Table 1.
Trials evaluating statins in HIV patients.
| Trial | Number of patients | Primary Outcome | Results | Comments | ||
|---|---|---|---|---|---|---|
| Atorvastatin | ||||||
| Atorvastatin 10-20 mg/day in patients treated with PI-containing ART with severe dyslipidemia [39] | 15 | Efficacy of atorvastatin in the treatment of dyslipidemia for 12 weeks | TC: 25% decrease TG: 35% decrease |
No cases of myopathy One patient experienced transaminitis that resolved within 3 months Decreased lipid values observed at 12 weeks and maintained through 15 months |
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| Prospective study of atorvastatin 10 mg/day in patients receiving ART ≥ 12 weeks with TC ≥ 240 mg/dL, with or without increased TG despite therapeutic lifestyle changes [40] | 20 | Efficacy of atorvastatin in the treatment of dyslipidemia for 24 weeks | TC: 27% decrease TG: 41% decrease LDL-C: 37% decrease HDL: 1.3 mg/dL increase |
No cases of myalgia, myositis, or increased CK Significant decrease in TC and LDL-C with atorvastatin |
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| Open-label, randomized, prospective study of atorvastatin 10 mg/day, pravastatin 20 mg/day, or rosuvastatin 10 mg/day in HIV-infected patients treated with PI-containing regimens ≥ 12 months and dyslipidemia > 3 months despite therapeutic lifestyle changes [41] | 85 | Evaluation of different statins in the management of PI-associated dyslipidemia | Overall:TC: 21% decrease LDL-C: 24% decrease Atorvastatin: TC: 20% decrease Pravastatin: TC: 18% decrease Rosuvastatin: TC: 25% decrease |
Favorable tolerability profile with significant efficacy among all statins Rosuvastatin more effective than atorvastatin or pravastatin in decreasing TC and LDL-C |
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| Randomized, double-blind, placebo-controlled trial of HIV-infected patients on ART ≥ 6 months with subclinical coronary atherosclerosis, arterial inflammation in the aorta, and LDL-C < 130 mg/dL treated with either atorvastatin 20-40 mg/day or placebo [42] | 40 (atorvastatin [n = 21] versus placebo [n = 19]) | Efficacy of statin treatment to reduce arterial inflammation regression of coronary atherosclerosis for 12 months | TC: 48% decrease TG: unchanged LDL-C: 39% decrease HDL: 1% increase |
Similar rates of myalgia, transaminitis, and CK elevation in atorvastatin group vs. placebo, 5 vs. 6, 2 vs. 3, 0 vs. 0, respectively Significant decreases in TC and LDL-C with atorvastatin vs. placebo |
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| Pravastatin | ||||||
| Pilot study of HIV patients receiving PI-containing regimens treated with pravastatin [50] | 19 | Efficacy of pravastatin 20 mg at bedtime in the treatment of dyslipidemia for 16 weeks | TC: 19% decrease TG: 37% decrease |
No adverse effects noted CD4 and HIV RNA has no significant change with pravastatin treatment |
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| Randomized, open-label comparative study of HIV patients receiving PI-containing regimens treated with pravastatin or diet only [51] | 31 | Efficacy of pravastatin 40 mg/day versus diet only in the treatment of dyslipidemia for 24 weeks | Pravastatin TC: 17% decrease LDL-C: 19% decrease Diet Only TC: 4% increase LDL-C: 6% decrease |
Despite numerical change, TC differences did not reach statistical significance There was no difference in HDL or TG All patients were male |
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| Open-label, randomized, prospective study of HIV patients receiving PI-containing regimens treated with pravastatin, fluvastatin, or fibrates [52] | 106 (pravastatin [n = 19] versus fluvastatin [n = 18] versus fibrate [n = 69]) | Efficacy and safety of pravastatin, fluvastatin or fibrates in the treatment of diet-resistant hypertriglyceridemia for 12 months | Statin (either) TC: 25% decrease TG: 35% decrease LDL-C: 26% decrease HDL: 24% increase |
