Pharmacokinetics of two common antiretroviral regimens in older HIV-infected patients: a pilot study.

OBJECTIVES: The pharmacokinetics (PK) of antiretrovirals (ARVs) in older HIV-infected patients are poorly described. Here, the steady-state PK of two common ARV regimens [tenofovir (TFV)/emtricitabine (FTC)/efavirenz (EFV) and TFV/FTC/atazanavir (ATV)/ritonavir (RTV)] in older nonfrail HIV-infected patients are presented. METHODS: HIV-infected subjects ≥ 55 years old not demonstrating the frailty phenotype were enrolled in an unblinded, intensive-sampling PK study. Blood plasma (for TFV, FTC, EFV, ATV and RTV concentrations) and peripheral blood mononuclear cells [PBMCs; for tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) concentrations] were collected at 11 time-points over a 24-hour dosing interval. Drug concentrations were analysed using validated liquid chromatography-ultraviolet detection (LC-UV) or liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. Noncompartmental pharmacokinetic analysis was used to estimate PK parameters [area under the concentration-time curve over 24 h (AUC0-24h ) and maximal concentration (Cmax )]. These parameters were compared with historical values from the general HIV-infected population. RESULTS: Six subjects on each regimen completed the study. Compared with the general population, these elderly subjects had 8-13% decreased TFV AUC0-24h and Cmax , and 19-78% increased FTC and RTV AUC0-24h and Cmax . Decreased ATV AUC0-24h (12%) and increased Cmax (9%) were noted, while EFV exposure was unchanged (5%) with a 16% decrease in Cmax . Intracellular nucleoside/tide metabolite concentrations and AUC are also reported for these subjects. CONCLUSIONS: This study demonstrates that the PK of these ARVs are altered by 5-78% in an older HIV-infected population. Implications of PK differences for clinical outcomes, particularly with the active nucleoside metabolites, remain to be explored. This study forms the basis for further study of ARV PK, efficacy, and toxicity in older HIV-infected patients.

Wide-field Fizeau imaging telescope: experimental results.

A nine-aperture, wide-field Fizeau imaging telescope has been built at the Lockheed-Martin Advanced Technology Center. The telescope consists of nine, 125 mm diameter collector telescopes coherently phased and combined to form a diffraction-limited image with a resolution that is consistent with the 610 mm diameter of the telescope. The phased field of view of the array is 1 murad. The measured rms wavefront error is 0.08 waves rms at 635 nm. The telescope is actively controlled to correct for tilt and phasing errors. The control sensing technique is the method known as phase diversity, which extracts wavefront information from a pair of focused and defocused images. The optical design of the telescope and typical performance results are described.

Phase-diversity wave-front sensor for imaging systems.

A phase-diversity wave-front sensor has been developed and tested at the Lockheed Palo Alto Research Labs (LPARL). The sensor consists of two CCD-array focal planes that record the best-focus image of an adaptive imaging system and an image that is defocused. This information is used to generate an object-independent function that is the input to a LPARL-developed neural network algorithm known as the General Regression Neural Network (GRNN). The GRNN algorithm calculates the wave-front errors that are present in the adaptive optics system. A control algorithm uses the calculated values to correct the errors in the optical system. Simulation studies and closed-loop experimental results are presented.

Comparison of methods for determining the second-order detection efficiency of a VUV spectrometer.

Four independent procedures were developed and tested to measure the apparatus response function of a VUV spectrometer-detector system for unpolarized 46-nm radiation dispersed in second order. These measurements were made to allow the use of continuum synchrotron radiation for the calibration of the response of the spectrometer-detector system for dispersion of 92-nm radiation in first order with full correction for the effects of synchrotron radiation dispersed in second order. In the first method, synchrotron radiation was used in combination with a thin Al foil to block out synchrotron radiation at 92 nm while allowing 46-nm radiation to enter the spectrometer. In the second as well as the third method NeII 46-nm line radiation was used to measure the response function in first and second order. The line radiation was produced by (1) an electron beam exciting a Ne gas target for which the resulting VUV light illuminated the entire grating and (2) a duoplasmatron VUV light source operating with Ne gas producing a small spot of radiation that was scanned across the surface of the spectrometer grating. In the fourth method the difference in the spectral distributions of synchrotron radiation produced by electrons with different kinetic energies was employed to deduce the second-order detection efficiency. The ratio of the second- to firstorder response function for 46-nm radiation could be determined to a precision of 6% using the bandpass filter and electron-beam methods, 10% using the duoplasmatron method, and 250% using the multiple electron energy method.