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TB and HIV | Co-infection, 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, S67http://cid.oxfordjournals.org/content/50/Supplement_3/”

In 2013 of the estimated 9 million people who developed TB an estimated 1.1 million (13%) were HIV positive. There were also in 2013 360,000 deaths from HIV associated TB equivalent to 25% of all TB deaths, and around 25% of the estimated 1.5 million deaths from HIV/AIDS.2“Global Tuberculosis Control 2014” www.who.int/tb/publications/global_report/

HIV infection and infection with TB bacteria are though completely different infections. If you have HIV infection you will not get infected with 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.3Suchindran, 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/

Winstone Zulu

Winstone Zulu 1964-2011

Winstone Zulu 1964-2011

One of the first people to speak out openly about the problems of TB and HIV co-infection was the Zambian Winstone Zulu. Winstone was a prominent global advocate on TB and HIV.

Winstone was the first person in Zambia to speak openly about being HIV positive. Also, although he himself survived TB he watched four of his brothers die from TB due to lack of access to anti TB drugs. He was moved to turn his personal loss into ceaseless advocacy for worldwide awareness for the fight against TB and TB-HIV co-infection.4“Tribute to Winstone”, Action www.action.org/blog/post/tribute_to_winstone

“There have been so few TB survivors who have stepped forward to share their stories. We need more advocates like Winstone to tell the world about TB and the effect it has on so many millions of people.”

Nelson Mandela

 

The natural history of TB in people with HIV

Demands for TB funding at an HIV conference © GHE

Demands for TB funding at an HIV conference © GHE

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.5Luetkemeyer, A. “Tuberculosis and HIV”, HIVInSite, http://hivinsite.ucsf.edu/ 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.6“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/

Symptoms of TB in people with HIV

HIV positive people with pulmonary TB may have the classic symptoms of 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.

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.7Sterling, T. “HIV Infection-Related Tuberculosis: Clinical Manifestations and Treatment” Clinical Infectious Diseases, 2010, Volume 50, Supplement 3, S223-S230http://cid.oxfordjournals.org/content/50/Supplement_3/”

Diagnosing TB and HIV in TB and HIV co-infection

Because of the limitations of current 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 Partnership’s Global Plan to Stop TB, now has as a target, that by 2015, all patients with TB should be tested for HIV.8“The Global Plan to Stop TB”, WHO, Geneva, 2011, 12 www.stoptb.org/global/plan/ In fact by 2013 just 48% of notified TB patients had a documented HIV test result.

Treating TB and HIV co-infection

Initiating treatment for either HIV or TB

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:9Piggott, D. “Timing of Antiretroviral Therapy for HIV in the Setting of TB Treatment” Clin Dev Immunol., 2011, 103917 www.hindawi.com/journals/cdi/”

  • 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.10“Discussion – Diagnosis of Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB_IRIS)”, HIVweb Study, 2011 //depts.washington.edu/ghivaids/reslimited/case3/

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, the WHO guidelines recommend starting HIV antiretrovirals between 2 and 8 weeks after starting 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.11“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

The Stop TB Partnership’s Global Plan to Stop TB had as a target, that by 2015, all HIV positive TB patients should be receiving antiretroviral treatment.12“The Global Plan to Stop TB”, WHO, Geneva, 2011, 12 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.13“Global Tuberculosis Control 2014”, WHO, Geneva, 2014, www.who.int/tb/publications/global_report/

HIV and MDR TB

The relationship between HIV infection and multi drug resistant (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 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.14Personal communication

The combination of MDR TB and HIV antiretroviral treatment requires adherence to between 6 and 10 daily medications for more than a year, and such regimes are characterised by high levels of toxicity and drug-drug interactions.

At the level of global TB control, a better understanding needs to be developed of how HIV infection impacts the epidemiology of drug resistant TB, in order that there will not be “a perfect storm” of a massive MDR TB/HIV co-epidemic.15Suchindran, 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/

Preventing TB and HIV co-infection

The prevention of TB and HIV coinfection must consist of TB prevention for people living with HIV, as well as HIV prevention services for people with either latent or active TB.

Preventing TB in people with HIV

Treatment of latent TB infection with Isoniazid has been found to be highly effective in preventing the progression from latent to active TB disease in HIV co-infected people.16Piggott, D. “Timing of Antiretroviral Therapy for HIV in the Setting of TB Treatment” Clin Dev Immunol., 2011, 103917 www.hindawi.com/journals/cdi/”

Preventing HIV in people with TB

The World Health Organisation recommends that a number of HIV related prevention services should be provided for people with TB by either TB programs or by referral to HIV/AIDS programs. Such services should include amongst other things, counseling, social support and the prevention and treatment of sexually transmitted infections.17Piggott, D. “Timing of Antiretroviral Therapy for HIV in the Setting of TB Treatment” Clin Dev Immunol., 2011, 103917 www.hindawi.com/journals/cdi/”

Integrating TB and HIV services

For many years TB and HIV programmes at worldwide, national and local levels have operated separately, with separate management and funding streams and with little coordination. As a result patients with HIV and TB have had to access different services for screening, testing, care, treatment and adherence support.

Many people have called for the integration of services, claiming that it would provide benefits for patients, health care providers and health systems, and that the continuing vertical response to the TB and HIV epidemics is ineffective and inefficient.18Uyei, J. “Integrated delivery of HIV and tuberculosis services in sub-Saharan Africa: a systematic review” The Lancet Infectious Diseases, Vol 11, November 2011, p855http://www.thelancet.com/journals/laninf/issue/current?tab=past2004 However, other people claim that there are cultural differences between the services which make integration in practice extremely difficult.

