increased low-density lipoprotein cholesterol and hyperglycemia in older EFV-treated patients
and increased amylase in older patients across treatments), bone mineral density (larger decreases in older patients across
treatments), and progression to severe vitamin D deficiency (greater in older versus younger EFV-treated patients).Conclusion:Efficacy and safety outcomes were generally similar in older versus younger patients in the ECHO and
THRIVE trials.
A 2 1/2-year-old child being treated with carbamazepine (CBZ) for a seizure disorder on two separate occasions experienced elevated CBZ serum concentrations (28 and 23.2 mg/L), severe liver damage (SGOT greater than 6000 IU, SGPT greater than 5000 IU), and central nervous system manifestations (coma, lethargy, seizures). During the first episode, the time course of CBZ concentrations exhibited a nonlinear decline and was accompanied by CBZ-10,11-epoxide concentrations that were elevated 4-fold compared to normal values. Cerebrospinal fluid concentrations of CBZ and CBZ-10,11-epoxide were also elevated, although their ratios to serum concentrations did not suggest enhanced permeability of the central nervous system to these substances. The concentrations of CBZ-10,11-epoxide but not CBZ were elevated for the duration of time that the patient was comatose, suggesting that this metabolite may contribute to the neurotoxic side effects observed with CBZ therapy.
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