In the past, organ transplantation usually has not been recommended in HIV+ people because of the fear that the transplant surgery and necessary immune-suppressive drugs would cause HIV disease to get worse. Also, there were concerns that HIV+ patients would not live long enough to justify the transplant. The widespread use of combination HIV drugs has improved the health of HIV+ patients, but also increased the chance of developing liver and kidney disease as HIV-infected people are living longer. Recently, researchers have begun to reconsider liver, kidney, and heart transplants in HIV+ patients.
One study, published in the journal Transplantation (76:2, p. 370, 2003), reported on 10 patients who received kidney transplants and 4 patients who received liver transplants. All patients had stable HIV disease, good T cell counts, and no history of an opportunistic infection or cancer. All patients who received a kidney transplant survived, while one liver-transplant patient died after complications from hepatitis C co-infection. Organ rejection (when the body's immune system fights the new organ) occurred in half of the kidney-transplant patients, but none of the liver-transplant patients. In general, there was no worsening of the HIV following the transplant in patients who took combination HIV therapy.
In addition, a study in The New England Journal of Medicine (348:23, p. 2323, 2003) reported a successful heart transplant in a patient with AIDS and serious heart problems, but who was responding well to HIV therapy. The patient previously had Kaposi's sarcoma (a type of skin cancer that is associated with AIDS) and the chemotherapy used to treat it may have caused the damage to his heart. Two years after the heart transplant, the patient is generally feeling well. However, he has suffered some complications, including anemia (that requires blood transfusions) and frequent episodes of rejection. While these results are promising, organ rejection and co-infection with hepatitis are still major problems in HIV+ transplantation recipients. In addition, there are complex and potentially dangerous interactions between HIV drugs and drugs used to prevent organ rejection. Regardless, these reports show that HIV+ status should not automatically disqualify someone from life-saving organ transplantation.
HIV-associated dementia (HAD) is a progressive brain problem that causes confusion, loss of memory, difficulties in thinking, and trouble keeping balanced. HIV-infected monocytes (a type of immune cell) carry HIV into the brains of infected people. These cells may release a substance that damages the brain and causes symptoms of dementia. Currently, doctors can only determine if a person is suffering from HAD by performing an MRI or lengthy medical evaluation. In a study described in the journal Neurology (60, p. 1931, 2003), researchers examined 21 HIV+ women and showed that HIV+ patients with HAD have a unique protein pattern compared to HIV+ patients without signs of HAD. One day, this new technique called "proteomic fingerprinting" (proteomics is the study of proteins) may allow doctors to find out if a person has initial signs of HAD by simply doing a blood test.
Lipodystrophy is common in many HIV+ people and can even affect HIV+ patients who have never taken HIV drugs. In addition, this condition is associated with other problems such as dyslipidemia and insulin resistance, which can lead to future heart problems. Researchers studied the effects of diet and exercise on lipodystrophy and metabolic changes in 120 people with HIV. They published their findings in the journal Clinical Infectious Diseases (36, p. 1593, 2003). Study participants completed questionnaires about their diet and exercise habits. These results show that diet and exercise can have a positive effect on some metabolic problems. While numerous dietary factors were studied, only vitamin E intake (from food and vitamin supplements) had any positive effect, including decreased amounts of body fat, possibly decreased insulin resistance, and improved blood pressure. Exercise led to decreased levels of triglycerides (a type of fat that travels in the blood), but did not decrease cholesterol. Exercise also increased muscle mass and possibly decreased insulin resistance. Another study, published in the Journal of Acquired Immune Deficiency Syndromes (33, p. 605, 2003) reported that antioxidant supplements (vitamin E, vitamin C, and N-acetyl cysteine) did not have a major effect on body fat changes in HIV+ patients with lipoatrophy (loss of body fat in areas such as the arms, legs, face, and buttocks). In addition, vitamin supplementation with these antioxidants was linked to increased insulin resistance, in contrast to the first study discussed above. However, this study was very small (10 patients) and sensitive imaging techniques, such as MRI or CT scans, were not used to measure changes in body fat.
A recent report in the journal AIDS (17, p. 1857, 2003) described 4 HIV+ patients with lipodystrophy who also had excess fat accumulation at the front of the neck. Currently, diagnosing the severity of lipodystrophy is difficult because both doctor and patient reports can vary. Machines that scan the body, such as computed tomography (CT) or dual-energy x-ray absorptiometry (DEXA), are more objective and less variable, but these scans can be expensive and the measurements they provide depend on the sex of the patient. This can be problematic since body fat composition differs considerably between men and women. In addition, fat loss of the face cannot be measured by these scans. A study in the Journal of Acquired Immune Deficiency Syndromes (33, p. 571, 2003) describes a scoring method, called the Lipodystrophy Case Definition (LDCD) score that may provide a better way to diagnose and to measure the severity of lipodystrophy in both men and women. The LDCD score uses several different categories that account for age, sex, stage of HIV by Centers for Disease Control and Prevention (CDC) classification, length of time of HIV infection, cholesterol level, waist-to-hip size ratio, trunk-to-limb fat ratio, percentage of leg fat, and other measurements. When researchers tested the scoring method in 417 patients with lipodystrophy and 371 patients in a control group with no signs of lipodystrophy, the LDCD score proved to be very accurate. The use of a scoring method like the LDCD score will be very helpful for large studies so that scores can be compared to one another more accurately.