Cholesterol changes versus baseline were significant, but no when compared to each other | ||
| Fibrates (any) TC: 22% decrease TG: 41% decrease LDL-C: 23% decrease HDL: 20% increase |
All agents demonstrated favorable tolerability | |||||
| Placebo-controlled, double-blind, crossover study of HIV patient receiving PI-containing regimens with pravastatin [53] | 20 | Efficacy of pravastatin 40 mg/day versus placebo in the treatment of dyslipidemia | TC: 18% decrease LDL-C: 21% decrease |
Significant decreases in TC and LDL-C with pravastatin vs. placebo No significant difference in flow-mediated dilation |
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| Randomized, crossover, double-blind placebo-controlled study of HIV-infected patients with dyslipidemia receiving PI-containing regimens with pravastatin [54] | 29 | Efficacy of pravastatin 40 mg/day versus placebo in the treatment of dyslipidemia for 8 weeks | Data only reported as median +/- interquartile ranges | Significant decreases in TC, LDL-C, and TG with pravastatin vs. placebo Significant increase in flow-mediated dilation with pravastatin |
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| Randomized, open-label study of HIV-infected patients with dyslipidemia receiving PI-containing regimens with pravastatin or fibrates versus switching to NNRTI [55] | 130 (pravastatin [n = 36] or bezafibrate [n = 31] versus nevirapine [n = 29] or efavirenz [n = 34] switch) | Efficacy of pravastatin or bezafibrate versus switching ART to NNRTI (NVP or EFV) in the treatment of mixed hyperlipidemia for 12 months | Nevirapine TG: 25% decrease LDL-C: 25% decrease Efavirenz TG: 9% decrease LDL-C: 9% decrease |
Significant decreases in TG and LDL-C with lipid medication versus switching to NNRTI | ||
| Comparable viral efficacy Switching to NVP demonstrated greater TG reduction than switching to EFV | ||||||
| Pravastatin TG: 41% decrease LDL-C: 40% decrease Bezafibrate TG: 47% decrease LDL-C: 35% decrease | ||||||
| Randomized, open-label, study of HIV-infected patients with dyslipidemia receiving ART with pravastatin, fenofibrate or both [56] | 174 (pravastatin [n = 86] or fenofibrate [n = 88]) | Efficacy of pravastatin or fenofibrate or both in the treatment of combined dyslipidemia for 48 weeks | Pravastatin (12 weeks) LDL-C 20% decrease TG 13% decrease Fenofibrate (12 weeks) LDL-C 8% increase TG 35% decrease HDL 11% increase |
Pravastatin significantly reduced LDL-C versus baseline and fenofibrate at 12 weeks Fenofibrate significantly reduced TG and increased HDL versus baseline and pravastatin at 12 weeks Over 75% of patients enrolled were initiated on dual-therapy |
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| Randomized, placebo-controlled study of HIV-infected patients with dyslipidemia receiving PI-containing regimens with pravastatin [57] | 33 (pravastatin [n = 16] versus placebo [n = 17]) | Efficacy of pravastatin 40 mg/day in the treatment of hypercholesterolemia for 12 weeks | Time-weighted change in TC decreased and subcutaneous fat increased with pravastatin | No change in TG versus placebo | ||
| Randomized, placebo-controlled study of HIV-infected patients with dyslipidemia receiving PI-containing regimens with pravastatin [46] | 21 (pravastatin [n = 12] versus placebo [n = 9]) | Efficacy of pravastatin 40 mg/day in the treatment of TC ≥ 213 mg/dL for 12 weeks | Data only reported as medians | TC and LDL-C decreased significantly with pravastatin No virological failure |
