Cholesterol and Triglycerides
**Cholesterol and triglycerides are two types of fats (lipids) that are carried (and can be measured) in blood.
These fats perform essential functions, including making effective cell structures and processing vitamins A, D, E and K.
Cholesterol and trigylcerides are often referred to as â€˜lipidsâ€™.
When levels are too high, this increases the risk of heart disease and stroke in the general population.
However, if this is a side effect of treatment for a short time, there may be differences to the general population where abnormal lipids are often increased and sustained for many years or decades.
HIV and Lipids
HIV itself (before treatment) reduces both good and bad cholesterol and triglycerides are higher. Starting treatment with any combination will reverse these lipid effects as part of a return-to-health effect.
Because many HIV drugs and lifestyle factors affect lipids this is complex to interpet.
Testing and Monitoring
Cholesterol and triglycerides should be checked when you are first diagnosed. They should also be checked before starting or changing treatment and then three months after any change.
Routine monitoring for someone on stable treatment should then involve testing lipids every 6-12 months.
Most clinics will do this at the same time as your CD4 and viral load, but you may need to ask whether this is being done. These tests are best done fasted (on an empty stomach) so don't eat or drink anything before your have your blood taken on those days.
Management of lipid levels should be part of an assessment of your risk for heart disease. This is also related to other risk factors, including lifestyle factors.
Lipids are first managed by diet and exercise, then by switching HIV treatment and then by using lipid lowering drugs.
Total cholesterol (TC) is measured first. If these results are high then a further test will break this down into two different types of cholesterol:
- High Density Lipoprotein (HDL) is 'good' cholesterol. It removes fats from your arteries.
- Low Density Lipoprotein (LDL) is 'bad' cholesterol. It is a small molecule that carries fats from the liver to other parts of your body and can lead to heart disease.
Target levels for total and LDL cholesterol and desirable levels for HDL cholesterol and triglycerides are shown in Table 5. Target levels are lower for people who already have high cardiovascular risk due to other factors. Each reduction in LDL by 1.0 reduces the risk of cardiovascular mortality by 20%.
The TC:HDL ratio is used to determine the importance of using lipid lowering drugs, but is not used for monitoring afterwards.
|Table 5: Target/Desirable Levels for Fasted Lipids (EACS Guidelines)|
|Total cholesterol (TC)||Less than 5.0 mmol/L (under 4.0 if high risk)|
|LDL cholesterol||Less than 3.0 mmol/L (under 2.0 if high risk)|
|HDL cholesterol||Higher than 0.9 mmol/L|
|Triglycerides||Less than 1.7 mmol/|
|Table 6: Factors That Can Affect Cholesterol and Triglycerides|
|HIV||TC is lower and TG is higher before HIV treatment|
|HIV treatment||Some drugs affect cholesterol (LDL and HDL) and TG|
|Ageing||Ageing can increase cholesterol and TG|
|Smoking||Smoking increases LDL. Quitting increases HDL and reduces TG|
|Diet||Diet affects blood lipids|
|Exercise||Exercise has a good impact on lipids|
|Other infections||Other health conditions can affect lipids.|
Key: TC = total cholesterol; TG = triglycerides; HDL = high density lipoprotein ("good cholesterol"); LDL = low density lipoprotein ("bad cholesterol"); TC:HDL ratio is often more important than individual levels, with a target of 4.5 or less. Note: HDL are large particles that can pick up LDL to be broken down and eliminated from your body. LDL are small particles that have a higher risk of getting stuck and causing a blockage.
Some guidelines see triglycerides (TG) as an independent risk factor for heart disease. Others state that the evidence for treating moderate triglycerides is less strong.
In the D:A:D study, most of the impact of high triglycerides was explained by other risk factors, but this still remained at +10% per year.
Although there is a lot of individual variability, target fasted levels of under 2.2 mmol/L are considered normal and of 2.2-4.4 mmol/L are borderline. Above this, the risk of heart disease increases.
Levels above 10 mmol/L are very high and need urgent treatment due to the increased the risk of pancreatitis.
Although less that 1.7 mmol/L is a target, treatment would not usually be used unless levels are over 2.3 mmol/L.
Changing HIV Drugs in Your Combination
Lipids generally improve after switching away from HIV drugs that have caused this change.
