As we age, there are common body changes that often result in physiological vulnerabilities and medical conditions as well as an increased risk of illnesses and diseases. For people with HIV, there is the added complexity of hidden effects from the virus itself or from the medications used to control HIV and prevent complications. It is not always possible to sort out a single cause for a specific problem in each individual, and multiple factors probably interact to influence the outcome. In this article I will discuss the effects of common aging processes, the known effects of the virus, and the results of certain HIV treatments. Fortunately, in many cases it is possible to address these comorbidities in beneficial ways.
The Immune System
Aging: Early in life, the thymus gland -- which produces CD4 and other immune cells -- begins to shrink, and the number of such cells diminishes as we grow older.
HIV: The virus attacks CD4 cells, and their reduced number makes people with HIV more vulnerable to infection, especially those who are older. So a normal process is accelerated and results in immunosenescence, or premature aging of the immune system.
Treatment: Combinations of HIV meds known as HAART (highly active antiretroviral therapy) can reduce but not eliminate the ongoing damage to CD4 cells. Sometimes older patients do not restore their CD4 counts to as high a level or as quickly as younger patients.
Aging: There is a gradual loss of muscle (lean body mass) with aging. Some of this is unavoidable (for example, longer completion times for older runners), but disuse as the result of a sedentary lifestyle also contributes. In addition, there is a redistribution of fat with more collection in the belly area, especially in men. This is the result of fat depositing around the abdominal organs, not under the skin. There is some loss of fat under the skin in the face and limbs.
HIV: Although in earlier days there was HIV-associated wasting disease, with HIV treatment there may not be enough virus left to affect muscle tissue directly. Disuse and disability are the more likely culprits. Sometimes the effect of peripheral neuropathy (nerve damage in the hands and feet) can mimic muscle problems when walking. HAART has been linked to changes in body shape (see article).
Treatment: Newer HAART regimens, at least in developed countries, have replaced those most likely to cause unwanted body changes, but switching drugs may not change body shape. Even when these drugs are avoided from the onset of therapy, there are still other contributing factors. Recently there has been increased use of products that can be injected under the skin of the face to replace lost fat cells.
Aging: Loss of bone, especially for women during and after menopause, is quite common and can occur in men at older ages.
HIV: There are some reports of accelerated bone loss in people with HIV, and studies are under way using sophisticated measures to determine how frequently this occurs.
Treatment: Calcium tablets in addition to high-calcium diets have been recommended. In cases of major bone loss (osteoporosis), there are medications that can be taken a few times or even just once a month to reverse the condition.
Aging: Because liver cells regularly rejuvenate themselves, the adverse effects of aging per se on this organ are minimal. What is more likely the cause of liver damage is the chronic abuse of alcohol or Tylenol (acetaminophen).
HIV: Although the virus may be present in liver cells, most damage is from the common coinfection with hepatitis, especially hepatitis C. HIV meds can also lead to liver problems, particularly Viramune (in women with higher CD4 counts) and Aptivus.
Treatment: Besides recommending alcohol and drug abstinence, it is possible to treat hepatitis with available drugs or to avoid hepatitis A and B with a vaccine. Switching HIV meds may be necessary in some cases.
Aging: The kidneys are major organs for detoxification, and usually operate quite adequately even at older ages. Most reported problems with kidney function are complications of other conditions, such as high blood pressure, diabetes, or recurrent urinary tract infections.
HIV: HIV has been associated with a specific type of kidney disease known as HIV-associated nephropathy. Although this condition is relatively uncommon, it appears to be more frequent in African-Americans than in other groups.
Treatment: HAART has resulted in some improvement in kidney function. Viread has been linked to minor loss in kidney function and should be avoided in people with kidney problems.
Aging: It is common to see a rise in blood pressure at older ages due to stiffening of the arteries. This is most evident with systolic blood pressure (the top value when reported), which increases cardiovascular risk. Diastolic blood pressure (the lower number) may stabilize with age, but elevations occur, leading to a diagnosis of high blood pressure (hypertension). Weight gain and salt intake over time are also factors.
HIV: It is controversial whether HIV itself can affect blood pressure, but HIV drugs can increase blood lipids (see below), leading to hypertension.
Treatment: Guidelines for treatment of hypertension have been established, and lowering blood pressure, both systolic and diastolic, has been found to decrease the risk of heart attack and stroke. Most blood pressure drugs can be used in people taking HIV meds, although the class called calcium channel blockers can be problematic with certain protease inhibitors.
Lipids (Blood Fats)
Aging: There tends to be an increase in cholesterol, including low density lipoprotein (LDL) cholesterol, or "bad" cholesterol, in people over 40. This rise may represent the cumulative effect of a high-fat diet in a genetically vulnerable individual. High density lipoprotein (HDL) cholesterol, or "good" cholesterol, is more stable. Both have an effect on the risk of heart attack. Triglycerides are the other major class of lipids, but the associated risk of heart attack is less definite.
HIV: In people who have progressed to AIDS, total cholesterol and LDL cholesterol tend to be lower. Successful HAART regimens usually restore lipid levels. Certain protease inhibitors, however, have been shown to elevate cholesterol and triglycerides, possibly leading to hypertension.
Treatment: Most experts recommend continuing the HAART regimen but adding a statin drug, such as Pravachol, but certain other statins interact with protease inhibitors and should be avoided. Another class of drugs, called fibrates, might be necessary if triglycerides remain substantially elevated. Switching to a different protease inhibitor or to a non-nucleoside reverse transcriptase inhibitor are other alternatives. As with blood pressure, cholesterol-lowering guidelines exist and it makes sense to apply them to people with HIV.
Aging: As we age, there is a tendency for problems in the way sugar is handled by the body, because the insulin necessary for metabolism is less effective. This can lead to diabetes, especially in those who are obese or have a family history of diabetes. In other individuals it is identified only with administration of a special test (a glucose tolerance test) and may not be a major problem. If this glucose abnormality is coupled with obesity, hypertension, high triglycerides, and low HDL cholesterol, it is referred to as the "metabolic syndrome."
HIV: Treatment with protease inhibitors has been associated with glucose intolerance. Such treatment could exacerbate a tendency toward the metabolic syndrome.
Treatment: If possible, a switch in regimen can be considered. With a successful HAART regimen, however, it may be better to continue the therapy and attempt to control glucose intolerance with weight reduction, exercise, and dietary changes. Such a strategy would also improve lipid and blood pressure abnormalities. There are also medications that are quite effective in controlling blood sugar.
Aging: In developed countries, the frequency of atherosclerosis (hardening of the arteries) and myocardial infarction (heart attack) increases with age. This is believed to be the cumulative effect of lifestyle and genetic factors present for a lifetime, rather than irreversible changes that are age-related. Besides hypertension, abnormal blood lipids, and diabetes, smoking is a strong predictor of cardiovascular disease and cancer.
HIV: Recent reports suggest that there may be an increase in the frequency of heart attacks in people with HIV. Although initially it was thought that this was most likely the result of the effect of HAART on cardiovascular risk factors, more recently it has been suggested that the virus itself may be having a direct negative effect on cardiovascular disease frequency.
Treatment: This observation would suggest that optimal HAART therapy is the best approach to minimizing heart attack risk, as well as continuing to address the known cardiac risk factors where possible.
Since HIV infection has become more controllable with HAART regimens and the life expectancy of people with HIV has increased, the issue of dealing with the comorbidities of aging has become much more important. Successful treatment should lead to longer life and successful aging for people with HIV.
Richard Havlik is a medical epidemiologist formerly with the National Institute on Aging.