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Sunday, September 03, 2006

Epidemiology of HIV / AIDS Long Term Survival Rates : Who Lives the Longest and Why?

Introduction To address the question “What is the epidemiology of people who live the longest with the HIV virus?” it is necessary to specify operational definitions. While HIV/AIDS has received a great deal of media attention over the years, variations in concepts related to long-term survivorship exist.
HIV and AIDS
The first concept is that of the AIDS (Acquired Immune Deficiency Syndrome) virus itself. HIV ( Human Immunodeficiency Virus) is the virus responsible for AIDS (According to the Centers for Disease Control although there are those who disagree). The term AIDS refers to the last stage(s) (generally stages 4 to 5) of HIV infection. The AIDS virus is actually two separate viruses: HIV-I and HIV-2. HIV-1 was formerly known as HTLV-3 and is associated with the development of AIDS in Africa, North and South America, and Europe. HIV-2 is found predominately in West Africa. There is speculation that variations in the form of the virus may account for some instances of long-term survivalship or that less aggressive sub-types exist.
Although media often uses the terms HIV and AIDS interchangeable, from a clinical perspective a person infected with the HIV virus does not have AIDS until specific criteria are met. In fact, some persons who test positive for HIV remain asymptomatic for years without AZT or protease inhibitors. To address the question “What is the epidemiology of people who live the longest with the HIV virus?” it is important to differentiate between persons who remain asymptomatic for longer than average and those who live longer once diagnosed with full-blown AIDS.

Long-Term Survivors
Five broad categories or stages of HIV infection exist:
ü Initial HIV infection.
ü PGL: Persistently enlarged lymph glands.
ü ARC: AIDS-related complex.
ü Full-blown AIDS
ü AIDS dementia.
The term “long-term survivor”(LTS) in relation to AIDS generally refers to a person surviving three or more years once diagnosed with AIDS. An AIDS diagnosis is made when the immune system fails as represented by one or more opportunistic infections or T-cell (a lymphocyte responsible for immune functioning) count below 200. Increasingly, viral load is used in addition to, or in place of, T-cell count.
The LTS criteria in relation to HIV is less consistent. Stable immuniological markers and high CD 4 and CD 8 counts (CD refers to “cluster determinant”: a cluster of antigens that antibodies react to and characterize the surface markings of a cell) over a 7 to 10 year period generally fall within the HIV LTS criteria. In addition, a separate LTS category exists: Long-Term Non-Progressors. Long-term non-progressors are generally defined as persons infected for 7-10 years who remain asymptomatic without the use of AZT or other medications. Estimates of long-term non-progressors range from less than one percent to approximately ten percent of affected individuals.
The Epidemiology Triangle
The epidemiology triangle serves as a useful example of major factors influencing the survival rates of HIV seropositive persons. In this case, time is the factor in question. The agent, in this case the presence of either HIV-I or HIV-2, is associated with LTS. The host, or the person infected, provides unique genetic material and psychological hardiness associated with LTS; and finally, the environment plays a major role in determining access to medication, health care, and support associated with LTS.
Psychological Hardiness
Consistent with other research into psychoimmunology, several studies have found a positive correlation between “hardy” personality/psychological characteristics and LTS. Long term survivors (LTS) take a more proactive role in treatment, exercise, nutrition, and lifestyle than short term survivors. Stress reduction, interpersonal relationships, coping skills, and realistic disease concept is associated with LTS. Realistic disease concept involves recognizing the diagnosis of HIV not as a death sentence, but rather a long term chronic condition with “highs and lows” which must be managed for optimum health. Termination of poor health habits and involvement in spiritual guidance, volunteer work, or other activities self reported to “give meaning to life” are also positively correlated with LTS.
Conversely, hopelessness; the feeling of powerlessness; continuation of poor health habits such as alcoholic consumption, multiple sexual partners, and drug usage; and social isolation are associated with increased acquisition of opportunistic infections and lower overall immune functioning. However, it should be noted, research in this area is far from conclusive. Psychological “hardiness” is closely related to environmental and physical functioning. Disparities in social support, resources, availability to medical care, and poor health itself may exacerbate the negative aspects of the HIV diagnosis.

