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TB & HIV Co-infection, statistics, diagnosis & treatment

TB and HIV co-infection

TB and HIV co-infection is when people have both HIV infection, and also either latent or active TB disease. When someone has both HIV and TB
each disease speeds up the progress of the other. In addition to HIV infection speeding up the progression from latent to active TB, TB bacteria
also accelerate the progress of HIV infection.1Mayer, K. Synergistic Pandemics: Confronting the Global HIV and Tuberculosis Epidemics Clinical
Infectious Diseases, 2010, Volume 50, Supplement 3, S67 http://cid.oxfordjournals.org/content/50/Supplement_3/
(http://cid.oxfordjournals.org/content/50/Supplement_3/S67.full)

HIV infection and infection with TB bacteria are though completely different infections. If you have HIV infection you will not get infected with TB
(https://www.tbfacts.org/tb/) bacteria unless you are in contact with someone who also is infected with TB bacteria. Although if you live in a country
with a high prevalence of TB this may have happened without you realizing it. Similarly if you have TB you will not get infected with HIV unless you
carry out an activity with someone who already has HIV infection, which results in you getting the virus HIV from them.

TB also occurs earlier in the course of HIV infection than many other opportunistic infections. The risk of death in co-infected individuals is also
twice that of HIV infected individuals without TB, even when CD4 cell count and antiretroviral therapy are taken into account.2Suchindran, S. Is
HIV infection a Risk Factor for Multi-Drug Resistant Tuberculosis? A Systematic Review PLoS one, May 2009, 4(5): e5561
http://www.plosone.org/article/ (http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005561)

The natural history of TB in people with HIV

When people have a damaged immune system, such as people with HIV who are not receiving
antiretroviral treatment, the natural history of TB is altered. Instead of there being a long latency phase
between infection and development of disease, people with HIV can become ill with active TB disease
within weeks to months, rather than the normal years to decades.

The risk of progressing from latent to active TB is estimated to be between 12 and 20 times greater in
people living with HIV than among those without HIV infection.3Luetkemeyer, A. Tuberculosis and HIV,
HIVInSite, http://hivinsite.ucsf.edu/ (http://hivinsite.ucsf.edu/InSite?page=kb-05-01-06) This also means
that they may become infectious and pass TB on to someone else, more quickly than would otherwise
happen. Overall it is considered that the lifetime risk for HIV negative people of progressing from latent
to active TB is about 5-10%, whereas for HIV positive people this same figure is the annual
risk.4Implementing the WHO Stop TB Strategy: a handbook for national tuberculosis control
programmes Geneva, World Health Organization, 2008, p67 www.who.int/tb/publications/2008/
(http://www.who.int/tb/publications/2008/en/)

Symptoms of TB in people with HIV A patient with HIV and TB in hospital in Nigeria
DAHW
HIV positive people with pulmonary TB may have the classic symptoms of TB
(https://www.tbfacts.org/symptoms-tb/), but many people with both TB and HIV infection have few symptoms of TB or even less specific ones. In
addition, up to a fifth of people with both pulmonary TB and HIV have normal chest X-rays. HIV positive people with TB may indeed frequently
have so called sub clinical TB, which often is not recognized as TB and subsequently there are delays in both TB diagnosis and TB treatment
(https://www.tbfacts.org/tb-treatment/).

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HIV infected people are also more likely than people who are not infected with HIV to have extra pulmonary TB. Forty to eighty percent of HIV
infected people with TB have extra pulmonary disease, compared with 10-20% of people without HIV.5Sterling, T. HIV Infection-Related
Tuberculosis: Clinical Manifestations and Treatment Clinical Infectious Diseases, 2010, Volume 50, Supplement 3, S223-S230
http://cid.oxfordjournals.org/content/50/Supplement_3/ (http://cid.oxfordjournals.org/content/50/Supplement_3/S223.long)

Global TB/HIV Co-infection statistics

In 2015 400,000 people who had both TB and HIV are estimated to have died, in addition to the 1.4 million people who died from TB
alone.6Global Tuberculosis Control 2016, WHO, Geneva, 2016, www.who.int/tb/publications/global_report/en/
(http://www.who.int/tb/publications/global_report/en/) Those people who have HIV and TB co-infection when they die, are internationally reported
as having died of HIV infection.7International Classification of Diseases (ICD), WHO, Geneva, 2010 www.who.int/classifications/icd/en/
(http://www.who.int/classifications/icd/en/) In total an estimated 1.2 million people died of HIV infection in 2014.8UNAIDS Report on the Global
AIDS Epidemic 2012, UNAIDS, 2012 www.unaids.org/en/resources/campaigns/20121120_globalreport2012/
(http://www.unaids.org/en/resources/campaigns/20121120_globalreport2012/) So:

Deaths from HIV and TB co-infection: 400,000

Deaths from TB alone: 1,400,000

Deaths from HIV alone: 800,000

So in 2015 more people died from TB than from HIV related infections.

