SUPPLEMENT ARTICLE

Tuberculosis and HIV Infection: The Global Setting

Paul Nunn,1 Alasdair Reid,3 and Kevin M. De Cock2
1

Stop TB Department and 2HIV/AIDS Department, World Health Organization, and 3Joint United Nations Programme on HIV/AIDS, Geneva, Switzerland

Tuberculosis (TB) and human immunodeciency virus (HIV) infection make each others control signicantly more difcult. Coordination in addressing this cursed duet is insufcient at both global and national levels. However, global policy for TB/HIV coordination has been set, and there is consensus around this policy from both the TB and HIV control communities. The policy aims to provide all necessary care for the prevention and management of HIV-associated TB, but its implementation is hindered by real technical difculties and shortages of resources. All major global-level institutions involved in HIV care and prevention must include TB control as part of their corporate policy. Country-level decision makers need to work together to expand both TB and HIV services, and civil society and community representatives need to hold those responsible accountable for their delivery. The TB and HIV communities should join forces to address the health-sector weaknesses that confront them both. One might have expected, some 23 years after the rst reports of HIV-associated tuberculosis (TB) [13], that there would be close coordination in policy making on TB/HIV matters internationally and that control programs would be working closely together at the country level. In fact, neither the TB nor the HIV community, in our view, has responded adequately to the problems posed by the interaction of TB and HIV infection. Almost all low-income countries have a TB control program, although some of these programs are very weak, but HIV treatment programs are in their infancy, and so is TB/HIV collaboration. This discordance is of real concern for individuals with HIV-associated TB, who can usually access treatment for TB but whose longerterm care is uncertain. Progress is slow because of inadequate political will and insufcient nancial, human, and institutional resources at the country level, with genuine technical difculties in coordinating a 6- to 8-month treatment regimen provided by one program and lifelong care provided by another. At both national and global levels, differences in the history and culture of control programs, exacerbated by territorial protectiveness, have slowed down policy making. In the present article, we set the scene for the articles that follow in this supplement by providing a brief historical background to the development of global TB and HIV control approaches. The epidemiologic prole of TB in Africa and the policy implications of the scaling up of HIV treatment for TB control programs have recently been reviewed [4], as have the rationale for collaboration between TB and HIV programs and the activities required at the country level [5]. These will, therefore, be covered only briey in this article. The array of institutions that are now addressing both HIV and TB at the global level will be described, and TB/ HIV-related policy questions of global relevance will be discussed. EPIDEMIOLOGIC SUMMARY
Potential conicts of interest: P.N., A.R., and K.M.D.C. are all staff members of the World Health Organization. Financial support: supplement sponsorship is detailed in the Acknowledgments. Reprints or correspondence: Dr. Paul Nunn, Stop TB Dept., World Health Organization/Organisation Mondiale de la Sante , CH-1211, Geneva, Switzerland (nunnp@who.int). The Journal of Infectious Diseases 2007; 196:S514 2007 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2007/19604S1-0003$15.00 DOI: 10.1086/518660

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The Joint United Nations Programme on HIV/AIDS (UNAIDS) estimated that there were 39.5 million people living with HIV infection at the end of 2006 [6], up from 37.5 million in 2003. Four million new infections occurred during 2006, with 3 million deaths caused by HIV. The greatest increases in prevalence were in Eastern Europe and Central Asia, while subTB and HIV Infection: The Global Setting JID 2007:196 (Suppl 1) S5

