Human Immunodeficiency Virus (HIV)

Original Editors - Holly Grant, Justin Klenke & Conner Zuber from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Holly Grant, Conner Zuber, Kim Jackson, Justin Klenke, Admin, Lucinda hampton, Vidya Acharya, Elaine Lonnemann, Gayatri Jadav Upadhyay, Ajay Upadhyay, Tarina van der Stockt, WikiSysop, Simisola Ajeyalemi, Karen Wilson, 127.0.0.1, Nupur Smit Shah, Wendy Walker and Naomi O'Reilly  

Definition/Description

AIDS, acquired immunodeficiency syndrome, is a contagious, chronic and life-threatening condition caused by the human immunodeficiency virus (HIV). Acquired means that the diease is not inherited or genetic in nature, but develops as a result of a virus. Immuno refers to the immune system, and deficiency means that the immune system is underperforming or hypoacive.  By damaging your immune system, HIV interferes with your body's ability to fight off viruses, bacteria and fungi that cause disease. HIV makes you more susceptible to certain types of cancers and to infections your body would normally resist. The cytopathogenic virus and the infection itself are known as HIV. "Acquired immunodeficiency syndrome (AIDS)" is the name given to the later and more serious stages of an HIV infection. 

According the AIDS.gov, 35.3 million people are currently living with HIV/AIDS worldwide. Though the spread of the virus has slowed in some countries, it has escalated or remained unchanged in others. The best hope for stemming the spread of HIV lies in prevention, treatment and education.

Prevalence

Prevalence is defined as the number of people living with HIV infection at the end of a given year. According to the CDC, at the end of 2010, about 1.1 million people in the United States were living with HIV/AIDS. Of those people, about 16% do not know they are infected. The prevalence of HIV is increased in African American males, male to male sexual relations, and age 25-34. The prevalence is 5 times greater in incarcerated populations than the general population at large. The high HIV transmission rates among inmates maybe related to homosexual encounters and potentially tattooing. Ethnicity is not directly related to AIDS risk, but it is associated with other determinants of health status such as poverty, illegal drug use, access to health care, and living in communities with a high prevalence of AIDS.
Incidence is the number of new HIV infections that occur during a given year. HIV infection is the 5th leading cause of death for people who are between the ages of 25-44 years old in the United States. In 2010, the CDC estimated that approximately 47,500 people were newly infected with HIV. There are four transmission categories of HIV: male to male sexual relations, heterosexual relations, injection drug users, and homosexual relations combined with injection drug users. Male to male sex accounted for 78% of new HIV infections among men and 63% of all new infections in 2010. Furthermore, black men represented 31% of all new HIV infections, in the United States, in 2010. Black/African American men and women were also strongly affected and were estimated to have an incidence rate that was 7 times as high as the incidence rate among whites. African-American's represent about 14% of the total United States population, but make up almost half of the people known that are suffering from AIDS. AIDS is the leading cause of death for African-American men between the ages of 35-44 years old in the United States. It is thought that approximately 5 million new HIV cases occur each year worldwide.

For complete HIV/AIDS prevalence and incidence statistics, please visit http://www.cdc.gov/nchhstp/newsroom/docs/2012/HIV-Infections-2007-2010.pdf or visit the HIV/AIDS page on the CDC website at http://www.cdc.gov/hiv/default.html.

Characteristics/Clinical Presentation

The clinical presentation of HIV and AIDS vary depending on which stage of infection the person is in.

Early infection:

When a person first becomes infected with HIV, many people will experience flu-like symptoms often described as "the worst flu ever." These symptoms usually occure within 2-4 weeks of becoming infected with HIV. Early signs and symptoms may include: fever, headache, sore throat, swollen lymph vessels, fatigue, muscle and joint aches and pain, and rash. GI complaints include change in bowel and bladder function, especially diarrhea. Cutaneous complaints are common and include: dry skin, new skin rashes, and nail bed changes. Because these are very common and present in a number of other diseases, a combination of complaints is more suggestive of HIV infection than any one sign/symptom. In addition, many people with HIV present with back pain, but the underlying cause may differ from person to person. Back pain may be due to: muscle weakness and atrophy that occurs as a result of the disease process. Back muscle weakness and atrophy can alter the person's normal postural alignment and may cause subsuquent backpain as well as a person's response to their medications may contribute to back pain as well. It has been reported that back pain is more likely to occur when the bodies T-cell count drops. Eventhough, the person may or may not exhibit symptoms they can still transmit the virus to others. Once, the virsus enters the person's body, the person's immune system comes under attack. The virus then starts to multiply in the person's lymph nodes and slowly degins to eradicate the helper T- cells, the white blood cells that help the immune system.

