Pharmacokinetics and safety of maraviroc in neonates.

OBJECTIVE: The aim of this study was to evaluate safety and pharmacokinetics of maraviroc administered with standard antiretroviral prophylaxis to HIV-1 exposed infants and to determine the appropriate dose of maraviroc during the first 6 weeks of life. DESIGN: A phase I, multicentre, open-label study enrolling two sequential cohorts. METHODS: IMPAACT 2007 participants enrolled by day 3 of life and were stratified by exposure to maternal efavirenz. Cohort 1 participants received two single 8 mg/kg maraviroc doses 1 week apart with pharmacokinetic sampling after each dose. Cohort 2 participants received 8 mg/kg maraviroc twice daily through 6 weeks of life with pharmacokinetic sampling at weeks 1 and 4. Maraviroc exposure target was Cavg at least 75 ng/ml. Laboratory and clinical evaluations assessed safety. RESULTS: Fifteen Cohort 1 and 32 Cohort 2 HIV-exposed neonates were enrolled (median gestational age 39 weeks, 51% male). All 13 evaluable Cohort 1 infants met the pharmacokinetic target. Median exposure for the 25 evaluable Cohort 2 infants met the pharmacokinetic target but variability was high, with 17-33% of infants below target at Weeks 1 and 4. Pharmacokinetic target achievement was similar between efavirenz exposure strata. No Grade 3+ toxicities, early study or treatment discontinuations due to maraviroc occurred. CONCLUSION: Median maraviroc exposure met the Cavg target in neonates receiving 8 mg/kg twice daily, although exposures were variable. Maternal efavirenz use did not impact maraviroc exposure and no discontinuations were due to maraviroc toxicity/intolerance. No infants acquired HIV-1 infection during follow-up. Maraviroc 8 mg/kg twice daily appears well tolerated during the first 6 weeks of life.

The Use of a Shared Services Model for Mycobacteriology Testing: Lessons Learned.

OBJECTIVES: Public health laboratories (PHLs) provide essential services in the diagnosis and surveillance of diseases of public health concern, such as tuberculosis. Maintaining access to high-quality laboratory testing is critical to continued disease detection and decline of tuberculosis cases in the United States. We investigated the practical experience of sharing tuberculosis testing services between PHLs through the Shared Services Project. METHODS: The Shared Services Project was a 9-month-long project funded through the Association of Public Health Laboratories and the Centers for Disease Control and Prevention during 2012-2013 as a one-time funding opportunity to consortiums of PHLs that proposed collaborative approaches to sharing tuberculosis laboratory services. Submitting PHLs maintained testing while simultaneously sending specimens to reference laboratories to compare turnaround times. RESULTS: During the 9-month project period, 107 Mycobacterium tuberculosis complex submissions for growth-based drug susceptibility testing and molecular detection of drug resistance testing occurred among the 3 consortiums. The median transit time for all submissions was 1.0 day. Overall, median drug susceptibility testing turnaround time (date of receipt in submitting laboratory to result) for parallel testing performed in house by submitting laboratories was 31.0 days; it was 43.0 days for reference laboratories. The median turnaround time for molecular detection of drug resistance results was 1.0 day (mean = 2.8; range, 0-14) from specimen receipt at the reference laboratories. CONCLUSIONS: The shared services model holds promise for specialized tuberculosis testing. Sharing of services requires a balance among quality, timeliness, efficiency, communication, and fiscal costs.

Evaluation of three influenza neuraminidase inhibition assays for use in a public health laboratory setting during the 2011-2012 influenza season.

OBJECTIVES: We evaluated the implementation of three commercially available neuraminidase inhibition assays in a public health laboratory (PHL) setting. We also described the drug susceptibility patterns of human influenza A and B circulating in Maryland during the 2011-2012 influenza season. METHODS: From January to May 2012, 169 influenza virus isolates were tested for phenotypic susceptibility to oseltamivir, zanamivir, and peramivir using NA-Fluor(TM), NA-Star®, and NA-XTD(TM) concurrently. A 50% neuraminidase inhibitory concentration (IC50) value was calculated to determine drug susceptibility. We used the standard deviation based on the median absolute deviation of the median analysis to determine the potential for reduced drug susceptibility. We evaluated each assay for the use of resources in high- and low-volume testing scenarios. RESULTS: One of the 25 2009 influenza A (H1N1) pandemic isolates tested was resistant to oseltamivir and peramivir, and sensitive to zanamivir, on all three platforms. Eighty-two influenza A (H3N2) and 62 B isolates were sensitive to all three drugs in all three assays. For a low-volume scenario, NA-Star and NA-XTD took 120 minutes to complete, while NA-Fluor required 300 minutes to complete. The lowest relative cost favored NA-Star. In a high-volume scenario, NA-Fluor had the highest throughput. Reagent use was most efficient when maximizing throughput. Cost efficiency from low- to high-volume testing improved the most for NA-Star. CONCLUSIONS: Our evaluation showed that both chemiluminescent and fluorescent neuraminidase inhibition assays can be successfully implemented in a PHL setting to screen circulating influenza strains for neuraminidase inhibitor resistance. For improved PHL influenza surveillance, it may be essential to develop guidelines for phenotypic drug-resistance testing that take into consideration a PHL's workload and available resources.