Saharan Africa remains host to nearly two-thirds of all prevalent cases. With regard to TB, the World Health Organization (WHO) estimated that, in 2004, there were 8.9 million new cases worldwide [7]. This represents a global growth in incidence of just 0.6% compared with 2003. In fact, TB incidence was stable or falling in 5 of 6 WHO regions, with only Africa experiencing an increase, as a result of the HIV infection epidemic (gures 1 and 2). Three-quarters of a million of these annual TB cases occurred in adults infected with HIV, and 250,000 of the 1.7 million deaths that occurred as a result of TB in 2004 were in HIV-infected individuals. Southern Africa is particularly hard hit, with a number of small countriesnotably Botswana, Lesotho, Namibia, and Swazilandnotifying TB in 10.5% of the population each year [7]. It is clear that the annual incidence of and mortality due to TB globally would be falling if it were not for HIV infection. However, there is some good news the annual increase in case notications from the WHO African Region has been slowing down since 2000, probably because of the decrease in HIV infection prevalence, suggesting that we could be on the threshold of an African, as well as a global, downturn in TB incidence. The impact of TB on HIV infection is less evident but nonetheless signicantglobally, 8% [7, 8] of HIV-related deaths were estimated to be caused by TB in 2004, increasing to 10% of HIV-related deaths of adults and children across the WHO African Region. Autopsy studies, however, have shown rates of TB in excess of 33% among people dying of AIDS [9]. TB is an increasingly frequent event among people receiving antiretroviral therapy (ART) globally, and it severely complicates management. HISTORICAL BACKGROUND When AIDS emerged in the 1980s, TB was a small component of public health in most developing countries, diagnosed by clinicians and treated largely by specialist physicians and their teams out of TB clinics and specialized hospitals [10, 11]. The burden of TB was underestimated [12], diagnosis was cumbersome [13], and a full course of treatment was often unavailable, especially in rural areas. National TB control programs (NTPs) existed in almost all countries but provided unsystematic management with uncertain results. However, the clinical picture of TB was well understood, and rifampin-based short-course regimens had made TB relatively easy to cure, provided the whole course was taken [14]. HIV infection, though, made diagnosis even more difcult [15], complicated management with concomitant infections, increased drug side effects [16, 17] and recurrence [18], and led to a 5-fold increase in mortality [19, 20]. However, the main impact was caused by the huge increase in cases, putting serious strain on the capacity of NTPs, their workforces, and their budgets [21]. TB,

even if associated with HIV infection, was seen as the responsibility of TB programs. During the 1990s, however, TB was increasingly prioritized [22] by the WHO, which, together with the International Union against Tuberculosis (as it was then called), showed that the estimated burden of TB was far greater than previously thought [12]. Karel Styblo had shown that treatment of TB, focused on the smear-positive, drug-susceptible cases, could interrupt transmission in the absence of HIV infection [23], and, moreover, it could be systematized and organized [24] and was highly cost-effective [25]. The WHO declared TB a global emergency in 1993, and the World Banks World Development Report on Investing in Health [26], demonstrating the low cost and high cost-effectiveness of TB control, further promoted TB control to health policy makers. The message resonated in industrialized countries, especially the United States, where TB was resurgent because of immigration and falling standards of TB control [27], as well as HIV infection [28], and the experience of New York City lent signicant support to the concept of directly observed therapy (DOT) [29]. In 1995, the WHO branded its control strategy as DOTSdirectly observed therapy, short course, in its original formulation. (Today, DOTS is used as a brand name, denoting a policy package of which directly observed therapy and short-course treatment are only a part. Other elements include political commitment; a secure, high-quality drug supply; bacteriological diagnosis; and outcome evaluation of every patient.) The WHO then set about converting countries to the cause. By 2004, 200 countries had adopted DOTS as the preferred strategy for addressing TB [7]. Such rapid expansion could probably have happened only with a clear, simple, one size ts all approach. The countries with the most effective DOTS programs were most able to resist

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Figure 1. Incidence estimates of all forms of tuberculosis (TB), per 100,000 general population, by year, 19902004 [7]. Africalow HIV denotes all sub-Saharan African countries where HIV infection prevalence in the adult (1549 years of age) population is 4%. Africahigh HIV denotes all sub-Saharan countries where HIV infection prevalence in the adult population is 14%. World exc AFR EEUR denotes the world with the exception of Africa and Eastern Europe.

