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Scaling up antiretroviral treatment in resource-limited settings: successes and challenges

Katabira, Elly Ta; Oelrichs, Robert Bb

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doi: 10.1097/01.aids.0000279701.93932.ef
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‘Therefore, we… commit ourselves to pursuing all necessary efforts to scale up nationally driven, sustainable and comprehensive responses to achieve broad multisectoral coverage for prevention, treatment, care and support, with full and active participation of people living with HIV, vulnerable groups, most affected communities, civil society and the private sector, towards the goal of universal access to comprehensive prevention programmes, treatment, care and support by 2010.’

Resolution adopted by the United Nations General Assembly. 60/262. Political Declaration on HIV/AIDS. 87th plenary meeting, 2 June 2006.


It was during the Vancouver International AIDS Conference of 1996 that the world realized that triple combination therapy with antiretroviral drugs had made a critical breakthrough in the care of HIV-infected individuals. In North America and Europe, these drugs had already reduced significantly the morbidity and mortality associated with HIV disease. Unfortunately, at that time that world did not include countries from the resource-limited settings where the HIV burden was overwhelming. It did not take long, however, for others to notice this imbalance, particularly activists and affected groups, who then put pressure on the international community, demanding that it be redressed. This led to the United Nations agencies, initially the Joint Program on HIV and AIDS (UNAIDS) and closely followed by the World Health Organization (WHO) and the World Bank, to put in place mechanisms to increase access to antiretroviral therapy (ART) and related care by those who needed it most, particularly from the resource-limited settings. UNAIDS put in place the Medical Access Programme in 1996–1998 in collaboration with some drug companies initially to benefit four countries (Uganda, Ivory Coast, Chile and Vietnam). This was followed by the World Bank, which allowed some countries to use a portion of their Multicountry AIDS Project (MAP) funds to buy antiretroviral drugs. The big push came from WHO through their ‘3by5’ programme, which aimed to put 3 million individuals on ART by the end of 2005. Although the campaign failed to reach the target of 3 million, in sub-Saharan Africa it was able to increase the number of individuals on ART from approximately 100 000 in 2003 to 810 000 by the end of 2005. Access was further acelerated by the introduction of the United States' President's Emergency Plan for AIDS Relief (PEPFAR) programme, which is now benefiting 15 countries most affected by the HIV epidemic and which contributes approximately 50% of its budget to treatment, and the Global Fund for AIDS, TB and Malaria. As well as increased funding, another major boost has come from the drug industries that have lowered the prices of brand name antiretroviral drugs as well as introducing generic versions of these products. The biggest question, however, remains starkly unanswered. How, in the face of an undiminished epidemic and the prospect of a rapidly increasing need for more expensive therapies, can this momentum for ART access be increased and sustained?


By the end of 2006, it was estimated that there were over 2 million HIV-infected infected in low and middle-income countries accessing ART. We should, however, bear in mind that this success has come through multiple contributions involving United Nations agencies, bilateral aid programmes, civil societies, donor communities, activists and people living with HIV and AIDS. All these stakeholders and many others have contributed substantial support aside from just the purchase of antiretroviral drugs, including training on the procurement and distribution of drugs and other supplies, the rehabilitation and strengthening of vital infrastructures and the training of doctors and other health workers.

More patients on treatment

In sub-Saharan Africa, by the end of 2003, it was estimated that only 100 000 patients (or approximately 2%) were accessing HAART out of 4.4 million who needed the treatment. By the end of 2006, however, it was estimated that the number had risen to 1 340 000 (28%) out of the 4.8 million in need (Table 1). This increase (from 2% in 2003 to 28% in 2006) was a big achievement compared with other global regions, particularly in the context of such a high burden of disease. Nevertheless, there remain many more patients yet to access ART, particularly children in need, only 13% of whom currently receive treatment.

Table 1:
Global coverage of antiretroviral therapy 2003–2006.

The ‘3by5’ WHO programme target for Uganda was 60 000 patients. By the end of 2005, it was estimated that approximately 80 000 patients were accessing HAART in the country. This had increased by the end of 2006 to 96 000 patients out of the estimated 230 000 in need (Fig. 1). The total number included 6000 children, although less than 10% were children under the age of 2 years. This successful acceleration of access was achieved through a number of efforts including: financial and infrastructure support from UNAIDS, WHO, the World Bank–MAP, the Global Fund and PEPFAR; the Uganda CARE programme, an initiative of some large employing companies such as Nile Breweries, the Bank of Uganda and others, who offered free ART for their employees and the reduction of prices of some of the drugs, particularly generic drugs. This meant that more patients could afford to buy the drugs either by themselves or with the help of their families, relatives and friends.

