Lovastatin: Immunomodulatory Value Evaluation

Phase 2

Completed

• Conditions: HIV Seropositivity
• Interventions: Other: placebo; Drug: Lovastatin

• Registration Number: NCT00721305
• Lead Sponsor: Universidad de Antioquia

Brief 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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2008-07-22
• Study First Submitted QC: 2008-07-23
• Study First Posted: 2008-07-24
• Study Start: 2008-08
• Primary Completion: 2011-07
• Study Completion: 2011-07
• Status Verified: 2011-09
• Last Update Submitted: 2011-09-30
• Last Update Posted: 2011-10-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 112

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	placebo	In this arm, subjects will receive placebo (2 tablets which will look externally identical to lovastatin: wrapped in the same way, with the same size, shape and color)
1	Lovastatin	In this arm, subjects will receive 40 mg of Lovastatin (2 tablets of 20 mg each, p.o.), in a daily doses, during twelve months

Primary Outcome Measures

Name	Time	Method
1. HIV-1 viral load measured as RNA copies per ml of peripheral blood 2. CD4 T-cell count measured as cells per ul of peripheral blood	Before, 6 and twelve months after the intervention

Secondary Outcome Measures

Name	Time	Method
CD8+ T cell count, CD4/CD8 ratio, Expression of CD38 and HLA-DR, Total serum cholesterol, Cellular cholesterol, Activity of LFA-1 and ICAM-1, Activity of Rho GTPases, Monthly frequency of AIDS defining diseases, hospitalization and mortality	Before, 6 and twelve months after the intervention

Trial Locations

Locations (1)

Group of Immunovirology, Research Universitary Center, University of Antioquia; 🇨🇴 Medellin, Antioquia, Colombia