Cytomegalovirus (CMV) is a common co-infection in HIV+ people and can lead to serious and even fatal opportunistic disease of the eye, colon, esophagus, and brain. While the occurrence of CMV-related organ disease has dramatically decreased since the introduction of powerful combination HIV therapy (also known as highly active antiretroviral therapy or HAART), it still affects HIV+ patients. A recent study, published in the journal Clinical Infectious Diseases (37, p. 567, 2003) wanted to find out which HIV+ patients were still at risk for developing CMV-related organ disease in the HAART era (roughly since 1996). Researchers examined 403 HIV+ people and found that CMV-related organ disease and death tended to occur in patients with low T cell counts and high viral loads. In addition, higher levels of CMV DNA in the blood also made a patient more likely to have organ disease or to die of organ disease. The researchers recommend screening for CMV DNA levels in HIV+ patients with low T cell counts and high viral loads because medications may stabilize the CMV infection and lessen the chances of getting CMV-related organ disease.
On the flip side, HAART can cause immune recovery, which is typically a "good thing;" however, this can lead to conditions such as "uveitis" or inflammation of the eye. A separate study, published in the British Journal of Ophthalmology (87, p. 853, 2003), examined 63 patients with CMV-related retinitis (inflammation of the retina of the eye) that had been previously treated and had healed. Unfortunately, in many of these patients, HAART also caused a variety of other inflammatory conditions, including cataract and glaucoma, which led to moderate to severe loss of vision.
The majority of patients who have had long-term viral control during the first 18 months of combination HIV therapy (also known as highly active antiretroviral therapy or HAART) are still alive 5 years later, compared to patients who had viral rebound or who did not respond to treatment, according to a study published in the Journal of Acquired Immune Deficiency Syndromes (33, p. 321, 2003). The researchers also examined cases of diabetes and hyperlipidemia (excess fat or lipids in the blood), conditions that are risk factors for heart disease and linked to the use of HAART. They found that the longer a patient received HAART, the more likely they were to develop these conditions. As a result, patients who achieved and maintained viral control developed these conditions more frequently because they consistently received HAART for longer periods of time.
Recent studies have examined structured treatment interruptions (STIs) to see if they are safe and if they benefit HIV+ patients. Giving patients a break from HIV drugs was thought to decrease drug side effects and give the immune system a chance to recover and to better fight HIV. Two recent studies show that STIs are not beneficial and could even be dangerous. One study, published in The New England Journal of Medicine (349:9, p. 837, 2003), examined the effect of STIs in 270 patients who had multi-drug resistant HIV and needed to switch HIV drugs (HAART) to try and control the virus. Patients were divided into 2 groups: those who immediately began a new drug combination and those who stopped taking HAART for 4 months before beginning a new drug combination (STI group). Researchers thought that a treatment interruption would cause the virus to switch from a drug-resistant form to a one that was more "natural" and sensitive to HAART. While this happened for many of the patients in the STI group, more patients experienced a worsening of their HIV disease, including lower T cell counts and higher viral loads, compared to those patients who continued on treatment without an interruption.
Another study, published in the Journal of Infectious Diseases (188, p. 388, 2003), followed patients divided into 2 groups: those who received HAART continuously and those who participated in a treatment interruption (stopped taking drugs for 4 weeks and then received HAART for 8 weeks). This study was stopped early because 5 patients in the STI group developed drug-resistant HIV. No patients who received continuous HAART developed any drug resistance. Overall, the treatment interruptions had no benefit on the patient and there were no significant differences in blood fat levels, liver function, T cell count, or viral load, compared to the patients who received continuous HAART. The development of drug-resistant HIV in these patients shows that STIs could endanger future treatments in these patients.
The idea of alternating HIV drug combinations is not new, but usually patients switch to a new combination after their virus becomes resistant to the first set of drugs. The SWATCH study (SWitching Antiviral Therapy Combination against HIV-1) examined what would happen if patients switched drug combinations before their current drugs actually stopped working. This study, published in the Annals of Internal Medicine (139, p. 81, 2003), examined 161 patients who had never before received highly active antiretroviral therapy (HAART). Patients either continuously received the same HAART regimen or switched between 2 different HAART regimens every 3 months. The researchers found that patients who switched regimens experienced viral rebound less than the patients who stayed on the same HAART. Factors such as T cell count, side effects, quality of life, and ability to take the drugs were the same for all of the patients, regardless of what treatment they received. However, these results must be interpreted with caution because the HIV drugs available today are better than those used when this study was done. In addition, the study did not examine the long-term effects of alternating treatment and how this switching approach might affect the course of HIV disease as well as death rates.
This article was provided by The Center for AIDS. It is a part of the publication HIV Treatment ALERTS!. Visit CFA's website to find out more about their activities and publications.