Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel

OBJECTIVE: To update recommendations for antiretroviral therapy for adult human immunodeficiency virus type 1 (HIV-1) infection, based on new information and drugs that are available. PARTICIPANTS: A 17-member international physician panel with antiretroviral research and HIV patient care experience initially convened by the International AIDS Society-USA in December 1995. EVIDENCE: Available clinical and basic science data including phase 3 controlled trials; data on clinical, virologic, and immunologic end points; research conference reports; HIV pathogenesis data; and panel expert opinion. Recommendations were limited to therapies available (US Food and Drug Administration approved) in 1999. CONSENSUS PROCESS: The panel assesses new research reports and interim results and regularly meets to consider how the new data affect therapy recommendations. Recommendations are updated via full-panel consensus. Guidelines are presented as recommendations if the supporting evidence warrants routine use in the particular situation and as considerations if data are preliminary or incomplete but suggestive. CONCLUSIONS: The availability of new antiretroviral drugs has expanded treatment choices. The importance of adherence, emerging long-term complications of therapy, recognition and management of antiretroviral failure, and new monitoring tools are addressed. Optimal care requires individualized management and ongoing attention to relevant scientific and clinical information in the field.     

Antiretroviral drug resistance testing in adult HIV-1 infection: recommendations of an International AIDS Society-USA Panel

Martin S. Hirsch, MD; Françoise Brun-Vézinet, MD; Richard T. D'Aquila, MD; Scott M. Hammer, MD; Victoria A. Johnson, MD; Daniel R. Kuritzkes, MD; Clive Loveday, MD, PhD; John W. Mellors, MD; Bonaventura Clotet, MD, PhD; Brian Conway, MD; Lisa M. Demeter, MD; Stefano Vella, MD; Donna M. Jacobsen; Douglas D. Richman, MD

JAMA. 2000;283:2417-2426.

Objective  Assays for drug resistance testing in human immunodeficiency virus type 1 (HIV-1) infection are now available and clinical studies suggest that viral drug resistance is correlated with poor virologic response to new therapy. The International AIDS Society–USA sought to update prior recommendations to provide guidance for clinicians regarding indications for HIV-1 resistance testing.

Participants  An International AIDS Society–USA 13-member physician panel with expertise in basic science, clinical research, and patient care involving HIV resistance to antiretroviral drugs was reconvened to provide recommendations for the clinical use of drug resistance testing.

Evidence and Consensus Process  The full panel met regularly between January and October 1999. Resistance and resistance testing data appearing in the last decade through April 2000 and presentations at national and international research conferences were reviewed. Recommendations and considerations were developed by 100% group consensus, acknowledging that definitive data to support final recommendations are not yet available.

Conclusions  Emerging data indicate that despite limitations, resistance testing should be incorporated into patient management in some settings. Resistance testing is recommended to help guide the choice of new regimens after treatment failure and for guiding therapy for pregnant women. It should be considered in treatment-naive patients with established infection, but cannot be firmly recommended in this setting. Testing also should be considered prior to initiating therapy in patients with acute HIV infection, although therapy should not be delayed pending the results. Expert interpretation is recommended given the complexity of results and assay limitations.

     

Prolonged effects of repeated social defeat stress on mRNA expression and function of mu-opioid receptors in the ventral tegmental area of rats.

Social defeat stress alters the activity of mesocorticolimbic dopamine projections from the ventral tegmental area (VTA), a process that has been implicated in the development of sensitization and drug-seeking behavior. We showed previously that acute brief social defeat stress increased short-term expression of mu-opioid receptor mRNA in the VTA. The present study assessed the presence and functional significance of mu-opioid receptor mRNA expression 1 week after the last episode of social defeat stress. Social defeat stress was induced in intruder rats during short confrontations with an aggressive resident rat, and subsequent exposures behind a protective screen once a day for 5 days. Regional mu-receptor mRNA levels were assessed by in situ hybridization histochemistry, and the amount of mRNA labeling was measured in the VTA and the substantia nigra (SN). Expression of mu-opioid receptor mRNA was significantly higher in defeated rats relative to handled control animals in the VTA, but not in the SN. In an additional group of rats, bilateral local intra-VTA injection of the selective mu-opioid receptor agonist DAMGO (1.0 microg per side) was performed 7-10 days after the last defeat stress or handling control procedure. Baseline motor activity did not differ between control and stressed rats. Intra-VTA DAMGO significantly increased locomotor activity in stressed rats compared to handled control rats. These results suggest that repeated social stress upregulates VTA mu-opioid receptors and can produce locomotor activation via stimulation of these receptors. This locomotor effect is probably the consequence of enhanced disinhibition of mesolimbic dopamine neurons.     

A retrospective examination of regional plus general anesthesia in children undergoing open heart surgery

The use of regional anesthesia in combination with general anesthesia for children undergoing cardiac surgery is receiving increasing attention from clinicians. The addition of regional anesthesia may improve clinical outcomes and decrease costs as a result of the reduced need for postoperative mechanical ventilation. The goal of this retrospective chart review was to evaluate whether spinal anesthesia (SAB) or epidural anesthesia (EPID) in combination with general anesthesia was associated with circulatory stability, satisfactory postoperative sedation/analgesia, and a low incidence of adverse effects. The medical records of 50 consecutive children having open heart surgery with SAB or EPID and general anesthesia between September 1996 and December 1997 were reviewed. We found no significant differences in the incidence of clinically significant changes in vital signs, oxygen desaturation, hypercarbia, or vomiting. Patients in the SAB group received significantly more sedative/analgesic interventions than those in the EPID group.     

Mono- and Diterpenes from Cell Cultures of Thuja occidentalis

Cell cultures of THUJA OCCIDENTIALIS L. were found to biosynthesize various mono- and diterpenes when grown on B5-medium. The identification of the constituents was achieved mainly by capillary GLC-MS using fused silica columns and E.I.-mass spectrometry. Monoterpenes of the menthane type were only isolated from the culture medium whereas diterpenes were found in the cell extracts. Thujaplicin derivatives, monoterpenes of an irregular type, were detected in the medium as well as in the cells. Major differences were found between the terpene composition of the cell culture extracts and those from THUJA leaves. The cell cultures accumulated some compounds which are presently unknown as constituents of THUJA plants. On the other hand, the cultures were evidently unable to synthesize the thujone type of monoterpenes.     

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