What is HIV-1–Associated Opportunistic Infections?
The human immunodeficiency virus (HIV) is a type of virus that can harm your immune system, especially a kind of white blood cells called CD4+ T lymphocytes, which are vital in fighting off infections. There are two different kinds – HIV-1 and HIV-2. HIV-1 is the type that most people around the world have, while HIV-2 mostly occurs in West Africa and is fairly rare. When someone with HIV doesn’t get treatment with antiretroviral medicines, their count of CD4+ cells can decrease, making them susceptible to all sorts of infections that normally wouldn’t affect someone with a healthy immune system. These are often referred to as opportunistic infections. If a person with HIV develops certain serious illnesses, or their CD4+ count falls under 200 cells/mm³ – which is very low – they are then defined as having AIDS. These patients can suffer from life-threatening opportunistic infections that are often hard to treat.
What Causes HIV-1–Associated Opportunistic Infections?
People with HIV, even if they have high counts of a specific type of immune cell called CD4+ cells, are more likely to develop both typical and opportunistic infections than people without HIV. Opportunistic infections are infections that occur more often or are more severe in people with weakened immune systems compared to people with healthy immune systems.
In people with HIV who have CD4+ cell counts less than 200 cells per millimeter, the risk of getting these infections and the possibility of death is really high. These individuals can catch a wide range of bacterial, viral, fungal, and protozoal infections. These can include infections like Toxoplasma gondii (a type of parasite), Pneumocystis jirovecii (a type of fungus), Cryptococcus neoformans (another type of fungus), Mycobacterium avium and Mycobacterium tuberculosis (types of bacteria), Cytomegalovirus and Herpes simplex viruses (types of viruses), and Histoplasma capsulatum (yet another type of fungus).
Risk Factors and Frequency for HIV-1–Associated Opportunistic Infections
In 2015, it was estimated that 1.1 million people in the US were living with HIV. By 2017, the estimated number of people with HIV worldwide had risen to 36.7 million. HIV is recognized as a major global health problem.
The virus is most commonly transmitted through unprotected sex, particularly between men; which accounts for 70% of new HIV infections in the US. Other common ways of transmission include using contaminated needles for drug use, receiving contaminated blood transfusions, and from mother to baby during or after childbirth.
The use of antiretroviral therapy (ART) has been successful in reducing HIV-related infections. However, those who discover their HIV status late or cannot keep the virus under control are at high risk for these infections.
Signs and Symptoms of HIV-1–Associated Opportunistic Infections
The effect of HIV on the immune system depends on the count of CD4+ cells in the body. CD4+ cells are vital immune cells, and their drop in number allows various infections, often dictated by the severity of the CD4+ suppression. The infections are categorized as follows according to the different CD4+ counts:
- All CD4+ counts: Mycobacterium tuberculosis could cause latent TB. Symptoms include fatigue, weakness, weight loss, fever, and chronic cough. Tuberculosis can affect all organ systems.
- CD4+ count less than 250: Coccidioidomycosis, an illness that originates from two soil-dwelling species. It could manifest as pneumonia with fever, cough, chest pain, or meningitis.
- CD4+ count less than 200: Pneumocystis jirovecii pneumonia (PCP) and Mucocutaneous candidiasis might start to show their symptoms such as fever, cough, and typical mouth infections, among others.
- CD4+ count less than 150: Histoplasma capsulatum, a fungal infection, might cause fever, muscle pain, chills, headaches and a dry cough.
- CD4+ count less than 100: Cryptococcus neoformans, Cryptosporidiosis, Herpes simplex viruses (HSV), and JC virus infections associated with conditions like meningitis, pneumonia, and progressive multifocal leukoencephalopathy (PML) could occur.
- CD4+ count less than 50: Conditions such as retinitis caused by Cytomegalovirus, Mycobacterium avium complex (MAC) which can damage any organ, and Toxoplasma gondii encephalitis which can cause fever and confusion may appear.
In addition to the above, people with HIV are susceptible to other infections such as Syphilis, human papillomavirus infection with predominantly mucosal infections, and Hepatitis B and C virus infections leading to chronic liver disease. Infections or their severity is often aligned with CD4+ cell count in the body.
