HIV coinfection with tuberculosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Leena Josephin Jetty, M.B.B.S[2]

HIV is considered a main cause of inability to control tuberculosis (TB) in high HIV settings. In spite of fewer people in USA suffering with TB, it remains a serious threat, especially for HIV-infected persons. In general, TB is one of the leading causes of death among HIV-infected patients. It is estimated that about 4.2% of Americans, with or without HIV infection, are infected with TB bacteria.

Untreated human immunodeficiency virus (HIV) infection markedly increases the risk of tuberculosis, which remains the most common cause of hospitalization and death globally among people with HIV infection in the era of antiretroviral therapy (ART).This is because tuberculosis progresses more rapidly as immunosuppression worsens. Second, it is more difficult to diagnose tuberculosis in people with HIV infection, which can result in a delayed or missed diagnosis.hallanges faced when dealing with HIV associated Tuberculosis include :

• Challenges related to diagnosing tuberculosis in people with HIV infection can result in diagnostic delays.
• Drug–drug interactions and immune reconstitution inflammatory syndrome (IRIS) complicate cotreatment of tuberculosis and HIV infection.
• Short regimens of rifapentine-based preventive therapy are effective, but access to these regimens is limited.

IRIS refers to a group of clinical syndromes associated with immune reconstitution which have been commonly linked to mycobacterial infections (TB and disseminated MAC disease).^[1]

Tuberculosis infection in HIV patients also affect the initiation of treatment. ^[2]

The likelihood of getting sick with other infections and diseases is much more in HIV-infected individuals. Tuberculosis (TB) is one of these diseases. TB commonly affects the lungs; however, It can sometimes affects other organs and body parts, such as the brain, heart, kidneys, or spine.

There are no differences between tuberculosis treatment in HIV-infected adults and adults TB patients without HIV infection. However, TB management in HIV-infected patients is complex and patients with both HIV and TB infections have to seek the medical care from a health care provider or providers with experience in the management of both HIV disease and TB. Because patients with HIV infection are often taking several drugs, some of which interact with anti-TB drugs, experts in the treatment of HIV-related TB should be consulted.

A new epidemiological model, developed by WHO, UNAIDS and the Stop TB Partnership, has reported that HIV/AIDS deaths can be reduced obviously through tuberculosis (TB) prevention and treatment. In 2009, almost one in four deaths among HIV-infected patients were as a result of TB, which is both curable and preventable nowadays.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

The likelihood of getting sick with other infections and diseases is much more in HIV-infected individuals. Tuberculosis (TB) is one of these diseases. TB commonly affects the lungs; however, It can sometimes affects other organs and body parts, such as the brain, heart, kidneys, or spine.

• HIV infection weakens the immune system allowing TB infection to activate and turn into active TB disease. Individuals with both TB infection and HIV infection has a very high risk of developing active TB disease. Without treatment, these two infections can work together, to shorten the life span of the person infected with both.

• In patients with advanced HIV disease, there is no sufficient cell-mediated immune response to create cavitation and usually presents with lobar, pleural or disseminated disease.
• TB pleural effusion is exudative, lymphocyte-predominant, and contains high adenosine deaminase levels.
• TB pleural effusion occurs as a result of hypersensitivity reaction to M.tuberculosis, so pleural fluid smear is often negative for acid-fast bacilli and pleural biopsy is the gold standard for confirming the diagnosis.
• Treatment of HIV has to be delayed 1-2 weeks after TB treatment to avoid immune reconstitution inflammatory syndrome (IRIS).

No, but having HIV increases the chance of progressing from Latent TB infection to active TB disease, but not everyone with HIV develops TB. For this reason, people with HIV should be screened for latent TB infection through tests such as tuberculin skin test (TST), interferon-gamma release assay (IGRA), or molecular diagnostics recommended by WHO.^[1] But it was found that the risk of TB coinfection is doubled in the first year after seroconversion even before the lymphocyte count starts to decline.So early initiation of ART is recommended.

TB is spread through the air from one person to another. The infectious droplets containing the mycobacteria are expelled into the air when a patient with TB disease of the lungs or throat coughs or sneezes. Individuals nearby may get exposed and inhale these mycobacteria and therefore they get infected. However, not everyone gets exposed and infected with TB mycobacteria becomes sick. As a result, two TB-related conditions exist: latent TB infection and active TB disease.

Most people who get exposed to TB mycobacteria and become infected are able to control the bacteria and stop them from growing. Consequently, the bacteria become inactive, but they remain dormant and alive in the body and can get activated later if the immune system is impaired and cannot control the growing of the mycobacterial infection. This is called latent TB infection. With impaired immune system, these mycobacteria begin to multiply in the body and cause active TB disease.

There are an estimated 9 to 14 million persons in the United States infected with TB bacteria. However, it has been reported that most people who have latent TB infection never develop active TB disease. In these people, the TB bacteria remain inactive for a lifetime without causing disease. Individuals with latent TB infection do not feel sick or spread TB mycobacteria to others. Since HIV affects the immune system, people with latent TB infection and HIV coinfection are at much higher risk of developing active TB disease. These mycobacteria begin to multiply in the body and cause active TB disease.

