Elsevier

The Lancet

Volume 375, Issue 9729, 29 May–4 June 2010, Pages 1906-1919
The Lancet

Series
The HIV-associated tuberculosis epidemic—when will we act?

https://doi.org/10.1016/S0140-6736(10)60409-6Get rights and content

Summary

Despite policies, strategies, and guidelines, the epidemic of HIV-associated tuberculosis continues to rage, particularly in southern Africa. We focus our attention on the regions with the greatest burden of disease, especially sub-Saharan Africa, and concentrate on prevention of tuberculosis in people with HIV infection, a challenge that has been greatly neglected. We argue for a much more aggressive approach to early diagnosis and treatment of HIV infection in affected communities, and propose urgent assessment of frequent testing for HIV and early start of antiretroviral treatment (ART). This approach should result in short-term and long-term declines in tuberculosis incidence through individual immune reconstitution and reduced HIV transmission. Implementation of the 3Is policy (intensified tuberculosis case finding, infection control, and isoniazid preventive therapy) for prevention of HIV-associated tuberculosis, combined with earlier start of ART, will reduce the burden of tuberculosis in people with HIV infection and provide a safe clinical environment for delivery of ART. Some progress is being made in provision of HIV care to HIV-infected patients with tuberculosis, but too few receive co-trimoxazole prophylaxis and ART. We make practical recommendations about how to improve this situation. Early HIV diagnosis and treatment, the 3Is, and a comprehensive package of HIV care, in association with directly observed therapy, short-course (DOTS) for tuberculosis, form the basis of prevention and control of HIV-associated tuberculosis. This call to action recommends that both HIV and tuberculosis programmes exhort implementation of strategies that are known to be effective, and test innovative strategies that could work. The continuing HIV-associated tuberculosis epidemic needs bold but responsible action, without which the future will simply mirror the past.

Introduction

“Only those who dare to fail greatly can ever achieve greatly.”

Robert Kennedy

We are at a watershed with the dual epidemic of tuberculosis and HIV. About 30 years ago, an ancient pathogen, Mycobacterium tuberculosis, and a new pathogen, HIV, began to interact to escalate the burden of disease, death, and misery in human populations. Our response to this onslaught, particularly in the killing fields of east and southern Africa, has been timid, slow, and uncoordinated. If this situation had been a war—more deaths from AIDS have been recorded than there were military deaths in World War II—our efforts would have been ridiculed as half-hearted and ineffectual. Implementation of effective policies, strategies, and guidelines has been inadequate, particularly for tuberculosis prevention.

This call to action focuses on sub-Saharan Africa, the epicentre of the HIV-associated tuberculosis epidemic. We begin by listening to people with HIV infection who have developed tuberculosis, to understand what they want from health services. We review the interim international policy guidelines for collaborative tuberculosis and HIV activities, and argue for a different conceptual approach that focuses on early diagnosis and treatment of HIV infection, which we believe will have the greatest effect in mitigation of the HIV-associated tuberculosis epidemic. We examine the logistics for delivery of tuberculosis prevention and HIV care, and make practical recommendations to scale up diagnosis, prevention, and treatment.

Key messages

  • •

    The WHO interim policy on collaborative tuberculosis and HIV activities (2004) was a milestone in the fight against the two diseases, but it failed to emphasise the crucial preventive role of antiretroviral treatment (ART) or to provide adequate guidance on management of suspected HIV-associated tuberculosis. The policy needs urgent revision and updating to incorporate recent data and field experience.

  • •

    Many people with HIV infection start ART too late, especially in Africa, and have already developed tuberculosis by the time that they present to health services for care. Rigorous implementation of recent international guidelines to ensure early start of ART could prevent some of these failed opportunities.

  • •

    Findings from mathematical models suggest that an innovative approach of frequent universal HIV testing combined with immediate or much earlier start of ART has the potential to greatly reduce tuberculosis incidence and HIV transmission. A research priority is how to use ART for maximum benefit to prevent HIV infection and HIV-associated tuberculosis.

  • •

    Much morbidity and mortality from tuberculosis could be prevented in people with HIV infection, even with the limitations of diagnostic technologies, by application and scale-up of the 3Is (intensified case finding, infection control, and isoniazid preventive therapy) in HIV and ART clinical services. This approach complements the effects of early start of ART and must be scaled up.

  • •

    Because early start of ART and efforts to prevent tuberculosis have not yet been implemented to scale, provision of good HIV care is vital for all HIV-infected patients with tuberculosis through provider-initiated HIV testing and counselling, co-trimoxazole prophylaxis, and ART. ART should be given to all tuberculosis patients co-infected with HIV, and given as early as possible during antituberculosis treatment.