Fig. 1:
Uganda in the African HIV epidemic. The percentage HIV prevalence in adults in Africa in 2005. Like most sub-Saharan African countries, Uganda has experienced a generalized epidemic, which, despite successful efforts in prevention, now shows evidence of newly increasing incidence. ART, Antiretroviral therapy.Symbol20–34%;Symbol10–< 20%;Symbol5–< 10%;Symbol1–< 5%;Symbol< 1%. Adapted from Report on the global AIDS epidemic 2006, UNAIDS, Geneva, 2006.

Th6 impact of antiretroviral therapy

Before the introduction of the accelerated access ART programme, 50–60% of hospital medical admissions in Uganda were caused by HIV-related problems. Many of these patients were terminally ill, and contributed to the high morbidity and mortality rates as well as to the extreme stress of health workers. With more individuals now receiving antiretroviral drugs, we are beginning to see the easing up of medical admissions with fewer HIV-related problems. Hospitals and other healthcare services are able to devote more resources to the management of other health conditions common in the community. At the patient level, there are numerous cases of individuals who have been resurrected by their being on ART. Patients who were bedridden, and just waiting to die, have had their quality of life improved so much that they have been able to go back to work.

Accelerated training programmes

One of the major requirements of successfully accelerated ART programmes was the presence of enough well-trained health workers to run the programme. The Ministry of Health (MoH) and other stakeholders such as the AIDS Support Organization, Mildmay International, the Joint Clinical Research Center and the Academic Alliance for HIV Care and Prevention in Africa at the Makerere University Infectious Diseases Institute and others mounted an expanded training programme to cover the country and other regions within Africa. The training engaged a wide range of health professionals involved in the care of HIV-infected patients, including doctors, nurses, clinical officers, counsellors and pharmacists or pharmacy technicians. The duration of the training varied from one week to up to a month and targeted specific areas of skills needed in successful ART delivery. Materials covered included initiating and monitoring ART, pre and post-HIV testing and adherence counselling as well as the basic principles of ART use.

One aspect of training that has been crucial in making accelerated access to ART possible is the involvement of community volunteers. This has meant that many patients can take their medications at home and be monitored by community volunteers who have been trained in ART monitoring and adherence principles. The volunteers also train members of the household so that they encourage and support the patient to take ART appropriately. This may be especially important at entry into the ART programme when the patient is commonly very sick and in need of intensive support and encouragement.

Rehabilitation of infrastructure

Most health infrastructure in sub-Saharan Africa has been run down over the years for various reasons. Many laboratories and other vital health system components were either non-functional or inadequate to support an effective ART programme. In Uganda a rehabilitation programme was initiated starting with the UNAIDS Medical Access Programme in 1998. Laboratory rehabilitation was also taken on by the Joint Clinical Research Center TREAT programme supported by PEPFAR. Regional and some district hospitals had their laboratories upgraded, and were provided with equipment and training to enable them to perform HIV testing and CD4 cell counting in selected locations. Viral load quantification was made available at some research centers. Some regional facilities were strengthened to function as referral centers for district and other smaller units engaged in the ART accelerated programme.

The MoH, through its AIDS Control Program undertook site assessment and accreditation of potential sites before they were designated as ART centers. The accreditation covered both private and public institutions and conducted evaluations on human capacity, storage space for drugs and relevant supplies and procurement facilities and capabilities. By June 2006, 124 such centers had been accredited in Uganda.

Strengthening procurement systems

Most smaller institutions, particularly at upcountry stations, did not have the procurement skills and capacity required to support an ART center. The MoH undertook training of their staff and also linked them in a network with other bigger units and the National Medical Stores, a government body charged with drug procurement and distribution across the country. The MoH also engaged ‘Deliver’, an institution supported by USAID, which provided technical skills in the estimation of drug needs and drug procurement to promote a nationwide logistics and distribution system. Where there was need to procure emergency drugs and supplies, the government also provided the necessary support and facilitation.

