**8.4. Fish oil**

The ability of fish oil, commonly known as omega-3 fatty acids (namely, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), to reduce elevated TG concentrations has been observed in different studies [128, 129]. HIV-1 patients using both HAART and fish oil showed an effective reduction in the concentration of TG [130]. This ability to reduce TG levels promotes a direct benefit in risk reduction of atherogenic cardiovascular disease through a combination of anti-inflammatory and anti-platelet actions [130-132]. For HIV-1 patients, the use of fish oil associated with fenofibrate showed additive effects in reduc‐ ing TG. Given these considerable results, the American Heart Association's (AHA) dietary guidelines, recommends that healthy adults have a minimum of two portions of fish per week, and those who have elevated TG should consume 2-4 g of EPA and DHA daily as a dietary supplement [130-133].

### **8.5. Niacin**

with PIs. However, concomitant use of both fibrates and statins can increase the risk of skeletal muscle toxicity and should be avoided [112-114]. In HIV-1 seronegative individuals, the use of a fibrate and a statin in a monotherapy regimen exhibits moderate lipid-lowering effects and good tolerability [114-116]. In HIV-1 patients, fibrates do not have the same efficacy of statins in preventing cardiovascular disease. Studies with HIV-1 patients treated with PI-based therapy and fibrates, including gemfibrozil, bezafibrateor fenofibrate, showed a significant reduction in the concentration of TC, TG and hypertriglyceridemia [113, 115, 116]. Fibrates appear as a suitable alternative for the treatment of dyslipidemia associated with HIV-1, especially in the presence of hypertriglyceridemia. Periodic monitoring of serum creatinine, CK, and transaminases should be performed when using fibrates [115-117]. The association between fibrates and statins has been used with relative safety and demonstrated in different studies with large numbers of HIV-1 patients volunteers, except for the use of the combination of statins and gemfibrozil, which is not recommended [116-118]. The use of statins, fibrates, or associated therapeutic agent has shown positive results in HIV-associated dyslipidemia. and the pravastatin/fenofibrate combination has accelerated the an improvement of lipid param‐

nelfinavir. Doses of 80 mg/day with NNRTIs, raltegravir and selzentry.

nelfinavir. Doses of 80 mg/day with NNRTIs, raltegravir and selzentry.

efavirenz. Doses of 80 mg/day with PIs, NNRTIs, raltegravir and selzentry. Fluvastatin Metabolized by CYP2C9, and occasional interactions with nelfinavir and efavirenz. Doses of 80

mg/day with PIs, NNRTIs, raltegravir and selzentry.

40 mg/day with NNRTIs, raltegravir and selzentry.

Considerable CYP3A4 metabolism. ↑ simvastatin levels with PIs and ↓ ↓ levels with efavirenz. Not recommended with atazanavir, atazanavir/ritonavir, fosamprenavir/ritonavir, saquinavir/ ritonavir, tipranavir/ritonavir, lopinavir/ritonavir, indinavir/ritonavir, darunavir/ritonavir and

Not recommended with atazanavir, atazanavir/ritonavir, fosamprenavir/ritonavir, saquinavir/ ritonavir, tipranavir/ritonavir, lopinavir/ritonavir, indinavir/ritonavir, darunavir/ritonavir and

Somewhat CYP3A4 metabolism, ↑ levels with PIs darunavir, lopinavir, saquinavir/ritonavir, fosamprenavir. ↓ levels with efavirenz. Doses of 20 mg/day with PIs, 80 mg/day with NNRTIs,

Reduced interaction with CYP450 metabolism, primarily renal excretion but 50% ↓ with lopinavir/ritonavir, 45% ↓ with nelfinavir, 80% ↑ with darunavir/ritonavir, and 40% ↓ with

Not CYP3A4 metabolized but 5x ↑ levels with lopinavir/ritonavir and darunavir/ritonavir (uncertain). Low starting doses (5-10 mg) recommended with PIs. Doses of 20 mg/day with PIs,

Inhibitors of intestinal cholesterol absorption are a class of drugs that prevent the absorption of cholesterol from the small intestine into the circulatory system. Ezetimibe is effective at lowering lipid levels because it has the ability to inhibit the intestinal absorption of cholesterol,

eters and is safe and efficacious [119-120].

**Table 4.** Statins to HAART-associated dyslipidemia.

**Drug Metabolism and Interactions**

raltegravir and selzentry.

142 Trends in Basic and Therapeutic Options in HIV Infection - Towards a Functional Cure

Simvastatin

Lovastatin

Atorvastatin

Pravastatin

Rosuvastatin

**8.3. Inhibitors of intestinal cholesterol absorption**

Niacin (water-soluble vitamin B3), or nicotinic acid, is a powerful reducing agent of serum lipids when administered at pharmacological doses. Its ability to reduce the levels of lipoproteins and apolipoprotein-B-containing lipoproteins and to raise HDL levels has been shown, characterizing it as an atheroprotective drug [134, 135]. Niacin has beneficial effects on cardiovascular risk factors, including lipoprotein (a), C-reactive protein (CRP), plateletactivating factor (PAF) acetylhydrolase, plasminogen activator inhibitor (PAI)- 1 and fibrinogen [136, 137]. The molecular mechanisms involving the action of niacin are not fully understood, but its effect on hypertriglyceridemia in uninfected individuals is recognized [135-137]. In HIV-1 patients, the use of niacin in an extended release formulation significant‐ ly reduced the levels of TC, TG and HDL. However, the use of niacin in HIV-1 patients with dyslipidemia need to be carefully monitored because the presence of adverse events have been commonly shown, including headache, flushing, pruritus, rash, hyperuricemia, and exacerbation of insulin resistance [138, 139].

#### **8.6. Other contributory agents to HIV dyslipidemia**

Other agents may contribute to HIV-associated dyslipidemia. The use of recombinant me‐ thionyl human leptin was associated with reduced insulin resistance and increased HDL levels [140]. Tetradecylthioacetic acid (TTA), an agent whose mechanism is still unknown, promotes a reduction in levels of plasma lipoproteins [141]. Additionally, Acipimox, a drug with sustained action and a structure similar to niacin, has been associated with decreased insulin resistance and significantly reduced levels of TG in HIV-1 adults [142]. In a double-blind study, the use of cholestin was able to reduce the levels of TC and LDL without modifying HDL and TG, and without showing adverse effects [143]. The use of L-carnitine (3 g/day) resulted in a significant reduction in serum TG in patients with HIV-associated dyslipidemia [144]. These and other drugs studied aimed to revert the HIV-associated dyslipidemia but require more control to be considered appropriate for the treatment of dyslipidemia.
