What is HIV / AIDS ?

Human Immunodeficiency Virus (HIV) is a virus which preys on the immune system eventually leaving the infected person susceptible to specific illnesses and diseases. Acquired Immunodeficiency Syndrome (AIDS) occurs when these specific illnesses arise as a result of the deteriorated immune system and can occur as late as 10 years after HIV infection.

HIV belongs to the group of human retroviruses and the subgroup of Lentiviruses. Retroviruses or ‘reverse viruses’ are unique in that they contain the enzyme, reverse transcriptase which allows the production of DNA from RNA. Lentiviruses or ‘slow’ viruses are characterized by their slow development and long incubation period.

The HIV virus is composed of:

• Outermost envelope studded with glycoproteins, gp120 and gp41 and MHC proteins.
• 2 single strands of RNA
• 3 enzymes: protease, integrase and reverse transcriptase
• P17 protein matrix (outer)
• P24 protein capsid (inner)

Figure 1. HIV virion (NIAID, 2009)

Epidemiology

The HIV epidemic has had a huge impact in Sub-Saharan Africa (Inungu & Karl, 2006; Mosam & Dlova, 2004). It is clear from Figures 1 and 2 (below) as well as from research (Shors, 2006; Cock & Weiss, 2000) that developing countries, particularly Asia and Africa, are where the greatest numbers of people living with HIV are and where most of the new infections occur.A literature review (Steen, Drage & Klouman, 2006) revealed that at least 90% of people infected with HIV were living in developing countries in Africa and Asia.

Studies (Steen et al., 2006) reveal that in general, rural populations are less affected than urban populations and that the people infected and the mode of transmission differs in Africa and Asia. Steen et al. (2006) specify that more women than men are infected in Africa and the mode of transmission is predominantly heterosexual. In contrast the main modes of transmission in Asia were found by Steen et al. (2006) to be via sex workers and their patrons, intravenous drug users and men having sex with men.

Figure 1. A Global view of HIV infection(UNAIDS, 2008).

http://www.unaids.org/en/KnowledgeCentre/HIVData/GlobalReport/2008/2008_Global_report.asp

Figure 2. Estimated number of people living with HIV Globally and in Sub- Saharan Africa

http://img.medscape.com/pi/emed/ckb/infectious_diseases/211212-1358427-211316-1377359.jpg

Origin of HIV

The true origins of HIV are not entirely known, however recent research suggests that it may have come from a strain of virus found in chimpanzees. In 1999, researchers found a strain of virus in chimpanzees called Simian Immunodeficiency Virus (SIV) that was almost identical to HIV-1 (the most prevalent form of HIV in humans).

In 2003, after 10 years of investigations, researchers Bailes and Colleagues claimed that chimpanzees were the source of HIV-1 and that at some point in time the virus crossed species from chimpanzees to humans. Studies suggest that HIV-1 was probably transfered between species around the early 1950s (Zhu et al., 1998), however the method of transfer is unknown and currently only theories exist to explain it. (For more information go to Origin of HIV Virus Theories).

How does HIV work?

HIV, unlike bacteria, can not multiply by itself because it does not have all the cellular apparatus to do so. Instead it selectively hijacks T helper cells (CD4 cells or CD4 lymphocytes) which contains all the apparatus for cell replication.

T helper cells are fundamental cells of the immune system because:

1) They recruit T cells to destroy the foreign substances such as Bacteria and viruses.

2) They stimulate B cells to produce antibodies so that the body can fight these bacteria/viruses if faced with them again in the future.

HIV acts by first binding to CD4 receptors and other markers on the surface of T helper cells. When the virus fuses to the cell membrane it opens up, spilling its contents into the T helper cell. With the help of HIV's enzymes (integrase) , HIV's RNA (genetic code) is inserted into the host cell's DNA, making it now a part of the genetic makeup of the T helper cell. This turns the T helper cell into a factory for the production of new viruses.

Figure 2. T helper cell infection by HIV (NIAID, 2009).

Breakthrough research has recently discovered that T cell infection can be transmitted from one T helper cell to another (Hubner et al., 2009). Before this breakthrough, scientists believed T cell infection could only occur by direct contact with a HIV virion. This discovery may be the reason why a cure for HIV has not yet been found.

The video below shows real footage of the newly discovered method of HIV spread.