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Figure 2. Estimated HIV infection prevalence (%) among new adult patients with tuberculosis (1549 years of age). Reprinted from the World Health Organization [7]. The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city, or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines denote approximate borders on which there may not yet be full agreement.

the impact of HIV infection on increasing the incidence of TB [30]; however, by 2001, it was clear that programmatic simplicity needed to adapt in response to increasing challenges [31, 32]. In spite of successes in China [33], Peru [34], Morocco [35], and other countries, TB rates were climbing globally and were especially uncontrolled in sub-Saharan Africa [36]. TB control efforts had to begin addressing more directly the difcult issues of multidrug resistance, involvement of communities, strengthening of health systems, development of new tools, and, especially, the impact of HIV infection on TB [37]. Meanwhile, most developing countries had responded to the seriousness of HIV infection and had established, by 1990, national AIDS control programs (NACPs) in their ministries of health. At the global level, early control efforts were stimulated by the Special (later Global) Programme on AIDS in the WHO. Perceptions of weakness in the leadership of the WHO in the eld of HIV, and the need to involve sectors other than health, led to the establishment of UNAIDS, which brought together, as cosponsors, the United Nations (UN) agencies involved in addressing HIV. UNAIDS focused on advocacy and establishing a multisectoral global response to HIV. The establishment of national AIDS commissions (NACs) in countries with a high HIV infection prevalence was intended to coordinate national efforts against HIV and involve all sectors, not

just the health sector. In some countries, though, this had the perverse effect of weakening the health sector response, because the shortage of suitably qualied human resources meant that NACs were often staffed, at least initially, by personnel from the NACPs, who could ill afford to lose them. The UN General Assembly Special Session on AIDS in 2001, however, was a major achievement and marked the rst time that a single disease had reached this level of global debate [38]. In the absence of effective treatment, NACPs focused on prevention of transmission through information, education, and communication, with a heavy emphasis on counseling for behavioral changes and the use of condoms, whereas NTPs focused on TB treatment. These efforts were limited, though, by a strong bias, especially in the worst-affected countries, against knowing ones HIV infection status if there was so little to offer in the way of treatment for HIV infection. In spite of the best efforts of NACPs, the HIV infection prevalence exceeded 40% among antenatal clinic attendees in the worstaffected countries in southern Africa [39]. HIV impactmitigation strategies, however, were transformed from 2001 onward by falling prices for triple-drug ART and by the drive to make such treatments available to the worlds poor through multilateral and bilateral programs [40].

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Figure 3. Development of policies for collaborative tuberculosis (TB)/HIV activities, 20022004. Adapted from the World Health Organization [7]. Data are for the 32 countries that have reported data for the 3 years, from among the 41 countries with the highest burden of HIV-infected patients with TB. The bars show the numbers of countries that had appointed a TB/HIV focal person within the national TB control program, that had a formal system for referring patients from HIV to TB services, and that had policies to perform intensied case nding (ICF) among people with HIV infection, to provide HIV testing and counseling to all patients with TB, to provide cotrimoxazole preventive therapy (CPT) to HIV-infected patients with TB, and to provide antiretroviral therapy (ART) to patients with TB.

THE GLOBAL RESPONSE TO TB/HIV INFECTION, RECENT INITIATIVES, AND ASSOCIATED POLICY ISSUES The TB communitys response to TB/HIV infection. At the global level, policy guidance on how to respond to the impact of HIV infection on TB has come mainly from WHOs Stop TB Department and the TB/HIV Working Group of the Stop TB Partnership (established by the WHO in 2000 to reach out to the many countries, public- and private-sector funding agencies, international organizations, nongovernmental and patient organizations, commercial enterprises, and individuals involved in, or wishing to contribute to, TB control) working in collaboration with the HIV Department of the WHO, the US Agency for International Development, the Centers for Disease Control and Prevention (CDC), and a number of other partners, notably TB nongovernmental organizations and HIV activists [4143]. The WHO is the agency responsible for setting international norms and standards in health, and its capacity to bring together all stakeholders on a given issue has been key. Driven by pleas for help from countries with a high HIV infection prevalence, this TB/HIV guidance addresses the practical realities of disease control in low-income countries and denes the additional acS8 JID 2007:196 (Suppl 1) Nunn et al.