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| Placebo-controlled, 2 × 2 factorial study of HIV patients receiving ART with pravastatin +/- Lisinopril without compelling indication [58] | 34 (pravastatin +/- lisinopril [n = 18] versus placebo +/- lisinopril [n = 16]) | Efficacy of pravastatin 20 mg/day with or without lisinopril with no statin indication for 4 months | No change in TC, LDL-C or inflammatory markers with pravastatin | No meaningful adverse effects Lisinopril reduced blood pressure |
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| Randomized, open-label, crossover study of HIV patients on ART with pravastatin, +/- phytosterols [59] | 36 | Efficacy of pravastatin 40 mg/day +/- phytosterols 2 g/day in patients with LDL-C ≥ 130 mg/dL for 12 weeks including a 4 week washout | Pravastatin LDL-C: 29% Phytosterols LDL-C: 9% Both LDL-C: 27% |
Adding phytosterols to pravastatin does not add any LDL-C benefit | ||
| Randomized, prospective comparator study of HIV-infected patients with dyslipidemia receiving PI-containing regimens with pravastatin versus ezetimibe + fenofibrate [60] | 42 | Efficacy of pravastatin 40 mg/day versus ezetimibe 10 mg/day + fenofibrate 200 mg/day in the treatment of dyslipidemia for 6 months | Pravastatin TC: 6% decrease LDL-C: 18% decrease Ezetimibe + Fenofibrate TC: 11% decrease LDL-C: 17% decrease |
Similar lipid parameter changes with combination non-statin therapy as with moderate-intensity statin Both arms were well tolerated |
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| Rosuvastatin | ||||||
| Rosuvastatin reduces vascular inflammation and T cell and monocyte activation in HIV-infected subjects on ART [65] | 147 (Rosuvastatin [n = 72] vs. placebo [n = 75]) | Assess changes in baseline to 48 weeks in plasma inflammatory and coagulation indices and markers of lymphocyte and monocyte activation | LDL-C: 23.4% decrease HDL: 0.7% increase TG: 5.5% increase |
Significant reduction in LDL-C with rosuvastatin vs. placebo No significant changes in HDL or TG Significant decrease in sCD14, Lp-PLA2, and markers of monocyte and lymphocyte activation in rosuvastatin vs. placebo |
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| Rosuvastatin versus pravastatin in dyslipidemic HIV-1 infected patients receiving PIs: a randomized trial [66] | 83 (Rosuvastatin [n = 41] vs. Pravastatin [n = 42]) | Compare the efficacy of rosuvastatin and pravastatin on plasma lipid levels in HIV-1 infected patients on at least one PIs after 45 days | Rosuvastatin: LDL-C: 37% decrease TG: 19% decrease HDL: 2.5% increase TC: 28% decrease |
Pravastatin: LDL-C: 19% decrease TG: 7% decrease HDL: no change TC: 14% decrease |
Significant reduction in LDL-C, TG, and TC with rosuvastatin vs. pravastatin No difference in HDL No renal, hepatic, or muscular events in either group |
|
| Rosuvastatin for the treatment of hyperlipidaemia in HIV-infected patients receiving protease inhibitors: a pilot study [67] | 16 | Evaluate rosuvastatin for the management of PI-related dyslipidemia in HIV-positive patients over 24 weeks | TC: 21.7% decrease TG: 30.1% decrease LDL-C: 22.4% decrease HDL: 28.5% increase |
Significant decreases in TC, LDL-C, and TG and significant increase in HDL with rosuvastatin No significant clinical or laboratory adverse effects |
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| Two-year treatment with rosuvastatin reduces carotid IMT in HIV type 1-infected patients receiving highly ART with asymptomatic atherosclerosis and moderate cardiovascular risk. AID Res Hum Retroviruses [68] | 36 | Assess changes in carotid IMT and evaluate effect on lipid parameters with rosuvastatin for 24 months | TC: 25.3% decrease LDL-C: 29.8% decrease HDL: 11.6% increase TG: 16.5% decrease Right internal carotid IMT: 23.7% decrease Left internal carotid IMT: 25.6% decrease Right carotid bifurcation IMT: 18.7% decrease Left carotid bifurcation IMT: 21.4% decrease |