Unlike most retroviruses, T helper cell infection with HIV results in cell death (Fan, Conner, & Villarreal, 1991) which severely affects the immune system’s ability to fight and protect itself against HIV and other foreign bodies. Every day millions of new viruses are made and millions of T helper cells are destroyed (Fan et al., 1991). The body’s natural defence tries to destroy all the virus copies and replace all of the lost T helper cells, however it can not quite match the rate of virus production or T helper cell destruction and the result over time is a gradual increase in the number of viruses and a gradual decline in the number of T helper cells. This means the infected individual has a compromised defence system and is more vulnerable to opportunistic infections.

Causes of HIV infection and AIDS

HIV is contracted only from transmission from one infected individual to another. An individual becomes ‘HIV infected’ as soon as the virus hijacks their immune cells which occurs almost immediately after transmission. Transmission occurs via a number of routes all involving the transfer of body fluids like blood or semen from one individual to another.

The most common routes of transmission are:

- Unprotected sexual contact (anal, oral or vaginal)

- Blood to blood contact (contaminated syringes)

- Perinatally (around or during childbirth)

Most recently, there has been a global rise in the incidences of HIV/AIDS in women, children and young adults (UNAIDS, 2008) . The increase in women and young adult HIV/AIDS cases is mostly because of an increase in risky sexual behaviours by women and young adults and an increase in intravenous drug use in young adults (UNAIDS, 2008). Children mainly contract HIV from their infected mother when in the womb, through breast milk, or during childbirth. Individuals with an existing sexually transmitted disease (STD) are more at risk of contracting HIV (Fleming and Wasserheit, 1999).

Transmission does not occur through casual contact such as hugging, shaking hands, kissing, sneezing, coughing, mosquitoes, other vectorial insects or through contact with the faeces and/or urine of HIV-infected babies.

AIDS is caused by HIV infection, after significant deterioration of the immune system has occurred. As mentioned, it can occur as long as 10 years after contracting HIV (Porth, 2005).

Signs & Symptoms

HIV/AIDS usually runs its course over 8 to 12 years and can be roughly split up into three phases (Porth, 2005).

1. Early acute phase or primary infection (PI),
2. Latency phase also known as the middle chronic phase which progresses to AIDS,
3. Last stage, sometimes referred to as the Crisis phase.

Early acute phase

During the acute phase there are a large number of copies of the viral DNA in the body (Porth, 2005). The viral load is important in distinguishing how recent the infection is (Iweala, 2004). In this first phase people infected by HIV tend to experience flu-like symptoms and may also display a bumpy, red rash and swollen lymph glands (Mandell et al. 2009). Antibodies to HIV are present by the third month after the infection and it is the detection of these antibodies, a process also known as seroconversion, which marks the shift to the second phase of HIV infection (Iweala, 2004).

Latency phase

During the second phase multiplication of the virus takes place in lymph nodes (Porth, 2005). Eventually the virus is no longer able to be contained in the lymph nodes and the immune system is compromised (Marieb, 2007). This phase commonly lasts about 10 years and during which the person may show no signs or symptoms however, the individual can still transmit the virus during this stage (Porth, 2005).

Crisis phase

HIV can be considered to have progressed to AIDS when the person’s CD4+T-cell count has been depleted to <200>+ T-cells play an important role in organising a person’s response to infection, (Port, 2005), so when these cells are depleted in HIV infection the immune system is not able to respond adequately and the individual becomes vulnerable to serious infections from what would normally be harmless organisms. In the AIDS stage the individual is also at risk of various cancers in addition to these opportunistic infections (OI) (Pratt, 2003). The signs and symptoms in this stage are very broad and specific to the type of AIDS-defining disease presented. Some very general signs and symptoms include weight loss, malnutrition, muscle wasting and diarrhoea.

There are tools which assist with HIV/AIDS diagnosis and clinical decision making that include a classification system based on CD4+ T-cell count and symptoms, categorisation and general clinical stages of HIV/AIDS infection.

Diagnostic Tests

Diagnostic tests for HIV are sometimes used to identify how recent or established an infection is, however the main goal of using these tests is to detect HIV infection early on (Iweala, 2004). This can be done by using samples of blood, saliva or urine to test for antibodies or antigens linked with HIV infection (Mandell et al., 2009).

A sample of blood in some form is used for several of the HIV diagnostic tests (Iweala, 2004). From this sample it is possible to identify whether there is HIV infection and what type of viral (HIV-1 or HIV-2) infection it is. The amount of viral particles in the blood (viral load) can also be determined from the sample as well as when the viral infection was contracted and whether there is resistance to HIV drugs (Iweala, 2004).

If there are no HIV antibodies present in the blood then the individual may be described as 'seronegative' or 'HIV-negative'. However, if a person is found to have evidence of HIV infection they may be considered 'HIV-positive' (Iweala, 2004). It takes a few months before HIV antibodies can be made and therefore a person may present as 'seronegative', while still being 'HIV positive'.

