By Lucca Munnik and Paula Cevaal
Tuberculosis (TB), an infectious bacterial disease, continues to be the leading cause of death amongst people living with HIV (PLHIV). Post-mortem observations have shown a prevalence of TB in HIV-positive bodies of 40%1, thus proving the high rate of co-infection of HIV and TB. TB was discussed in the article “Opportunistic Infections”, which provided a brief description of the disease itself and explained that PLHIV that have a suppressed immune system, are at higher risk of the disease. In this article a more detailed overview of TB and its relation to HIV will be given.
TB Basics
Primary tuberculosis infection develops when a person inhales viable tuberculous bacteria that have been transmitted through aerosols. Usually, these bacteria reside in an inactive state, resulting in a latent infection without any symptoms. As explained in the “Opportunistic Infections” article, people with a weakened immune system are more susceptible for reactivation of these latent bacteria. This reactivation will result in active TB and symptoms that can be life-threatening if left untreated2. This does not mean that PLHIV are more prone to being infected with TB, but rather that their latent TB is more prone to being reactivated, therefore causing disease. In the majority of cases, TB manifests in the lungs, resulting in symptoms that include chronic cough, chest pain, fever and night chills3. TB can however also infect the brain, causing a more severe disease called TB meningitis which results in symptoms such as headache, vomiting, visual disturbance and others4 .
Diagnosis of TB in PLHIV
TB diagnosis is usually performed by checking for the bacteria in a sputum sample of the patient by using a microscope. In PLHIV, diagnosis of TB is however particularly challenging because PLHIV often release fewer bacteria in their sputum5 . This has resulted in delayed diagnosis (and thus delayed initiation of anti-TB treatment) in PLHIV. Luckily, recent scientific discoveries have lead to a new diagnostic tool that can detect TB at an early stage. However, implementation of this new tool is slow, and the lack of integration of HIV and TB healthcare unfortunately still result in a high prevalence of TB amongst PLHIV6.
Treatment
As previously mentioned, PLHIV are more susceptible to develop active TB. Therefore, it is important to begin treatment immediately when symptoms of TB develop. TB treatment consists of two phases; initial phase and continuation phase. The initial phase consists of 2 months of intensive treatment with a combination of drugs, usually being isoniazid, rifampicin, pyrazinamide and ethambutol. Isoniazid and rifampicin are then continued for another 4 months in the continuation phase7.
In immunocompetent people, anti-TB treatment is sufficient to treat active TB. However, for PLHIV it is essential that they continue or initiate ART, as a recovering immune system is required to eradicate (and thus cure) the TB. The WHO guidelines for ART in TB-infected PLHIV recommend nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitor (NNRTI) for first line therapy8. However, almost one in five of those initiating ART and anti-TB treatment at the same time (usually upon diagnosis of TB) face complications9. These complications are known as TB-IRIS and result in paradoxical worsening of symptoms despite ART and anti-TB treatment being in place. The majority of cases of TB-IRIS can effectively be treated with immunosuppressants such as prednisone.4
Prevention
Given the high prevalence of TB in PLHIV, the WHO guidelines recommends preventive therapy to all PLHIV that do not show symptoms of active TB. The recommended preventive therapy consists of only isoniazid which contrasts to the combination treatment prescribed to those with active TB. However, several aspects should be noted. Firstly, this preventive therapy does not cure latent TB but only serves to prevent reactivation. Secondly, implementation of these WHO recommendations is slow, because of the healthcare workers’ concerns of inducing resistance by commonly prescribing this drug10. Generally, co-morbidities due to TB infection can be prevented by initiating ART as early as possible after HIV diagnosis. WHO guidelines recommend initiation of ART to everyone living with HIV, in contrast to earlier days when ART was only started when the CD4 count was below a certain limit. Unfortunately, many people still present at clinics with a very low CD4 count and are thus at risk of TB.5 Further integration of healthcare towards HIV and TB will be key to decreasing global mortality due to TB in PLHIV.
1 Gupta, R. K., Lucas, S. B., Fielding, K. L. & Lawn, S. D. Prevalence of tuberculosis in post-mortem studies of HIV-infected adults and children in resource-limited settings: a systematic review and meta-analysis. AIDS 29, 1987–2002 (2015).
2 World Health Organisation (2004). TB/HIV a Clinical Manual. 2nd ed. Geneva: WHO.
3 Lawn, S., Meintjes, G., McIlleron, H., Harries, A. and Wood, R. (2013). Management of HIV-associated tuberculosis in resource-limited settings: a state-of-the-art review. BMC Medicine, 11(1).
4 Walker, N. F., Scriven, J., Meintjes, G. & Wilkinson, R. J. Immune reconstitution inflammatory syndrome in HIV-infected patients. HIV. AIDS. (Auckl). 7, 49–64 (2015).
5 Hosseinipour, M. C. et al. Empiric Tuberculosis Therapy versus Isoniazid in Advanced HIV- infected Adult Outpatients Initiating Antiretroviral Therapy: a Multi-Country Randomized Controlled Trial. Lancet 387, 1198–1209 (2016).
6 Dominique, J., Ortiz-Osorno, A., Fitzgibbon, J., Gnanashanmugam, D., Gilpin, C., Tucker, T., Peel, S., Peter, T., Kim, P. and Smith, S.
7 World Health Organization Europe (n.d.). Management of Tuberculosis and HIV Coinfection. Europe.
8 Swaminathan, S., Padmapriyadarsini, C. and Narendran, G. (2011). Diagnosis & treatment of tuberculosis in HIV co-infected patients. The Indian Journal of Medical Research, 134(6), p.850.
9 Namale, P. E. et al. Paradoxical TB-IRIS in HIV-infected adults: a systematic review and meta-analysis. Future Microbiol. 10, 1077–1099 (2015)
10 Dheda, K., E Barry, C. and Maartens, G. (2016). Tuberculosis. The Lancet, 387, pp.1211-1226.