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Continuing Education for Health Professionals

KY: HIV/AIDS

Module 4

Cause of HIV/AIDS

The HIV Virus

illustration: HIV Virus

HIV has a protein shell, a lipid membrane, and glycoproteins that dot the outer surface of the virus. Source: Illustration provided by 3DScience.com.

AIDS is a complex condition caused by the human immunodeficiency virus, which attacks the cells of the immune system and progressively destroys the body’s ability to fight infection and disease. People with damaged immune systems are vulnerable to diseases that do not threaten people with healthy immune systems. AIDS is acquired—it is not hereditary and it is not passed casually from one person to another—and it is a syndrome because it causes a combination of symptoms, diseases, and infections.

HIV-1 and HIV-2

Two types of HIV are known: the most common HIV-1, which is responsible for the worldwide AIDS epidemic, and the immunologically distinct HIV-2, which is much less common and less virulent but produces clinical findings similar to HIV-1. The HIV-1 type itself includes four groups (M, O, N, and P), having different geographic distributions but all four producing similar clinical symptoms. The HIV-1 M group further splits into 9 subtypes (A through J) (Santoro & Perno, 2013).

T-helper Lymphocytes

When HIV enters the bloodstream it looks for T-helper lymphocytes, white blood cells essential to the functioning of the immune system. The T-helper lymphocytes are also referred to as T4 or CD4 cells and are the primary target for HIV infection. These cells regulate immune response when disease-causing organisms such as bacteria or viruses enter the body. When HIV attacks a T-helper lymphocyte, the T-helper cell sends signals to other cells, which produce antibodies to fight the infection. HIV infects and destroys the T-helper lymphocytes and damages their ability to signal for antibody production.

HIV Entry into a T-helper Cell

illustration: HIV entry into T-helper cell

The top panel shows HIV attaching itself to a T cell (surface shown in pale blue). The second and third panels show HIV (dotted with red glycoproteins) successively attaching to the T cell and depositing HIV particles into the T cell. Source: Sougrat et al., 2007. Image courtesy of PLoS Creative Commons Attribution 2.5 license.

The CD4 T-lymphocytes coordinate a number of important immune functions. Loss of these functions causes a progressive impairment of the immune system. Disease manifestations range from asymptomatic infection to life-threatening conditions characterized by severe immunodeficiency, serious opportunistic infections, and cancers. A strong association exists between the development of life-threatening opportunistic illnesses and both the absolute number and percentage of CD4+ T- lymphocytes. As the number of CD4+ T-lymphocytes decreases, the risk and severity of opportunistic illnesses increases.

Stages of Infection

HIV infection has a well-documented progression. If a person is infected with HIV and does not get treatment, the virus will eventually overwhelm the immune system and lead to Acquired Immune Deficiency Syndrome (AIDS).

Acute Infection

Within 2–4 weeks after being infected with HIV, many, but not all, people develop flu-like symptoms, often described as “the worst flu ever.” Symptoms can include fever, swollen glands, sore throat, rash, muscle and joint aches and pains, fatigue, and headache. This is called “acute retroviral syndrome” (ARS) or “primary HIV infection,” and it’s the body’s natural response to the HIV infection.

During this early period of infection, large amounts of virus are being produced in the body and there is a great risk of transmitting the virus to another person because of the high levels of virus in the blood. The virus uses the body’s CD4 cells to replicate, which destroys the CD4 cells; because of this, an individual’s CD4 count can fall rapidly. Eventually the immune response will begin to bring the level of virus in the body back down to what is called a viral set point, which is a relatively stable level of virus in the body. At this point, the CD4 count begins to increase, but it may not return to pre-infection levels. It may be particularly beneficial to begin ART during this stage.

Key Points About Acute Infection

  • Flu-like symptoms occur—“The worst flu ever!”
  • CD4 count can fall rapidly.
  • Great risk of transmitting HIV exists because of high levels of virus in the blood.
  • Antiretroviral therapy may be beneficial at this stage.