Later infection:

A person may remain symptom free for as long as 8-9 years, but as the virus continues to multiply and destroy immune cells, the person may begin to develop chronic symptoms and or acquire mild infections. Chronic symptoms seen in this stage are but not limited to the following: swollen lympth nodes-which is often one of the first signs of HIV infection, diarrhea, weight loss, fever, cough and shortness of breath.

Latest phase of infection:

Usually, after a person has been infected with HIV for 10 years or more the last phase of HIV conmenses. More serious symptoms of the virus start to appear and the infection may then meet the offical definition of AIDS. Some of the signs/symptoms of later infection are: Kaposi's sarcoma, multiple purple blotches and bumps on skin, HTN (pulmonary and or cardiac), dyspnea, syncope, chest pain, non-productive cough, easy bruising, thrush, muscle atrophy and weakness, back pain, poor wound healing, HIV related dementia (memory loss, confusion, behavioral change, imparired gait), and distal symmetric polyneuropathy (pain, numbness, tingling, burning, weakness, and atrophy).    By the time AIDS develops, the person's immune system has been severly damaged, making the person susceptible to many opportunistic infections such as TB, Pneumocystsis carinii, pneumonia, lymphoma, thrush, herpes 1 and 2, toxoplasmosis and cansisiasis. They are called "opportunistic" infections or diseases because they take advantage of the compromised immune system to infect and destroy the person's body. Under normal conditions, a person would not be affected to the degree of severity they are under the presence of these infections with normal immune function.  The signs and symptoms of some of these infections may include but not limited to the following: soaking night sweats, shaking chills or fecer higher than 100 degrees F (38 C) for several weeks, dry cough and shortness of breath, chronic diarrhea, persistant white spots or unusual lesions on the person's tongue or in thier mouth, headeaches, blurred and distorted vision, weight loss. In 1993, the CDC redefined AIDS to mean the presence of HIV infection as shown by a positive HIV antibody test with the presense of at least one of the following:

The development of an oppertunistic infection-an infection that occurs when your immune system is impaired such as Pneumocystis Carinii Pneumonia (PCP)

A CD4 lymphocyte, helper T cell count of 200 or less. Normal count ranges from 800 to 1,200.

 

Associated Co-morbidities

AIDS is an unique disease in that no other known infectious disease attacks the immune system directly in the same manner as AIDS. Because the immune system is greatly affected many patient's suffering from AIDS may present with the folllowing co-morbidities among others:

• Cancer (especially with the apperance of the highly unsual Kaposi's Sarcoma)
• Non-Hodgkin's Lymphoma
• AIDS-related primary central nervous system lymphoma
• Hepatocellular carcinoma
• Tuberculosis (pulmonary and extrapulmonary TB)
• HIV neurologic disease
• AIDS dementia complex/HIV encephalopathy
• Progressive multifocal leukoencephalopathy
• Vacuolar myelopathy (most common in the Thoracic spine)
• inflammatory polyneuropathies
• sensory neuropathies
• mononeuropathies
• inflammatory demylinating polyneuropathy (similar to Guillain-Barre syndrome)
• Cytomegalovirus
• hypersensitivity disorders

Medications

When HIV was first indentified there were few drugs to treat the virus and opportunistic infections associated with it. Since then, a number of medications have been developed to treat both HIV/AIDS and opportunistic infections. Anti-retroviral medications have provided HIV-positive Americans with an increased quality of life and extended life. No drug/treatment can cure HIV/AIDS, many of the drugs used have side effects that can be severe, and most drug therapies are expensive. In addition, after 20 years on AIDS medications, some people develop resistance to the drugs and no longer respond to treatment.

Anti-retroviral drugs inhibit the growth and replication of HIV at various stages of its life cycle. Seven classes of these drugs are available:

• Nucleoside analoque reverse transcriptase/NRTIs
• protease inhibitors/PIs
• Non-nucleoside reverse trabscriptase inhibitors/NNRTIs
• Nucleotide reverse transcriptase inhibitors/NtRTIs
• Fusion inhibitors
• Integrase inhibitors
• Chemokine co-receptor inhibitors

A person's response to any of these medications is measured by viral load. Viral load is tested at the start of any treatment and then every three to four months while undergoing therapy.

