5. 7 Tuberculosis (TB)
Type of infection
TB (tuberculosis) is a bacterial infection. It is most widely known as an infection of the lungs (pulmonary TB). TB is caused by Mycobacterium tuberculosis.
TB can also affect other parts of the body including the brain, lymph nodes, stomach, liver, bones and even muscles.
TB is transmitted by air from someone with active infection. For example if someone sneezes, coughs, sings or shouts without covering their mouth.
Most 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 HIV treatment (ART).
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 another part of the body are different (eg TB in the brain leads to confusion, etc).
Active TB can be diagnosed by several different types of test. These are microscopy, molecular testing and culture of sputum and/or body fluid or tissue samples. However, tests looking for an immune response are no longer used in people living with HIV.
It is also important to test for resistance to TB drugs.
Latent TB is diagnosed using a blood test called an interferon gamma release assay, or IGRA. This is generally in people who are well but who may bave been exposed to TB as a child.
People with HIV from countries with high and medium rates of TB should be tested for latent TB. This should be treated if testing positive, especially in people newly diagnosed with HIV.
Latent TB is not active and is not infectious. However HIV can sometimes make diagnosis of latent TB more complex. Skin tests that show previous exposure to TB are not accurate in HIV positive people with a CD4 count under 400 cells/mm3.
However, since 2010, WHO recommend using the GeneXpert test to diagnose TB, especially in people living with HIV in countries with a lot of TB. This test is more accurate and also includes information about resistance to a main TB med. This link has more info:
Active TB is infectious.
Although there is no simple blood test for active TB, lateral flow urine lipoarabinomannan assay (LAM) tests are increasingly used in many countries.
LAM tests have been recommended in WHO guidelines since 2015 but only in some people depending on symptoms and CD4 count. (See link below).
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.
If you have active TB, TB medication is usually started first. If you are not already taking ART, the ART should also be started. The time to starting ART depends on your CD4 count.
- People not already taking ART should be offered ART within 4 weeks of a TB diagnosis.
- People with very low CD4 counts (less than 50 CD4 cells) should be started on ART within 2 weeks of starting treatment for TB.
- People who develop TB on ART with undetectable HIV viral loads should not stop ART.
Up-to-date information about possible drug interactions is available on the Liverpool HIV Drug Interactions website (www.hiv-druginteractions.org).
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.
Good adherence is essential
Even though you will feel better after a few weeks, the whole 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).
Multi-drug resistant TB (MDR-TB)
If TB develops resistance to first-line drugs, treatment becomes more difficult and complex.
About ten years ago,bedaquiline and delamanid were approved for treating MDR-TB. For an update on TB drugs in development see the TAG pipeline reports linked below.
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 (800 mg rather than 600 mg) when using TB treatment. A Thai study suggested that the dose change may not be needed in people who weigh under 50 kg.
Efavirenz should not be used by pregnant women or women who may become pregnant. For children with low weight, abacavir + 2 other nukes are recommended.
Summary of TB drug interactions
- 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.
- 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.
- 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 HIV treatment (ART).
- People with a CD4 count between 100-200, usually start ART 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 ART. Some countries also recommend ART 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
Isoniazid 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 diarrhoea.
- Red-orange discolouration of body fluids (eg urine).
- Low white blood cells.
- Low platelets.
- Vision and hearing problems.
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.
Links and research
- TB and HIV coinfection (from the i-Base training manual)
- UK (BHIVA) guidelines on HIV and TB coinfection.
- Online resource on drug interactions between HIV and TB drugs TB and ARV drug interactions
- Ongoing research including looking for new and better treatment for TB, including for multidrug resistant TB.
- Reach is also looking into short and more effective combinations of TB drugs.
- WHO updates policy for the use of lateral flow urine lipoarabinomannan assay (LF-LAM) for diagnosing active tuberculosis in people living with HIV (2020 report)
Resources on TB research and drug development.
- Tuberculosis pipeline report (December 2022)
- Tuberculosis diagnostics report (November 2022)
- Tuberculosis vaccines report October 2022
- 2022 Report on TB Research Funding Trends
- TB treatment results from the 2022 Union World Conference on Lung Health
- 1/4/6×24 community campaign materials
Access to the short-course treatment and prevention regimens in the 1/4/6×24 campaign.
Last updated: 1 January 2016.