tivities that need to be taken on by the health system in general and by TB and AIDS control programs in particular, while avoiding the creation of a third program. The policy assumes, for effective case management, that patients with TB and HIV coinfection need to receive services directed at both infections at the same time and place. Although heavily inuenced by the African situation, the policy addresses all settings. In 2004, this series of policy documents and guidelines culminated in the Interim Policy on Collaborative TB/HIV Activities [44], which lays out a 12point policy package (Appendix A). What has been achieved to date? Between 2002 and 2004, there was a signicant increase in the number of countries with the highest burdens of HIV-associated TB adopting these policies (gure 3) [7]. Of the 211 countries reporting to the WHO, 53% have a policy of offering HIV testing to patients with TB; however, in 2004, only 4.2% of 4.4 million notied patients were reported to have been tested. Forty-six countries (23%) reported that they routinely assessed patients with TB for eligibility to receive ART, but only 9388 patients with TB were reported to have started ART in 2003 (gure 4). However, there are 2 major drawbacks to these data. First, they are heavily weighted by information from TB programs, with little infor-

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Figure 4. HIV testing and the provision of care for patients with tuberculosis (TB), 2003. Adapted from the World Health Organization [7]. Shown are the numbers of patients with TB who were tested for HIV (black bars), who were HIV positive (red bars), who were given cotrimoxazole preventive therapy (CPT) (yellow bars), and who had antiretroviral therapy (ART) initiated (green bars), for every 100 HIV-infected patients estimated to have TB in each World Health Organization region. For the European Region, the number of patients tested and HIV positive are for 2004. The South-East Asian Region reported 5 HIV-infected patients with TB in 2003. Data for the Region of the Americas exclude Brazil. AFR, African Region; AMR, Region of the Americas (excluding Brazil); EMR, Eastern Mediterranean Region; EUR, European Region; SEAR, South-East Asian Region; WPR, Western Pacic Region.

mation coming from HIV programs on case nding for TB, isoniazid preventive therapy, or TB infection control in health care settings. Second, there is a long delay in reporting, because these data are only reported with the outcomes of treatment, which are not available until 1 year from the time of recruitment of the last patient in the cohort. From other sources, however, we know that several countries are moving faster. For example, in Malawi, during the rst half of 2005, 6651 patients with TB (49%) were tested for HIV, of whom 67% had positive results (Malawi Ministry of Health, personal communication). During the third quarter of 2005, 7784 adults started ART, of whom 1363 (18%) were patients with TB. In other words, at that time, approximately one-third of all patients with TB requiring treatment for HIV infection were receiving it. During 2004, Rwanda performed HIV testing on 48% of the 6167 patients with TB registered nationally, of whom 48% were found to be HIV positive (Programme National Integre de la Lutte contre la Tuberculose, Annual Report 2005). In the last quarter of 2005 in Kenya, of the 37,641 patients with TB notied, 37% were tested for HIV, of whom 57% were found to be positive. By the end of the quarter, 1270 patients were receiving ART, and 3458 were receiving cotrimoxazole (J. Mansoer and J. Chakaya, personal communication). Funding support for collaborative TB/HIV activities. Fund-