Section snippets

What do HIV-infected people with tuberculosis want from health services?

By the time people with HIV infection seek help from health services because of cough, fever, and weight loss, they are weak and frightened, and poorer because of transport and other costs that are imposed on their often meagre household budgets (panel 1). The health facility that greets them is overcrowded, with few health-care workers and no privacy. People with HIV infection might not know why they are ill, but they do know what they need: rapid and free-of-charge diagnosis of HIV infection

The interim policy on collaborative tuberculosis and HIV activities

From the mid-1980s, tuberculosis programmes in countries with high prevalence of HIV infection, particularly in sub-Saharan Africa, faced increasing challenges: rising tuberculosis case notifications; disproportionally more patients with smear-negative disease6 and drug-related side-effects;7 high case fatality;8 high rates of tuberculosis recurrence;9 and increased transmission of M tuberculosis within congregate settings. In industrialised countries in the 1990s, outbreaks of

HIV testing and early start of ART for tuberculosis prevention

Although use of ART results in major reductions in rates of tuberculosis in HIV treatment cohorts,29, 30, 31, 32 the effect on tuberculosis control in the community is limited by the fact that so many patients, particularly in sub-Saharan Africa, are diagnosed with HIV and start ART at low CD4 cell counts of 100–150 cells per μL.33 A large proportion of people with HIV infection first presents with active tuberculosis and a CD4 cell count of less than 200 cells per μL.22, 23, 29, 30, 31, 32, 34

Prevention of tuberculosis with the 3Is

While early HIV diagnosis and treatment is being evaluated and scaled up, much morbidity and mortality from tuberculosis in people infected with HIV could be prevented by application of the 3Is—intensified case finding, infection control, and isoniazid preventive therapy—even with the limitations and constraints of current diagnostic technologies. Intensified case finding promotes early start of tuberculosis treatment, which reduces HIV-related tuberculosis disease and death, and simultaneously

Prevention of tuberculosis in HIV-infected infants and children: BCG vaccination

Tuberculosis is also an important cause of death and disease in children with HIV infection, and is even more difficult to diagnose than HIV-related tuberculosis in adults.83 Prevention of HIV infection in parents and mother-to-child transmission of HIV infection will probably have the greatest effect on reduction of HIV-associated tuberculosis in children.

BCG, a live attenuated Mycobacterium bovis vaccine, is almost universally given soon after birth in sub-Saharan African countries, where the

HIV care for HIV-infected patients with tuberculosis

With tuberculosis prevention efforts not yet implemented to scale, the other main emphasis of the tuberculosis and HIV interim policy is to provide good HIV care for HIV-infected people who develop tuberculosis. Provider-initiated HIV testing and counselling, co-trimoxazole preventive therapy, and ART should be regarded as the basic standard of care, and yet gaps in implementation remain large. About 40% of all patients with tuberculosis are not tested for HIV, and a large proportion with HIV

Interaction with general health systems

The organisation of disease-specific programmes has implications for the general health system, and raises two questions: what are the ways in which overall strengthening of health systems can contribute to improved performance and collaboration of HIV and tuberculosis programmes; and how can HIV and tuberculosis programmes contribute to strengthening of health systems?116

In response to the first question, disease-specific programmes for HIV and tuberculosis stand to benefit from improvements

Conclusions

The advent of ART has been the most important event in tuberculosis control since the epidemic of HIV-associated tuberculosis began. However, the full potential of ART, in combination with HIV testing, tuberculosis screening, infection control, and isoniazid and co-trimoxazole preventive therapy, has yet to be realised. HIV programmes, particularly at the level of service delivery, need to take tuberculosis far more seriously than at present and engage more actively with civil society in

Search strategy and selection criteria

We searched PubMed and Google Scholar with search terms that included, but were not restricted to, “tuberculosis HIV”, “tuberculosis HIV testing”, “tuberculosis cotrimoxazole prophylaxis”, “tuberculosis antiretroviral therapy”, “isoniazid preventive therapy”, “intensified TB case finding”, “tuberculosis infection control”, and “tuberculosis Africa”. Further publications were identified from references cited in relevant articles, reports, workshops, and conference proceedings. We reviewed

References (138)

  • K Kranzer et al.

    Yield of HIV-associated tuberculosis during intensified case finding in resource-limited settings: a systematic review and meta-analysis

    Lancet Infect Dis

    (2010)
  • B Mosimaneotsile et al.

    Value of chest radiography in a tuberculosis prevention programme for HIV-infected people, Botswana

    Lancet

    (2003)
  • M Badri et al.

