The extraordinary success of antiretroviral therapy (ART) in the North during the closing years of the last century directly led to the United Nations' resolutions in 2000, about universal access to HIV treatment, and to the inclusion of this target among the Millenium Development Goals . A previous AIDS supplement, supported by the French Agency for AIDS Research (ANRS) and published as early as 2003, presented the evaluation of the first national pilot programs for access to antiretroviral HIV treatment in three African countries (Côte d'Ivoire, Senegal and Uganda). These results contributed to a consensus on the feasibility of scaling-up access to HIV treatment in low-resource settings, an issue that had been heavily debated among clinical, public health and development experts . Since then, antiretroviral therapy coverage rose from 7% in 2003 to 42% in 2008, with especially high coverage achieved in eastern and southern Africa (48%) .
There are no longer doubts that access to ART results in a remarkable reduction in mortality, which may be as high as 95% in comparison to no intervention . In addition, retention in care and treatment may exceed levels seen in the North: for example, a remarkable 79% of adults enrolled in the early stages of Botswana's antiretroviral therapy scale-up are alive five years later . On a macro scale, Bendavid and Bhattacharya  found that after four years of the US President's Emergency Plan for AIDS Relief (PEPFAR) funding and support for ART, HIV-related deaths decreased in sub-Saharan African focus countries compared with control countries, although trends in adult prevalence did not differ. Despite the community stigma, political denial and tensions between government policy and medical practice, South Africa with the largest number of HIV infected individuals is also home to the largest antiretroviral therapy program in the world with accelerating impact. In the Western Cape Province, six-month mortality among patients at an HIV treatment centre fell from 12.7% to 6.6% between 2001/2002 and 2005 as access expanded . The recent statement, on World AIDS Day on December 1st 2009, about universal access to HIV care and treatment by the new South-African President, Jacob Zuma, raises hope that South Africa will henceforth assume a leadership role in the region .
However, scaling-up access to HIV treatment in Africa, home to two thirds of those living with HIV/AIDS, poses new and largely unexplored challenges in the delivery of a complex set of public health, medical and psychosocial interventions. The transition from an emergency response to robust and sustainable health services delivery systems for HIV is a work in progress. Building these systems must be mindful of cultural context and existing health systems in the affected communities. The most recent  report on the epidemic describes a highly varied picture of remarkable progress in some African countries and huge unmet needs in others. Access to treatment in Africa is often taking place in the context of fragile states, struggling with social, political and economic turmoil, where investment in healthcare systems has been limited. Particularly in resource limited settings, there is an unavoidable competition for infrastructure, resources and personnel between donor driven programs targeting specific diseases (ie. AIDS, TB and malaria) and long standing programs in primary care, maternal and infant health.
The “Maximizing Positive Synergies Collaborative Group” (MPSCG), coordinated by WHO, has recently synthesized the existing evidence regarding interactions between disease-targeted programs and country health systems . Although it concluded that this impact “on health outcomes and health systems, though variable, has been positive on balance and has helped to draw attention to deficiencies in health systems”, available evidence also pointed out that further improvements and efficiency gains are needed especially to strengthen the health workforce, align health information systems, and to reduce out-of-pocket payments for financing health-care expenditures.
Operational research encompasses a broad range of investigation, primarily the evaluation of outcomes among the health programs. Systematic observation and analysis of data collected alongside ART programs can provide guidance to implementers and policy makers with the aim of achieving sustainable access to care. Critical in any operational research project is the development of partnerships and capacity building between the wide array of actors who contribute to deliver healthcare, including national health services, community based organizations and advocacy groups, national and transnational NGOs, as well as the international donor agencies on the one hand, and academic researchers and research organizations on the other . There are certainly general principles of treatment that can be broadly applied and evaluated in Africa. But ultimately, in each context, it may be anticipated that the design of programs for access to ART will vary. Critical unanswered questions remain about how access to ART will impact social stigma, individual risk behavior and ultimately the course of the epidemic. Because of the heterogeneity of affected populations and societies, the psychosocial and behavioral consequences of ART access and methods to ensure adherence, retention and to provide sustained treatment across Africa are not likely to be distilled to a single set of best practices. Thus, in the face of the HIV epidemic in Africa, operational research is a process of “learning by doing” in each of the diverse contexts, sharing the outcomes and observations among countries and programs. A myriad of local evaluations of process and outcome may be the most flexible way to effect sustainable implementation of ART access and the development of robust medical and social responses to AIDS in various contexts across a continent. One regrets that in spite of significant investment in evaluation exercises, global health initiatives such as the Global Fund to fight AIDS, Tuberculosis and Malaria (GFATM), PEPFAR or the World Bank still have limited contributions to effective operational research [12,13].