The most recently measured CD4+ T-lymphocyte count is the strongest predictor of the risk of tuberculosis in people who are receiving ART. In the PopART trial, it was found that the risk of tuberculosis was 73% lower among people starting ART with a CD4+ T-lymphocyte count of more than 500 per microliter than those starting ART when the CD4+ T-lymphocyte count was 500 or less per microliter.

Progressive CD4+ T-lymphocyte depletion, which is characteristic of untreated HIV infection, is associated with impaired containment of Mycobacterium tuberculosis. CD4+ T lymphocytes produce interferon-γ which activates macrophages infected with M. tuberculosis and facilitate intracellular killing. This is a key step in granuloma formation, which is critical for limiting the growth and spread of M. tuberculosis. Granulomas in patients with hiv show variation from those who donot have it.Some of the variations include:

• reduced numbers of CD4+ T lymphocytes,
• alterations in macrophage activation and maturation (fewer epithelioid and Langhans giant cells),
• increased neutrophil infiltration and necrosis,
• an increase in the viral load.

moreover thy are poorly organised which facilitates dissemination. HIV alters adaptive immune-cell populations and function in multiple ways,preferential depletion of effector memory CCR5+ CD4+ T lymphocytes occurs at mucosal sites. Selective depletion of M. tuberculosis–specific CD4+ T lymphocytes occurs during early HIV infection. HIV-associated chronic immune activation results increased expression of exhaustion markers such as programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin domain 3 (Tim-3), which lead to impaired pathogen-specific responses. Increased type 1 interferon signaling in response to HIV infection may inhibit protective immune responses directed against M. tuberculosis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

• About 1.1 million individuals were living with HIV infection at the end of 2006. As many as 21% of infected people are unaware of having the infection.
• It is estimated that about 4.2% of Americans with or without HIV infection are infected with the TB bacteria. In 2009 there were approximately 13 million Americans with latent TB infection (LTBI).
• In 2009, among persons with TB who had a documented HIV test result, more than 10% (690 of 6,743) were co-infected with HIV.
• In 2006, the HIV status of 1 in 5 patients with TB was not known, even though CDC recommends that all persons with TB be tested for HIV.
• In 2006, nearly 20% of patients with TB and HIV died. Persons with HIV and TB accounted for 32% of those who died during TB treatment and 51% of those who received a TB diagnosis after death.
• In 2005, of the TB patients reported to be co-infected with HIV, 63% were non-Hispanic blacks.
• World Health Organization (WHO) has reported that the risk of developing TB is approximately 16-27 times greater in HIV-infected individuals than in those without HIV infection.
• In 2015, WHO reported approximately 10.4 million cases of TB disease worldwide. Out of them, 1.2 million [11%] were having HIV infection. About 60% of TB cases among people having HIV infection were not diagnosed or treated, leading to approximately 390,000 TB-related deaths among people living with HIV in 2015.
• The relative risk of tuberculosis among people with HIV infection increases exponentially as CD4+ T-lymphocyte counts decline.
• The risk is increased by a factor of more than 25 when the CD4+ T-lymphocyte count is less than 200 per microliter, as compared with a count of 1000 per microliter.
• Southern Africa and East Africa were the worst affected; in South Africa, the incidence increased by a factor of more than 3 during the 1990s and early 2000s.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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• HIV infection is considered a common critical risk factor for progression from latent TB infection to active TB disease.
• Progression to TB disease is often rapid among HIV-infected persons and can be fatal.
• Rapid progressive expansion of TB outbreaks can occur in HIV-infected patient groups.
• Because many individuals do not perceive themselves to be at risk for HIV or do not disclose their risks, the targeted HIV testing based on physician assessment of patient risk behaviors fails to detect a large number of individuals who have HIV infection.
• Routine HIV testing may decrease the stigma linked to testing.
• With early diagnosis of HIV, appropriately timed interventions can slow the disease progression, reduce the mortality rate, and improve the outcome and quality of life.
• Identifying TB patients, suspects, and contacts who are HIV infected allows for optimal TB testing of these groups and provides opportunities to prevent TB in those without disease.

• According to CDC, HIV screening is recommended for all TB patients after the patient is notified that testing will be done, unless the patient declines (i.e., opt-out screening).
• Routine HIV testing is also recommended for persons suspected of having TB disease and contacts to TB patients.
• Individuals who are at high risk for HIV infection should perform at least annual HIV screening.
• Prevention counseling and separate written consent for HIV testing are no longer be necessary.

Opt-out screening refers to HIV testing after patient notification that the test will be done, and although the patient may decline or defer testing, it is highly recommended.

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Until the a couple of years ago Tuberculosis was visualised in a dichotomous state of Latent phase or Active disease.But with the recent advances in the Imaging modalities and screening tests TB is conceptualized as a continuous spectrum of disease stages from latent to subclinical to symptomatic, active disease.

• In people with HIV and Mild immuno-suppression ,it usually presents as in people without hiv i.e as pulmonary tuberculosis.
• People with HIV infection who have severe immunosuppression (CD4+ T-lymphocyte count, <200 per microliter)most commonly present to the clinic with Extra Pulmonary Tuberculosis.The most common sites being Lymph nodes,Liver,Spleen, Serosal surfaces ( resulting in Effusions) and CNS.

People with severe immunosuppreession can have accelerated progression of disease course and many a times it mimics acute bacterial infections.

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