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To safely progress toward direct potable reuse (DPR), it is essential to ensure that DPR systems can provide public health protection equivalent to or greater than that of conventional drinking water sources. This study collected data over a one-year period from a full-scale DPR demonstration facility, and used both performance distribution functions (PDFs) and quantitative microbial risk assessment (QMRA) to define and evaluate the reliability of the advanced water treatment facility (AWTF). The AWTF's ability to control enterovirus, Giardia, and Cryptosporidium was characterized using online monitoring of surrogates in a treatment train consisting of ozone, biological activated carbon, microfiltration, reverse osmosis, and ultraviolet light with an advanced oxidation process. This process train was selected to improve reliability by providing redundancy, defined as the provision of treatment beyond the minimum needed to meet regulatory requirements. The PDFs demonstrated treatment that consistently exceeded the 12/10/10-log thresholds for virus, Giardia, and Cryptosporidium, as currently required for potable reuse in California (via groundwater recharge and surface water augmentation). Because no critical process failures impacted pathogen removal performance during the yearlong testing, hypothetical failures were incorporated into the analysis to understand the benefit of treatment redundancy on performance. Each unit process was modeled with a single failure per year lasting four different failure durations: 15 min, 60 min, 8 h, and 24 h. QMRA was used to quantify the impact of failures on pathogen risk. The median annual risk of infection for Cryptosporidium was 4.9 × 10 -11 in the absence of failures, and reached a maximum of 1.1 × 10 -5 assuming one 24-h failure per process per year. With the inclusion of free chlorine disinfection as part of the treatment process, enterovirus had a median annual infection risk of 1.5 × 10 -14 (no failures) and a maximum annual value of 2.1 × 10 -5 (assuming one 24-h failure per year). Even with conservative failure assumptions, pathogen risk from this treatment train remains below the risk targets for both the U.S. (10 -4 infections/person/year) and the WHO (approximately 10 -3 infections/person/year, equivalent to 10 -6 DALY/person/year), demonstrating the value of a failure prevention strategy based on treatment redundancy., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

BENCHMRK-1 and -2 are ongoing double-blind phase III studies of raltegravir in patients experiencing failure of antiretroviral therapy with triple-class drug-resistant human immunodeficiency virus infection. At week 96 (combined data), raltegravir (400 mg twice daily) plus optimized background therapy was generally well tolerated, with superior and durable antiretroviral and immunological efficacy, compared with optimized background therapy alone.

Raltegravir, a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, has pH-dependent solubility. Raltegravir plasma concentration increases with omeprazole coadministration in healthy subjects; this is likely secondary to an increase in bioavailability attributable to increased gastric pH. Increased gastric pH has been reported in HIV-1-infected individuals, and the effects of omeprazole in this intended population may be diminished. Further investigation is necessary.

A prospective, open-label study was conducted to assess the response to indinavir, efavirenz, and adefovir in human immunodeficiency virus (HIV)-infected patients experiencing viral rebound while receiving therapy with nelfinavir-containing regimens, to determine whether the protease genotype influenced the outcome of the salvage regimen. Genotyping from 29 nelfinavir failures revealed D30N in 17 (59%) and L90M in 11 (38%) cases. Suppression to <400 viral RNA copies/mL was achieved at week 48 in 56% of patients with the D30N virus versus 18% of patients with the L90M virus.

This was a randomized, double-blind, placebo-controlled parallel study in human immunodeficiency virus type 1 (HIV-1)-uninfected healthy subjects to investigate the pharmacokinetic interaction between indinavir (IDV) and ritonavir (RTV). Subjects were allocated to treatment groups of IDV given with RTV in the following milligram doses twice daily: 800 mg of IDV-100 mg of RTV (800-100 mg), 800-200, 800-400, and 400-400 mg, placebo of IDV with RTV doses of 100, 200, and 400 mg, and placebo of both IDV and RTV. Doses of both drugs were administered for 14 days with a low-fat meal and one dose on day 15 with a high-fat meal. Blood was obtained for drug concentration measurements on days 14 and 15. Seventy-three volunteers enrolled in the study: 29 men and 44 women. Fifty-three volunteers completed the study. When compared to standard historical data for 800 mg of IDV every 8 h (q8h), the IDV area under the concentration-time curve for 24 h (AUC(24)) of IDV-RTV regimens 400-400, 800-100, and 800-200 mg were at least 1.4, 2.3, and 3.3 times higher, respectively, regardless of meal. The concentrations at the end of the dosing interval were 10 to 25 times higher than that observed in the standard regimen of 800 mg of IDV q8h for IDV-RTV 800-100 and 800-200 mg regimens, respectively. RTV at 200 mg maximally enhanced the IDV profile. Improved tolerability was associated with IDV-RTV 800-100 mg versus IDV-RTV 800-200, 800-400, and 400-400 mg q12h. The advantages of IDV-RTV twice daily over 800 mg of IDV q8h include no food restrictions and twice-daily dosing. Also, the regimens achieve levels of IDV that may be helpful in suppressing strains of HIV-1 that have reduced susceptibility to IDV or other protease inhibitors.