Clinical Latency

Following the acute stage of HIV infection, the disease moves into what is called the clinical latency stage. Latency describes a period where a virus is living or developing in a person without producing symptoms. During the clinical latency stage, people who are infected with HIV experience no HIV-related symptoms, or only mild ones. This stage is sometimes called asymptomatic HIV infection,* or chronic HIV infection.

*Asymptomatic HIV infection—the person is infectious but looks and feels healthy. The virus is active and continuing to damage the immune system.

During the clinical latency stage, the HIV virus continues to reproduce at very low levels although it is still active. If antiretroviral therapy has been started, an individual may live with clinical latency for several decades because treatment helps keep the virus in check. For people who are not on antiretroviral therapy, the clinical latency stage lasts an average of 10 years, but some may progress faster through this stage. During this symptom-free stage people are still able to transmit HIV to others, even if they are on antiretroviral therapy, although antiretroviral therapy greatly reduces the risk of transmission.

If individuals have HIV and are not on ART, their viral load will eventually begin to rise and their CD4 count will begin to decline. As this happens, they may begin to have constitutional symptoms of HIV as the virus levels increase in the body.

AIDS

AIDS is the most advanced stage of HIV infection and is determined by a CD4+ T-lymphocyte count of <200 cells/µL* or a CD4+ percentage of <14% and the appearance of specific conditions or diseases known as “AIDS-defining conditions” (see box below). These measures identify those who are severely immunosuppressed, who are in greatest need of close medical followup, and who are at greatest risk for the full spectrum of severe HIV-related morbidity.

*In someone with a healthy immune system, CD4 counts are between 500 and 1,600 cells/mm3.

In the advanced stage of HIV infection the immune system is already badly damaged and becomes vulnerable to infections and infection-related cancers called opportunistic infections. People are considered to have progressed to AIDS if they develop one or more opportunistic illnesses, regardless of their CD4 count.

Without treatment, people who progress to AIDS typically survive about 3 years. If a dangerous opportunistic illness occurs, life expectancy without treatment falls to about 1 year. However, with antiretroviral therapy and a low viral load, a person may have a near-normal lifespan and will most likely never progress to AIDS.

The natural history of HIV infection has been altered dramatically in developed countries because of antiretroviral medications. In countries where there is no access to these medications, or in cases where people do not become aware of their HIV infection until very late, the disease progresses as described above.

AIDS-Defining Conditions

  • Bacterial infections, recurrent (2 or more episodes in 2 months)
  • Candidiasis of bronchi, trachea, or lungs
  • Candidiasis of esophagus
  • Cervical cancer, invasive, confirmed by biopsy
  • Coccidioidomycosis, disseminated or extrapulmonary
  • Cryptococcosis, extrapulmonary
  • Cryptosporidiosis, chronic intestinal (>1 month’s duration)
  • Cytomegalovirus disease (other than liver, spleen, or nodes)
  • Encephalopathy, HIV-related
  • Herpes simplex: chronic ulcers (>1 month’s duration) or bronchitis, pneumonitis, or esophagitis
  • Histoplasmosis, disseminated or extrapulmonary
  • Isosporiasis, chronic intestinal (>1 month’s duration)
  • Kaposi sarcoma
  • Lymphoma, Burkitt, immunoblastic, or primary central nervous system
  • Mycobacterium avium complex (MAC) or Mycobacterium kansasii, disseminated or extrapulmonary
  • Mycobacterium tuberculosis, pulmonary or extrapulmonary
  • Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
  • Pneumocystis jirovecii ( formerly carinii) pneumonia (PCP)
  • Progressive multifocal leukoencephalopathy (PML)
  • Salmonella septicemia, recurrent (non-typhoid)
  • Toxoplasmosis of brain
  • Wasting syndrome attributed to HIV ((involuntary weight loss >10% of baseline body weight) associated with either chronic diarrhea (two or more loose stools per day for ≥1 month) or chronic weakness and documented fever for ≥1 month)

Source: Bidwell, 2011.

Non AIDS Defining Cancers

Since the introduction of combination antiretroviral therapy, there has been a dramatic decrease in the incidence of AIDS-related morbidity and mortality in HIV-positive patients. However, while the incidence of AIDS-defining cancers has steadily declined, there have been reports of an apparent increase in the number of non AIDS-defining cancers and increases in cancer-related mortality. This apparent increase in incidence may in part simply reflect the normal ageing process in this population (Worm et al., 2013).

