Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Highly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregulatory effects, related and unrelated to their cholesterol-lowering activity that can be useful to control HIV-1 infection.</p> <p>Methods/design</p> <p>Randomized, double-blinded, placebo controlled, single-center, phase-II clinical trial. One hundred and ten chronically HIV-1-infected patients, older than 18 years and naïve for antirretroviral therapy (i.e., without prior or current management with antiretroviral drugs) will be enrolled at the outpatient services from the most important centres for health insurance care in Medellin-Colombia. The interventions will be lovastatin (40 mg/day, orally, for 12 months; 55 patients) or placebo (55 patients). Our primary aim will be to determine the effect of lovastatin on viral replication. The secondary aim will be to determine the effect of lovastatin on CD4+ T-cell count in peripheral blood. As tertiary aims we will explore differences in CD8+ T-cell count, expression of activation markers (CD38 and HLA-DR) on CD4 and CD8 T cells, cholesterol metabolism, LFA-1/ICAM-1 function, Rho GTPases function and clinical evolution between treated and not treated HIV-1-infected individuals.</p> <p>Discussion</p> <p>Preliminary descriptive studies have suggested that statins (lovastatin) may have anti HIV-1 activity and that their administration is safe, with the potential effect of controlling HIV-1 replication in chronically infected individuals who had not received antiretroviral medications. Considering that there is limited clinical data available on this topic, all these findings warrant further evaluation to determine if long-term administration of statins may benefit the virological and immunological evolution in HIV-1-infected individuals before the use of antiretroviral therapy is required.</p> <p>Trial registration</p> <p>Registration number NCT00721305.</p

Functional significance of MRI defined mesial temporal sclerosis in temporal lobe epilepsy

The functional significance of MRI-defined mesial temporal sclerosis in temporal lobe epilepsy (TLE) is not completely established. In order to study the possible relationship between signals of mesial temporal sclerosis on MRI and interictal SPECT findings we selected 18 patients with complex partial seizures, unilateral temporal EEG focus and normal CT. The EEG focus was defined by the presence of interictal sharp waves and slow background on several scalp EEG obtained during many years of follow up in all patients and by ictal recordings with sphenoidal electrodes in 12 patients. Group I comprised patients (n=11) in whom MRI showed mesial temporal sclerosis; group II patients (n=7) had normal MRIs. All patients were submitted to interictal 99m-Tc HMPAO injections with concomitant EEG monitoring. Lateralized hypoperfusion ipsilateral to the EEG was found in 13 patients (72%). In all Group II and in 6 Group I patients a temporal hypoperfusion was found. This SPECT study showed a higher positivity rate in patients with normal MRI than previously reported. On the other hand, in all these group II patients a neocortical origin of epileptic focus was suspected on clinical or electroencephalographic basis. Positive SPECT findings may be at least as prevalent in neocortical as in mesiolimbic epilepsy