Also in 2015 there were an estimated 10.4 million new cases of active TB worldwide. Globally 11% of the incident TB cases in 2015 are estimated
to have been among people living with HIV.

Estimated WHO TB mortality statistics for HIV positive people 2015 by age & region

Region Total TB Mortality 0 14 years TB Mortality Male >15 years

Africa 295,000 34,000 142,000

Americas 5,890 200 3,870

Eastern Mediterranean 2,970 310 1,760

Europe 4,870 47 3,490

South-East Asia 74,300 6,100 49,500

Western Pacific 5,750 270 4,250

Global Total 389,000 41,000 204,000

Globally in 2015 55% of notified TB patients had a documented HIV test result. This is an 18 fold increase in testing coverage since 2004. In the
African region where the burden of HIV associated TB is highest 81% of TB patients had a documented HIV test result.

Diagnosing TB and HIV in TB and HIV co-infection

Because of the limitations of current TB tests (https://www.tbfacts.org/tb-tests/), it is even more difficult to diagnose TB in HIV positive individuals,
than to diagnose TB in people without HIV infection. Many people with HIV will have a false negative result from a TB sputum smear test. This can
result in a large number of cases of active TB disease going undiagnosed.

By contrast the diagnosis of HIV in people with TB should always be straightforward because of the availability of quick and cheap point of care
diagnostics for HIV infection. The Stop TB Partnerships Global Plan to Stop TB had as a target, that by 2015, all patients with TB should be tested
for HIV.9The Global Plan to Stop TB, WHO, Geneva, 2011, 12 www.stoptb.org/global/plan/ (http://www.stoptb.org/global/plan/)

Treating TB & HIV co-infection

The proportion of known HIV positive TB patients on antiretroviral therapy (ART) was 78% globally, and above 90% in India, Kenya, Malawi,
Mozambique, Namibia and Swaziland.

Initiating treatment for either HIV or TB

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The decision to initiate treatment for either HIV or TB when there is co-infection, should take into account a number of factors including:

Has the person got symptoms of, and is ill with either TB, or some other HIV related opportunistic infection?

Is the person already having treatment for either TB or HIV infection?

What drugs are available for the treatment of HIV infection, and indeed TB, if the person is not already receiving treatment?

If there is a need for both HIV and TB treatment, are there experienced health care workers and/or guidelines available to provide the
necessary expertise on this?

Providing HIV antiretroviral therapy and anti TB drug treatment together

The provision of HIV antiretroviral therapy and anti TB drug treatment at the same time involves a number of potential difficulties
including:10Piggott, D. Timing of Antiretroviral Therapy for HIV in the Setting of TB Treatment Clin Dev Immunol., 2011, 103917
www.hindawi.com/journals/cdi/ (http://www.hindawi.com/journals/cdi/2011/103917/)

Cumulative drug toxicities

Drug drug interactions

A high pill burden

The Immune Reconstitution Inflammatory Syndrome (IRIS)

Immune Reconstitution Inflammatory Syndrome (IRIS)

IRIS refers to a phenomenon experienced by people with HIV who have recently started antiretroviral therapy. The partial recovery of the immune
system can result in an exaggerated inflammatory response against any concurrent opportunistic infection. Tuberculosis Immune Reconstitution
Syndrome (TB IRIS) refers specifically to IRIS that occurs when a patient has active Mycobacterium tuberculosis infection. TB IRIS is estimated to
occur in 11% to 45% of patients co-infected with TB and HIV.11Discussion Diagnosis of Tuberculosis Immune Reconstitution Inflammatory
Syndrome (TB_IRIS), HIVweb Study, 2011 //depts.washington.edu/ghivaids/reslimited/case3/
(http://depts.washington.edu/ghivaids/reslimited/case3/discussion.html)

Starting both HIV antiretroviral and anti TB drug therapy

For adults with both TB and HIV infection, who need to receive both antiretrovirals and TB drugs (https://www.tbfacts.org/tb-drugs/), the WHO
guidelines recommend starting HIV antiretrovirals between 2 and 8 weeks after starting TB treatment (https://www.tbfacts.org/tb-treatment/) for
those individuals who have a CD4 count of less than 200mm3. For people with both TB and HIV it is not now considered necessary to delay the
initiation of antiretroviral therapy until TB treatment has been completed.12Antiretroviral Therapy for HIV Infection in Adults and Adolescents:
Recommendations for a public health approach 2010 revision, WHO, Geneva, 2010, 45 www.who.int/hiv/topics/treatment/en/index.html
(http://www.who.int/hiv/topics/treatment/en/index.html)

The Stop TB Partnerships Global Plan to Stop TB had as a target, that by 2015, all HIV positive TB patients should be receiving antiretroviral
treatment.13The Global Plan to Stop TB, WHO, Geneva, 2011, 12 www.stoptb.org/global/plan/ (http://www.stoptb.org/global/plan/) But actually by
2013 it was estimated that only 70% of notified TB patients co-infected with HIV were receiving ART.14Global Tuberculosis Control 2014, WHO,
Geneva, 2014, www.who.int/tb/publications/global_report/ (http://www.who.int/tb/publications/global_report/en/)

