Monday, 8 October 2018

HIV RNA expression inhibitors may restore immune function in HIV-infected individuals

Immune activation and inflammation persist in most treated HIV-infected individuals and is associated with excess risk of mortality and morbidity. A new study by Boston University School of Medicine (BUSM) researchers suggests that use of HIV RNA expression inhibitors as adjunct therapy might diminish atypical inflammation and restore immune function in HIV-infected individuals on combination antiretroviral therapy (cART).

HIV-1-infected individuals have excess risk of developing non-AIDS complications such as cardiovascular atherosclerosis, neurocognitive dysfunctions, non-AIDS cancers, osteoporosis, and renal disorders. Systemic chronic immune activation has been postulated to lead to these non-AIDS complications.

Despite long-term viral suppression by cART, it has remained unclear how chronic inflammation is induced in HIV-infected individuals. In this study, BUSM researchers identified a mechanism of HIV-1-induced chronic immune activation and T cell dysfunction. In studies performed with primary human macrophages and T cells, they found that persistent infection of macrophages with HIV-1 and expression of intron-containing HIV-1 RNA alone even in the absence of infectious virus production lead to induction of type I interferon (IFN-I)-dependent pro-inflammatory responses and immune exhaustion of co-cultured T cells. They believe that these findings might provide an explanation for the observed chronic inflammation-associated morbidities in HIV-infected individuals who are on cART.

"We hope our study will broaden knowledge of host-HIV interactions and might help to reduce inflammation-associated disorders caused by chronic viral infections," said Rahm Gummuluru, PhD, corresponding author and associate professor of microbiology.


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Friday, 5 October 2018

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Wednesday, 3 October 2018

“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 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.


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 (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 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 (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.

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.