Lipodystrophy and Women
Of all the unintended effects from taking anti-HIV therapy, perhaps none is more visible than lipodystrophy. Lipodystrophy can diminish a person's physical and emotional well-being, leading to an increased risk of heart disease, diabetes and depression. This issue of Wise Words explains the many aspects of this condition. The cover article provides a brief overview of lipodystrophy, including a discussion of its effects on women living with HIV.
What Do We Mean by Lipodystrophy?
Lipodystrophy is an umbrella term, covering three separate and possibly related changes in the way our bodies handle fat cells. Lipodystrophy includes both gains and losses in the body's stores of fat and changes in the amount of fat circulating in the blood. Scientists haven't yet agreed on the best way to measure or describe these dysfunctions and predicting who is at most risk for them is difficult.
Soon after the introduction of powerful anti-HIV therapy, there was an increase in reports of body shape changes. Abdominal (tummy) fat gain (truncal or central obesity) was among the first complication noticed. The abdominal fat gained is underneath the muscle wall (visceral fat) and feels firm to the touch, as opposed to under the skin (subcutaneous) and soft to the touch. This softer fat is what most people accumulate with typical weight gain.
People also began noticing gains in fat on the back on the neck (buffalo hump or dorsal fat pad), around the neck, and underneath the breasts. The term used by doctors for all these kinds of fat gains is lipohypertrophy. Some people with HIV experienced these body shape changes before the availability of potent anti-HIV therapy, but it was not happening at the rate seen afterwards.
While some people gained unwanted fat, others lost fat in very specific areas -- most commonly the face, arms, legs and butt. The medical term for this is lipoatrophy and is sometimes called peripheral wasting or facial wasting. This condition has been observed since the early days of HIV and since the very first anti-HIV drugs were used.
Fat in the Blood
Lastly, doctors began noticing increases in the amount of certain fats -- called cholesterol and triglycerides -- circulating in people's blood. This is known as hyperlipidemia or dyslipidemia, and it has been linked to higher rates of heart disease and diabetes-like symptoms. Before the availability and use of anti-HIV drugs, HIV disease progression was associated with decreases in cholesterol levels, particularly "good" cholesterol. An increase in this blood fat is uniquely associated with using certain anti-HIV drugs.
What Causes Lipodystrophy?
At various times, lipodystrophy has been blamed on individual drugs, entire drug classes, and HIV itself. Despite ongoing research, its cause(s) remain uncertain. However, some important observations have been made.
Several studies show a strong link between using protease inhibitors (PIs) and dyslipidemia. Research suggests that some PIs pose more of a risk, most notably ritonavir (Norvir) and Kaletra (lopinavir+ritonavir).
A number of studies have linked nucleoside analogue (NRTI) drugs to lipoatrophy, especially d4T (stavudine, Zerit). Moreover, using NRTIs has been associated with a change in the way cells store and use energy (mitochondria) and with accumulation of fat in the liver.
Although some links have been observed between anti-HIV drugs and symptoms of lipodystrophy, no cause and effect relationship has been established. There are several theories on the root cause of lipodystrophy -- including damage to mitochondria and immune system recovery. Some researchers believe that each of the three dysfunctions described above may have similar but different causes. Until there is better and more convincing research, we cannot know for sure. For more information about mitochondrial toxicity, call Project Inform's Infoline.
What About Lipodystrophy and Women?
Both men and women can experience any of the symptoms of lipodystrophy. Some studies show small differences in the overall rate of lipodystrophy, with women having a somewhat higher risk. Other studies show no difference.
However, women can experience lipodystrophy differently than men. Women seem more likely to experience breast enlargement and overall weight gain. They may be less likely to have facial wasting and higher levels of cholesterol and triglycerides.
Lactic Acidosis and Liver-Related Problems
A relatively rare but serious side effect is the build-up of lactic acid in the body, called lactic acidosis. One result of this is liver problems, including liver enlargement (hepatomegaly) with fat deposits (fatty liver or steatosis). This could result in liver failure and death. Symptoms of lactic acidosis include lab abnormalities, severe nausea, vomiting, and shortness of breath. Although a risk for lactic acidosis and liver problems is associated with all NRTIs, it may be even more of a concern with using specific ones, including d4T and d4T + ddI (didanosine, Videx). People who are overweight and/or those who have used NRTIs for a long time are at greater risk for this side effect. Women, particularly overweight women, appear to have greater risk for this side effect than men. The risk for severe (and possibly fatal) lactic acidosis appears to be greater among pregnant women who are using anti-HIV therapy that includes d4T and ddI.