ing for TB and HIV control is crucial: for 21 of the 22 countries that contribute 80% of the worlds burden of TB, NTP budgets have doubled between 2002 and 2006, to $990 million [7]; however, although budgets for collaborative TB/HIV activities are increasing, they have remained small (1%5% of the total budget), with some exceptions, such as Kenya, whose 2006 budget of $26 million has approximately one-third set aside for TB/HIV activities. TB/HIV activities and the new Stop TB Strategy and Plan. Further impetus for the implementation of TB/HIV activities (gure 4) is likely to come from the new Stop TB Strategy, which was launched in early 2006 [37] (Appendix B). Although DOTS remains at the center of TB control, the new strategy aims to expand care beyond DOTS, given that DOTS alone is insufcient in settings with a high HIV infection prevalence [31]. Thus, for the rst time, TB/HIV activities are no longer optional for NTPs but are an integral part of their activities. The Global Plan to Stop TB, 20062015, provides guidance on scaling up TB control activities [45]. The plan goes beyond the existing targets of at least 70% case detection and 85% treatment success and aims to achieve the TB-specic Millennium Development Goal [46] (i.e., to have begun reducing the incidence of TB) and the Stop TB Partnership goals of halving the 1990 levels of prevalence and mortality by 2015. If the plan
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is fully implemented, 50 million patients will be treated for TB over 10 years, including 800,000 for multidrug-resistant TB. Some 14 million lives will be saved between 2006 and 2015. The plan recognizes that Africa (because of HIV infection) and Eastern Europe (because of multidrug-resistant TB) will need more time than other regions to reach the Millennium Development Goal targets, but they will nevertheless make signicant gains by 2015. With respect to TB/HIV issues, the plan aims to expand implementation of collaborative activities in line with scaling up toward universal access [47], and milestones are laid out for 2006 and 2010. If the plan is fully funded, by 2015, some 29 million patients with TB will be counseled about and tested for HIV infection, and nearly 210 million people with HIV infection will be screened for TB. More than 3 million patients with TB and HIV infection will be receiving ART, and a similar number will have completed a course of isoniazid preventive therapy. The total cost of the plan is $56 billion, and the importance of HIV infection for the scale-up of TB control is illustrated by the $6.7 billion (12%) required for TB/HIV activities. The estimated funding gap is $31 billion, because approximately $25 billion is projected to be available from existing sources. Success in achieving these intensely ambitious goals depends not only on mobilizing political commitment and sufcient funds but also on simultaneous improvements within the wider health system. Without more worker-friendly policies and genuine involvement of the private sector, adequate numbers of sufciently trained personnel are unlikely to be available for TB work. Reaching the plans targets, much less the Millennium Development Goals, for Africa will be extremely difcult without signicant improvements in national infrastructures, which, in turn, depend on improvements in governance and economic performance, as well as donor commitment. The HIV communitys response to the TB/HIV interaction. The HIV community has, until recently, mostly viewed TB as just one of the many problems with which HIV-infected patients have to contend [38]. The focus has been on the core business of prevention of HIV transmission [39] and, more recently, expanding the availability of ART [48], from which people with TB would naturally benet. More recently, however, the HIV community has recognized the need for a coordinated approach to the dual TB/HIV infection epidemic [49]. HIV-associated TB is specically addressed in the UNAIDS and WHOs recent policy document on HIV counseling and testing [50], which recommends that all patients with TB be offered an HIV test. However, the contribution that the TB community can make in scaling up toward universal access to HIV infection prevention, treatment, care, and support has not yet been fully realized. Arguably, the most signicant initiative for TB control since
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the introduction of DOTS is the drive to scale up treatment with antiretroviral drugs [4]. Negotiated reductions in prices opened the way for the WHO to announce, in September 2003, its intention to have 3 million people in need of ART receiving it by the end of 2005 [48]. At that time, some 400,000 (or 7%) of people estimated to be in need in the developing world were thought to be receiving ART. By the end of 2005, thanks to bilateral and multilateral efforts, 1.3 million people in need were estimated to be receiving ART, and 18 countries had achieved 150% coverage [51]. More importantly, the number of people receiving ART in Africa had risen from 100,000 to 810,000. The 3 by 5 initiative had failed to reach its target but had changed the paradigm from one that viewed such treatment as too expensive, not cost-effective, and too difcult in such poor countries to one based on the right to treatment, with clear evidence that it was feasible. Many countries seemed stimulated by the setting of countryspecic targets as a component of a worldwide effort, although opinions seem divided on the value of setting the global target. Partnerships were essential to the successes. Building the boat while sailing worked, thus moving faster than the previous, more linear approach to global initiatives [52]. Greater progress might have been achieved with more consistent, clearer direction regarding the technical components of the strategy and with more attention paid to partnership building within the WHO as well as outside of it, but the WHO has also been praised for facilitating a difcult task that many thought impossible and for the radical philosophic shift inherent in a global AIDS treatment agenda. The 3 by 5 initiative probably accelerated the implementation of TB/HIV collaborative activities a little, and some countries targeted patients with TB (see above) [53], but inclusion of NTPs in country-level programming of activities should have been greater. The proportion of patients receiving ART who were referred from TB programs is not reported [51]. High rates of TB occurring in patients receiving ART, however, cause major problems [63] in the absence of established collaboration between TB and HIV services. Patients are often not screened adequately for TB at the start of ART, sputum-negative TB is difcult to diagnose, and infection control is often nonexistent. These problems can best be addressed by establishing collaborative mechanisms between the 2 programs that clearly lay out how referrals should be done and who is responsible for which elements of care. In sum, the HIV community has yet to respond fully to the challenges of the TB/HIV interaction. The 3 by 5 initiative, like DOTS and child health, has also illustrated the enormous gaps in poor countries health care infrastructure, including insufcient numbers and quality of human resources [54, 55], training institutions unable to respond to the demand for more trained workers, detrimental employment policies [56, 57], weak or nonexistent laboratories

