Determining the fitness of drug-resistant human immunodeficiency virus type 1 (HIV-1) strains is necessary for the development of population-based studies of resistance patterns. For this purpose, we have developed a reproducible, systematic assay to determine the competitive fitness of HIV-1 drug-resistant mutants. To demonstrate the applicability of this assay, we tested the fitness of the five most common nevirapine-resistant mutants (103N, 106A, 181C, 188C, and 190A), with mutations in HIV-1 reverse transcriptase (RT), singly and in combination (for a total of 31 variants) in a defined HIV-1 background. For these experiments, the 27 RT variants that produced viable virus were cocultured with wild-type virus without nevirapine. The ratios of the viral species were determined over time by utilization of a quantitative real-time RT-PCR-based assay. These experiments revealed that all of the viable variants were less fit than the wild type and demonstrated that the order of relative fitness of the single mutants tested was as follows: 103N > 181C > 190A > 188C > 106A. This order correlated with the commonality of these mutants as a result of nevirapine monotherapy. These investigations also revealed that, on average, the double mutants were less fit than the single mutants and the triple mutants were less fit than the double mutants. However, the fitness of the single and double mutants was often not predictive of the fitness of the derivative triple mutants, suggesting the presence of complex interactions between the closely aligned residues that confer nevirapine resistance. This complexity was also evident from the observation that all three of the replication-competent quadruple mutants were fitter than most of the triple mutants, and in some cases, even the double mutants. Our data suggest that, in many cases, viral fitness is the determining factor in the evolution of nevirapine-resistant mutants in vivo, that interactions between the residues that confer nevirapine resistance are complex, and that these interactions substantially affect reverse transcriptase structure and/or function.

Akathisia is a common and potentially debilitating adverse effect of many psychotropic agents. To a physician not specifically screening for this phenomenon, symptoms can appear similar to depression, anxiety, and/or psychosis. Further complicating matters, akathisia may also occur at different points during the treatment period with varying levels of severity in terms of patient distress. Treatment options have been limited by our somewhat poor understanding of akathisia’s neurological basis, but dopamine dysregulation is theorized to play a central role. Most pharmacotherapy regimens focus on beta-adrenergic antagonists (eg, propranolol, the current gold-standard), which are thought to affect noradrenergic inputs into the dopamine pathways of the brain. However, new research suggests a role for serotonin-based pharmacotherapy, particularly those affecting 5-HT2a/c receptors (eg, mirtazapine) in regulating dopamine. [ Psychiatr Ann . 2014; 44(8):391–396.]

The authors present the case of an inpatient hospitalized at the Veterans Affairs psychiatric unit diagnosed with Wernicke–Korsakoff syndrome to promote awareness of this prevalent yet often underdiagnosed and undertreated condition. Although Veterans present with a unique predisposition for alcohol abuse, it remains problematic in the general population as well. Analysis from 2000 to 2003 reveals alcohol use in the past month in Veterans at 56.6% and 50.8% in comparable non-Veterans. According to the National Survey on Drug Use and Health, it is estimated that of those who are 18 and older, 86.4% have used alcohol, 26.9% have engaged in binge drinking in the past month, 7% engaged in heavy alcohol use in the past month, and 6.2% (15.1 million) carried the diagnosis of alcohol use disorder., The lifetime prevalence of alcohol abuse in the general population is estimated to be between 4.5% and 13.2%. Primary care providers should maintain a high degree of vigilance in evaluating patients for timely diagnosis and prompt treatment of those suspected to have thiamine deficiency. Indeed, Wernicke’s encephalopathy carries a significant level of morbidity and mortality associated with the syndrome, even in cases when it does not present with all of the classic signs. This article aims to raise the primary and ambulatory care provider’s ability to recognize the condition, emphasize a low threshold to treat, and highlight current treatment recommendations.

This report attempts to highlight that use of an antipsychotic and concurrent chronic use of methamphetamine can cause drug-induced parkinsonism. Methamphetamine is usually not encountered in the list of agents that induce drug-induced parkinsonism and so its consideration particularly during chronic use by a patient who is also on an antipsychotic is worthwhile because of its popularity as an illegal narcotic. This case report describes just such a case of drug-induced parkinsonism which is a subacute syndrome that mimics Parkinson's disease. Although less alarming than dystonia, it is more common, more difficult to treat and can be the cause of significant disability during maintenance treatment especially in the elderly. In most cases, symptoms are reversible in days or weeks, but occasionally, especially in the elderly, or if long-acting injectable antipsychotics are used-as in this case-symptoms may last for weeks or months. The report also illustrates the neuronal workings due to chronic methamphetamine-use and the additive effects of dopamine blockade by antipsychotics such as haloperidol.