    Short-term risk of AIDS or death in people infected with HIV-1 before antiretroviral therapy in South Africa: a longitudinal study

    Lancet

    (2006)
  • B Rekha et al.

    Childhood tuberculosis—global epidemiology and the impact of HIV

    Paediatr Respir Rev

    (2007)
  • B Bourdin Trunz et al.

    Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness

    Lancet

    (2006)
  • SZ Wiktor et al.

    Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Cote d'Ivoire: a randomised controlled trial

    Lancet

    (1999)
  • ET Santos Filho et al.

    Estratégias de controle da tuberculose no Brasil: articulação e participação da sociedade civil

  • A Van Rie et al.

    Counselling and testing of TB patients for HIV: evaluation of three implementation models in Kinshasa, Congo

    Int J Tuberc Lung Dis

    (2008)
  • I Makwiza et al.

    Who has access to counseling and testing and antiretroviral therapy in Malawi—an equity analysis

    Int J Equity Health

    (2009)

  • The national tuberculosis health sector strategic plan for Ghana

    (2009–2013)
  • R Colebunders et al.

    A review of the diagnosis and treatment of smear-negative pulmonary tuberculosis

    Int J Tuberc Lung Dis

    (2000)
  • MY Diul et al.

    Tuberculosis case fatality rates in HIV prevalence populations in sub-Saharan Africa

    AIDS

    (2001)
  • EL Korenromp et al.

    Effects of human immunodeficiency virus infection on recurrence of tuberculosis after rifampicin-based treatment: an analytic review

    Clin Infect Dis

    (2003)
  • B Edlin et al.

    An outbreak of multidrug-resistant tuberculosis among hospitalized patients with the acquired immunodeficiency syndrome

    N Engl J Med

    (1992)
  • M Heijnders et al.

    The fight against stigma: an overview of stigma-reduction strategies and interventions

    Psychol Health Med

    (2006)
  • KM De Cock et al.

    Will DOTS do it? A reappraisal of tuberculosis control in countries with high rates of HIV infection

    Int J Tuberc Lung Dis

    (1999)

  • Interim policy on collaborative TB/HIV activities

    (2004)

  • Strategic framework to decrease the burden of TB/HIV

    (2002)

  • Guidelines for implementing collaborative TB and HIV programme activities

    (2003)
  • SR Anderson et al.

    An analysis of interaction between TB and HIV/AIDS programmes in sub-Saharan Africa

    (2001)
  • A Miranda et al.

    Impact of antiretroviral therapy on the incidence of tuberculosis: the Brazilian experience, 1995–2001

    PLoS One

    (2007)
  • SD Lawn et al.

    Tuberculosis among HIV-infected patients receiving HAART: long term incidence and risk factors in a South African cohort

    AIDS

    (2005)
  • SD Lawn et al.

    Burden of tuberculosis in an antiretroviral treatment programme in sub-Saharan Africa: impact on treatment outcomes and implications for tuberculosis control

    AIDS

    (2006)
  • D Moore et al.

    Prevalence, incidence and mortality associated with tuberculosis in HIV-infected patients initiating antiretroviral therapy in rural Uganda

    AIDS

    (2007)

  • The Global Plan to Stop TB 2006–2015

    (2006)

  • The Stop TB Strategy: building on and enhancing DOTS to meet the TB-related Millennium Development Goals

  • Global tuberculosis control 2009: epidemiology, strategy, financing

  • The Global Plan to Stop TB 2006–2015. Progress report 2006–2008

  • Global tuberculosis control: a short update to the 2009 report

  • SD Lawn et al.

    Short-term and long-term risk of tuberculosis associated with CD4 cell recovery during antiretroviral therapy in South Africa

    AIDS

    (2009)
  • BG Williams et al.

    Antiretroviral therapy for TB control in the era of HIV/AIDS

    Science

    (2003)

  • Starting antiretroviral therapy earlier yields better clinical outcomes

  • SD Lawn et al.

    Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa

    AIDS

    (2008)
  • P Nunn et al.

    Tuberculosis control in the era of HIV

    Nat Rev Immunol

    (2005)

  • Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach (2006 revision)

  • Rapid advice: antiretroviral therapy for HIV infection in adults and adolescents (Nov 30, 2009)

  • NN Bock et al.

    Tuberculosis infection control in resource-limited settings in the era of expanding HIV care and treatment

    J Infect Dis

    (2007)
  • GJ Churchyard et al.

    Tuberculosis preventive therapy in the era of HIV infection: overview and research priorities

    J Infect Dis

    (2007)
  • EL Corbett et al.

    Epidemiology of tuberculosis in a high HIV prevalence population provided with enhanced diagnosis of symptomatic disease

    PLoS Med

    (2007)

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