Tuberculosis (TB) is a serious respiratory (lung) disease that can be life-threatening if not treated correctly. TB is, in fact, the world's most common disease caused by an infectious organism. 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 establishes infection. Even though 150,000 people in the United States have been infected with this bacteria, most people (between 90 and 95 percent) 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 of 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 HIV-positive people, particularly those with CD4 cell counts below 200, the bacteria can also infect the lymphatic system (i.e., the lymph nodes and the spleen).
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 and 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 (phlegm) 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 any of the drugs commonly used to treat tuberculosis.
If someone has a positive PPD but does not have any 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 (discussed in next section). If someone has a positive PPD and has signs and symptoms of tuberculosis, he or she is said to have active TB. Treatment is necessary for someone with active TB, which usually involves a combination of antibiotics to treat the infection (also discussed in next section).
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 latent TB infection treated?
If you 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:
- Isoniazid (Nydrazid): One of the most effective antibiotics used to control TB. It can cause liver problems and tingling/numbness of the hands and/or feet (peripheral neuropathy). It is usually taken with a second drug, pyridoxine, to help prevent peripheral neuropathy. You will probably take this drug (300 mg), 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. This is called directly observed therapy, or DOT. 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 (Rifadin): Only needs to be taken once a day for a total of four months. However, there are a number of concerns when it comes to using this drug in combination with anti-HIV medications. Rifampin can interact with many protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Thus, 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 (discussed above). The rifampin option is best for people who will have a hard time sticking to the strict nine-month isoniazid course and are not taking either a PI or a NNRTI. If you are prescribed rifampin, it is very important that you take it exactly as your doctor tells you to and that you continue taking this medication 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.
Two potential side effects of TB therapy are liver damage (hepatitis) and damage to the nerves in the feet, hands and face, called neuropathy. It is recommended that people being treated for latent tuberculosis be monitored at least once every month to monitor adherence to treatment and for side effects. People who are exposed to TB that is suspected to be resistant to isoniazid or rifampin may need to receive additional medication. In these cases it is recommended that a person work with local public health authorities and an expert on multi-drug resistant TB to determine the best alternative regimens.
How is active TB treated?
Active TB is treated using a combination of drugs (antibiotics). As with HIV, in which a combination of three antiretroviral drugs is used 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 is 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 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 (e.g., positive PPD, abnormal chest X-ray, etc.). In cases where it is suspected that a person has been exposed to drug-resistant TB, their provider should consult about treatment with local public health authorities as well as an expert on multi-drug-resistant TB.
For the first two months of therapy, a combination of four drugs are usually prescribed, all of which are taken by mouth:
- Isoniazid (Nydrazid): One of the most effective antibiotics used to control TB. It can cause liver problems and tingling/numbness of the hands and/or feet (peripheral neuropathy). It is usually taken with a second drug, pyridoxine, to help prevent peripheral neuropathy.
- Rifampin (Rifadin): Another powerful antibiotic needed to manage TB. It can cause nausea, vomiting, diarrhea, rash, liver problems, red-orange discoloration of body fluids (e.g., urine), 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 antiretroviral (ARV) 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 (Myambutol) 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 (i.e., direct exposure to someone known to have a drug-resistant strain of the bacteria) or confirmed by testing—additional drugs are often added to this combination. Additional drugs include: capreomycin (Capastat Sulfate), kanamycin (Kantrex), amikacin (Amikin), ethionamide (Trecator-Sc), ciprofloxacin (Cipro), ofloxacin (Floxin), lomefloxacin (Maxaquin), clofazimine (Lamprene), cycloserine (Seromycin), and/or aminosalicylic acid (Paser). These drugs can also be used as a substitute for other anti-TB drugs that cause side effects.
Treatment guidelines published by the National Institutes of Health (NIH), Centers for Disease Control (CDC) and the Infectious Disease Society of America (IDSA) recommend that all HIV-positive people being treated for active TB should report to a clinic to receive their medications under observation, DOT, to guard against the potential for the development of drug resistance.
Here are the 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 (four months). These drugs can be taken either every day or two to three times a week. If you have less that 100 CD4 cells, experts recommend taking rifabutin every day or three times a week (but not two 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 isoniazid 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 (four months).
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. There are a number of potential side effects of tuberculosis treatment, including stomach problems, rash, hepatitis and neuropathy. Because the recommended treatments for TB are the most effective and generally the least toxic, it is recommended that your doctor consult with a TB specialist in the event of a serious side effect and verify that it is the TB medication causing the side effect before stopping or switching TB treatment.
The Centers for Disease Control (CDC) in Atlanta published treatment guidelines for TB that make recommendations for dose changes when using rifampin with HIV medications. The guidelines may be found here. In general, the most recent guidelines recommend that people taking ARV treatment along with TB treatment should avoid using protease inhibitors whenever possible. For people who are not currently taking either ARV or TB medications, some doctors would recommend starting TB medications first followed by ARV medications a few weeks or months later, depending on their CD4 count and overall health.
Although relatively rare, some people experience a "flare" of TB symptoms within the first few months after starting ARV treatment. This is called immune reconstitution inflammatory syndrome, or IRIS. This most commonly happens when a person starts ARV treatment with a CD4 count of 200 or less, and when starting ARV treatment within the first two months after starting TB treatment. If your TB treatment has been successful, but you suddenly begin experiencing TB symptoms, such as fevers, breathing problems and swollen lymph nodes, within the first few weeks after starting ARV treatment you should tell your doctor right away. It is important that your TB doctor and HIV doctor consult carefully to determine whether you are experiencing IRIS or the possibility that your TB medications are no longer working.
Can pregnant women take TB treatment?
It is recommended that HIV-positive pregnant women receive the same TB treatment as non-pregnant adults. Rifampin, however, can cause a bleeding disorder in babies born to women who took TB treatment during pregnancy. To guard against this disorder, babies born to pregnant women on TB treatment should receive a single 10 mg dose of vitamin K.
Are there any experimental treatments?
If you would like to find out if you are eligible for any clinical trials that include new therapies for the treatment or prevention of TB, visit ClinicalTrials.gov, a site run by the U.S. National Institutes of Health. The site has information about all HIV-related clinical studies in the United States. For more info, you can call their toll-free number at 1-800-HIV-0440 (1-800-448-0440) or email firstname.lastname@example.org.
Last Revised: January 19, 2016