Tuberculosis (TB)

What is it?

Tuberculosis (TB) is a serious respiratory disease that can be life-threatening if not treated correctly. TB is, in fact, the world's most common disease caused by an infectious organisms. Nearly 2 billion people in the world are diagnosed with TB every year, a disease that is also responsible for the deaths of nearly 3 million people annually.

In industrialized nations such as the United States, TB was well on its way to becoming extinct 15 years ago. With the HIV epidemic, however, TB rates started increasing again between 1985 and 1992. Since 1992, the total number of TB cases has once again decreased. However, in certain groups of people in the U.S. - such as people immigrating to the United States from countries where TB rates are very high - the TB rate is increasing. In 2000, there were 17,531 cases of TB. Although the number of TB cases continues to decrease, it remains one of the most common causes of sickness and death in U.S. residents infected with HIV. In fact, TB is the number - one cause of death of HIV-infected people across the globe.

Mycobacterium tuberculosis, the bacteria that causes TB, is spread from one person to another. Using microscopic drops of fluid produced by the lungs, the bacteria can travel from the lungs of an infected person and be deposited in the lungs of someone nearby. Once inside the lungs, the bacteria established infection. Even though 150,000 people in the United States have been infected with the bacteria, most people have immune systems that are healthy enough to prevent the bacteria from ever causing TB. In people with HIV, the immune system may eventually lose control to the bacteria, causing the infection to spread and cause active disease. This process can take many months or years. In other words, Mycobacterium tuberculosis can remain alive in someone's body for many years, but may only become active - i.e., cause tuberculosis - once the immune system becomes damaged.

Tuberculosis almost always causes disease of the respiratory system. In HV-positive people, particularly those with T-cell counts below 200, the bacteria the bacteria can also infect the lymphatic system

Compared to HIV-negative patients with TB, HIV-positive people with the disease may see their symptoms develop faster and with greater intensity. Treating TB in HIV-infected patients may also need to be more aggressive in order to clear the bacteria from the body.
What are the symptoms of TB?

Cough is a main symptom of tuberculosis, along with night sweats, chills, weight loss, fever, and fatigue.

How is TB diagnosed?

To test for Mycobacterium tuberculosis infection, a skin test called PPD can be performed in a clinic or doctor's office. PPD stands for purified protein derivative. It contains pieces of the bacteria and is injected directly under the skin. If someone has been exposed to the bacteria in the past, the immune system will immediately recognize the PPD, resulting in a firm, relatively large bump at the site of the injection. If this reaction occurs, a person is said to have a positive PPD.

A positive PPD generally calls for additional testing. An X-ray of the chest is performed to look for signs of active disease. Blood tests, along with sputum samples, may also be sent to a lab for analysis. If the bacteria is found in these samples, it may be tested further to see if it is resistant to nay of the drugs commonly used to treat tuberculosis.

If someone has a positive PPD but does not have nay signs or symptoms of active disease, he or she is said to have latent TB infection. It is generally recommended that people with latent TB infection begin taking drug therapy to prevent the infection from developing further. If someone has a positive PPD and has signs and symptoms of tuberculosis, her or she is said to have active TB, usually involves a combination of antibiotics to treat the infection.

PPD testing in people with HIV can be problematic. As discussed above, PPD testing doesn't test for the presence of Mycobacterium tuberculosis, but instead looks for signs that the immune system is currently fighting the bacteria. In HIV-infected patients with compromised immune systems, there might not be enough immune activity to either fight the infection or respond to the PPD test. In other words, the bacteria might be present but is not being recognized by the immune system and, as a result, may not show up using PPD testing.

Because PPD testing may not be reliable in HIV-positive people with compromised immune systems, a diagnosis of TB might not be made until symptoms are reported and X-rays or blood tests are performed. For some HIV-positive people with compromised immune systems, it is better to be safe than sorry. For example, if an HIV-positive person lives in the same house or works with someone who has active TB and may be spreading Mycobacterium tuberculosis, it is generally recommended that the HIV-positive person be isolated from the person with active TB and to begin treatment.

How is TB treated?

Treating TB depends on the situation. As discussed in the previous section, there are treatments for latent TB infection and treatments for active TB.

If your have latent TB infection - that is, a positive PPD test without any signs or symptoms of active TB- your doctor will probably prescribe one of these two possible treatments:

Treatments for latent TB infection (LTBI)
Ÿ Isoniazid: One of the most effective antibiotics used to control TB. It can cause liver problems and tingling/numbness of the hands and/or feet. It is usually taken with a second drug, pyridoxine, to help prevent peripheral neuropathy. You will probably take this drug, every day, for nine months. Alternatively, isoniazid can be given twice a week for a total of nine months. However, if the twice-weekly dosing schedule is used. You will need to report to a clinic to receive your medication to make sure that you are not missing any of your doses. Some people take isoniazid for only six months. However, this is not recommended for people infected with HIV.

It is very important that you take your isoniazid and pyridoxine exactly as your doctor tells you to and that you continue taking these medications until your doctor tells you that it is time to stop. This is necessary to prevent the bacteria from becoming resistant to isoniazid. If the bacteria becomes resistant to isoniazid, you can develop active TB that is harder to treat.