Blood may be collected from a vein or by a finger prick, though there are other options including providing saliva or urine samples for the tests (Iweala, 2004). The diagnostic tests that use saliva or urine may be as reliable in giving a correct result as the tests that use blood samples if done at the right time, but they don’t allow as much investigation into the infection as the blood samples do (Mandell et al. 2009).

HIV Diagnostic Tests

1. Enzyme Linked Immunosorbent Assay (ELISA) and Western Blot

The ELISA test and Western Blot are the most common tests for HIV and are used to detect whether the person has proteins that fight HIV (HIV antibodies) (Iweala, 2004). The ELISA test is done first (Porth, 2005) and if it shows positive then the Western Blot assay is also done. Most often these tests can accurately detect the presence of HIV antibodies. However if the tests are done during the "window period" (before sercoconversion has taken place), a false negative test is possible (Mandell et al. 2009). For this reason, negative tests usually require a follow up test 3 months later (Fahey & Flemming, 1997).

2. Detuned Assay

This test gives an indication of how recent the HIV infection is (Mandell et al. 2009). Iweala (2004) explains that a second test is done on the sample of a person who has a positive result using the ELISA test and if the HIV infection is recent (within 129-180 days) the test result for the detuned assay will be negative. This is an important test because it can show new infections and how prevalent HIV infection is for the general public (Iweala, 2004).

3. Urine and Salivary Tests

These tests are used to concentrate specific antibodies for the ELISA and Western blot tests (Mandell et al., 2009). An example of an approved oral test is the Orasure test which is sold over the counter (Porth, 2005).

4. Rapid Tests

Rapid tests don’t require highly trained people to do them; the results are comparably reliable to ELISA and Western Blot test results (if there isn’t a high risk of acute HIV infection) and may be produced within an hour (Iweala, 2004, Mandell et al., 2009, Pascoe et al., 2009).

Additional Tests

1. HIV nucleic acid-based assays

According to Iweala (2004) this test is used after a person has been confirmed to have an HIV infection to find out the viral load. The viral load can then be used as an indication of how effective the medication is for the person as well as the development and likely timeline of the infection (Mandell et al., 2009).

2. p24 antigen detection

This type of test is not used often but when it is used it gives an indication of the levels of a specific antigen in the sample and can be used to clarify results from a Western blot test.

3. Peripheral blood mononuclear cell culture

This test takes places over a period of at least 28 days and can be used to detect HIV infection in infants. However, it is expensive and used in predominantly in research settings (Iweala, 2004).

Testing should be done for all pregant women and regularly for any individual who is at risk of contracting HIV. (For more information on HIV risk factors click here)

Prognosis

The prognosis for HIV/AIDS sufferers is affected by many factors including (Oppenheim, 2009):

• Age
• CD4 count
• Viral load
• Access to treatment types
• Response and adherence to treatment.

For those who are HIV positive and able to obtain combination antiretroviral therapy (cART), their prognosis is considerably better than what it was in the 1990’s (Oppenheim, 2009).

At one period in time, the prognosis for HIV infection was death within months of diagnosis, however this has changed with the use of Highly Active Antiretroviral Therapy (HAART) (Corless & Nicholas, 2000). Recent evidence shows that 80% or more of people who have gone from stage 1 to stage 2 of HIV infection are still living 10 years later and overall are experiencing less AIDS-defining illnesses (Oppenheim, 2009).

Figure 1. The relationship between viral load and CD4 count in HIV/AIDS progression (Pantaleo et al, 1993).

Management of HIV/AIDS

Management of HIV and AIDS is very complex and will vary according to the stage of HIV infection and the type(s) of AIDS associated illnesses that may be present. Furthermore, HIV/AIDS also affects sufferers socially and psychologically and these areas need to be addressed when determining management and treatment strategies.

Management and treatment strategies include:

• Counselling

For those newly diagnosed with HIV the disease process is usually discussed, a number of necessary tests are taken and assistance is provided to help reduce the likelihood of secondary transmission (Hammer, 2005). It is important to note that many years of good quality life are still possible, particularly for those who have no symptoms (asymptomatic) of HIV and who do not have other diseases at the same time (Hammer, 2005).

• Behaviour modification

This includes changing diet/nutrition, high risk behaviours, exercise, support groups and education.