This usually involves switching from a protease inhibitor (PI) to nevirapine, raltegravir or to another PI that affects lipids less (atazanavir/r or darunavir/r). Tenofovir has a slighter better lipid impact compared to abacavir.
Nevirapine may help by increasing HDL (good cholesterol). The boosting dose of ritonavir to some extent reduces the benefits of protease inhibitors with better lipids profiles.
The debate on the impact of different strategies on reducing risk for heart disease is likely to develop and change over the next few years.
The choice of switch drugs will depend on your previous treatment history and previous history of resistance.
Treatment and Management
Options to improve lipids include lifestyle changes (diet etc), switching HIV meds and using lipid lowering drugs.
Cholesterol and triglyceride levels can often be improved by diet changes (especially reducing saturated fat, trans fat, cholesterol and alcohol and increasing fibre) and by starting or increasing exercise.
Weight loss, if you are overweight, will have a positive impact on lipids too.
Omega-3 can reduce triglyceride levels. Taking a supplement may be more effective that just changing diet.Â For example, a 4 gram (g) daily dose Omacor, (90% omega-3 acid ethyl esters) is equivalent to 150 g mackerel or 700 g tuna or 1.1 kg cod or 280 g salmon or 1.7 kg eel or 850 g shrimps.
Lifestyle targets for the general population for people at risk of heart disease or diabetes are listed in Table 7.
|Table 7: Lifestyle Targets to Reduce Risk of Heart Disease (From the UK Guidelines)|
|1||Do not smoke|
|2||Maintain ideal body weight for adults (body mass index 20- 25 kg/m2) and avoid central obesity (waist circumference in white caucasians less than 102 cm in men and less than 88 cm in women (for Asian/Oriental people this is less than 90 cm in men and less than 80 cm in women)|
|3||Keep total dietary intake of fat to (30% of total energy intake)|
|4||Keep the intake of saturated fats to (10% of total fat intake)|
|5||Keep the intake of dietary cholesterol to less than 300 mg/day|
|6||Replace saturated fats by an increased intake of monounsaturated fats|
|7||Increase the intake of fresh fruit and vegetables to at least five portions per day|
|8||Regular intake of fish and other sources of omega 3 fatty acids (at least two servings of fish per week)|
|9||Limit alcohol intake to less than 21 units/week for men or less than 14 units/ week for women|
|10||Limit the intake of salt to less than 100 mmol/l day (less than 6 g of sodium chloride or less than 2.4 g of sodium per day)|
|11||Regular aerobic physical activity of at least 30 mins per day, most days of the week, should be taken (for example, fast walking/ swimming)|
Source: JSB2 guidelines, 2003
Lipids generally improve after switching away from HIV drugs that cause this side effect.
If diet, supplements, exercise and switching treatment (if appropriate) are not enough, then lipid-lowering drugs are generally more effective. They are widely used and have a low risk of side effects. Fibrates reduce triglycerides and increase HDL cholesterol and statins reduce LDL cholesterol.
Lipid-lowering drugs need to be prescribed by an HIV-specialist as they can interact with HIV drugs. For example some statins should never be used and some require increased or decreased dosing when used with PIs or NNRTIs.
Studies are also looking at metformin (an insulin sensitising drug), rosiglitazone and growth hormone.
A study of HIV positive men looking at the effects of exercise and testosterone found that testosterone significantly reduced levels of â€˜goodâ€™ cholesterol (HDL). This is a concern for people with lipodystrophy who already have elevated triglycerides and â€˜badâ€™ cholesterol (LDL).
Although muscle gain and fat loss were greater in the testosterone group, levels of good cholesterol increased in people who used exercise without testosterone, and this may be more appropriate for people with lipodystrophy.
Although anabolic steroids can increase muscle mass they can also reduce fat, and have the potential to worsen lipoatrophy and lipid levels.
European AIDS Clinical Society (EACS) metabolic guidelines
ESC/EAS Guidelines for the management of dyslipidaemias (Eur Heart Jour, 2011)
Increased Blood-Sugar Levels and Risk of Type 2 Diabetes
Associated drugs: some protease inhibitors and some nukes
Glucose and Insulin
Glucose is a type of sugar. Your body relies on glucose to provide energy. A hormone called insulin processes the sugar and allows it to enter cells.
Insulin also regulates production of new glucose by the liver, levels of glucose in the blood, and metabolic aspects of fat cells.
