CMV Encephalitis/Radiculitis: The Difficulty in Diagnosing in an Intubated Patient.

Cytomegalovirus (CMV) can cause severe disease including colitis, pneumonitis, and less commonly encephalitis, in profoundly immunocompromised individuals. CNS imaging findings are nonspecific and diagnosis is made by identifying CMV in cerebral spinal fluid through PCR testing or cell culture. Early initiation of antiviral therapy is key with an overall poor outcome. Here we present a patient with newly diagnosed AIDS and pneumocystis jiroveci pneumonia who was febrile and remained encephalopathic for the first 6 weeks of his admission despite treatment and extensive work up for encephalopathy. Ultimately, he was diagnosed with CMV encephalitis and radiculitis and failed to improve significantly. This case is important because of multiple points (1) the uncommon presentation of CMV encephalitis/radiculitis occurring over 1 month into a hospitalization; (2) in the era of highly active antiretroviral therapy (HAART) severe complications of AIDS are rarely seen by newer generations of physicians and are not typically thought of; (3) the difficulties in evaluating altered mental status and weakness in an intubated patient receiving sedation. In immunosuppressed patients on mechanical ventilation, early evaluation with LP should be considered when altered mental status and fever of unclear etiology are present.

Effects of minocycline and valproic acid coadministration on atazanavir plasma concentrations in human immunodeficiency virus-infected adults receiving atazanavir-ritonavir.

Minocycline and valproic acid are potential adjuvant therapies for the treatment of human immunodeficiency virus (HIV)-associated cognitive impairment. The purpose of this study was to determine whether minocycline alone or in combination with valproic acid affected atazanavir plasma concentrations. Twelve adult HIV-infected subjects whose regimen included atazanavir (300 mg)-ritonavir (100 mg) daily for at least 4 weeks were enrolled. Each subject received atazanavir-ritonavir on day 1, atazanavir-ritonavir plus 100 mg minocycline twice daily on days 2 to 15, and atazanavir-ritonavir plus 100 mg minocycline twice daily and 250 mg valproic acid twice daily on days 16 to 30 with meals. The subjects had 11 plasma samples drawn over a dosing interval on days 1, 15, and 30. The coadministration of minocycline and valproic acid with atazanavir-ritonavir was well tolerated in all 12 subjects (six male; mean [+/- standard deviation] age was 43.1 [8.2] years). The geometric mean ratios (GMRs; 95% confidence interval [CI]) for the atazanavir area under the concentration-time curve from 0 to 24 h at steady state (AUC(0-24)), the plasma concentration 24 h after the dose (C(min)), and the maximum concentration during the dosing interval (C(max)) with and without minocycline were 0.67 (0.50 to 0.90), 0.50 (0.28 to 0.89), and 0.75 (0.58 to 0.95), respectively. Similar decreases in atazanavir exposure were seen after the addition of valproic acid. The GMRs (95% CI) for atazanavir AUC(0-24), C(min), and C(max) with and without minocycline plus valproic acid were 0.68 (0.43 to 1.06), 0.50 (0.24 to 1.06), and 0.66 (0.41 to 1.06), respectively. Coadministration of neither minocycline nor minocycline plus valproic acid appeared to influence the plasma concentrations of ritonavir (P > 0.2). Minocycline coadministration resulted in decreased atazanavir exposure, and there was no evidence that the addition of valproic acid mediated this effect.

Mechanisms for the deterioration in glucose tolerance associated with HIV protease inhibitor regimens.

The mechanisms responsible for the deterioration in glucose tolerance associated with protease inhibitor-containing regimens in HIV infection are unclear. Insulin resistance has been implicated as a major factor, but the affected tissues have not been identified. Furthermore, beta-cell function has not been evaluated in detail. The present study was therefore undertaken to assess the effects of protease inhibitor-containing regimens on hepatic, muscle, and adipose tissue insulin sensitivity as well as pancreatic beta-cell function. We evaluated beta-cell function in addition to glucose production, glucose disposal, and free fatty acid (FFA) turnover using the hyperglycemic clamp technique in combination with isotopic measurements in 13 HIV-infected patients before and after 12 weeks of treatment and in 14 normal healthy volunteers. beta-Cell function and insulin sensitivity were also assessed by homeostasis model assessment (HOMA). Treatment increased fasting plasma glucose concentrations in all subjects (P < 0.001). Insulin sensitivity as assessed by HOMA and clamp experiments decreased by approximately 50% (P < 0.003). Postabsorptive glucose production was appropriately suppressed for the prevailing hyperinsulinemia, whereas glucose clearance was reduced (P < 0.001). beta-Cell function decreased by approximately 50% (P = 0.002), as assessed by HOMA, and first-phase insulin release decreased by approximately 25%, as assessed by clamp data (P = 0.002). Plasma FFA turnover and clearance both increased significantly (P < 0.001). No differences at baseline or in responses after treatment were observed between drug naïve patients who were started on a nucleoside reverse transcriptase inhibitor (NRTI) plus a protease inhibitor and patients who had been on long-term NRTI treatment and had a protease inhibitor added. The present study indicates that protease inhibitor-containing regimens impair glucose tolerance in HIV-infected patients by two mechanisms: 1) inducement of peripheral insulin resistance in skeletal muscle and adipose tissue and 2) impairment of the ability of the beta-cell to compensate.