“AIDS-defining” conditions

HIV is a virus that attacks CD4 cells (T cells). These white blood cells serve as helper cells for the immune system. CD4 cells send a biological SOS signal to other immune system cells to go on the offensive against infections.

When a person contracts HIV, the virus merges with their CD4 cells. The virus then hijacks and uses the CD4 cells to multiply. As a result, there are fewer CD4 cells to fight infections.

Opportunistic infections and diseases

With HIV, a weakened immune system increases vulnerability to several opportunistic infections, cancers, and other conditions. The CDC refers to these as “AIDS-defining” conditions. If someone has one of these conditions, the HIV infection has advanced to stage 3 HIV (AIDS), regardless of the number of CD4 cells in their blood.

Following are some of the more common opportunistic diseases. Becoming knowledgeable about these health risks is the first step in protecting against them.

Candidiasis

Candidiasis encompasses several infections in different areas of the body caused by Candida, a genus of fungi. These infections include oral thrush and vaginitis. A fungal infection is considered AIDS-defining when found in the esophagus, bronchi, trachea, or lungs.

Powerful and sometimes quite toxic antifungal medications are used to treat candidiasis. A healthcare provider will recommend a specific medication based on the location of infection.

For instance, they may prescribe these medications for vaginitis caused by candidiasis:

• butoconazole (Gynazole)
• clotrimazole
• miconazole (Monistat)

If systemic infection is present, treatment may include medications like:

• fluconazole (Diflucan)
• itraconazole (Sporanox)
• posaconazole (Noxafil)
• micafungin (Mycamine)
• amphotericin B (Fungizone)

Cryptococcal meningitis

Cryptococcus is a common fungus found in soil and bird droppings. Some varieties also grow in areas surrounding trees, and one variety particularly prefers eucalyptus trees. If inhaled, Cryptococcus may cause meningitis. This is an infection of the membranes around the brain and spinal cord.

Very potent (and quite often toxic) antifungal medications are used to initially treat cryptococcal meningitis, as are frequent spinal taps. These medications may include in combination:

• amphotericin B
• flucytosine (Ancobon)
• fluconazole
• itraconazole

This condition can be fatal if not treated promptly. Long-term suppressive therapy is often used with somewhat less toxic medications for people with HIV.

Cryptosporidiosis

A tiny parasite that lives in the intestines of humans and animals is responsible for cryptosporidiosis. Most people get the disease by drinking contaminated water or eating contaminated produce.

Cryptosporidiosis is an unpleasant diarrheal illness for healthy people. However, for those who are HIV-positive, it can last longer and cause more severe symptoms.

A medication called nitazoxanide (Alinia) is normally prescribed to treat the disease.

Cytomegalovirus

Cytomegalovirus (CMV) is virus most commonly thought of as causing serious eye disease in people with weakened immune systems. It can potentially lead to blindness.

CMV can also lead to illness in other areas of the body, such as the digestive tract and parts of the nervous system.

There are currently no medications to cure CMV. However, several powerful antiviral medications can treat the infection. These include:

• gancliclovir (Zirgan)
• valgancilovir (Valcyte)
•  foscarnet (Foscavir) 
• cidofovir (Vistide)

In people with severely weakened immune systems, these CMV medications often need to be given at significant doses over the long term.

However, the damage from CMV infection may slow with the use of antiretroviral therapy. This can result in the rebuilding of the immune system (as demonstrated by clinically significant rises in CD4 count). Anti-CMV therapy may potentially be changed to easier-to-tolerate suppressive treatments.

Herpes simplex viruses

Herpes simplex virus (HSV) is characterized by sores on the mouth, lips, and genitals. Anyone can get herpes, but people with HIV experience increased frequency and severity of outbreaks.

There is no cure for herpes. However, relatively easy-to-tolerate medications, taken long term, can alleviate symptoms of the virus.

Pneumocystis pneumonia

Pneumocystis pneumonia (PJP) is a fungal pneumonia that can be fatal if it’s not diagnosed and treated early. PJP is treated with antibiotics. The risk of a person with HIV developing PJP rises so high that preventive antibiotic therapy may be used if their CD4 count drops below 200 cells per microliter (cells/µL).

