AIDS defining illnesses are potentially life threatening diseases that can occur in people living with HIV. The diagnosis of an AIDS defining illness can confirm that HIV has progressed to AIDS.

Another way for doctors to determine this is by measuring a person’s cluster of differentiation 4 (CD4) cell count. CD4 cells are a type of white blood cell. HIV attacks the body’s CD4 cells, weakening the immune system.

AIDS defining illnesses can be severe, especially in people who are not taking antiretroviral medication.

Keep reading to learn more about AIDS defining illnesses, including what they are, risk factors, and a look at how they differ from opportunistic infections.

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AIDS defining illnesses are diseases that occur in people living with HIV. They are one of the indications that HIV has progressed to AIDS, the most severe form of the disease.

AIDS defining illnesses can differ in severity, and some occur more frequently than others. According to the Centers for Disease Control and Prevention (CDC), they are less common now since the introduction of antiretroviral therapy (ART).

However, some may still develop an AIDS defining illness if:

  • they do not know they have HIV
  • they do not take ART
  • ART is unable to kill the virus

Doctors can also make a diagnosis of AIDS when CD4 levels fall below 200 cells per milliliter (ml), if they develop certain opportunistic infections, or both. Common AIDS defining illnesses include:

Pneumocystis jiroveci pneumonia (PJP)

A fungus known as Pneumocystis jirovecii causes this type of pneumonia. It is a major cause of infection in people with HIV, with nearly 400,000 cases worldwide each year.

Symptoms include:

  • cough
  • shortness of breath on exertion
  • fever
  • tachycardia

Doctors may prescribe a combination of intravenous (IV) antibiotics for severe infections. People with an increased risk of PJP may need antibiotics to prevent a fatal infection before it can develop.


A group of fungi known as Candida can cause candidiasis infections. One of the most common fungi is Candida albicans. While candidiasis can affect many parts of the body, doctors associate oral infections with immunocompromised individuals.

People with this infection may experience difficulty or pain when swallowing food. Doctors will recommend antifungal therapy to treat it.


Coccidioides fungus can cause coccidioidomycosis, or as it is sometimes known, “valley fever.” Infection can occur if someone inhales the fungal spores.

People with this infection may feel generally unwell or have no symptoms. Antifungal drugs, such as azoles and amphotericin B, can treat this infection.

Cryptococcal meningitis

This form of meningitis results from a fungal infection that causes inflammation in the brain and spinal cord.

HIV-associated cryptococcal meningitis accounts for approximately 150,000–200,000 deaths annually. People with the disease may experience:

  • fever
  • headache
  • confusion
  • nausea
  • behavioral changes

Doctors may prescribe antifungal therapy starting with a combination of liposomal amphotericin B and flucytosine. The long-term use of fluconazole is important for rebuilding the body’s immune system. People generally respond to treatment, and symptoms lessen.


This disease is due to the fungus Histoplasma capsulatum. It can enter the lungs and cause infection long after initial contact with the fungus.

The symptoms may be flu-like, including fever, weight loss, and fatigue. Histoplasmosis becomes AIDS defining when the fungus spreads outside the lungs and affects other parts of the body. This may cause liver or spleen enlargement, pulmonary symptoms, and adrenal gland issues.

Treatment may involve intravenous liposomal amphotericin and then administering the antifungal drug itraconazole for severe cases.


Cryptosporidium, a type of parasite, causes cryptosporidiosis. It causes severe diarrhea and abdominal pain. Doctors treat it with antiparasitic drugs, such as nitazoxanide and azithromycin.


Toxoplasmosis is a Toxoplasma gondii infection. This parasite lives in animal feces and contaminated foods.

When CD4 count drops dramatically, below 50 cubic ml, there is a greater risk of developing encephalitis, or brain inflammation, from toxoplasmosis. Prevention measures include giving people medication, especially if antibodies for the parasite are in the blood.

Cytomegalovirus (CMV)

CMV infections can affect many parts of the body. When it affects the eye, it causes CMV retinitis. Without treatment, the disease may advance quickly.

CMV can cause increased floaters in the eye, or a loss of peripheral vision. However, not all individuals experience symptoms. There is a range of oral and intravenous antiviral drugs options that can be effective against CMV infections.

Mycobacterium avium complex (MAC)

Mycobacteria cause MAC. In a person with AIDS, the infection can spread throughout the body. Symptoms may include fever, night sweats, abdominal pain that last several weeks. MAC typically affects people with CD4 counts below 50 microliters.