Reduction of drug prices and other related costs

One other key contribution to the success of the accelerated ART access programmes in Uganda and many other resource-limited countries was the reduction in the costs of drugs and supplies that were vital in the management of HIV disease. The production of fixed-dose combination tablets by generic companies in Thailand and India, and the large discounts offered by research and development-based companies means that a first-line ART regimen is now available at 1% of its price in the late 1990s. This unprecedented fall in cost has brought the drugs within the reach of many more individuals. Dramatic price reductions combined with simplified technologies have also expanded the availability of HIV serology and CD4 cell quantification from reference level laboratories to provincial or even district settings.


As the number of individuals initiated on ART programmes across the African continent grows, so do the challenges to maintain the momentum so far achieved and also sustain those already under care. The goals of providing treatment include ensuring that patients continue to receive quality services at minimal cost, resulting in better quality of life, reduced mortality and better drug adherence with delayed development of antiretroviral drug resistance. Sustaining the programmes themselves will depend heavily on our success in reinvigorating prevention efforts and managing the financial implications of programme dependence on long-term, international assistance.

Training enough health workers

In some countries with a mature HIV epidemic, the number of HIV-infected individuals who need HAART now and who will need it in the near future is still very large. In Uganda a large pool of well-trained healthcare professionals and community volunteers is required to provide adequate coverage. This means relentless and continued training of those already in service and of new recruits. The training needs to be innovative, of rigorously high quality, and able to keep up with the new developments of drugs and other approaches in AIDS care. On the other hand, the training must be user friendly and be delivered closer to where the action is, i.e. at the ART centers. It should also be able to cope with the ever-changing population of community volunteers, constantly requiring introductory and ongoing education.

Retaining those trained

The constant presence of the brain drain in sub-Saharan Africa should not be ignored. It is not surprising that many health workers trained within the country move to greener pastures with their newly acquired skills. World Bank research that measures the extent of the brain drain as part of the International Migration and Development Program notes that in 2004, although having only five doctors per 100 000 people, 286 of the total 1188 Ugandan doctors were currently working overseas, the majority in the United States and Canada ( Health workers move out of their countries for many reasons. Some include: for better pay; in search of better facilities to enable them to utilize their acquired skills more effectively; to follow their spouses or guardians; and in search of additional training, where they may end up staying for better jobs.

Authorities in resource-limited settings have done all that they can to keep these health workers in their home countries. Unfortunately, in most donor-supported programmes, remunerations beyond what governments pay are never considered. It is common knowledge, however, that government pay packages are often inadequate.

Deploying those trained where they are needed most

As the ART access programmes move into rural areas where the majority of patients reside, it is becoming very difficult to deploy health workers to them. These institutions are situated in unfavorable locations, with limited facilities to support adequately the newly deployed health workers. Such facilities include schools for their children, decent housing, access to other amenities such as the Internet and a quick and regular transport system. Finding the means to fulfill the requirements of trained health workers before deploying them to remote areas where the need is greatest is a pressing problem, and one the training and deploying agents find very difficult to address.

Rehabilitating and maintaining health system infrastructure

Effective ART programmes require robust infrastructure in terms of laboratory, logistics, pharmacy, information management and other facilities. Modern, automated laboratory equipment is complicated to use, expensive and difficult to maintain. It may be easy to train or retrain technicians to use them, but often regular maintenance requires outside technical support. Proper quality control of laboratory testing services also requires robust links to external sources of proficiency testing and a reliable flow of often costly reagents. Aside from the initial expense of equipment and training, these recurrent costs of quality management may be beyond the means of some smaller laboratories.

Sustaining procurement of drugs and supplies

Sustaining efficient procurement and distribution practices to meet the drugs and supplies requirements of an ever-growing number of individuals who initiate ART will be a tough challenge. In order to avoid drugs expiring on the shelves of smaller treatment centers, careful estimates of drug requirements need to be made on an individual basis by each treatment unit. In addition, there should be options that allow the transfer of drugs from a poorly performing unit to a site of higher demand. This requires a flexible and highly coordinated national system for forecasting, procurement and distribution, capacity for which needs to be built and sustained in the country's higher authorities.

