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The article presents a study which investigates the Ca2+-properties of cardiac myocytes and troponin extracted from the explanted heart of a patient with genetic dilated cardiomyopathy (DCM) due to the cTnC G159 mutation. It notes that cTnC expression was shown by mass spectroscopy, and that thin filaments constituted with muscle proteins were examined by in vitro motility assay. It suggests that DCM phenotypes result from the uncoupling of the phosphorylation-Ca2+ link.

Objective: The primary objectives of this study were to evaluate the safety, tolerability, and antiviral activity of pegylated interferon-alpha (PegIntron) in HIV-1 treatment-experienced patients failing their current antiretroviral regimen., Design: This was a phase II, multicenter, randomized, double-blind, placebo-controlled study., Methods: Patients were randomized to receive either weekly subcutaneous PegIntron 0.5, 1.0, 1.5, or 3 microg/kg or placebo added to their failing antiretroviral regimen for the first 4 weeks of study. Individuals who achieved more than 0.5 log10 reduction in HIV RNA at week 4 were allowed to continue study medication with optimization of their antiretroviral therapy for an additional 24 weeks., Results: In the 259 patients included in the intent-to-treat analysis, changes in plasma HIV RNA from baseline to week 4 were -0.25 (P > 0.5), -0.46 (P = 0.024), -0.39 (P = 0.008), -0.53 (P < 0.001), and -0.17 (P > 0.5) log10 copies/ml in the 0.5, 1.0, 1.5, and 3.0 microg/kg and placebo arms, respectively. No significant changes were seen in CD4 T-cell parameters in any of the treatment or control arms. Adverse events (most commonly fever, flu-like symptoms, other constitutional symptoms, and psychiatric symptoms) resulted in discontinuation of study medication in 13, 17, 16, 28, and 2% of patients in the 0.5, 1.0, 1.5, 3.0 microg/kg, and placebo group, respectively., Conclusion: The demonstration of significant antiviral activity in a heavily pretreated patient population with acceptable toxicity and only weekly dosing makes PegIntron a potentially valuable therapy for patients with HIV infection that warrants further investigation in a broader population of patients.

Week 48 HIV-RNA treatment response to the protease inhibitor tipranavir co-administered with ritonavir was compared with that of lopinavir co-administered with ritonavir in patients whose baseline isolates had varying lopinavir genotypic mutation scores. With increasing lopinavir mutation scores, the proportion of patients achieving a week 48 treatment response was increased in the tipranavir/ritonavir compared with the lopinavir/ritonavir arm. Tipranavir/ritonavir therapy improves treatment response rates compared with lopinavir/ritonavir in patients whose viruses have reduced susceptibility to lopinavir/ritonavir.

Objective: TMC125-C223 is an open-label, partially blinded, randomized clinical trial to evaluate the efficacy and safety of two dosages of etravirine (TMC125), a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against wild-type and NNRTI-resistant HIV-1., Design: A total of 199 patients were randomly assigned 2: 2: 1 to twice-daily etravirine 400 mg, 800 mg and control groups, respectively. The primary endpoint was a change in viral load from baseline at week 24 in the intention-to-treat population., Methods: Patients had HIV-1 with genotypic resistance to approved NNRTIs and at least three primary protease inhibitor (PI) mutations. Etravirine groups received an optimized background of at least two approved antiretroviral agents [nucleoside reverse transcriptase inhibitors (NRTI) and/or lopinavir/ritonavir and/or enfuvirtide]. Control patients received optimized regimens of at least three antiretroviral agents (NRTIs or PIs and/or enfuvirtide)., Results: The mean change from baseline in HIV-1 RNA at week 24 was -1.04, -1.18 and -0.19 log10 copies/ml for etravirine 400 mg twice a day, 800 mg twice a day and the control group, respectively (P < 0.05 for both etravirine groups versus control). Etravirine showed no dose-related effects on safety and tolerability. No consistent pattern of neuropsychiatric symptoms was observed. There were few hepatic adverse events, and rashes were predominantly early onset and mild to moderate in severity., Conclusion: Etravirine plus an optimized background significantly reduced HIV-1-RNA levels from baseline after 24 weeks in patients with substantial NNRTI and PI resistance, and demonstrated a favorable safety profile compared with control.

Objective: To examine the prevalence and clinical correlates of subsequently measurable viremia in HIV-infected patients who have achieved viral suppression below the limits of quantification (< 50 copies/ml)., Design: Non-randomized dynamic cohort study of ambulatory HIV patients in nine HIV clinics in eight cities., Patients: Patients had two consecutive HIV-1 RNA levels < 50 copies/ml (minimum, 2 months apart) that were followed by at least two more viral level determinations while remaining on the same antiretroviral therapy (ART) between January 1997 and June 2000 (median 485 days). Transiently viremic patients were defined having a subsequently measurable viremia but again achieved suppression < 50 copies/ml., Results: Of the 448 patients, 122 (27.2%) had transient viremia, 19 (4.2%) had lasting low-level viremia and 33 (7.4%) had lasting high-level viremia (defined as 50-400 and > 400 copies/ml, respectively). Only 16 (13.1%) of those who had transient viremia later had persistent viremia > 50 copies/ml. The occurrence of transient viremia did not vary with whether the patient was ART-naive or experienced (P = 0.31), or currently taking protease inhibitors or not (P = 0.08). On consistent ART, the median percentage increase in CD4 cell count was statistically different between subgroups of our cohort (Kruskal-Wallis, P = 0.002)., Conclusions: Transiently detectable viremia, usually 50-400 copies/ml, was frequent among patients who had two consecutive HIV-1 RNA levels below the limits of quantification. In this analysis, such viremia did not appear to affect the risk of developing lasting viremia. Caution is warranted before considering a regimen as 'failing' and changing medications., (Copyright 2002 Lippincott Williams & Wilkins)