Operational issues in scaling up access to ART
This supplement presents original results documenting the progress, as well as obstacles, in scaling up HIV treatment in Africa. Papers from Burkina-Faso and Cameroon are based on operational research carried out alongside the national ART programs of these two countries that have been directly supported by ANRS. Other papers present fruitful experiences from operational research in additional African countries (Botswana, Lesotho, Mozambique and South Africa) while one paper (Celletti et al., S45–S57) focuses on a multi-country effort associating four African countries (Ethiopia; Malawi; Namibia and Uganda) and Brazil. It must be noted that the paper by Bassett et al. (S37–S44) about initiation of ART in Durban, Kwazulu-Natal, South Africa, one of the epicenters of the epidemic, was awarded the joint International AIDS Society (IAS)/ ANRS “Young Investigator Prize” for Operations Research at the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, that took place in Capetown in July 2009. Finally, one paper (Jerome & Ivers, S73–S78) deals with rural Haiti, a non-African country, whose experience with ART in very deprived and vulnerable populations has been worthwhile for other low-resource settings.
The process of improving and sustaining access to ART begins with surveillance and testing to understand the magnitude of the epidemic locally, and requires assessment and consultation with Ministries, healthcare providers, communities and stakeholders to identify the key operational issues in access. Access to ART begins with the effective implementation of voluntary testing on a scale not yet realized, effective post-test counseling, linkage to care, and has already led to monitoring, care and retention of 3 million people on ART in Africa. How to accomplish each of these tasks with health systems that are often insolvent and frequently understaffed is the focus of the papers presented in this supplement. All papers emphasize that advances in access to ART have only been made possible through implementation of innovative ways of delivering and monitoring care, and also illustrate some of these innovations.
Clinical research programs continue to evaluate new, less toxic and potentially less costly drug cocktails, more effective monitoring algorithms and programs to reinforce and maintain treatment adherence that would be better adapted to the practical constraints of health systems with very scarce resources. Notably, the DART study results in Uganda and Zimbabwe suggest that some of the accepted guidelines for laboratory monitoring need careful reassessment , and the forthcoming results of the STRATALL study in Cameroon will evaluate the impact of the WHO public health approach to monitor ART at a decentralized level of care . Similarly, the management of first-line ART is fraught with issues even in the choice of Non-nucleoside reverse transcriptase inhibitors (NNRTIs). Consideration of Efavirenz and Nevirapine as first line NNRTIs as described in the paper by Wester et al. (S27–S36) in Botswana reflect trade-offs among cost, potency, potential side-effects and concerns about teratogenicity and toxicity. These issues will continue to expand as additional drugs become available and as the price proposed by pharmaceutical firms for new first-line and for second-line regimens, as recommended by WHO, remain prohibitively high compared to those of the “old” generation of antiretroviral drugs .
It is estimated that at least 57 countries, mostly in sub-Saharan Africa, face crippling health workforce shortages, and there are simply not enough physicians and nurses on the ground to begin to address the magnitude of the HIV epidemic through traditional clinic based care. Rational redistribution of tasks between physicians and other healthcare personnel, and the introduction of community and family health aids and NGO volunteers, as medical officers, adherence counselors or treatment “buddies” is a key part of the “task-shifting” agenda articulated by WHO . The multi-country paper by Celletti et al. (S45–S57), papers by Sherr et al. (S59–S66) on Mozambique, Jerome and Ivers (S67–S72) on Haiti and Ivers et al. (S73–S78) on the Haiti-Lesotho collaborative model detail the certain conditions that have to be fulfilled for the reorganization of clinical services under a task shifting model to be successful.