Significant reductions in TC, LDL-C, TG, IMT with rosuvastatin No serious adverse events reported |
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| Other statins | ||||||
| Fluvastatin | ||||||
| Placebo-controlled, double-blind, randomized cross-over study of HIV-infected patients with dyslipidemia receiving PI-containing regimens treated with fluvastatin [78] | 16 | Safety and efficacy of fluvastatin 40 mg/day in the management of dyslipidemia for 4 weeks | TC: 54% decrease TG: 18% decrease |
Significant reduction in TC with fluvastatin vs. placebo | ||
| Prospective, non-randomized, open-label study of treatment-experienced HIV-infected patients on ART ≥ 2 years with hypercholesterolemia despite therapeutic lifestyle changes [79] | 25 (fluvastatin [n = 12] vs. pravastatin [n = 13]) | Compare the effectiveness fluvastatin and pravastatin for the treatment of hypercholesterolemia and potential interactions with ART for 12 weeks | Fluvastatin: TC: 19% decrease LDL-C: 30% decrease Pravastatin: TC: 14% decrease LDL-C: 14% decrease |
Greater reductions in TC and LDL-C with fluvastatin compared to pravastatin No changes in ART serum concentrations |
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| Pitavastatin | ||||||
| After 52 weeks, pitavastatin is superior to pravastatin for LDL-C lowering in patients with HIV [84] | 252 (Pitavastatin [n = 126] vs. Pravastatin (n = 126])* *99 vs. 91 patients completed 52 weeks |
Evaluate long-term (52 weeks) safety and efficacy of pitavastatin vs. pravastatin in HIV-infected adults with dyslipidemia | Pitavastatin LDL-C: 29.7% decrease TC: 19.1% decrease TG: 2.0% decrease HDL: 8.9% increase |
Pravastatin LDL-C: 20.5% decrease TC: 13.7% decrease TG: 6.3% decrease HDL: 7.2% increase |
Safety profiles were similar between agents Pitavastatin displayed a significantly greater decrease in LDL-C and TC at 52 weeks No difference in changes in TG or HDL |
|
| Effects of pitavastatin on lipid profiles in HIV-infected patients with dyslipidemia and receiving ATV/RTV: a randomized, double-blind, crossover study [85] | 24 (Pitavastatin [n = 12] vs. placebo [n = 12]) | Determine efficacy and safety of pitavastatin in HIV-infected patients with dyslipidemia who are receiving ATV/RTV at 12 weeks | TC: 13.7% decrease LDL-C: 21.8% decrease TG: 24.6% increase HDL: 5.3% increase |
Significant decrease in TC and LDL-C at 12 weeks with pitavastatin vs. placebo No difference in TG or HDL No adverse events reported in pitavastatin group |
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| Simvastatin | ||||||
| Retrospective chart review of HIV-infected men receiving EFV-based ART and concomitant simvastatin 20 mg/day [92] | 13 | Evaluate the safety and efficacy of simvastatin for treatment of dyslipidemia for up to 6 months | TC: 20% decrease TG: 21% decrease LDL-C: 36% decrease |
No cases of myalgia, myositis, or increased CK Reduction in TC, TG, and LDL-C values with simvastatin |
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PI, protease inhibitor; ART, antiretroviral therapy; TC, total cholesterol; TG, triglycerides; LDL, low-density lipoprotein; HDL, high-density lipoprotein; CK, creatinine kinase; HIV, human immunodeficiency virus; NNRTI, nonnucleoside reverse transcriptase inhibitor; NVP, nevirapine; EFV, efavirenz; sCD14, soluble CD14; Lp-PLA2, Lipoprotein-associated phospholipase A2; carotid IMT, carotid intima-media thickness; ATV/RTV, atazanavir/ritonavir.