Testing for HIV-1–Associated Opportunistic Infections
In patients with HIV, it’s vital to regularly monitor the levels of a certain type of white blood cell called CD4+ cells. This helps to spot and treat infections early on, and can indicate when preventative treatments should start. Let’s explain some specific testing details for different infections.
Mycobacterium tuberculosis: All HIV positive patients should be tested for this. A skin test, called a Tuberculin skin test (TST), which checks their reaction to TB bacteria, is performed. However, this test can be less effective in patients who’ve been vaccinated or who have weak immune systems. An alternative is the Interferon-gamma release tests (IGRA), which is more consistent and accurate. If any abnormalities are found in a chest x-ray, more tests would be performed.
Coccidioidomycosis: This infection is diagnosed by isolating the organism in a sample or viewing it under a microscope. Testing fluid from the spinal cord can be used to detect meningitis, although this only works in less than 30% of cases.
Pneumocystis jirovecii pneumonia: Identifying this organism in tissue or lung fluid samples helps diagnose this condition. Different stains are used to view the details of the organism under a microscope.
Mucocutaneous candidiasis: White sores that can be scraped off, especially in the mouth or throat, suggest this condition. The presence of Candida yeast forms in tissues or cultures confirms this.
Histoplasma capsulatum: It’s a bit tricky to detect this in blood or urine tests. This organism grows slowly, making cultures require weeks. But they’ve been found in more than 85% of AIDS patients’ sample tissues.
Cryptosporidiosis: These small parasites are identified through the microscope in stool or tissue samples.
Herpes simplex viruses (HSV): Tests which identify HSV DNA, viral cultures and antigen detection are used for detecting skin lesions.
Microsporidiosis: Microsporidia, tiny single-celled parasites, can be spotted under the microscope using different types of stains.
JC virus infection: Progressive multifocal leukoencephalopathy (PML) linked with JC virus infection is diagnosed by an MRI and evidence of JC virus DNA in the spinal cord fluid.
Mycobacterium avium complex (MAC): Cultures of blood, lymph node, or other sterile tissues coupled with symptom observation help diagnose disseminated MAC infection.
Toxoplasma gondii encephalitis (TE): Detection of antibodies against Toxoplasmas in the body along with CT or MRI imaging and tissue biopsy can establish the diagnosis.
Bartonellosis: Culture tests are difficult but they can be performed with specialized tubes. Serologic tests developed by Centers for Disease Control and Prevention can also aid in detecting the bacteria.
Syphilis: Various techniques like dark-field microscopy, silver stain, direct fluorescent anti-Treponema antibody, and serological tests are useful in diagnosing syphilis. Cerebrospinal fluid examination helps diagnose neurosyphilis.
Human papillomavirus infection: Visual inspection of warts usually suffices followed by a biopsy if required.
Hepatitis B and C virus infections: All HIV positive individuals should be tested for Hepatitis B and C. Blood tests can help detect ongoing infections. Liver biopsy might be performed to evaluate the effects of hepatitis C on the liver.
Treatment Options for HIV-1–Associated Opportunistic Infections
All people living with HIV/AIDS are considered suitable for a potent form of treatment known as highly active antiretroviral therapy (HAART). This treatment helps in reducing illness and death associated with the disease and also lowers the risk of passing the infection onto others. Generic tablet compositions containing drugs like Rilpivirine, Emtricitabine, Tenofovir, Dolutegravir, Abacavir, and Lamivudine are commonly used in this therapy.
In addition to this, HIV/AIDS patients often experience opportunistic infections, which are caused by different organisms, and this needs to be addressed. Opportunistic infections are infections that occur more often and are more severe in people with a weakened immune system.
For instance, patients who are at a higher risk of developing a parasitic disease called Toxoplasmosis, could be given medications like Trimethoprim-sulfamethoxazole, Dapsone-Pyrimethamine, or Leucovorin. If the patient is pregnant, Spiramycin can be recommended to prevent the infection from being passed onto the baby.