One of the most innovative contributions of HIV programs has been to promote meaningful multi-stakeholder partnerships between governments, civil society and affected communities at the global and local levels. Civil society has critically important roles ranging from advocacy, demand creation, and service delivery, to policy-setting and providing oversight by emphasizing accountability to service users . Papers by Desclaux et al. (S79–S85) on Burkina-Faso and Ivers et al. (S73–S78) on the south-south collaboration between Haiti and Lesotho illustrate how such involvement of civil society offer opportunities for creative operational research.
Quite logically, it is the relationship between scaling up access to HIV treatment and health systems strengthening that bears the greatest scrutiny across most of the papers of this supplement. In a comprehensive evaluation of ART access through a national program in Cameroon, Boyer et al. (S5–S15) present analysis from the EVAL study where the quality and quantity of care at central, provincial and district levels was contrasted. This evaluation clearly shows that decentralization of ART delivery can increase equity in access for the poorest sectors of people living with HIV while maintaining clinical effectiveness, and even improving adherence and quality of life. Experiences in other African countries, like Uganda, suggest that even further decentralization of ART may be effective and cost-effective , but this needs more investigation and may differ according to each specific socio-economic and health systems context.
Future challenges for long term sustainability of ART
In this supplement, another paper on Cameroon by Marcellin et al. (S17–S25) provides compelling evidence that access to ART at higher CD4 levels reduces reported risk behaviors and can improve quality of life. This paper, and the one from Bassett et al. (S37–S44) describing considerable gaps in bringing and retaining people with AIDS into treatment in a well resourced program in South Africa, supports the recent revision of WHO guidelines . These new guidelines increase the recommended CD4 count for starting treatment to 350 cc/mm3 (rather than the previous lower 200 threshold) and imply that an additional number of 5 million HIV-infected patients world-wide should be considered eligible for immediate access to ART. These papers, however, anticipate some of the new challenges and tensions that would logically derive from this extension of treatment eligibility and from the urgent need to revisit the relationship between HIV prevention and treatment.
Despite the actions of many agencies and national health autorities, an estimated 1.9 million [1.6 million–2.2 million] new HIV infections occurred in sub-Saharan Africa in 2008. This high incidence, and consequent increase in unmet treatment needs over time, represents an additional key challenge for ART program scale up to remain feasible and sustainable . The recognition that the speed at which people are infected exceeds the speed at which they can be put on treatment has been a powerful message to advocate for enhancing prevention efforts. Treatment programs offer many opportunities to strengthen prevention, through increased uptake of testing, viral load reduction in patients and models of “prevention counseling” for and by positive people. These synergies should be fully recognized and monitored. As an illustration, in a paper on Cameroon in this supplement (Marcellin et al. [S17–S25]), patients not yet on ART reported more frequent inconsistent condom use compared to those on ART, confirming positive effects of intense patient-healthcare worker contact on behavior.
(Re)-emphasizing and maximizing synergies between the ART roll out and prevention is essential and urgent but should be seen as a component of a comprehensive “Treatment and Prevention Combination” approach, including behavioral, social and structural interventions.
Over the coming decade, the challenges of expanding, enhancing and sustaining treatment for the more than 22.4 million people living with HIV in Africa, will consume immense monetary, human and social resources. Evaluating the long-term outcomes of access to ART on a population level across diverse urban and rural and multiple cultural contexts in Africa present a formidable challenge. If the patterns of behavior and transmission observed in the North are any indication, large-scale access to care may increase transmission of drug resistant viruses . The best way to prevent this will be the development of robust and affordable programs for retention, monitoring and management of ART by skilled providers and robust systems of care.
Papers in this supplement support the optimistic view that innovative solutions can be found to tackle the multiple medical, public health, socio-economic and logistic issues related to long term sustainability of ART programs in Africa. Ensuring their financial sustainability through appropriate growth of domestic and international funding however remains a prerequisite for success, and this is far from guaranteed in the context of one of the worst economic crises the world has ever faced. Because overall demand has been higher than anticipated in the funding scenario of its previous replenishment, the Global Fund faces a resource gap for the period 2009–10 for the first time since its creation. Its future contribution to scaling up the response to the HIV epidemic will depend on the willingness of donor governments to provide significantly higher pledges for its next replenishment (2011–2013) than the 9.8 billion US$ obtained for the previous one (2008–2010) . In the US, a debate is growing about whether or not a further expansion of PEPFAR would be the best use of international health funding .