Genetic Factors
Some LTS are genetically more “hardy” and naturally secrete proteins (cytokines) that inhibit HIV replication in much the same manner as protease inhibitors. Other LTS are believed to have a less aggressive form of HIV. A strong immune function, the existence of greater numbers of cytokines, neutralizing factors, and specific allele sequences are associated with LTS by providing a natural resistance to HIV. By slowing the replication of HIV in the body, “blocking” the receptor sites, and successfully minimizing the amount of “free floating” virus; the individuals immunity remains functional for longer periods of time. This is particularly interesting when taken with non-use of AZT or other medications as exhibited by many of the LTS. However, protection afforded these individuals is relatively rare. Neutralizing factors apparently provide some degree of protection from the virus but can not be replicated in the laboratory or outside of the individual. Research on specific allele sequences capable of deterring the binding and replication of the virus are intriguing genetic variations which provide a degree of protection to the few individuals with this specific mutation. Currently the production of cytokines is one of the more promising areas of research with protease inhibitors attempting to mimic the genetic hardiness exhibited by LTS.
Despite variations in psychological and environmental attributes, LTS and asymptomatic non-progressors are identified in all cohorts of HIV seropositive populations. It is unknown if asymptomatic non-progressors are a unique subset of individuals possessing a “natural immunity” to HIV, or if they are simply extended LTS who will manifest symptoms at some point in the future. Originally researchers hoped to eradicate HIV through protease inhibitors or naturally induced immune functions, however, the virus continues to reside in the lymph glands after blood levels are indectable. Once protease inhibitors or the immune response is inhibited, the virus begins replicating almost immediately. Still, protease inhibitors and so called “drug cocktails” have proven the most effective treatment for the majority of HIV seropositive individuals. In fact, the use of these drug regimens is now one of the major factors associated with LTS.
Socio-environmental Factors
Socio-economic aspects influence LTS. Although asymptomatic and slow progressors are found in all cohorts of HIV seropositive populations, access to medical care, medications, and education remain major determinants of LTS for the majority of HIV patients. Early detection of opportunistic infections or other health problems, the availability of protease inhibitors and strong social support are positively associated with LTS.
As the use of “drug cocktails” has extended the life of many HIV persons, the environment has become of greater concern than ever. Access to medications is expensive (Approximately $20,000 per year) and unavailable to many clients whose only medical care is state provided. Low income and subsidized housing can further compromise nutritional and environmental stressors. Clients dependent on food stamps are often incapable of providing grooming and other essential necessities for daily living not allocated/allowed in the food stamp program.
Internationally this becomes even more apparent. Countries disproportionately affected by HIV are associated with greater levels of poverty, drug usage, and sexual commerce while least able to address the spiraling effects of the disease.
Summary
My response to the question “What is the epidemiology of people who live the longest with the HIV virus?” is threefold:
1. Long term survivors are more likely to exhibit psychological “hardiness”. Rather than considering the disease in a fatalistic manner, the diagnosis as HIV positive is likely to encourage a LTS to “take stock” in their life to find meaning and fulfillment. They are more likely to engage in exercise and nutrition programs designed to promote health and well-being, educate themselves on treatment options and factors influencing their health, and take a proactive role in their own medical care. Likewise, these individuals are more likely to deliberately attempt to eradicate stress…both physical and mental… from their lives.
2. Long term survivors are often characterized by genetic “hardiness”. Some HIV seropositive individuals have been found to produce more cytokines which inhibit the replication of HIV, have less aggressive forms of HIV, strong immune systems, neutralizing factors, or specific allele sequences associated with LTS. These genetic variations have been shown to inhibit the replications or mutation of HIV thereby delaying onset of symptoms. In a small percentage of HIV positive individuals, the virus seems to have little effect. These non-progressors are not yet clearly understood. The use of AZT and other medications is not a statistically significant variant among this group.

3. Long term survivors are associated with positive socioeconomic variables. Although asymptomatic and slow progressors are found in all cohorts of HIV seropositive populations, access to medical care, medications, and education remain major determinants of LTS. Protease Inhibitors are perhaps the single greatest determinant of LTS for the majority of HIV positive individuals today, yet many persons cannot afford the high cost of life sustaining medications. Early detection of opportunistic infections, adequate nutrition, provision of necessities for daily living, and strong social support are all associated with LTS.

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