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[58], monitoring and evaluation systems, crumbling communications networks, corrupt commodity-procurement practices, and weak distribution systems. If the world is serious about improving health in the developing countries, then these gaps will need to be bridged. Unprecedented investments from national and external governments [59] will be required, as will an unusual degree of coordination within the health system. Multilateral efforts. There are currently 3 major sources of nancial support for HIV and TB control at the global level, which are actual or potential supporters of a combined approach to TB and HIV. These are the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM), the World Bank, and the US Presidents Emergency Plan for AIDS Relief (PEPFAR). The GFATM has transformed the national-level picture for TB control resources, as well as for TB/HIV collaborative activities. However, it is a limited instrumentits only recourse, if things are not going right, is to withdraw its support. The GFATM administers funds donated by governments and foundations to support efforts to ght the 3 diseases and strengthen health care service delivery in eligible recipient countries. Proposals from countries and nongovernment institutions are prepared according to evolving guidelines, presented to the GFATM through the secretariat, and evaluated by a technical review panel, which recommends selected proposals for approval of the governing board. The rst 4 rounds of proposals between 2002 and 2004 included components on TB control, TB/HIV, HIV, and malaria, as well as integrated proposals. The TB/HIV proposals were generally of poor quality, and after the publication of the WHO policy on TB/HIV collaboration, the fth round, in 2005, recommended that all TB and all HIV proposals include TB/HIV activities. The proportion of proposals with specic TB/HIV activities increased with time (table 1). Not surprisingly, the proportion was higher in sub-Saharan Africa, rising from two-thirds in the rst round to nine-tenths in the fth. In the rest of the world, 42% of the approved TB proposals had specic TB/HIV activities, increasing from 22% in round 1 to 57% in round 5. In contrast, PEPFAR, with an initial $15 billion budget, is the umbrella program with oversight over all of the US governments AIDS developmental assistance funding in scores of countries, but with a particular focus in 15 countries. This assistance includes that provided by the CDC and the US Agency for International Development. PEPFAR is showing increasing commitment to TB/HIV activities, involving a number of US contractors, notably Family Health International and Management Sciences for Health, as well as US universities, such as Columbia, Harvard, and Yale. Collaborative TB/HIV activities are seen as contributing to achieving PEPFARs goals of having 2 million people receiving ART and 10 million people with HIV infection receiving care (by the end of 2008). How-

