Our results suggest that at the doses used, the combination of FTC and tenofovir administered to SIV-infected macaques chronically exposed to daily CBA administration does not result in overt toxicity. CBA administration did not prevent or delay the ART-mediated reduction in viral load. Following ART, circulating levels of total protein and creatinine were significantly higher than baseline values in both sucrose- and alcohol-treated animals, but still within a normal range. No evidence of ART toxicity was observed in either CBA- or SUC-administered macaques. Conclusions These findings indicate that CBA does not attenuate effectiveness of NRTI suppression of viral load, nor does it appear to interact with NRTI to produce toxicity during the initial 2 months of treatment. We conclude that while efforts to reduce AUD in PLWHA should be a priority, and that counseling on the importance of adherence to ART even on drinking days should also be promoted. obtained from the breeding colonies at the TNPRC were studied as previously described. Animals were individually housed in a Biosafety Level-2 (BSL-2) containment building. Experimental protocol Twenty four age- and body weight-matched animals were randomized first to either chronic binge alcohol (CBA) or isocaloric sucrose (SUC) treated groups. Three months after initiating the CBA or SUC administration protocols, animals were infected intrarectally with simian immunodeficiency computer virus (SIVmac251) as detailed below. Approximately two and a half months after SIV inoculation, animals were further randomized to ART+ or ART? groups. ART was continued throughout the study period. The data reported reflect the period of infection prior to and during the initial 2 months after initiation of ART. Thus, four experimental groups (N=6 per group) were studied: CBA/SIV/ART+; CBA/SIV/ART?; SUC/SIV/ART+; and SUC/SIV/ART?. Daily CBA (or SUC) administration was initiated three months prior to SIV inoculation and continued throughout the duration of the study, with the exception of the days when biological sampling was performed, as previously described (Bagby et al., 2003). Briefly, animals were fitted with a gastric catheter and catheter-protecting jacket and tether attached to a swivel that allowed animals to move about their cages during alcohol administration. CBA consisted of daily ethanol (~13 to 14 g ethanol/Kg body weight/wk; 30% w/v water) administered via the chronically-fitted intra-gastric catheter to ensure maximal control of the amount of alcohol animals received throughout the course of the study. This approach of intra-gastric delivery over voluntary alcohol consumption was selected to reduce experimental variability and make sure chronic binge-like intoxicating blood alcohol concentrations CPI-169 between 50C60 mM as previously reported. Chronic binge alcohol consumption CPI-169 was chosen as a model to examine hazardous drinking patterns frequently observed in PLWHA. Though not perfect in replicating AUD it does represent the most frequent pattern of alcohol abuse and is associated with numerous comorbid conditions (CDC). Blood alcohol levels were measured on a weekly basis at 2 h after starting the binge protocol. Adjustments that did not vary between ART+ and ART? animals were made to make sure alcohol concentrations remained within the 50C60 mM range. Time-matched control monkeys were subjected to CPI-169 the same surgical procedures, but received an isocaloric SUC infusion. Total calories provided by alcohol and sucrose averaged 15% of daily intake. Animals were provided ad libitum with Monkey chow (Lab Fiber Plus Primate diet-DT, PMI Nutrition International, St. Louis, MO) and supplemented with fruits, vitamins and Noyes treats (Research Diets, New Brunswick, NJ). Three months after initiating CBA or SUC administration, animals were inoculated intrarectally with 100 TCID50 (50%tissue culture infectious doses) of SIVmac251 provided by Dr. Preston Marx at the TNPRC (Ling, 2002). Inoculation was performed at the conclusion of an alcohol or sucrose session to simulate contamination during an alcohol-binge episode. The progression of SIV disease was monitored throughout the study period through clinical and biochemical parameters including complete blood count (CBC) and enumeration of lymphocyte subsets, serum chemistries (protein, albumin, globulin, alanine aminotransferase (ALT), amino aspartate aminotransferase (AST), alkaline phosphatase (ALK) and plasma SIV gagRNA. Serum chemistries were determined using a Cobas Mira Chemistry Analyzer (Roche, Rotkreutz, Switzerland) at the Clinical Chemistry Laboratory at the TRPRC. Table 1 summarizes the range of normal values as well as the range of values obtained from animals in the present LMAN2L antibody study. Serum globulins were calculated as the difference between total serum protein and albumin. Clinical variables monitored included: body weight and temperature,.
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