Side Effects of Medication:

Delayed toxicity with long term treatment for HIV-1 infection with antiretroviral therapy occurs in a substantial number of affected indivduals. The more common symptoms occuring with toxicity are:

• rash
  
• nausea
  
• headaches
  
• dizziness
  
• muscle pain
  
• weakness
  
• fatique
  
• insomia
  

Hepatotoxicity is also a common complication which may manifest itself with the following signs/symptoms:

• carpal tunnel syndrome
  
• liver palms
  
• asterixis
  
• and other signs of liver impairment
  

Lipodystrophy is a condition that is also associated with antiviral therapy. It manifests itself in body fat redistribution in the following areas:

•  abdomen
• upper body
• breasts
  

Atripla

Epzicom

Diagnostic Tests/Lab Tests/Lab Values

Early diagnosis is important so that early preventative therapies may be initiated and sex partners can be notified of their risk of HIV and get tested for the presence of the HIV antibody. Screening for AIDS is done by a fingerstick blood test, the HIV-1 antibody enzyme immunoassay test. The blood test looks for the presence of antibodies to HIV-1. The test only indicates if person has been exposed to the virus. Antibody testing is not always reliable because the body takes varying amounts of time to produce a detectable level of antibodies. Consequently, a person who does have HIV could test negative for the for HIV antibodies. Antibody testing is also unreliable in neonates because transferred maternal antibodies are present for 6-10 months in the neonate. The Western blot test is a more expensive test and can be used when there is concern about false-positive results. HIV RNA viral loading is another test that can be done in the lab. It measures the plasma HIV RNA assay.  A new quick test has been developed called the OraQuick Rapid HIV Antibody Test and it is almost 100% accurate and the results are available in 20 minutes. A positive OraQuick test requires additional confirmation testing. This is a rapid non-invasive test that uses saliva and or a gum swab to detect the presence of HIV antibodies. The advantages to rapid testing is that indivuals with positive results can recieve treatment quickly and education about how to prevent transmission of the illness to others and can partake in counseling services. The disadvantage of this quick test is that it can not detect the HIV infection in people who were exposed less than 3 months prior to taking the test. It has been estimated that one third of all indivuals who do get tested for the presence of HIV do not return to get the results of their test.  

Causes

Around the late 1970's and 80's doctors began noticing that an increasing number of people were suffering from serveral unusual and rare illnesses. At first, little was known about what was happening to these inital victims of AIDS. Doctors were unsure as to what was causing the condition. Many of the first people diagnosed with this strange new condition were homosexual men and because of this the condition was labeled GRID, gay related immunodefiency. However, the condition soon started showing up in men and women intravenous drug users and hemophiliacs. The first reported AIDS cases were in the United states in 1981. 1983, the Institut Pasteur in France regonized that the virus that was causing so much panic was the result of AIDS. The virus that resulted from AIDS was then named HIV, human immunodefiency virus. Researchers in France, now understood that the virus passed from each person via the exchange of semen, blood and or vaginal secreations during sexual contact. Researchers also learned that AIDS weakens the immune system by destroying the bodies white blood cells specifically the helper T-cells. Helper T- cells help the body fight off viruses and bacteria that enter the body. In 1985 another breakthrough took place, a blood test for the presence of HIV antibodies in the person's blood stream. The first smaple of HIV infected blood dates back to 1959 but computer analysis dates the emergence date back to the 1930's.  

There has been many theories and much speculation as to where the AIDS virus first orginated. AIDS used to be a very rare and isolated virsus that affected a few types of monkeys and chimpanzees in Africa. AIDS is related to another virus, Simian Immunodefiency virus that affects monkeys and apes. It was thought that humans were first exposed to AIDS when they caught the monkeys for food and kept them as pets and or if they were scratched and bitten by an infected moneky/ape.