Salmonella septicaemia

Commonly referred to as “food poisoning,” salmonellosis is a bacterial infection of the intestines. The bacteria responsible is most often transmitted via food or water that has been contaminated with feces.

The U.S. Food and Drug Administration (FDA) reports that those with weakened immune systems, such as people living with HIV, have at least a 20 times greater risk of salmonellosis. Salmonellosis can spread into the blood, joints, and organs.

Antibiotics are commonly prescribed to treat this infection.

Toxoplasmosis

Toxoplasmosis is caused by parasites in contaminated food. The disease can also be contracted from cat feces.

The risk of significant disease from toxoplasmosis infection rises substantially once the CD4 count drops below 100 cells/µL. An HIV-positive person should ideally avoid all contact with cat feces or any other source of toxoplasmosis exposure.

People who have severely weakened immune systems (less than or equal to 100 CD4 cells/µL) should receive the same preventive antibiotic therapy as that for PJP.

Toxoplasmosis is treated with antimicrobial medications such as trimethoprim-sulfamethoxazole (Bactrim).

Tuberculosis

Tuberculosis (TB) may seem like a disease from the past, but it’s actually the leading cause of death for individuals who have HIV.

TB is caused by Mycobacterium tuberculosis bacteria and is spread through the air. TB generally affects the lungs and has two forms: latent TB and active TB disease.

Individuals with HIV are more likely to become sick with TB.

The disease is treated over the course of six to nine months with a combination of several medications, including:

• isoniazid (INH)
• rifampin (Rifadin)
• ethambutol (Myambutol)
• pyrazinamide

With treatment, both latent and active TB can be managed, but without treatment, TB can lead to death.

Mycobacterium avium complex (MAC)

Mycobacterium avium complex (MAC) organisms are present in most everyday environments. They rarely cause problems for people with healthy immune systems. For those with weakened immune systems, however, MAC organisms can make their way into the body through the GI system and spread. When the organisms spread, they may lead to MAC disease.

This disease causes symptoms such as fever and diarrhea, but it usually isn’t fatal. It can be treated through antimycobacterials and antiretroviral therapy.

Opportunistic cancers

Invasive cervical cancer

Cervical cancer begins in the cells lining the cervix. The cervix is located between the uterus and vagina. Cervical cancer is known to be caused by the human papillomavirus (HPV). Transmission of this virus is extremely common among all sexually active women. But studies have clearly demonstrated that the risk of contracting HPV rises substantially as HIV progresses.

For this reason, HIV-positive women should undergo regular pelvic exams with Pap tests. Pap tests can detect early cervical cancer.

Cervical cancer is considered invasive when it spreads outside the cervix. Treatment options include surgery, radiation therapy, or chemotherapy.

Kaposi sarcoma

Kaposi sarcoma (KS) is linked to infection by a virus called human herpes virus 8 (HHV-8). It causes cancerous tumors of the body’s connective tissues. Dark, purplish skin lesions are associated with KS.

KS isn’t curable, but its symptoms often improve or resolve completely with antiretroviral therapy. Several other treatments are available for people with KS. These include radiation therapy, intralesional chemotherapy, systemic chemotherapy, and retinoids.

Non-Hodgkin’s lymphoma

Non-Hodgkin’s lymphoma (NHL) is a cancer of lymphocytes, cells that are part of the immune system. Lymphocytes are found throughout the body in such places as the lymph nodes, digestive tract, bone marrow, and spleen.

Various treatments are used for NHL, including chemotherapy, radiation therapy, and stem cell transplants.

Source: https://www.healthline.com/health/hiv-aids/opportunistic-infections

Study shows how HIV is shielded from Immune Attack

Scientists from UNSW Sydney and the UK have discovered that the human immunodeficiency virus (HIV) hijacks a small molecule from the host cell to protect itself from being destroyed by the host's immune system.

The finding, as well as details of the new strategy that enabled it, are published as back-to-back papers in eLife. They identify a new target for antiviral therapy against HIV and provide a method for testing and measuring new drugs designed to target the capsid.

UNSW Ph.D. student Chantal Márquez is involved in both studies and is the first author of the paper describing the new method.

HIV forms a protein shell—called a capsid—that shields its genetic material from host defence mechanisms as it enters the cell and makes its way to the nucleus to establish infection.

