Antiretroviral Effect of Lovastatin on HIV-1-infected Individuals Without Highly Active Antiretroviral Therapy (HAART): A Phase-II Randomized Clinical Trial (RCT)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 112
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
1
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
干预措施: Lovastatin (Drug)
2
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)
干预措施: placebo (Other)
结局指标
主要结局
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
时间窗: Before, 6 and twelve months after the intervention
次要结局
- 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)
研究者
Carlos Julio Montoya Guarin
Associated Professor
Universidad de Antioquia