Type of infection

TB (tuberculosis) is a bacterial infection that is most widely known as an infection of the lungs (pulmonary TB). It is caused by Mycobacterium tuberculosis.

It can more rarely affect other parts of the body including the brain, lymph nodes, stomach, liver, bones and even muscles.

TB is transmitted from someone with active infection when they sneeze, cough, sing or shout without covering their mouth.

The majority of people are exposed to TB in childhood, when they breathe in spores. TB then usually stays dormant for many years.

The risk of TB becoming active again is less than 10% over the lifetime of an HIV-negative adult, but is about 10% per year in an HIV-positive person who does not have access to ARVs.

Main symptoms

For pulmonary TB:

• Chronic productive cough.
• Shortness of breath.
• Fatigue, fever, night sweats and weight loss.

People can have active infection for 1-2 years before they develop symptoms.

Symptoms of TB in other part of the body are different (eg TB in the brain leads to confusion, etc).

Diagnosis

The distinction between active and inactive TB is very important.

Inactive TB is not infectious.
When TB is inactive it is called latent . HIV makes diagnosis of latent TB is complex. Skin tests that show previous exposure to TB are not accurate in HIV-positive people with a CD4 count under 400 cells/mm³.

Active TB is infectious.
There is no simple blood test for active TB. Pulmonary TB will show on a chest X-ray. When TB is active, it can usually be grown in the lab from a sample of spit or blood. These tests are accurate if the result is positive, but not if the result is negative as infection can be missed.

Treatment

A 2-month course of a combination of 4 antibiotics (isoniazid, rifampicin, pyrazinamide and ethambutol), followed by a 4-month course of a combination of 2 antibiotics (isoniazid and ethambutol).

The dose of this drug depends on the body weight of the person being treated.

Adherence is critical

Even though you will feel better after a few weeks, the whole six-month course needs to be completed, otherwise:

• Infection will return.
• Resistance to TB drugs will develop.

TB that is resistant to first-line treatment requires longer treatment (sometimes for two years) and use of different, usually less effective drugs.

TB treatment is often given as DOT (Directly Observed Therapy, where a nurse or other healthcare worker sees you take every dose).

Is HIV treatment the same for people with TB coinfection?

HIV treatment is recommended for anyone who also has active TB infection, even if the CD4 count is higher than 200 cells/mm³.

Interactions between ARVs and TB treatment

Because of the interaction between rifampicin-based TB treatment and ARVs, different HIV drugs are recommended.

The dose of efavirenz is higher (800mg rather than 600mg) when using TB treatment, although a study in Thailand suggested that the dose change may not be needed in people who weigh under 50 kg.

Efavirenz should not be used by pregnant woman or women who may become pregnant. For children with low weight, abacavir + 2 other nukes are recommended.

Summary of TB drug interactions

Rifampicin

• Do not take with any PI or nevirapine because rifampicin reduces these drugs to very low levels. Ritonavir boosting should not be used to overcome this, as a study with boosted saquinavir resulted in high rates of serious liver toxicity.
• May also interact with other drugs taken by people with HIV .

Rifabutin

• Do not take with nevirapine.
• Interacts with PIs and efavirenz, but appropriate dose adjustments can be made. TDM (therapeutic drug monitoring) of ARVs is recommended if available.
• Levels are increased by PIs.

Izoniazid

• Risk of neuropathy is likely to be increased in people using d4T.

How to use ARVs with active TB infection

There are very few trials of how to treat TB in HIV coinfection, so recommendations are based on expert guidelines.

• People with a CD4 count under 100, can start TB meds for 2 weeks and then start ARVs.
• People with a CD4 count between 100-200, usually start ARV treatment within the first 2 months of TB treatment.
• People whose CD4 count is between 200-350 can usually finish the 6-month course of TB treatment before starting ARVs. Some countries recommend also ARV treatment at CD4 counts higher than 350.

Starting ARV treatment, especially at very low CD4 counts, can make the immune system over-react – if this happens it complicates TB treatment and needs special management.

TB drug side effects

Izoniazid can cause peripheral neuropathy (PN) – tingling or numbness of the hands or feet. Pyridoxine (vitamin B6) is sometimes given to help reduce this. PN can also be caused by HIV and by ARV drugs including d4T, ddI, and 3TC. This risk increases when both isoniazid and these ARVs are used over the same period.

Other side effects:

• Liver problems
• Nausea, vomiting and diarrhea
• Rash
• Red-orange discolouration of body fluids (eg urine)
• Low white blood cells
• Low platelets
• Vision and hearing problems

Prophylaxis

This is recommended in some circumstances, usually where people share the same confined living or working space.

• The whole family will often receive treatment if someone in the household has active TB.
• Secondary prevention – to prevent either TB coming back or reinfection – is rarely recommended. This is because treatment is difficult to tolerate, and the risk of resistance is high.

Research

There is an urgent need for accurate tests for TB. These may be available in the future. They would dramatically improve treatment of HIV-positive people with TB.

Other treatments are also being studied.

TB and ARV drug interactions