Before combination antiretroviral therapy, and in its early stages, the survival of HIV-positive patients diagnosed with cancer was significantly poorer than that of uninfected patients with cancer. These findings may be attributable to more advanced cancer stage and low performance status at cancer diagnosis and other HIV-associated opportunistic diseases among HIV-positive patients as well as the impact of an increased burden of traditional risk factors, such as smoking. There are only limited data on the underlying causes of death in HIV patients with a non AIDS-defining cancer (Worm et al., 2013).

Oral Manifestations

Oral manifestations are common in people with HIV infection and are considered one of its earliest clinical features. By some estimates, more than 90% of AIDS patients will have at least one HIV-related oral manifestation in the course of their disease (KCHFS, 2011).

For some patients, the presence of oral lesions may be the first sign of HIV infection, leading to testing and diagnosis, while for others oral lesions may signify a decline in immune function. Lesions caused by oral candidiasis or hairy leukoplakia in particular are highly suggestive of HIV in patients with no other obvious cause of immunodeficiency (McPhee & Papadakis, 2011). Patients with candidiasis have been shown to have a high rate of progression to AIDS (KCHFS, 2011).

In developed countries, CD4 lymphocyte counts and HIV viral load are the two main laboratory markers that are used to determine disease progression. However, in certain developing countries, people do not always have access to these tests, and severity of the oral lesions can serve as good indicators of disease progression (Krishna et al., 2011).

HIV and Oral Lesions

The EC-Clearinghouse on Oral Problems Related to HIV Infection and the World Health Organization Collaborating Centre on Oral Manifestations of the Immunodeficiency Virus have developed guidelines listing three groupings of oral lesions associated with HIV/AIDS:

Group 1: Lesions strongly associated with HIV infection

  • Candidiasis
  • Hairy leukoplakia
  • Kaposi’s sarcoma
  • Non-Hodgkin’s lymphoma
  • Periodontal disease (linear gingival erythema, necrotizing ulcerative gingivitis, necrotizing ulcerative periodontitis)

Group 2: Lesions less commonly associated with HIV infection

  • Bacterial infections
    • Mycobacterium avium complex (mycobacterium tuberculosis)
    • Melanogic hyperpigmentation
    • Necrotizing (ulcerative) stomatitis
    • Salivary gland disease
    • Dry mouth due to decreased salivary flow
    • Unilateral/bilateral swelling of salivary glands
    • Thrombocytopenia purpura
    • Nonspecific ulcerations
  • Viral infections
    • Herpes simplex virus
    • Human papillomavirus
    • Condyloma acuminatum
    • Focal epithelial hyperplasia
    • Verruca vulgaris
    • Varicella zoster virus

Group 3: Lesions seen in HIV infection

  • Bacterial infections
    • Actinomyces israelii
    • Escherichia coli
    • Klebsiella pneumoniae
    • Cat-scratch disease
    • Drug reactions (ulcerative, erythema multiforme, lichenoid, toxic epidermolysis)
    • Epithelioid (bacillary) angiomatosis
  • Fungal infection other than candidiasis
    • Cryptococcus neoformans
    • Geotrichum candidum
    • Histoplasma capsulatum
    • Mucormycosis (zygomycosis)
    • Aspergillus flavus

Source: Krishna et al., 2011.

Oral Exam

Examination of the oral cavity should be included in both the initial and interim physical examination of all HIV-infected patients. Clinical appearance and symptoms may be nonspecific or atypical. Patients with lesions suspected to be oral manifestations of HIV disease should be referred to a dental health expert with experience in treating oral lesions associated with HIV/AIDS. Other oral lesions may be a sign of a systemic disease, a side effect of medications, or a result of poor oral hygiene (Bidwell, 2011).

Careful diagnostic techniques are required, including laboratory tests for viruses, fungi, and bacteria, and biopsy of lesions. Aggressive treatment is needed because response to treatment can be slow. Relapse and recurrence is common and resistance to treatment must be taken into consideration (KCHFS, 2011).

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