• Antiretroviral therapy (ART):

ART aims to improve a person’s survival without disease by both prolonging the functioning of their immune system and keeping viral replication to a minimum (Hammer et al., 2008). (For more information go to Antiretroviral Management of HIV/AIDS post)

Antiretroviral Management of HIV/AIDS

Antiretroviral therapy aims to improve and prolong the functioning of the immune system by keeping a low viral load (<55,ooo copies/mL OR <50 HIV RNA copies/mL plasma) (BHIVA, 2001). They do so by stopping the action of one of the three viral enzymes that are involved in HIV replication.

Antiretrovials are generally classed into 5 groups:

Non-nucleoside reverse transcriptase inhibitors (NNRTI)

Nucleoside reverse transcriptase inhibitors (NRTI)

Protease inhibitors

Entry/Fusion inhibitors

Integrase inhibitors

Figure 1. Sites of antiretrovial medication action (Davies, 2000).

Viral load and CD4 count are the main measurements considered when determining whether antiretroviral therapy should be sought (Hammer, 2005). These measurements indicate what stage the disease is at, how the person is likely to respond to therapy and what the outcomes may be (Masci, 2001). A combination of antiretrovirals (Combination Antiretroviral Therapy or CART) is commonly used because it proves to be most effective (Zuniga et al., 2008). CART does however need changing over time to remain effective.

Current guidelines recommend antiretroviral therapy for:

1. Those who have symptomatic HIV (Hammer et al., 2008)
2. Those who are asymptomatic but have a CD4 count of less than 350/µL (Hammer et al., 2008).
3. Specially considered people who have a CD4 count >350/µL as there is insufficient evidence to guide therapy above this level. Consideration is based on the individual’s willingness to comply, any existing comorbidities, the risk they are of other diseases not related to AIDS and the risk of HIV progression (Zuniga et al., 2008).
   

Things to consider when determining ART options:

• Presenting symptoms of HIV infection: fever, swollen glands, fever, swollen lymph glands, headaches, seizures, persistent coughing, chest pain, nausea, enlargement of the spleen, gastrointestinal bleeding and diarrhoea.
• Amount of functioning (immunocompetant) lymphocytes (white blood cells)
• HIV related complications: Screening for diseases associated with HIV such as tuberculosis, oral candidiasis, certain types of pneumonia etc should be done.
• History of mental illness
• The likelihood of treatment adherence as well as living conditions. Commitment and adherence is vital to the success of HIV treatment.
• Substance abuse: this is important as it affects whether the antiretroviral treatment will be effective. If there is substance abuse then the treatment is not likely to be as effective (Masci, 2001).
• Comprehension: counselling should be done to ensure the person infected with HIV understands the disease, modes of transmission and is able to alter any risky behaviours.
• Pregnant women with co-morbidites and with HIV related kidney damage (Zuniga et al., 2008).
• Dietary patterns: correct timing of meals has to be emphasised as antiretrovirals differ with some having to be taken on an empty stomach and others with meals
  

Challenges Include (Zuniga et al., 2008):

• Drug toxicities for antiretroviral therapy
• Maintaining adherence
• Drug resistance: if the virus has a long enough exposure to the medication, it can develop a resistance to it and then the treatment will no longer be effective.
• Drug interactions
• The trade-off between funding development of drugs for those already on ART and providing ART to those newly diagnosed with HIV (Zuniga et al., 2008).
• The expense of long term treatment. For example the cost was nearly $619,000 in the USA for lifetime treatment for one person on antiretroviral therapy (Zuninga et al., 2008).
• Access to ART: 90% of those living with HIV are living in developing nations with limited access to medical treatment(Zuniga et al, 2008).

Physiotherapy Management of HIV/AIDS

With recent advancements in medication, HIV/AIDS sufferers in developed countries are living longer (Palella et al., 1998) and as a consequence there is a growth in the number of people with chronic health conditions, musculoskeletal problems and physical disabilities (O’Brien et al., 2004) associated with AIDS. These trends all contribute to the growing demand for physiotherapy management of AIDS.

Most physiotherapy treatments for people with AIDS involve managing their pain, treating related musculoskeletal problems, peripheral neuropathies, general rehabilitation (Galantino & McReynolds, 1995) and health education (Useh, Akinpelu, & Makinde, 2003). However all treatments will be specific to the AIDS-defining illness that a patient presents.


Figure 1. Physiotherapist treating a malnourished child (IHI, 2005).

Physiotherapists may prescribe exercise programs to manage some of the chronic health conditions that may occur as a result of AIDS. Conditions include type 2 diabetes (associated with ART), insulin resistance, elevated blood triglycerides (Gale, 2003) and unwanted changes in weight and body composition (O’Brien et al, 2004).