In the case of another infection, Pneumocystis jirovecii, the drug Trimethoprim-sulfamethoxazole can be administered as preventive therapy to all HIV positive patients, including pregnant women, who have a CD4+ count less than 200 cells/mm3. CD4+ count is a key measure of the strength of the immune system and the progression of HIV or AIDS.
For the treatment of a fungal infection of the brain (Cryptococcus Neoformans), a combination therapy of Flucytosine and Amphotericin B is typically used. Post-treatment, they might be put on a maintenance dose of Fluconazole. Secondary prophylaxis, or additional preventive therapy, may be needed if the CD4+ count falls below 100 cells/mm3.
There are various other infections that patients might be prone to, and each of these requires a different approach. For example, Mycobacterium avium complex (MAC) -related infections are typically treated using Clarithromycin, and Mycobacterium Tuberculosis can be treated using a combination of drugs including Isoniazid, Pyrazinamide, Rifampin or Rifabutin, and Ethambutol.
Moreover, infections like Cytomegalovirus, Herpes Simplex Viruses, Histoplasma Capsulatum, Coccidioidomycosis, Mucocutaneous Candidiasis, Cryptosporidiosis, Microsporidiosis, JC virus infection, Bartonellosis, Syphilis, Human Papillomavirus infection, Hepatitis B, and Hepatitis C, all have very specific treatments and drugs to prevent and manage the infections.
While every infection has its specific line of treatment, the ultimate goal for all patients is to restore and maintain their CD4+ cells count above 100 cells/mm3. This essentially helps in reversing the clinical symptoms of the opportunistic infections as it strengthens the immune system.
What else can HIV-1–Associated Opportunistic Infections be?
When diagnosing certain conditions such as central nervous system toxoplasmosis, doctors might need to consider other diseases that could cause similar symptoms. Such conditions include:
- CNS lymphoma
- Brain abscesses
- Various infections (e.g. by Rubella, Cryptococcus neoformans, Aspergillus species, and Nocardia species)
- Mycosis fungoides (a type of skin cancer)
- Sarcoidosis (inflammation that occurs in various organs)
- Syphilis
- Tuberculosis
- Leukemia
- Lymphoma
- Fungal endophthalmitis (inflammation of the internal coatings of the eye)
Similarly, for conditions like Pneumocystis jirovecii pneumonia, it’s also necessary to consider various diseases that present similar symptoms, such as:
- Acute respiratory distress syndrome
- Cytomegalovirus infection
- Viral pneumonia
- Lung cancer
- Tuberculosis
The same goes for conditions like Mycobacterium avium complex (MAC), where the doctors also need to consider diseases like Mumps, Parotid Tumors, Lung cancer, Aspergillosis, Tuberculosis, amongst others.
For Mycobacterium tuberculosis, other conditions like Tularemia, Actinomycosis, Syphilis, Leishmaniasis could show similar symptoms. Cytomegalovirus could resemble conditions like HIV/AIDS, Toxoplasmosis, and autoimmune hepatitis. Herpes simplex encephalitis could mimic conditions like Neurosyphilis and Paraneoplastic encephalomyelitis. Histoplasma capsulatum could be confused with conditions like Sarcoidosis, different types of pneumonia or Tuberculosis.
What to expect with HIV-1–Associated Opportunistic Infections
The outlook for people with AIDS who acquire additional diseases (known as opportunistic infections) is often not very good. However, if patients consistently follow their antiretroviral therapy (ART – a treatment used to manage the HIV infection), they can lower the chance of getting these infections, which could ultimately lead to better health outcomes for those living with HIV.
Possible Complications When Diagnosed with HIV-1–Associated Opportunistic Infections
People with HIV/AIDS are more vulnerable to certain infections because their immune system is weaker. As the disease gets worse, their immune system gets weaker, putting them at higher risk of these infections. Besides these infections, people with HIV/AIDS might also experience non-infectious issues like brain issues related to HIV, a certain type of cancer called high-grade B-cell lymphoma, an HIV-linked condition causing severe weight loss, and kidney problems associated with HIV.
- Increased vulnerability to certain infections due to weakened immune system
- HIV-related brain conditions
- High-grade B-cell lymphoma (a type of cancer)
- Severe weight loss caused by HIV
- Kidney problems associated with HIV
