HIV coinfection with tuberculosis

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 * Ujjwal Rastogi, MBBS [mailto:urastogi@perfuse.org]

Overview
HIV is the main reason for failure to meet Tuberculosis (TB) control targets 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 fact, worldwide TB is one of the leading causes of death among people infected with HIV. It is estimated that about 4.2% of Americans, with or without HIV infection, are infected with TB bacteria. People infected with HIV are more likely than uninfected people to get sick with other infections and diseases.

IRIS is a group of clinical syndromes associated with immune reconstitution that have been observed most commonly for mycobacterial infections (TB and disseminated MAC disease).

Tuberculosis infection in HIV patients also affect the initiation of treatment.

Pathophysiology: The connection between TB and HIV
People infected with HIV (the virus that causes AIDS) are more likely than uninfected people to get sick with other infections and diseases. Tuberculosis (TB) is one of these diseases. TB is a disease that usually affects the lungs. It sometimes affects other parts of the body, such as the brain, the kidneys, or the spine.

HIV infection weakens the immune system. If a person’s immune system gets weak, TB infection can activate and become TB disease. Someone with TB infection and HIV infection has a very high risk of developing TB disease. Without treatment, these two infections can work together, to shorten the life of the person infected with both.

Do all people with HIV get TB disease?
No, but it does increases the chance of getting TB disease if patient have both TB infection and HIV infection. For this reason, if patient have HIV infection, the doctor must also get a TB skin test.

What is the difference between latent TB infection and active TB disease?
TB is spread through the air from one person to another. The bacteria are put into the air when a person with TB disease of the lungs or throat coughs or sneezes. People nearby may breathe in these bacteria and become infected. However, not everyone infected with TB bacteria becomes sick. As a result, two TB-related conditions exist: latent TB infection and active TB disease.

In most people who breathe in TB bacteria and become infected, the body is able to fight the bacteria and stop them from growing. The bacteria become inactive, but they remain alive in the body and can become active later. This is called latent TB infection. However, TB bacteria can become active if the immune system can’t stop them from growing. These bacteria 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. 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. A person with latent TB infection does not feel sick and cannot spread TB bacteria to others. Because HIV weakens the immune system, people with latent TB infection and HIV infection are at very high risk of developing active TB disease. These bacteria begin to multiply in the body and cause active TB disease.

Epidemiology & Demographics

 * Approximately 1.1 million persons were living with HIV infection at the end of 2006. As many as 21% of infected persons are unaware of their 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.

Risk Factors
The risk of developing tuberculosis (TB) is estimated to be between 20-37 times greater in people living with HIV than among those without HIV infection. In 2009, there were 9.4 million new cases of TB, of which 1.2 (13%) million were among people living with HIV. Of the 1.7 million people who died of TB, 400 000 (24%) were living with HIV. TB is a leading cause of morbidity and mortality among people living with HIV.

Screening
Importance of screening


 * HIV infection is the most important known risk factor for progression from latent TB infection to TB disease.
 * Progression to TB disease is often rapid among HIV-infected persons and can be fatal.
 * In addition, TB outbreaks can rapidly expand in HIV-infected patient groups.
 * Targeted HIV testing based on provider assessment of patient risk behaviors fails to identify a substantial number of persons who are HIV infected. This is because many individuals may not perceive themselves to be at risk for HIV or do not disclose their risks.
 * Routine HIV testing also reduces the stigma associated with testing.
 * When HIV is diagnosed early, appropriately timed interventions can lead to improved health outcomes, including slower progression and reduced mortality.
 * 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.

Recommendations


 * CDC recommends HIV screening for all TB patients after the patient is notified that testing will be performed, 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.
 * Persons at high risk for HIV infection should be screened for HIV at least annually.
 * Prevention counseling and separate written consent for HIV testing should no longer be required.

What is opt-out screening?

Opt-out screening is defined as performing HIV testing after notifying the patient that the test will be performed, and although the patient may decline or defer testing, it is strongly recommended.

Diagnosis
A new rapid diagnostic test for TB disease, the Xpert MTB/RIF assay (which is not currently approved by the US Food and Drug Administration for use in the US), is expected to reduce patient and health service diagnostic delays, decentralize the diagnosis of MDR TB and HIV-associated TB, and accelerate patient access to appropriate care. Evidence suggests that use of the test might double the number of HIV-associated TB cases diagnosed in areas with high rates of TB and HIV.

Rapid HIV tests, using fingerprick or oral specimens, can also be used. Results are available in about 20 minutes. The rapid HIV test kits cost about $10. Although the rapid HIV test kits cost more than standard lab assays, they have been shown to be cost-effective. Also they increase patients’ acceptance to HIV testing. Another option is to collect oral swab specimens and use standard lab assays.