Why Does Lipodystrophy Matter?
Lipodystrophy can have profound effects on physical well-being. Fat increases can have several effects, from a greater likelihood of diabetes and heart disease to developing sleep disorders, which carry their own health risks. Increases in cholesterol and triglycerides are believed to lead to a higher risk of heart disease. Indeed the research is showing an increased risk of heart disease for people living with HIV, especially those taking anti-HIV drugs.
The emotional impact of lipodystrophy is also critical. Lipodystrophy can change the way our bodies look, including perhaps the most personal and identifiable part of us, our face. These changes can make people feel marked by their disease and can lead to social isolation and depression. This can be particularly hard for people who want to keep their HIV status secret. Fear of lipodystrophy is a common reason for delaying or not taking anti-HIV therapy.
Lipodystrophy remains one of the great mysteries of HIV disease. While important research continues, more is clearly needed. There have been advances in treating fat accumulation (see Human Growth Hormone below), cosmetic treatments for facial wasting, some success with changing therapy, and recent guidelines published for treating dyslipidemia. More research will hopefully lead to further advances toward preventing and treating lipodystrophy.
Human growth hormone (HGH) is also known as somatropin (Serostim). HGH is approved in the U.S. for treating AIDS-related wasting syndrome. HGH is currently being researched in a large study as a way to treat lipodystrophy. It is believed that HGH may help reduce the amount of fat accumulating in the gut, breasts and back of the neck in people with lipohypertrophy. The study also hopes to learn whether low-dose maintenance therapy will keep the fat from returning. HGH is typically used once a day. The drug must be injected under the skin either using a needle or a coiled spring mechanism that injects drug (without a needle) in a pressure stream.
Limitations and Side Effects
Though HGH may prove useful for treating lipohypertrophy, it does not cure it. One side effect is higher glucose (sugar) levels in the blood, which may worsen or increase risk of diabetes. Others include muscle and joint pain, swelling of the hands/feet, and carpal tunnel syndrome (pain, numbness and tingling in the hands/wrists). HGH may also stimulate a tumor to grow. So if you have tumors or cancers that are not under control, HGH should not be used. HGH also increases HIV replication in test tubes, so people taking it should be on effective anti-HIV therapy.
Our Current Situation
It will be some time before early results will be available from this large study. Until then, this use of HGH will remain "off-label". This means that a doctor can write a prescription for HGH, but it is not approved by the FDA for treating lipohypertrophy.
Since HGH is not approved for treating lipohypertrophy, it may be difficult or impossible to get it paid for or reimbursed by insurance or other payment programs. It is very expensive. The high cost and difficulty getting programs to cover HGH makes it a prime target for fraud. You may have seen ads for over-the-counter, "herbal" or "natural" HGH or substances that claim to increase the body's production of HGH. These products are NOT the same as the HGH you get with a doctor's prescription, and many if not all are highly suspect.
If you have lipohypertrophy, you can talk to your healthcare provider about whether HGH may be an option. If you have other questions, call Project Inform's Infoline at 1-800-822-7422.
There are currently no drugs approved to treat the causes of lipoatrophy. Studies have found that people with lipoatrophy who take a regimen with d4T can reverse fat loss to some degree by swapping it with abacavir (Ziagen). Switching from d4T to tenofovir (Viread) may produce similar results. Because d4T is believed to be a major culprit in lipoatrophy, avoiding it or switching to a viable substitute drug if lipoatrophy is a problem may be a reasonable thing to try.
Sculptra: One Treatment for Facial Wasting
The accumulation of fat around the abdomen, breasts and neck (called lipohypertrophy) is a significant and visible problem for people living with HIV.
Increases in the amount of certain fats, called cholesterol and triglycerides, circulating in the blood is called hyperlipidemia. Hyperlipidemia is a problem for many people living with HIV who are taking or have taken anti-HIV drugs. Mounting evidence suggests that this increase in blood fats puts people at an increased risk of heart disease.
What to Do: Prevention
This article was provided by Project Inform. It is a part of the publication WISE Words. Visit Project Inform's website to find out more about their activities, publications and services.