We now know that AIDS is caused by the spread of the HIV virus. The virus is spread though sexual contact, needles, or a syringe that is shared by intravenous drug users; transfusion of infected blood or blood products; or perinatal transmission from infected birthing or breastfeeding a child from an infected mother. HIV is not transmitted through casual contact such as: the shared use of utensils, food, cups, towwls, razors, toothbrushes or even kissing. Transmission always involves exposure to some body fluid from an infected client. The greatest concentrations of the virus have been found in blood, semen, cerebrospinal fluid, and cervical/vaginal secreations. HIV has been found to be in low concentrations in tears, saliva, and urine, but no cases of transmisson have been reported via these routes. The primary cause of AIDS is the type 1 retrovirus or HIV and transmission of the HIV virus happens with partaking in high risk behaviors. High risk behaviors are defined and include: unprotected anal and oral sex, having 6 or more sexual partners in the past year, sexual activity with someone known to carry HIV, exchanging sex for money or drugs and  injecting drugs.   

Population groups at the greatest risk are: commercial sex workers (prostitutes) and their clients, homosexual men, injection drug users, blood recipients, dialysis recipients, organ transplant recipients, and fetuses of HIV infected mothers, and people with other sexually transmitted diseases. People who already have a sexually transmitted disease are 3-5 times more likely to come in to contact with the HIV virus compared with people without STDs. Transmission of HIV varies by gender. In 2004, 57% of male infections were related to men who had sex with other men, 19% were related to injection drug users, and 17% were related to heterosexual sex. For females in 2004, 70% of new HIV infections were related to heterosexual sex and 29% resulted from injection drug use.

Systemic Involvement

HIV is described mainly as a infection of the immune system resulting in progressive and profound immune suppresion. The progression of the illness can have an effect on the following systems: musculoskeletal, neurologic/neuromuscular, cardiopulmonary, and the integumentary system. Some of the clinical manifestations of HIV on the musculoskeletal system is but not limited to: Myalgia/arthralgia, Rheumatologic manifestations, inflammed joints and associated disorders like: Reiter's syndrome, reactive arthritis, psoriatic arthritis, Myositis/pyomyositis, connective tissue diseases, Avascular necrosis, Musculoskeletal pain syndrome/HIV wasting syndrome, Myopathy, Pelvis pain, Extrapulmonary tuberculosis, delayed healing and Myositis ossificans.

HIV can hav the following implications on the neurologic/neuromuscular system: gait disturbances, intention tremor, delayed response of reflexes, HIV associated dementia, social withdraw, irritability, depression, apathy, lethargy, memory impairment, confusion, disorientation, ataxia, leg weakness with gait disturbances, loss of fine motor coordination, incontinence, paraplegia, Guillian-Barre syndrome, headaches, seizures, Radiculopathy, peripheral neuropathy, brachial neuropathy, and vacuolar spinal myelopathy.

The cardiopulmonary system can display the following clinical signs/symptoms: dyspnea, especially on exertion, nonproductive cough, hypoxia symptoms, pericardial effusion, cadriomyopathy, endocarditis and vasculitis. 

The integumentary system can display the following clinical manifestations: hair loss, basal cell carcinoma, Kaposi's sarcoma, mucocutaneous ulcers, rashes, Urticaria, delayed wound healing.  

Medical Management (current best evidence)

It is important to note that there is currently no cure for AIDS, but recent medical advantages have been made that have allowed AIDS to become a chronic and manageable condition. Currently researchers are working on the development of a vaccine, but until a vaccine is developed the primary goal of intervention will be focused on stopping HIV from replicating, to increase the number of CD4 cells, and to slow the progression of the disease. Medical management centers on CD4 count and viral load. When CD4 drops below 500 cells/mm3 a protease inhibitor drug called HAART that supresses HIV replication and reduces the amount of the virus in the blood to an undetectable level is administered. HAART and other drugs do not completely eradicate the virus and lifelong treatment is required until a method for permanent eradication is developed. medical efforts are centered around four main things: 1. simplifying the drug regimens to improve compliance and adherence 2. developing alternative for those patients whose who current medications and treatments have failed 3. preventing the viral rebound or preventing the high levels of the virus when drugs are discontinued 4. management of the wide array of pharmological side effects. Non-pharmacological intervention includes: nutrional conseling, exercise, mental health support, and alternative and complimentary interventions. AIDS is associated with mucle wasting, nutritional deficencies and extreme weight loss which can contribute to immune dysfunction and increased rate of disease progression. These effects can be subsided with proper nutrition. The use of alternative and complimentary therapies are still under investigation and are a source of controversy.  