To read more about other lab test, click here.

Symptoms

 * In early-stage HIV infection (CD4 count >300 cells per µL), TB typically presents as a pulmonary disease.


 * In advanced HIV infection, TB often presents atypically with extrapulmonary (systemic) disease a common feature.


 * Symptoms are usually constitutional and are not localized to one particular site, often affecting bone marrow, bone, urinary and gastrointestinal tracts, liver, regional lymph nodes, and the central nervous system.

Treatment
Recommendations for treating tuberculosis in adults with HIV infection are, with a few exceptions, the same as those for adult TB patients who are not HIV infected. However, managing HIV-related TB is complex and people with HIV and TB should seek care from a health care provider or providers with expertise in the management of both HIV disease and TB. Because persons with HIV infection are often taking numerous medications, some of which interact with anti-TB medications, experts in the treatment of HIV-related TB should be consulted.

Role of treatment

 * Without treatment, as with any other opportunistic infection, HIV and TB can work together to shorten the life of the person infected.
 * Someone with untreated latent TB infection and HIV infection is much more likely to develop active TB disease during his or her lifetime than someone without HIV infection.
 * Among people with latent TB infection, HIV infection is the strongest known risk factor for progressing to active TB disease.
 * A person who has both HIV infection and active TB disease has an AIDS-defining condition.
 * Since viral load is the single greatest risk factor for all modes of HIV transmission, ART use decreases the risk that HIV will be transmitted from one person to another.

Recommended Regimen
The recommended treatment of TB disease in HIV-infected adults (when the disease is caused by organisms that are known or presumed to be susceptible to first-line drugs) is a 6-month regimen consisting of:
 * For the first 2 months
 * An initial phase of isoniazid (INH), a rifamycin, pyrazinamide (PZA), and ethambutol (EMB).
 * For the last 4 months
 * A continuation phase of INH and a rifamycin.


 * Patients with advanced HIV (CD4 counts < 100/µl) should be treated with daily or three-times-weekly therapy in both the initial and the continuation phases.
 * Twice weekly therapy may be considered in patients with less-advanced immunosuppression (CD4 counts ≥ 100/µl).
 * Once-weekly INH/rifapentine in the continuation phase should not be used in any HIV-infected patient.

Duration of treatment

 * Six months
 * For adults with HIV, even for patients with culture-negative TB.


 * Nine months (extend continuation phase to 7 months)
 * For HIV-infected patients with delayed response to therapy (e.g., culture positive after 2 months of treatment).

Drug Interactions
A major concern in treating TB in HIV-infected persons is the interaction of rifampin (RIF) with certain antiretroviral agents (some protease inhibitors [PIs] and nonnucleoside reverse transcriptase inhibitors [NRTIs]).

Rifabutin, which has fewer problematic drug interactions, may be used as an alternative to RIF.

WHO Recommendations
In addition to initiating earlier antiretroviral therapy (ART), WHO recommends the implementation of the Three I's for HIV/TB to reduce the burden of TB among people living with HIV:
 * Intensified TB case finding,
 * Isoniazid preventive therapy,
 * Infection control for TB.

WHO recommends that the Three I's for HIV/TB in addition to ART be part of a TB prevention package and that emphasize that they should be core components of HIV services with AIDS programmes and service providers taking the primary responsibility for the Three I's for HIV/TB.

Prevention
A new epidemiological model, developed by WHO, UNAIDS and the Stop TB Partnership, shows it is possible to reduce HIV/AIDS deaths impressively through tuberculosis (TB) prevention and treatment. In 2009 almost one in four deaths among people living with HIV were due to TB, a disease that is both curable and preventable. The model estimates that through the scaled-up implementation of WHO-recommended collaborative TB/HIV activities, it is possible to save a million lives by the end of 2015.

A publication 'Time to act: Save a million lives by 2015 – Prevent and treat tuberculosis among people living with HIV' was launched on June 6, 2011 at the UN headquarters in New York. It calls for the following actions:
 * Testing for HIV and TB should be provided every three years in places where both diseases are prevalent.
 * Prompt TB treatment needs to be provided to every person living with HIV with active TB - or else treatment to prevent TB.
 * HIV and TB treatment must be accessible and of good quality so that people living with HIV are cured of TB.
 * Antiretroviral therapy (ART) should be started early, which will help prevent TB, since people living with HIV are far less likely to become ill with and die of TB if they begin ART before their immune systems begin serious decline.
 * People who are HIV-positive and diagnosed with active TB should start ART regardless of the status of their immune systems.

Related Chapters

 * Coinfection
 * AIDS
 * HIV disease
 * Hepatitis C with HIV coinfection
 * Hepatitis B with HIV coinfection
 * Immune reconstitution inflammatory syndrome ‎