“The different histories and cultures of the TB and HIV communities raise many challenges in achieving an effective and productive partnership … TB services are geared towards chronic care services with simple and standardized technical procedures, while HIV/AIDS services are clinically oriented and tend to be more individual patient oriented.”19“Scaling up prevention and treatment for TB and HIV – Report of the Fourth Global TB/HIV Working Group Meeting” Stop TB Partnership, 2004 www.who.int/tb/publications/tbhiv_addis_report/

There are also differences between TB and HIV as diseases, which have influenced the way that services have developed. HIV is an incurable disease for which life long medication is required. HIV positive people will often attend HIV services for many years, building up a sometimes close relationship between health professional and patient. HIV is not transmitted through casual contact with someone else with HIV, and HIV patients will often form themselves into self help groups, which include advocating for better services.

By contrast TB is a curable disease, and within two years of developing symptoms most people who are able to obtain treatment for their active TB will be cured. So TB patients will usually not have such a long term relationship with the health professionals who provide their treatment. In addition, as patients with active TB who are not on effective treatment, can pass on the disease to others, there is not the same tendency for people with active TB to form self help groups.

The different means of transmission are another reason why total integration of services is extremely difficult. People with active TB, who could pass on TB to people with HIV, should not be encouraged to come to the same part of a building at the same time as people with HIV, because of the risk of transmission.

Global policy on HIV and TB services

Although complete integration of HIV and TB services may be difficult, it is clear that a greater awareness of the problem of TB for people with HIV, and closer collaboration between services has already resulted in significant benefits. In 2012 the World Health Organisation (WHO) claimed that 900,000 lives had already been saved over six years by protecting people living with HIV from TB.

The WHO HIV/TB policy includes:20“WHO policy on collaborative TB/HIV activities” WHO, 2012 www.who.int/tb/publications/2012/tb_hiv_policy

  • The provision of antiretroviral therapy for all HIV positive TB patients, regardless of their CD4 count.
  • Provision of co-trimoxazole to provide TB patients with HIV with protection against lung and other infections.

In addition it is recommended that there should be surveillance of HIV and TB amongst health care workers, and that health care workers who are HIV positive, should be moved from areas with high TB exposure.

The stigmas of TB and HIV/AIDS

The stigmas of HIV and TB have come full circle.

In the early days of the HIV/AIDS epidemic, people were said to have died of TB when they had actually died of AIDS.21Eddie 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. 22Personal communication

References

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1. Mayer, K. “Synergistic Pandemics: Confronting the Global HIV and Tuberculosis Epidemics” Clinical Infectious Diseases, 2010, Volume 50, Supplement 3, S67http://cid.oxfordjournals.org/content/50/Supplement_3/”
2. “Global Tuberculosis Control 2014” www.who.int/tb/publications/global_report/
3. 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/
4. “Tribute to Winstone”, Action www.action.org/blog/post/tribute_to_winstone
5. Luetkemeyer, A. “Tuberculosis and HIV”, HIVInSite, http://hivinsite.ucsf.edu/
6. “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/
7. Sterling, T. “HIV Infection-Related Tuberculosis: Clinical Manifestations and Treatment” Clinical Infectious Diseases, 2010, Volume 50, Supplement 3, S223-S230http://cid.oxfordjournals.org/content/50/Supplement_3/”
8. “The Global Plan to Stop TB”, WHO, Geneva, 2011, 12 www.stoptb.org/global/plan/
9. Piggott, D. “Timing of Antiretroviral Therapy for HIV in the Setting of TB Treatment” Clin Dev Immunol., 2011, 103917 www.hindawi.com/journals/cdi/”
10. “Discussion – Diagnosis of Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB_IRIS)”, HIVweb Study, 2011 //depts.washington.edu/ghivaids/reslimited/case3/
11. “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
12. “The Global Plan to Stop TB”, WHO, Geneva, 2011, 12 www.stoptb.org/global/plan/
13. “Global Tuberculosis Control 2014”, WHO, Geneva, 2014, www.who.int/tb/publications/global_report/
14. Personal communication
15. 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/
16. Piggott, D. “Timing of Antiretroviral Therapy for HIV in the Setting of TB Treatment” Clin Dev Immunol., 2011, 103917 www.hindawi.com/journals/cdi/”
17. Piggott, D. “Timing of Antiretroviral Therapy for HIV in the Setting of TB Treatment” Clin Dev Immunol., 2011, 103917 www.hindawi.com/journals/cdi/”
18. Uyei, J. “Integrated delivery of HIV and tuberculosis services in sub-Saharan Africa: a systematic review” The Lancet Infectious Diseases, Vol 11, November 2011, p855http://www.thelancet.com/journals/laninf/issue/current?tab=past2004
19. “Scaling up prevention and treatment for TB and HIV – Report of the Fourth Global TB/HIV Working Group Meeting” Stop TB Partnership, 2004 www.who.int/tb/publications/tbhiv_addis_report/
20. “WHO policy on collaborative TB/HIV activities” WHO, 2012 www.who.int/tb/publications/2012/tb_hiv_policy
21. Eddie Vulani Maluleke in Nobody Ever Said AIDS:Stories & Poems from Southern Africa, Rasebotsa et al, 2004
22. Personal communication