Using a new single-molecule microscopy technique—developed at UNSW's Single Molecule Science in the Faculty of Medicine—the research teams found that HIV specifically incorporates a small molecule from the host cell—inositol hexakisphosphate—to strengthen its capsid. The host inadvertently provides the key for the virus infecting it to lock down the protective shell, keeping the genetic cargo safe until it is released into the nucleus.

"The HIV capsid falls apart within minutes once it's isolated from the virus," said Associate Professor Till Böcking, who led the UNSW team involved in both studies.

"Our strategy lets us study exactly how a native capsid breaks apart in real-time without taking it out of the viral membrane."

With the help of Associate Professor Stuart Turville of the Kirby Institute, the team engineered viruses with fluorescent tags to monitor the viral capsid using fluorescence microscopy.

"We can now see the effect of different molecules on the capsid, and pinpoint precisely when it cracks open and begins to collapse," says Associate Professor Böcking.

"Capsids need to be much more stable inside a cell because the infection process takes hours, not minutes—so we wanted to find out what keeps it stable inside a cell," says Dr. David Jacques of Single Molecule Science, who is an author of both studies.

The researchers found that inositol hexakisphosphate, which is abundantly present inside mammalian cells, makes the capsid much stronger, stabilizing it for 10-20 hours.

"It's like a switch. When you bind this molecule, you stabilize the capsid, and release the molecule to open it up," explains Associate Professor Böcking.

"The HIV capsid has been intensively studied, but the question of how it can simultaneously be both stable and poised to 'uncoat' has been one of the great unanswered questions in HIV biology," says Dr. Leo James, leader of the research team at the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK.

Most of the currently approved HIV therapies target enzymes needed at different stages of the virus' life cycle, but none of them are directed at the HIV capsid. New drug alternatives could improve the treatment of HIV with reduced toxic effects.

Source: https://medicalxpress.com/news/2018-07-hiv-shielded-immune.html

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Babies who dodge HIV may not be unscathed

Exposure to the virus, the mother's microbiome, and drugs each could cause harm.

Up to half of babies born to HIV-infected mothers become infected themselves either in utero, during labor, or through breastfeeding, unless the mothers and babies are treated with antiretroviral (ARV) drugs. But several studies suggest an additional burden for the many children in Nigeria who dodge transmission from their mothers, whether by luck or treatment: They may still suffer from growth retardation, immune abnormalities, and even an increased risk of mortality. “Exposed, uninfected children are a growing population, and they're neglected,” says virologist Nicaise Ndembi of the Institute of Human Virology, Nigeria (IHVN) in Abuja.

At the University of Benin Teaching Hospital in Benin City, Ndembi is a co–principal investigator (co-PI) of a study exploring what happens to those exposed, uninfected children and why. “There's a growing body of data that suggests they're very different from normal infants,” says another co-PI, epidemiologist Man Charurat of IHVN.

Theoretically, the harm could come from the mother's poor health, or from exposure to viral proteins or to the ARV drugs given to treat the mother and the baby to prevent transmission. “It's a really complicated picture,” says Claire Thorne, an epidemiologist at University College London who is trying to separate the effects of HIV exposure from exposure to ARV drugs.

The IHVN team is exploring whether an HIV-caused condition called “leaky gut” may transfer from mother to uninfected child. HIV preferentially destroys immune cells in the gut shortly after infection, leading to an overstimulated immune system, inflammation, and a permeable gut. That could alter the mother's microbiome, and she might pass the altered bacteria to her child during birth or breastfeeding. The Benin researchers suspect the child's altered microbiome then increases diarrhoea, impedes proper absorption of nutrients, and slows growth.

The IHVN study, which began in 2014 and will run through next year, compares 300 uninfected children, half of whom were exposed to HIV during their first 2 years of life. The researchers are analyzing stool samples from mothers and their children to see whether HIV alters the genera of bacteria that live in their guts. Researchers also are giving the children a dose of two sugars and then testing their urine to see whether their intestines have compromised permeability. “If we can identify problems, we can begin to look at interventions,” Ndembi says.

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Source: http://science.sciencemag.org/content/360/6394/1168.full