Lovastatin: Immunomodulatory Value Evaluation (LIVE)

Universidad de Antioquia

Status and phase: Completed; Phase 2

Conditions: HIV Seropositivity

Treatments: Other: placebo; Drug: Lovastatin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00721305

COLCIENCIAS 111540820508

Details and patient eligibility

About

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.

Full 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.

Enrollment: 112 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

112 participants in 2 patient groups, including a placebo group

1

Experimental group

Description:

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

Treatment:

Drug: Lovastatin

2

Placebo Comparator group

Description:

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)

Treatment:

Other: placebo