The AIDS Beacon™

The use of antiretroviral medications has greatly increased the longevity of patients with HIV. However, liver failure, heart disease and neurological changes can often result from its use.

Patients taking protease inhibitors or nucleoside reverse transcriptase inhibitors are at a higher risk of body fat redistribution and heart disease, according to an article published in the New England Journal of Medicine.

Body fat redistribution was evident in 20 to 35 percent of patients after one to two years on antiretroviral medication. Typically, fat accumulates in the mid-section or fat is lost from the face and limbs. Some patients may experience both symptoms. Sex, age and race have been shown to affect the severity. The study showed that fat accumulation was more frequent in women.

Increased levels of fat can accumulate in organs and the blood, increasing the risk of heart disease and diabetes.

The study also showed that older age and lower CD4 count may account for more noticeable fat loss from the body. CD4, or white blood cell count, is typically lower in those with HIV.

Antiretroviral medication is typically given in a combination with three or more other drugs, known as highly active antiretroviral therapy (HARRT). There are currently seven different classes of antiretroviral drugs, each producing a unique set of potential side effects.

The three classes that are most commonly prescribed are nucleoside reverse transcriptase Inhibitors (NRTIs), protease inhibitors, and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Each class of drugs works to target a different part of the HIV replication lifecycle.

During infection, HIV targets CD4 cells by programming these cells to carry out replication of the virus.

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

NRTIs work to inhibit the conversion of RNA (the genetic material of viruses) to DNA. This conversion is necessary for the virus to infect CD4 cells. This class of drugs mimics protein building blocks that convert RNA to DNA and thereby inhibits its conversion by the virus. By preventing this process, new viral cells cannot be produced.

Common drugs in this class include zidovudine (Retrovir), Epzicom (abacavir/lamivudine) and Combivir (zidovudine/lamivudine).

According to HIV InSite, a project by the University of California San Francisco, the most common side effects with these drugs are acidosis, hepatic steatosis and body fat redistribution (as shown in the study by the New England Journal of Medicine).

Acidosis is a decrease in the pH of the blood. Respiratory acidosis, which is an increase of carbon dioxide in the blood, can also occur. This can be potentially dangerous for several reasons, including inadequate delivery of oxygen through out the body. Symptoms can include increased heart rate, shortness of breath and headaches.

Mild acidosis occurs in 10 to 40 percent of patients on antiretroviral therapy, according to AIDSMap, a non-profit organization in England.

Hepatic steatosis is when fat accumulates in the liver. Often, there are no symptoms from this occurrence. If the condition is detected early on, liver damage does not normally occur.

Side effects of Epzicom include a rash in about 50 percent of people, fever, nausea, vomiting and headache. Zidovudine has been shown to cause fatigue, nausea and headache, which normally subside after two to four weeks. Hyperpigmentation, or darkening, of the skin and nails can also occur. Combivir, which has active ingredients from both zidovudine and Epzicom, can produce similar side effects.

Protease Inhibitors

Protease inhibitors work to block the enzyme protease from cleaving protein segments in cells infected with HIV. Without the ability to cut, CD4 cells cannot produce new viruses. All protease inhibitors have gastrointestinal side effects.

Common drugs in this class include Norvir (ritonavir), Kaletra (lopinavir/ritonavir), and Prezista (darunavir).

Side effects may include accumulation of fat in the blood, diabetes and body fat redistribution problems. It also may increase the risk of bleeding in hemophiliacs (individuals who have an inability to form blood clots), according to HIV InSite.

According to AIDSMap, a study in Australia showed that 83 percent of patients taking this class of drugs experienced fat distribution changes. Eleven percent of patients had severe changes.

Prezista has been shown to cause rash and elevation of liver enzymes. Norvir and Kaletra frequently cause nausea, vomiting and diarrhea. Norvir can also have significant interactions with other medications.

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

NNRTIs are similar to NRTIs in that they also affect the conversion of RNA to DNA. However, instead of mimicking protein building blocks, NNRTIs bind directly to the enzyme reverse transcriptase and therefore does not allow DNA to be formed.

Common drugs in this class include Rescriptor (delavirdine), Sustiva (efavirenz) and Viramune (nevirapine).

HIV InSite listed rash and toxic epidermal necrolysis, or cell death to the top layer of skin, as frequent side effects.

Rescriptor is less potent than other drugs in this class and therefore is not as commonly used as Sustiva or Viramune. It has been shown to cause nausea and vomiting. Side effects of Sustiva include drowsiness, confusion, abnormal dreams and abnormal levels of fat in the blood (which can lead to heart problems). Viramune has been shown to cause rash and liver failure.

Dealing With Side Effects

Continuation of some form of drug therapy is the best way to prevent HIV from developing into AIDS. However, certain side effects may be severe enough to warrant discontinuation or alteration of medications.

Dietary changes, exercise and cholesterol-lowering medications may be used to counteract concerns of heart disease in patients taking protease inhibitors or nucleoside reverse transcriptase inhibitors. In people with prior elevated risks for heart disease, a physician may have other recommendations, such as the use of a different class of drugs.

Symptoms of nausea, vomiting and diarrhea should be discussed with a physician. These could be signs of liver damage. In some cases, symptoms will subside or a physician may decide to change medication.

Body fat redistribution can be treated in several ways. Dietary changes or certain medications such as Glucophage (metformin) may be ordered for those who have fat accumulation in their body. For those who appear to be losing fat, injections of human growth hormone may be given.

As always, side effects that do not subside should be discussed with a physician to determine what necessary actions should be taken.

For more information on the heart disease and fat abnormalities, visit the article in the New England Journal of Medicine.