Insulin resistance is the term for when this system fails to work properly. Although your body produces more insulin to compensate, if insulin resistance continues, and sugar levels remain high, you can develop diabetes.
Insulin levels are difficult to measure, but glucose levels, usually checked by fasting or non-fasting blood tests, are routinely used for monitoring risk.
Types of Diabetes
Type-2 diabetes mellitus (T2DM) is an adult illness that usually develops slowly. It can take years or decades for mild insulin resistance to progress to diabetes, but the impact on the risk of heart disease is serious.
Some protease inhibitors can increase glucose levels and the risk of Type-2 diabetes.
Type-2 diabetes is different from Type-1, which is caused by low insulin production, often in childhood, and which is managed by insulin injections.
Risk of Long-Term Health Problems
High untreated blood-sugar is related to many long-term health problems. This can include the kidneys, nerves, eyes and vision, risk of heart disease and stroke, erectile dysfunction in men and pregnancy complications in women.
Diabetes can increase the risk of having a heart attack as much as smoking.
Fat and sugar metabolism are also closely linked and insulin resistance is a complication of HIV therapy that is getting more focus. It is directly related to some protease inhibitors and possibly indirectly related to older nukes through their effect on fat distribution. Changes in blood glucose levels and insulin sensitivity are closely related to other symptoms of lipodystrophy.
What Can Help
As with HIV-negative people, mild insulin resistance can be managed by diet, exercise and stopping smoking. Switching HIV drugs associated with increases in blood-glucose is recommended when appropriate.
Dietary advice involves reducing processed sugars, refined and fast foods, white flour and potatoes as they all cause quick sugar 'highs'. Complex carbohydrates (wholemeal bread, wholemeal and al-dente pasta, porridge, most vegetables) provide energy more slowly with less impact on sugar levels.
Metformin may help people with insulin resistance and fat accumulation. Pioglitazone may help people with insulin resistance and fat loss. Drug interactions with HIV drugs (PIs and NNRTIs) means that drug-level monitoring (TDM) should be used to confirm dosing.
Symptoms of High Blood-Sugar, and Diabetes
- Feeling thirsty or excessively hungry
- Feeling tired
- Low concentration
- Blurred vision
- Unexplained weight loss
- Frequent need to urinate
- Slow healing of cuts
- Tingling in hands or feet (neuropathy)
- Nausea and vomiting
Risk Factors for Abnormal Glucose
- Liver damage or coinfection with hepatitis C
- Family history of diabetes
- Overweight (BMI higher than 30)
- Lipodystrophy or lipoatrophy
- Low exercise
- Age over 40
- High blood pressure (over 130/85 but this depends on age and other risk for heart disease)
- High cholesterol and triglycerides (over 1.7 mmol/L) and low HDL (good) cholesterol (less than 0.9 mmol/L)
- History of insulin resistance or high glucose
- Other meds, including niacin, glucocorticoids, megestrol and Growth Hormone and some PIs
Tests to Diagnose and Monitor Glucose and Insulin Levels
Fasting glucose test
Measures blood sugar after an 8-hour fast. This should be measured before starting and after switching treatment, and at least annually after this.
Fasting levels over 5.6 mmol/L in plasma indicate insulin resistance, and the need for an oral glucose tolerance test (OGTT).
Random glucose test
Unfasted glucose levels are less accurate but are taken shortly after someone has had something to eat or drink. If it is greater than 5.17 mmol/L other tests are run. Diabetes is over 11.1 mmol/L.
Oral glucose tolerance test (OGTT)
Monitors levels of glucose every 30-60 minutes for two hours after fasting for 8-hours and then drinking a measured glucose drink. Healthy glucose on this test should be less than 3.62 mmol/L. If it is greater than 5.17 mmol/L other tests are run. Diabetes is over 11.1 mmol/L.
This tests how much glucose adheres to red blood cells. It is used to determine average glucose levels over several months. Normal range for someone without diabetes is 4-6% and managed treatment for someone with diabetes should aim to keep this under 7%.
Fasting insulin test -- and results used to calculate HOMA-IR score (Homeostatic: Model Assessment-Insulin Resistance).
Measuring glucose is generally preferred to measuring insulin directly.
Insulin tolerance test (also called glycemic clamp)
This is where insulin is infused by intravenous line, and glucose given until normal blood sugar levels are reached. This is expensive and again is rarely used.
European AIDS Clinical Society (EACS) metabolic guidelines