ever, the budget allocation to TB/HIV activities is still small in proportion to the total. The World Bank has been supporting countries HIV control efforts through the multicountry AIDS programs. These programs have, so far, placed almost no emphasis on TB/HIV collaboration [60]. The G8 countries appear to be increasingly engaged in health matters in the developing world, starting in Okinawa in 2000 and receiving the Africa Commission Report [61] at Gleneagles in 2005, under the presidency of the United Kingdom. The report was clear on the need for rebuilding systems to deliver public services in order to tackle diseases such as TB and malaria effectively [61, p. 15] and gave top priority to scaling up to deal with HIV, recommending that the WHOs Two diseases, one patient strategy should be supported to provide integrated TB and HIV care [61, p. 197]. However, translation of this policy into increased resources has yet to be seen. CONCLUSIONS AND WAYS FORWARD The overriding need is for acceleration of country-level implementation. To achieve this, there are several priorities. The rst is greater coordination between the TB and HIV communities at the global level. The main global institutions setting the global direction for funding in health need to agree that TB/HIV control is a priority issue, make it clear to all countries and development agencies that they have reached consensus, and ensure that funding follows. The HIV and Stop TB departments in the WHO agree on the importance of TB/HIV control and have jointly published the policy framework [44]. The GFATM is supporting countries that seek funding for collaborative TB/HIV activities as dened by the WHO policy. UNAIDS, PEPFAR, and the World Bank now need to make it clear that they, too, see TB control as an essential component of HIV control (TB is not yet featured in UNAIDS corporate priorities) and that they support this policy, by including TB/ HIV components in their work plans and ensuring that adequate human and nancial resources are available.

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Table 1. The Global Fund to Fight AIDS, Tuberculosis and Malaria.

Total no. of approved TB proposals 12 25 17 21 22 Total 97 No. (%) of approved proposals including TB/HIV 4 (33) 13 (52) 9 (53) 14 (67) 20 (91) 60

Round of application 1 2 3 4 5

NOTE. TB, tuberculosis.

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Although there have been signicant increases in collaborative activities since 2003, when compared against need, progress remains insufcient. The second priority, therefore, is to change the behavior of decision makers and health care workers: although the new TB strategy is signicantly more inclusive than DOTS alone, it needs to be fully disseminated, understood, and implemented by TB workers at all levels. Similarly, those working in HIV control need to understand the importance of TB control for their work and include screening for TB, isoniazid preventive therapy, and TB infection control in their HIV control activities. Clear, consistent messages from the WHO and all its partners are essential. The third priority is to expand and strengthen the capacity to deliver treatment and achieve universal access. Even after 10 years of the DOTS strategy, poor persons throughout the developing world still have difculty in gaining access to quality TB treatment, and, in many countries, the availability of ART is restricted to a handful of major centers and district general hospitals. Decentralization of care has to be a major feature of ART expansion [62]. The drive for universal access presents great opportunities for the HIV and TB communities to develop shared goals and joint work plans. One key issue is for each country to decide how ART can be delivered to patients with TB. There is a range of possibilities, from full integration of TB and HIV service delivery [63], to combined clinics, to separate treatment centers but with effective referral links between the two [4]. A review and analysis of current experiences around the world would be a useful start. Linked to this is the question of whether integration of HIV and TB control programs is desirable at the national level. The experience of DOTS delivery over the past decade suggests strongly that ensuring clear responsibility and accountability for each component of care delivery, together with adequate human and nancial resources, works, while a number of experiments with integration that have ignored this approach have failed [64, 65]. What is important is that, at the service delivery level, there is the closest coordinationeven integrationof care, and that from local settings up to the national level there is clear accountability. Fourth, the TB community must follow the example of the HIV community and involve civil society, community representatives, and patients in advocacy for TB control. Patient and community representatives can play a major role in identifying problems with TB control at the local level and in holding to account those responsible. They are also often the best advocates for change in local or national management policies. Fifth, new tools are denitely needed, and global institutions need to support research and development into better diagnostic tests, new anti-TB drugs, and new, more effective vaccines. Last, in resource-poor countries, both HIV and TB control confront the same weaknesses in the health system and in other
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sectors. An alliance of the 2 communities at the global level to address health system strengthening would make a lot of sense. Collaboration in the development of community-based care [66] and in the involvement of the private sector in public health service delivery for both diseases [67, 68] are just 2 potentially fertile areas. The role of the World Bank, as the largest international organization committed to nancial support of development, is key in addressing these multisectoral issues. Just as HIV infection and TB are inextricably linked, control of the 2 diseases cannot be dissociated. There is room for improvement in collaboration from the global level all the way to the local level.
Acknowledgments
We thank Gerald Friedland, for helpful comments and endless patience, and we acknowledge the help of Brian Williams and his colleagues at the World Health Organization, who provided epidemiologic background information for the article. Supplement sponsorship. This article was published as part of a supplement entitled Tuberculosis and HIV Coinfection: Current State of Knowledge and Research Priorities, sponsored by the National Institutes of Health Division of AIDS, the Centers for Disease Control and Prevention Division of TB Elimination, the World Bank, the Agence Nationale de Recherches sur le Sida et les He patites Virales, and the Forum for Collaborative HIV Research (including special contributions from the World Health Organization Stop TB Department, the International AIDS Society, and GlaxoSmithKline).

