lovastatin: immunomodulatory value evaluation

Conditions: HIV Seropositivity

Summary: the purpose of this study is to determine whether the long-term administration of statins may benefit the clinical and immunological evolution in hiv-1-infected individuals before the use of antiretroviral therapy is required.

despite the fact that haart produces a decrease in hiv-1 replication and plasma hiv-1 rna levels, and allows an increase in the cd4 t-cell count that leads to a diminution in the incidence of opportunistic infections and mortality, the cost and complexity of haart regimens, the growing list of long-term side effects, and the eventual development of resistance have underscored the immediate need for additional therapeutic approaches. statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunological effects that are related and unrelated to their cholesterol-lowering activity. hiv-1 requires cholesterol and lipid rafts for several key stages of its replication cycle; statins-mediated depletion of cholesterol alters the capacity of a cell to form lipid rafts and decreases the hiv-1 infectivity. on the other hand, statins may exert significant modulator effects in the balance of the cytokine network, and alter the activity of rho gtpases and lfa-1 and icam-1 adhesion molecules. preliminary studies showed that statins (lovastatin) had anti hiv-1 activity, and that its administration was safe and efficient to control hiv-1 infection in chronically infected individuals who did not receive haart (in terms of decreasing viral load and increasing cd4 t-cell count). because very limited clinical data are available on this topic, this study will be conducted.

Eligibility criteria:
inclusion criteria: * asymptomatic hiv-1 seropositive individuals, with age ≥ 18 years, who are haart naive * hiv-1 infection confirmed by: * positive western-blot test dated at least six months before admission to the study; * a western-blot test within the last six months, which was also positive for the p31 and p66 bands * detectable viral load \< 100,000 copies/ml * cd4+ t cell count ≥ 350 cells/ul exclusion criteria: * inability or unwillingness of patients to give written informed consent. * main residence outside medellin and its metropolitan area, or any indication of difficulties in the follow-up period * participation in other clinical trials * evidence that the patient will exhibit low adherence to intervention and follow-up (morisky-green test) * pregnancy or breastfeeding * any type of antiretroviral treatment before admission to the study, and therapy with lipid-lowering drugs during the last six months * antecedents of allergy, contraindications or intolerance to statins * patients receiving medications which can generate relevant interactions with lovastatin: clarithromycin, erythromycin, azithromycin, itraconazole, ketoconazole, nefodozone, cimetidine, rifampin, phenobarbital, carbamazepine, phenytoin. * unwillingness to avoid the consumption of citrus paradise (grapefruit juice) or saint john's wort (hypericum) * opportunistic infections or any type of aids-defining disease * chronic active hepatitis (b or c) * any hepatocellular disease, indicated by elevation of liver enzymes (ast or alt) more than twice the reference value * renal failure, indicated by serum creatinine ≥ 2 mg/dl * myopathy, indicated by an elevation of creatine phosphokinase (cpk) more than five times the reference values * infection or acute disease that requires in-patient treatment * active substance-related disorders

Keywords: type 1 human immunodeficiency virus infection lovastatin adaptive immunity cellular cholesterol rho gtpases lymphocyte function-associated antigen-1