HIV and MDR TB

The relationship between HIV infection and multi drug resistant MDR-TB (https://www.tbfacts.org/mdr-tb/) is not well understood, but there is
currently no evidence supporting an association between MDR TB and HIV outside of institutional outbreaks of MDR TB. However, the high
number of deaths from MDR and XDR TB (https://www.tbfacts.org/xdr/) in people who have both TB and HIV can have devastating and
demoralizing effects on communities, and this has already been seen in South Africa.15Personal communication

The combination of MDR TB and HIV antiretroviral treatment requires adherence to between 6 and 10 daily medications for more than a year.
These regimes often have high levels of toxicity and drug-drug interactions.

The stigmas of TB and HIV/AIDS

The stigmas of HIV and TB have come full circle.

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In the early days of the HIV/AIDS epidemic, people were said to have died of TB when they had actually died of AIDS.16Eddie Vulani
Maluleke in Nobody Ever Said AIDS:Stories & Poems from Southern Africa, Rasebotsa et al, 2004

We all died

Coughed and died

We died of TB

That was us

Whispering it at funerals

Because nobody ever said AIDS

Now in the townships of South Africa, people will enter the shack (township home) of someone with HIV, but they will stop at the door if the
person has XDR TB. 17Personal communication

References

1. Mayer, K. Synergistic Pandemics: Confronting the Global HIV and Tuberculosis Epidemics Clinical Infectious Diseases, 2010, Volume 50, Supplement
3, S67 http://cid.oxfordjournals.org/content/50/Supplement_3/ (http://cid.oxfordjournals.org/content/50/Supplement_3/S67.full)
2. Suchindran, S. Is HIV infection a Risk Factor for Multi-Drug Resistant Tuberculosis? A Systematic Review PLoS one, May 2009, 4(5): e5561
http://www.plosone.org/article/ (http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005561)
3. Luetkemeyer, A. Tuberculosis and HIV, HIVInSite, http://hivinsite.ucsf.edu/ (http://hivinsite.ucsf.edu/InSite?page=kb-05-01-06)
4. Implementing the WHO Stop TB Strategy: a handbook for national tuberculosis control programmes Geneva, World Health Organization, 2008, p67
www.who.int/tb/publications/2008/ (http://www.who.int/tb/publications/2008/en/)
5. Sterling, T. HIV Infection-Related Tuberculosis: Clinical Manifestations and Treatment Clinical Infectious Diseases, 2010, Volume 50, Supplement 3,
S223-S230 http://cid.oxfordjournals.org/content/50/Supplement_3/ (http://cid.oxfordjournals.org/content/50/Supplement_3/S223.long)
6. Global Tuberculosis Control 2016, WHO, Geneva, 2016, www.who.int/tb/publications/global_report/en/
(http://www.who.int/tb/publications/global_report/en/)
7. International Classification of Diseases (ICD), WHO, Geneva, 2010 www.who.int/classifications/icd/en/ (http://www.who.int/classifications/icd/en/)
8. UNAIDS Report on the Global AIDS Epidemic 2012, UNAIDS, 2012 www.unaids.org/en/resources/campaigns/20121120_globalreport2012/
(http://www.unaids.org/en/resources/campaigns/20121120_globalreport2012/)
9. The Global Plan to Stop TB, WHO, Geneva, 2011, 12 www.stoptb.org/global/plan/ (http://www.stoptb.org/global/plan/)
10. Piggott, D. Timing of Antiretroviral Therapy for HIV in the Setting of TB Treatment Clin Dev Immunol., 2011, 103917 www.hindawi.com/journals/cdi/
(http://www.hindawi.com/journals/cdi/2011/103917/)
11. Discussion Diagnosis of Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB_IRIS), HIVweb Study, 2011
//depts.washington.edu/ghivaids/reslimited/case3/ (http://depts.washington.edu/ghivaids/reslimited/case3/discussion.html)
12. Antiretroviral Therapy for HIV Infection in Adults and Adolescents: Recommendations for a public health approach 2010 revision, WHO, Geneva,
2010, 45 www.who.int/hiv/topics/treatment/en/index.html (http://www.who.int/hiv/topics/treatment/en/index.html)
13. The Global Plan to Stop TB, WHO, Geneva, 2011, 12 www.stoptb.org/global/plan/ (http://www.stoptb.org/global/plan/)
14. Global Tuberculosis Control 2014, WHO, Geneva, 2014, www.who.int/tb/publications/global_report/
(http://www.who.int/tb/publications/global_report/en/)
15. Personal communication
16. Eddie Vulani Maluleke in Nobody Ever Said AIDS:Stories & Poems from Southern Africa, Rasebotsa et al, 2004
17. Personal communication

TBFACTS.ORG - Information about Tuberculosis

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Main Author : Annabel Kanabus

Citation : Kanabus, Annabel "Information about Tuberculosis", GHE, 2016, www.tbfacts.org

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