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APPENDIX A

THE GLOBAL POLICY FOR COLLABORATIVE TUBERCULOSIS (TB)/HIV ACTIVITIES [44] Establish mechanisms for collaboration Set up a coordinating body for TB/HIV activities Conduct surveillance of HIV infection prevalence among patients with TB Carry out joint TB/HIV planning Conduct monitoring and evaluation Decrease the burden of TB among people living with HIV infection Establish intensied TB case nding Introduce isoniazid preventive therapy Ensure Mycobacterium tuberculosis infection control in health care and congregate settings Decrease the burden of HIV infection among patients with TB Provide HIV testing and counseling Introduce HIV infection prevention methods Introduce cotrimoxazole preventive therapy Ensure HIV care and support Introduce antiretroviral therapy

APPENDIX B THE STOP TB STRATEGY [37] Goal To reduce the global burden of tuberculosis (TB) by 2015, in line with the Millennium Development Goals and the Stop TB Partnership targets Objectives Achieve universal access to high-quality diagnosis and patient-centered treatment Reduce the human suffering and socioeconomic burden associated with TB Protect poor and vulnerable populations from TB, HIVassociated TB, and multidrug-resistant TB Support the development of new tools and enable their timely and effective use Targets Millennium Development Goal 6, target 8: halt and begin to reverse the incidence of TB by 2015 Targets linked to the Millennium Development Goals and endorsed by the Stop TB Partnership By 2005: Detect at least 70% of new sputum smear positive TB cases and cure at least 85% of these cases By 2015: Reduce the prevalence of and number of deaths due to TB by 50% relative to those in 1990 By 2050: Eliminate TB as a public health problem (1 case per million population) Components of the Stop TB Strategy 1. Pursue high-quality DOTS expansion and enhancement Achieve political commitment with increased and sustained nancing Detect cases through quality-assured bacteriologic methods Standardize treatment with supervision and patient support Establish an effective drug supply and management system Implement a monitoring and evaluation system and impact measurement 2. Address HIV-associated TB, multidrug-resistant TB, and other challenges Implement collaborative TB/HIV activities Prevent and control multidrug-resistant TB Address prisoners, refugees, and other high-risk groups and special situations 3. Contribute to health system strengthening Actively participate in efforts to improve systemwide policy, human resources, nancing, management, ser-

vice delivery, and information systems Share innovations that strengthen systems, including the Practical Approach to Lung Health Adapt innovations from other elds 4. Engage all care providers Introduce public-public and public-private mix approaches Apply the International Standards for TB Care 5. Empower people with TB, as well as communities Advocate, communicate, and mobilize society to control TB Encourage community participation in TB care Apply the Patients Charter for Tuberculosis Care 6. Enable and promote research Conduct program-based operational research Increase investment in research to develop new diagnostics, drugs, and vaccines
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