PETRA: Module 1, Chapter 2

Primary Infection

Primary HIV infection is the first stage of HIV disease, when the virus first establishes itself in the body (1). Two to four weeks after exposure to the virus, up to 87% of HIV-infected persons suffer flu-like symptoms for a few days, indicating that their immune systems are fighting the newly introduced HIV. This sickness is called acute HIV syndrome. Its symptoms include fevers, chills, headaches, night sweats, rashes, and swollen glands (2).

It usually takes 6-12 weeks for the immune system to produce antibodies to fight against the virus. This means that a newly infected person's blood may not test positive for HIV antibodies in the first few weeks after becoming infected. Newly infected people are highly contagious during primary infection because large quantities of HIV are present in their genital fluids (3).

Seroconversion

“Seroconversion” describes the time when the body begins producing antibodies to the virus. Most people develop antibodies within three months. Some people can take up to six months to develop antibodies to HIV (1).

Chronic HIV Infection

Asymptomatic period
After the primary infection, HIV+ people then enter an asymptomatic period (that is, a time when they have no signs or symptoms of HIV disease). This period is also called "clinical latency." The duration of people's asymptomatic period varies, and is influenced by their overall health and immune system functioning.

Immune System Decline
Although HIV+ people have no symptoms during the asymptomatic period, their immune systems are already suffering from the presence of HIV. The virus is actively multiplying, and infecting and killing immune system cells (3). HIV levels (“plasma viral load”) in an HIV+ person’s body correlates with the rate of CD4+ cell decline (immune system decline). This means that the more HIV a person has in his or her body--that is, the higher the plasma viral load--the lower his or her number of health-protecting CD4+ cells. The more HIV levels increase and numbers of CD4+ cells decrease, the faster a person progresses to AIDS and death (3).

When HIV levels are not detectable in an HIV+ person's body, he or she has a stable CD4 lymphocyte count. At some point in most people’s HIV disease, the person’s immune system decline quickens, and the virus rapidly replicates (3).

The graph below shows how the average person with HIV CD4+ cell counts and plasma viral loads change over the course of HIV disease. As the graph shows, the natural progression of HIV disease (in the absence of treatment) is fairly slow, taking a decade or more from infection to the development of severe immunodeficiency (3). The line with closed green circles on it charts the average number of CD4+ cells (the immune cells that HIV attacks) in HIV+ people's bodies over time. The line with open blue circles on it charts the average number of HIV particles in HIV+ people's bodies over time.

Mild, Non-specific Symptoms
Once the immune system is damaged, many people will begin to experience some mild symptoms. These include:

- Swollen lymph nodes that persist for more than 3 months
- Fatigue
- Weight loss
- Frequent fevers and sweats
- Persistent or frequent yeast infections (oral and vaginal)
- Persistent skin rashes & flaky skin
- Pelvic inflammatory disease (PID) that does not respond to treatment
- Short-term memory loss
- Frequent or severe herpes infections with oral, genital, or anal sores
- Shingles (a nerve disease)

Advanced HIV Disease/ Clinical AIDS

More Severe Symptoms, Opportunistic Infections and Diseases, “Living with AIDS”
The Centers for Disease Control and Prevention (CDC) has two different sets of criteria for diagnosing AIDS. Both sets of criteria include the presence of HIV or HIV antibodies in the blood or tissues. In addition, the first set of criteria specifies the number of CD4+ cells that signals AIDS. The second set of criteria specifies the 26 opportunistic infections that signal AIDS.

CDC AIDS CRITERIA: SET 1

An HIV infection, confirmed by testing, plus a CD4+ T-cell count of less than 200 per cubic millimeter of blood (healthy adults usually have CD4+ T-cell counts of 1,000 or more) (4).

CDC AIDS CRITERIA: SET 2

An HIV infection, confirmed by testing, plus one of 26 clinical conditions, primarily opportunistic infections that do not normally affect healthy people, including certain kinds of pneumonia or tuberculosis (PCP) (4). In people with AIDS, these infections are often severe and sometimes fatal, because of the people's compromised immune systems.