                                                                         

Physical Therapy Management (current best evidence)

The role of physical therapy and rehab in the care and treatment of AIDS has changed drastically since the 1980's when AIDS first emerged as a global concern. In the 1980's a person with AIDS often developed PCP pneumonia and other oppertunistic infections and quickly succumbed to the disease. During the 1980's the phyical therapist's job consisted mainly of pain control, teaching energy conservation techniques, and instruction in the use of assisted devices, Because AIDS has changed over the years from an acute to a subacute/chronic illness chronic conditions such as cardiovascular disease, rheumatologic, and musculoskeletal conditions are much more common in those living with HIV. Hence, physical therapists are generally focused on assisting the individual with the managment of physical dysfunctions related to this chronic disease.  

The individual suffering with AIDS/HIV may demonstrate clinical manifestations of overalapping pathological processes and HIV related physical disabilities that need appropriate rehabilitation intervention. For example, lesions of the CNS can be a site of more than one oppertunistic disease process or the individual may suffer a stroke in addition to already having an existing peripheral neuropathy and or other neuromuscular manifestations.

The therapist may can also be involved in wound care when integumentary impairment is caused by HIV oppertunistic infections while also providing intervention to relieve problems associated with rheumatologic dysfunctions. In addition to physical fitness and strength training therapists must look at:

• quality of life issues
• work simplifiction
• ADLs
• community managment skills (how to access transportation, socialization opportunities, shopping, banking, ability to access and negotiate health care and insurance systems)
• home care programs must be simple and easily incorperated into the patient's life and ADLs.
• proprioceptive neuromuscular facilitation and Bobath techniques may be more beneficial for the lower level functioning clients. 
• Soft tissue and joint moblization
•  stretching
• gait and balance training
• desensitization techniques
• microcurrent electroacupuncture has also been reported to reduce pain, improve functional status, and increase percieved strength

For patients with painful myopathy in the large muscle groups, progressive resistive training with weights/elastic bands/tubing to strengthen specific muscles may be beneficial. Muscle spasms accompanying myopathy may respond well to gentle but consistent stretching exercises. Post exercise soreness is common in AIDS patients experiencing muscle pain. A longer rest period between exercises may be necessary. In addition, cardiopulmonary complications in advanced stages of AIDS contribute to morbidity and mortality. Muscle and joint mobilization techniques and breathing exercises are essential for the patient that has been immobilized for any length of time as a result of respiratory or other disease involvement.

Exercise and HIV/AIDS

Early Stage HIV:

Exercise is considered safe for people with HIV and is an important way to increase the CD4 cells at earlier stages of the disease, possibly delaying symptoms while increasing muscle strength and size. During asymptomatic HIV metabolic parameters are within normal limits, with no limitations placed on the individual. Patients with asymptomatic HIV should be encouraged to exercise regularly, including both aerobic and resistance exercise components.

Advanced Stage HIV:

In this stage functional capacity is reduced, requiring more individualized exercise prescription and lower intensities. Neurologic dysfunction and deconditioning are common. Regular physical activity and exercise are just as important in this group but are more difficult and symptom limited. Among people with HIV who have known acrdiovascular disease, pulmonary limitations, or muscle dysfunction, exercise prescription should address impairments and limitations. Collaboration with the physician to determine any contraindications for exercise is advised. Strenuous exercise training is not recommended; aerobic exercise at moderate levels of intensity is suggested with medical clearance. 20 minutes of continious or interval aerobic training at least three times a week is suggested for improved cardiopulmonary fitness and improved psychologic status. Supervised aerobic exercise training safely decreases fatique, weight, BMI, fat and central fat in HIV-1-infected individuals. Exercise in this stage may or may not affect dyspnea. In addition, exercise also has beneficial effects for those with AIDS-related wasting syndrome. Exercise can help gain and build lean body mass which may offset some of the effects associated with wasting syndromes. 

The Big Picture:

Exercise can provide the following benefits for patients suffering from HIV/AIDS:

• Pain relief
• Reduction of muscle atrophy  
• Regularity of bowels
• Enhances immune function (by increasing T helper/ inducer CD4 cells and activating CD8 cells)
• Improves cardiovascular function
• Improves pulmonary function
• Improves endurance
• Helps prevent pneumonia and other respiratory infections
• Reduces anxiety and improves mood
• Exercise training at 70-80%of maximal heart rate is recommended to achieve the benefits listed above. Higher intensities increase strength and aerobic fitness, but have not been shown to change total lymphocyte cell counts or ratios. A RPE of greater than 14 is not recommended.