Sustaining adequate adherence

The achievement of large numbers of individuals initiated on HAART in the past few years has been possible because of relatively cheap and available first-line antiretroviral drug combinations, especially stavudine–lamivudine–nevirapine. Unfortunately, some of these drugs are prone to short and long-term toxic effects, which may also precipitate drug failure, thus requiring the use of expensive second-line ART regimens. The durability of the first-line drugs also depends critically on those using them achieving a high adherence rate, ideally of up to 95%, in order to prevent the development of resistance, and the subsequent transmission of those resistant strains. The adherence rates in sub-Saharan Africa have so far been very good, many examples exist indicating that patients are at least as able to comply with therapy in Africa as they are in the developed world. No one knows, however, what will happen to these rates in the years to come because, at the moment, ART is for life. The rate of failure of first-line ART in current treatment cohorts will be a key factor in determining their sustainability.


More than 10 years ago, the prospect of providing ART in resource-limited settings was grim. When triple therapy was declared in 1996 to be the best option for the effective treatment of HIV-infected individuals there was only hope that this opportunity could be extended to countries with the highest burden. This hope was gradually realized when various stakeholders pledged to support the universal access to ART by those who need it most. This pledge has so far been successful, and over 2 million are now on ART, approximately 28% of those in need.

The road to success has however been bumpy, further exposing the inequalities and deficiencies of many health systems in countries with a heavy HIV burden. More than ever before, international support is making substantial resources available for the HIV response; however, the volatility and targeted nature of these resources present their own problems of fiscal management in countries with very limited capacity (Fig. 2). Turning the promise of these funds into broad and sustainable health system outcomes is the new challenge that must be engaged by international donor agencies.

Fig. 2:
The volatile nature of contributions to HIV/AIDS initiatives at the country level. Trends in external HIV/AIDS funding commitments are shown for selected African countries from 2000 to 2004. The surge in total international funding for the HIV/AIDS response belies the instability of resources at the country level. Significant fiscal ramifications revolve around the jump in external funding that reached, for example, approximately 1000% in Swaziland between 2002 and 2004. In some cases HIV/AIDS monies exceeded 150% of the government's total allocations for health.SymbolMalawi;SymbolMozambique;SymbolSwaziland;SymbolTanzania;SymbolUganda. Adapted from Lewis M. Addressing the challenge of HIV/AIDS: macroeconomic, fiscal and institutional issues. Center for Global Development working paper no. 58. 2005.

In 2006, almost 700 000 individuals worldwide received ART for the first time; however, 4.3 million adults and children were newly infected with HIV. Clearly, our efforts to expand access to treatment must occur in the context of a reinvigorated programme of prevention. Interventions focused on treatment alone will have only a limited effect on reducing incidence, even at high levels of coverage (Fig. 3). A synergistic combination of treatment and prevention may, however, result in a dramatic long-term net reduction of resource needs for both activities.

Fig. 3:
The synergy of treatment and preventive interventions. The graph shows the projected HIV incidence among adults in Sub-Saharan Africa, 2003–2020, under different intervention scenarios. The model demonstrates that treatment alone has only a marginal effect on incidence. By combining treatment with effective prevention programmes, the impact of both is enhanced.SymbolBaseline;Symbolprevention-centered;Symboltreament-centered;Symbolcomprehensive response. Redrawn from Salomon, et al. Integrating HIV prevention and treatment: from slogans to impact. PloS January 2005.

Throughout Africa, progress in expanding access to treatment and care for AIDS is visible. Shortages of well-trained health workers to deliver and monitor ART have been or are being addressed by scaling up comprehensive training programmes. Inadequate infrastructures such as laboratory and procurement services have been or are being rehabilitated and equipped with modern technologies to ensure better quality of care. Nevertheless, there are numerous challenges that will continue to need our constant attention and efforts. The challenges especially include retaining well-trained and motivated health workers, maintaining patient adherence to minimize the development of drug resistance, and the continuing commitment of donor communities and affected governments to invest in the universal access to treatment, prevention, support and care by all those who need it. In spite of these and more challenges, we cannot turn back now.

Disclaimer: The production of this special Supplement was supported by the World Bank, the Joint United Nations Programme on HIV/AIDS and the World Health Organization. The findings, interpretations and conclusions presented in this paper do not necessarily reflect the views of these institutions or their constituent agencies or governments.


HIV; AIDS; resource-limited; antiretroviral therapy

© 2007 Lippincott Williams & Wilkins, Inc.