How a doctor prevents and treats MAC depends on an individual’s situation. If a person is not already undergoing ART, a doctor may initiate this immediately. If that is not possible, they may receive medications to prevent widespread MAC.

If someone has an infection, doctors may use a combination of antimycobacterial drugs, such as azithromycin or clarithromycin.

Tuberculosis (TB)

TB occurs due to the Mycobacterium tuberculosis bacteria. The World Health Organization (WHO) estimates TB to be the cause of death in 13% of people with AIDS. It leads to lung infections and may cause a cough, tiredness, weight loss, and fever.

Recommendations for treating TB in people with HIV are the same as treating adults without the virus. A doctor may prescribe the following antituberculosis drugs in specific regimens:

  • isoniazid
  • rifampin
  • ethambutol
  • pyrazinamide

Salmonella septicemia

People can get Salmonella from contaminated food or water sources. In individuals with HIV, the bacteria can enter the blood and move to other parts of the body, causing serious illness.

People tend to get gastroenteritis symptoms with this disease. Doctors may prescribe an antibiotic known as fluoroquinolone to treat it.


Individuals with HIV can experience persistent pneumonia infections. Various bacteria, viruses, and fungi can cause it. Therefore, it is advisable to get annual vaccines for influenza, PCV13, and PCV23 to help prevent this.

HIV-related leukoencephalopathy

Human polyomavirus 2, or JC virus, causes this disease in people with HIV. Symptoms can vary but may include:

  • clumsiness
  • progressive weakness
  • visual and speech changes

There are limited treatment options for this disease. The main approach to therapy is reversing the damaged immune system’s response to the HIV infection.

HIV wasting syndrome

Wasting refers to unintentional loss of more than 10% of a person’s body weight across 30 days, along with weakness and diarrhea. There are no standard treatment options for this syndrome.

People living with HIV have higher rates of developing certain cancer types compared with the general population. Some of the most common are:

  • Cervical cancer: Human papillomavirus (HPV) is a virus that can cause infections in the cells lining the uterus. Some types of HPV cause cervical cancer. It is very important that people with HIV undergo regular screening for cervical cancer.
  • Non-Hodgkin lymphoma (NHL): Doctors associate an aggressive form of NHL with HIV. This is a cancer of the white blood cells, or lymphocytes. Sometimes, an Epstein-Barr virus infection can cause some types of NHL.
  • Kaposi sarcoma (KS): KS is the result of an infection with human herpesvirus-8. It can appear as raised or flat pink or purple spots on the skin.

Taking combination ART therapy as a doctor recommends can lower the risk of KS and NHL in people with HIV. This is most likely because the therapy is working to reduce HIV levels in the blood, allowing the immune system to fight off viruses.

However, ART does not prevent all types of HIV-related cancer.

Opportunistic infections occur when a microbe that does not typically cause disease in humans takes advantage of a weakened immune system and begins growing in high numbers.

Some AIDS defining illnesses are opportunistic infections, but not all. For example, candidiasis is an opportunistic infection because Candida yeasts commonly live in humans without causing illness. Pneumonia is not an opportunistic infection because the microbes that cause it are always harmful.

Opportunistic infections are usually more severe in people living with HIV and can even be life threatening. Doctors can use the presence of some opportunistic infections to diagnose AIDS, even if someone’s CD4 count is within expected ranges.

Several factors may increase the chances of someone with HIV developing an AIDS defining illness. They include:

  • not taking ART drugs or prophylaxis
  • having a very low CD4 count
  • a history of TB
  • exposure to sexually transmitted infections
  • exposure to germs
  • drinking untreated or unsafe water
  • sharing needles to inject drugs
  • consuming certain foods, such as undercooked eggs or unpasteurized dairy

Avoiding these things, wherever possible, can reduce the risk of an immunocompromised person contracting a dangerous illness.

Some AIDS defining illnesses are more severe than others and can affect people differently. As such, the prognosis varies across cases. However, the outlook for people with HIV has improved since the 1990s.

Healthcare professionals recommend that individuals with HIV commence ART immediately and try to live a healthy lifestyle wherever possible.

People living with HIV can develop AIDS defining illnesses for a variety of reasons, such as not taking ART medication. Screening for these diseases and getting an early diagnosis are very important.

Generally, the outlook for people with HIV is much better than it was before the advent of effective medication. With the introduction of ART and the use of preventive medications, there has been a decrease in AIDS defining illnesses.

Many infections can occur in people living with HIV, but only some are AIDS defining. A doctor may advise taking preventive measures, such as vaccines, to reduce the risk of getting some of them.