Standard AIDS/HIV precautions for therapists and other health care workers:

• Use protective barriers (gloves, glasses, gowns) when handling blood, body fluids, and infectious fluids.
• Wash hands and mucous membranes
• Prevent needle/scalpel sticks
• Use ventilation devices for resuscitation
• Don't treat a patient with HIV/AIDS if you have open wounds or skin lesions until lesions have healed.
• If pregnant take extra precautions
• For the therapist, exclude internal pelvic floor examination and wound care including debridement and dressing changes.  

Alternative/Holistic Management (current best evidence)

According to a study done by Smith and Hale, there is little evidence available on the effectiveness of alternative/holistic therapies and interventions.

• Acupuncture
• Tai Chi
• Yoga

All interventions have provided some positive indications which warrent further study and are currently being looked into to assess validation and consolidation of outcomes.

The Mayo Clinic recommends that patients suffering from HIV/AIDS take an active role in thier own care to help them stay healthy longer. Some lifestyle and home remedies suggested were:

• Eat healthy (emphasize fresh fruits and vegetables, whole grains and lean protein)
• Avoid foods that may put you at risk for infection such as: unpasteurized dairy products, raw eggs and raw seafood
• Drink pure/filtered water
• Keep hands clean
• Give away pets or take very good care of companion animals (pets may carry parasites that can cause infections in people who are HIV positive)
• Get enough sleep
• Get regular exercise
• Find ways to relax

Differential Diagnosis

Many indivduals with HIV/AIDS may remain asymptomatic for years, with a mean time of 10 years between exposure and development. Virtually, all the findings in the initial onset of AIDS may be found/mimic other diseases such as:

• Fever
• Headaches
• Night sweats
• Fatigue
• HTN
• Back pain
• Pulmonary complications ex. cough and SOA
• GI complaints (change in bowel habits and function)
• Cutaneous complaints (dry skin, new rashes, nail bed changes)
• Poor wound healing
• Thrush
• Easy Bruising
• Weight loss

 All of these signs/symptoms may be associated with other diseases, a combination of complaints is more suggestive of HIV infection than any one symptom alone.

Case Reports

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1. http://proquest.umi.com/pqdweb?did=45570719&sid=1&Fmt=4&clientId=1870&RQT=309&VName=PQD

2. http://proquest.umi.com/pqdweb?did=1514003&sid=2&Fmt=6&clientId=1870&RQT=309&VName=PQD

3. http://proquest.umi.com/pqdweb?did=1513826&sid=3&Fmt=6&clientId=1870&RQT=309&VName=PQD

Recent Related Research (from Pubmed)
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Bibliograpy

1. Catherine C. Goodman, Kenda S. Fuller. Pathology Implications for the Physical Therapist. St. Louis, Missouri. Saunders, an imprint of Elsevier Inc. 2009: 427-430.

2. O'Brien K, Tynan AM, Nixon S, Glazier RH. Effects of progressive exercise in adults living with HIV/AIDS: systematic review and meta-analysis of randomized trials. AIDS Care. July 2008; 631-653.

3. Smith C, Hale L. The Effects of Non-Pharmacological Interventions on Fatigue in Four Chronic Illness Conditions: A Critical Review. Physical Therapy Reviews. 2007; 12: 324-334.

4. Beer L, Fagan J, Valverde E, Bertolli J. Health-Related Beliefs and Decisions about Accessing HIV Medical Care among HIV-Infected Persons Who Are Not Receiving Care. AIDS PATIENT CARE and STDs. 2009; 23: 785-792. 

5. HIV/AIDS in the United States. CDC's Department of health and human services.2008. Available at: http://www.cdc.gov/hiv/resources/factsheets/us.htm. Accessed Febuary 16, 2010.

6. HIV/AIDS. Mayo Clinic web site. 2008. Available at:http://www.mayoclinic.com/health/hiv-aids/DS00005/DSECTION=symptoms. Accessed Febuary 22, 2010.

7. Catherine C. Goodman, Teresa Kelly Synder. Differential Diagnosis for Physical Therapists: Screening for Referal. Elsevier Science. 2006.