Aerobic exercise improves cardiovascular fitness and mental well being while resistive exercise training increases muscle mass, strength and body weight in HIV/AIDS sufferers (O’Brien et al., 2005). Despite these positives, aerobic or/and weights training has no effect on immune status, CD4 count and/or viral load (O’Brien et al., 2004; O’Brien et al., 2008) and therefore exercise can only be used to manage HIV/AIDS rather than to reverse or stop its progression. High quality evidence suggest that 20 minutes of aerobic exercise three times a week for four weeks may be safe and may improve fitness and well being for adults living with HIV/AIDS (O’Brien et al., 2005), however as yet there exist no clear or definite exercise guidelines for AIDS sufferers.

Ultimately physiotherapy treatment can provide relief and improve functional ability, independence and quality of life in AIDS patients.

Figure 1. Illustrates areas of brain tissue loss in AIDS sufferers (Thompson et al., 2005). Recent research found that one of the main areas of brain damage in AIDS suffers if the motor cortex (are of brain that controls movement). This explains the presentation of abnormal gait in many poeple with AIDS. Physiotherapy treatment is essential to regain normal movement control and function.

Some musculoskeletal conditions that can arise from HIV infection:

Inflammatory Arthropathies:

• Arthralgia
• Acute Symmetric Polyarthritis
• Hypertrophic Osteoarthropathy
• Reiter Syndrome
• Psoriatic Arthritis
• HIV-Associated Arthritis
• Osteonecrosis

Myopathies:

• Pyomyositis
• Pyomyositis
• Zidovudine Myopathy

Infections:

• Septic Arthritis
• Tuberculosis Osteomyelitis
• Bacillary angiomatosis

Neoplastic (tumorous) Condition:

• Non-Hodgkins Lymphoma

Many of the above conditions can be managed with appropriate physiotherapy treatment.

Physiotherapy Treatment Goals

1st stage or Primary infection (PH):

• Build muscle mass, and strength
• Develop aerobic fitness for psychological well being, overall health

2nd stage or Asymptomatic (Latency Phase):

• Increase and maintain muscle mass, muscle strength and cardiovascular fitness

3rd stage or Symptomatic HIV infection/AIDS (Crisis Phase):

• Provide physiotherapy to treat specific AIDS defining illness
• Maintain or promote physical mobility and ambulation
• Pain management
• Maintain respiratory, circulatory function
• Promote physical and functional independence
• Reduce disability and physical impairment
• Prevent muscle atrophy

End stages goals (palliative care) (Crisis Phase):

• Provide honest and continual education to patient and family regarding status of HIV infection and AIDS.
• Pain management
• Prevent muscle and joint contractures

AIDS-defining illnesses

"AIDS defining illnesses" according to the Centers for Disease Control and Prevention (CDC, 2008):

• Bacterial infections, multiple or recurrent
• Candidiasis, pulmonary (bronchi, trachea or lungs)
• Cervical cancer, invasive
• Coccidioidomycosis, disseminated or extrapulmonary (valley fever)
• Cryptococcosis, extrapulmonary
• Cryptosporidiosis, chronic intestinal (> 1 month duration)
• Cytomegalovirus disease (other than liver, spleen, or nodes)
• Cytomegalovirus (CMV) retinitis (loss of vision)
• Encephalopathy, HIV-related neurological problem
• Herpes simplex: chronic ulcer(s) (>1 month duration); or bronchitis, pneumonitis, or esophagitis
• Histoplasmosis, disseminated or extrapulmonary
• Isosporiasis, chronic intestinal (>1 month duration)
• Kaposi's sarcoma
• Lymphoid interstitial pneumonia or pulmonary lymphoid hyperplasia complex
• Lymphoma, Burkitt's
• Lymphoma, immunoblastic
• Lymphoma, primary, of brain
• Mycobacterium avium complex or Myocobacterium kansasii, disseminated or extrapulmonary
• Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary)
• Mycobacterium infections, other species or unidentified species, disseminated or extrapulmonary
• Pneumocystis carinii pneumonia (PCP)
• Pneumonia, bacterial and recurrent
• Progressive multifocal leukoencephalopathy (PML)
• Salmonella septicemia, recurrent
• Toxoplasmosis of brain
• Wasting due to HIV

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Video Reference

Hubner, W., McNerney, G. P., Chen, P., Dale, B. M., Gordon, R. E., Chuang, F. Y. S., Li, X., Asmuth, D. M., Huser, T., and Chen, B. K. (2009). Auantitative 3D videao microscopry of HIV transfer across T cell virological synapses. Science, 323(5922), 1743-1747.