• Rifampin + Pyrazinamide : Combining these two powerful antibiotics has been shown to prevent LTBI from progressing to active TB, especially in HIV-positive people. If these two drugs are taken every day, treatment for latent TB infection can be completed in as little as two months, as oppossed to the longer isoniazid. However, this combination of drugs was studied in HIV-positive people before the protease inhibitors and non-nucleoside reverse transcriptase inhibitors were approved. We now know that rifampin can interact with many PIs and NNRTIs. Thus, if you are taking either a PI or an NNRTI, it is recommended that you take rifabutin instead of rifampin. But even rifabutin can interact with some anti-HIV medications. Thus, there are rules that doctors and HIV positive people need to be aware of :
• To be on the safe side, it is generally recommended that HIV-positive people who are taking either a PI or NNRTI follow the nine-month isoniazid treatment option. The rifabutin/pyrazinamide option is best for people who will have a hard time sticking to the strict nine-month isoniazid course.
• Rifampin or rifabutin should not be used by HIV-positive people who are taking either the original version of saquinavir or the NNRTI delavirdine. In this case, the nine-month course of isoniazid is the best option.
• The rifabutin dose will depend on the PI or NNRTI you are taking. If you are taking either ritonavir or lopinavir, the rifabutin dose in 150 mg twice a day. If you are taking any of the other protease inhibitors, the correct rifabutin dose is 150 mg once a day. If you are taking the NNRTI efavirenz, the rifabtuin dose is 450 mg to 600 mg once a day. It is very important that you take your rifampin and pyrazinamide exactly as your doctor tells you to and that you continue taking these medications until your doctor tells you that it is time to stop. This is necessary to prevent the bacteria from becoming resistant to these two drugs. If the bacteria becomes resistant to the drugs. You can develop active TB that is harder to treat.

Active TB is treated using a combination of drugs. As with HIV, in which a combination of three antiretroviral drugs issued to help prevent resistance and keep viral load undetectable, tuberculosis is usually treated with a combination of four drugs to maintain control over the infection.

Some people are infected with strains of Mycobacterium tuberculosis that are resistant to one or more of the drugs commonly used to treat tuberculosis. This problem a becoming more and more common in some areas of the United States, including heavily populated cities like New York. As a result, testing the bacteria for drug resistance as a part of diagnosing TB is sometimes recommended.

Unfortunately, both a confirmed diagnosis and drug-resistance testing take a long time. Growing out Mycobacterium tuberculosis in test tubes can take more than a week, and drug resistance testing can take as long as a month. Thus, treatment is often started if key signs and symptoms are present.

For the first two months of therapy, a combination of four drugs are usually prescribed, all of which are taken by mouth:

• Isoniazid: One of the most effective antibiotics used to control TB. It can cause liver problems and tingling/numbness of the hands and/or feet. It is usually taken with a second drug, pyridoxine, to help prevent peripheral neuropathy.
• Rifampin : Another powerful antibiotic needed to manage TB. It can cause nausea, vomiting, diarrhea, rash, liver problems, red-orange discoloration of body fluids, along with a decrease in white blood cells and platelets. Rifampin can be a problem for some HIV-positive people. This is because it interacts with many of the medications used to treat HIV. It is not recommended that people stop their anti-HIV medications in order to treat their TB. Instead, your doctor will probably need to change the dose of either the rifampin or the anti-HIV medications to make sure that you are being treated correctly without the risk of additional side effects. If rifampin cannot be used, an alternative drug - rifabutin - will be prescribed.
• Pyrazinamide: The dose of this drug depends on the body weight of the person being treated. Its side effects are similar to those of rifampin.
• Ethambutol or streptomycin: Like pyrazinamide, the dose of these two drugs depends on the body weight of the person being treated. Ethambutol can cause vision problems and can cause hearing problems.

To help make these drugs easier to take, some of them have been combined into single pills. For example, if you take isoniazid and rifampin, your doctor can write a prescription for Rifamate, a capsule that contains both drugs. Two Rifamate capsules are taken twice a day, almost always in combination with other antibiotics. If your doctor has recommended a combination of isoniazid, rifampin, and pyrazinamide, you may be able to take Rifater, a tablet that contains all three drugs. Depending on how much you weigh, you will need to take four, five, or six Rifater tablets once a day, always on an empty stomach.

If a drug-resistant strain of Mycobacterium tuberculosis is present - either suspected by a doctor or confirmed by testing - additional drugs are often added to this combination. Additional drugs include: capreomycin, kanamycin, amikacin, ethionamide, ciprofloxacin, ofloxacin, lomefloxacin, clofazimine, cycloserine, and/or aminosalicylic acid. These drugs can also be used as a substitute for other anti-TB drugs that cause side effects.

Here are three ways tuberculosis can be treated using these drugs.

Standard course of therapy:

• This is the most common method used to treat TB, especially for HIV-positive people. For the first eight weeks of treatment, the four drugs listed above are used every day. After two months of therapy have been completed, isoniazid and rifabutin are continued for an additional 16 weeks. These drugs can be taken either every day or two or three times a week. If you have less that 100 T-cells, experts recommend taking rifabutin every day or three times a week. You will probably have to go to a clinic - or have a trained medical professional watch you take your medication every time you take your isonaizid and rifabutin during this period, especially if you are only taking them two or three times a week.
  First alternative course of therapy:
• For the first two weeks of treatment, the four drugs listed above are used every day. After two weeks of daily treatment have been completed, the same four drugs are taken two times a week for an additional eight weeks. After a total of eight weeks of four -drug treatment have been completed, isoniazid and rifabutin are continued for an additional 16 weeks.

These drugs can be taken either two or three times a week. Like the standard course of therapy, you will probably have to go to a clinic - or have a trained medical professional watch you take your medication - every time you take your medication.

Second alternative course of therapy:

For six months, the four drugs listed above are used three times a week. The dose of each drug will remain the same for the entire six months and you will need to take all four drugs until therapy is officially completed. Like the standard course of therapy, you will probably have to go to a clinic - or have a trained medical professional watch you take your medication - every time you take your medication.

It is very important that you take your medications exactly as your doctor tells you to and that you continue taking them until your doctor tells you that it is time to stop. This is necessary to prevent the bacteria from becoming resistant to the drugs. If the bacteria becomes resistant to these drugs, the TB may return and may be more difficult to treat.