Opportunistic infections are infections that are caused by bacteria, funguses, or viruses that do not cause disease in people with normal immune systems. In HIV+ people, however, these disease-causing agents take the "opportunity" to flourish in the absence of a normal immune response (1).

Opportunistic infections that – accompanied by a positive HIV test – indicate AIDS include:

Pneumocystis Carinii Pneumonia (PCP) (a kind of pneumonia)
Kaposi's Sarcoma (KS) (a kind of cancer)
HIV wasting syndrome (extreme weight loss)
Non-Hodgkin's lymphoma (a kind of cancer)
Cryptococcosis, extra pulmonary (a parasitic infection, initially of the lungs, that spreads to other parts of the body)
HIV encephalopathy (AIDS Dementia)
Mycobacterium Avium Intracellulare (MAC or MAI) (a bacterial infection of the lungs)
Candidiasis (Yeast Infection) of the trachea, bronchi, or lungs
Candidiasis (Yeast Infection) of the esophagus
Cryptosporidiosis, chronic intestinal (a bacterial infection of the intestines)
Cytomegalovirus disease (CMV) (a kind of eye infection)
Tuberculosis (outside of the lungs)
Herpes simplex virus infection
Progressive Multifocal Leukoencephalopathy (PML) (a nervous system disorder)
Primary lymphoma of the brain (a cancer)
Toxoplasmosis of the brain (a parasitic infection of the brain)
Histoplasmosis (a fungal infection that often scars the lungs)
Isoporiasis, chronic intestinal (protozoa, or tiny animal-like organisms, that infect the intestines)
Coccidioidomycosis (a fungal infection)
Salmonella septicemia (a bacterial infection)
Bacterial infections, recurrent, <13 years
Lymphoid interstitial pneumonia/pulmonary lymphoid hyperplasia, <13 years (lung diseases)
Pulmonary tuberculosis
Recurrent bacterial pneumonia (two or more episodes in one year)
Invasive cervical cancer

Symptoms of opportunistic infections common in people with AIDS

Coughing and shortness of breath
Seizures and lack of coordination
Difficult or painful swallowing
Mental symptoms such as confusion and forgetfulness
Severe and persistent diarrhea
Fever
Vision loss
Nausea, abdominal cramps, and vomiting
Weight loss and extreme fatigue
Severe headaches
Coma

HIV Disease in Children

In the early stages of HIV disease, children who are HIV+ may be frequently ill or have slowed growth. At later stages, children get the same opportunistic infections as adults do, and may also experience severe forms of common childhood bacterial infections, such as pink eye (conjunctivitis), ear infections, and tonsillitis.

References:
1. San Francisco AIDS Foundation. AIDS 101: Guide to HIV Basics- The Stages of HIV Disease. San Francisco AIDS Foundation, 1998. Retrieved on January 26, 2004 from http://www.thebody.com/sfaf/stages.html.

2. Bradley Hare, C. Clinical overview of HIV disease HIV InSite Knowledge Base Chapter. San Francisco, CA: Center for HIV Information, University of California, San Francisco, 2004. Retrieved on June 1, 2004 from http://www.hivinsite.com/InSite?page=kb-03-01-01.

3. Institutes of Allergy and Infectious Diseases (NIAID). HIV Infection and AIDS: An Overview. National Institutes of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, October 2003. Retrieved on January 14, 2004 from http://www.niaid.nih.gov/factsheets/hivinf.htm.

4. Centers for Disease Control and Prevention (CDC). Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Morbidity and Mortality Weekly Report 1992; 41(RR-17):1-19, 1993.

5. Pantaleo, G., Graziosi, C., and Fauci, A.S. New concepts in the immunopathogenesis of human immunodeficiency virus infection. New England Journal of Medicine, 328(5):327-235, 1993.