Demonstrations, as presented in this supplement, contribute evidence-based advocacy in favor of sustainability of HIV/AIDS treatment and provide clear examples of how health systems are adapting to meet the challenges of HIV. Of course, we also present these examples to underscore the importance of continuing, flexible operational research and evaluation to maintain international and domestic funding, the life-blood of treatment access for millions in Africa, and around the world.
1. United Nations General Assembly Special Session (UNGASS). Declaration of Commitment on HIV/AIDS, 25–27 June 2001, United Nations, New-York.
2. Katzenstein D, Laga M, Moatti JP. The evaluation of the HIV/AIDS Drug Access Initiatives in Cote D'Ivoire, Senegal and Uganda: how access to antiretroviral treatment can become feasible in Africa. AIDS 2003; 17:S1–S4.
3. WHO/UNICEF/, UNAIDS. Towards universal access: scaling up priority HIV/AIDS interventions in the health sector
. Geneva, 2009.
4. Mermin J, Were W, Ekwaru JP, Moore D, Downing R, Behumbiize P, et al
. Mortality in HIV-infected Ugandan adults receiving antiretroviral treatment and survival of their HIV-uninfected children: a prospective cohort study. Lancet 2008; 371:752–759.
5. Bussmann H, Wester CW, Ndwapi N, Grundmann N, Gaolathe T, Puvimanasinghe J, et al
. Five-year outcomes of initial patients treated in Botswana's national antiretroviral treatment program. AIDS 2008; 22:2303–2311.
6. Bendavid E, Bhattacharya J. The President's Emergency Plan for AIDS Relief in Africa: an evaluation of outcomes. Ann Intern Med 2009; 150:688–695.
7. Boulle A, Bock P, Osler M, Cohen K, Channing L, Hilderbrand K, et al
. Antiretroviral therapy and early mortality in South Africa. Bull WHO 2008; 86:678–687.
9. UNAIDS/WHO. 09 AIDS epidemic outlook
. Geneva, 2009.
10. World Health Organization Maximizing Positive Synergies Collaborative Group (MPSCG). An assessment of interactions between global health initiatives and country health systems
11. Theobald S, Taegtmeyer M, Squire SB, Crichton J, Nhlema-Simwaka B, Thomson R, et al
. Towards building equitable health systems in Sub-Saharan Africa: lessons from case studies on operational research
. Health Res Policy Syst
:26. [Epub ahead of print].
12. Holmes CB, Williams-Sherlock MA, Bouey PD. Monitoring and evaluation of PEPFAR treatment programmes. Lancet 2009; 374:1146–1147.
13. Peersman G, Rugg D, Erkkola T, Kiwango E, Yang J. Are the investments in national HIV monitoring and evaluation systems paying off? J Acquir Immune Defic Syndr 2009; 52(Suppl 2):S87–S96.
14. DART Trial Team. Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial.Lancet
2009; Dec 9 [Epub ahead of print].
15. Kouanfack C, Montavon C, Laurent C, Aghokeng A, Kenfack A, Bourgeois A, et al
. Low levels of antiretroviral-resistant HIV infection in a routine clinic in Cameroon that uses the World Health Organization (WHO) public health approach to monitor antiretroviral treatment and adequacy with the WHO recommendation for second-line treatment. Clin Infect Dis 2009; 48(9):1318–1322.
18. Atun R, Dybul M, Evans T, Kim JY, Moatti JP, Nishtar S, Russell A. Venice Statement on global health initiatives and health systems. Lancet 2009; 374:783–784.
19. Jaffar S, Amuron B, Foster S, Birungi J, Levin J, Namara G, et al.
; on behalf of the Jinja trial team. Rates of virological failure in patients treated in a home-based versus a facility-based HIV-care model in Jinja, southeast Uganda: a cluster-randomised equivalence trial
2009; Nov 23. [Epub ahead of print].
20. Crowley S, Rollins N, Shaffer N, Guerma T, Vitoria M, Lo YR. New WHO HIV treatment and prevention guidelines
2009 Nov 30. [Epub ahead of print].
21. Van Damme W, Kober K, Laga M. The real challenges for scaling up ART in sub- Saharan Africa. AIDS 2006; 20:653–656.
22. Ndembi N, Goodall RL, Dunn DT, McCormick A, Burke A, Lyagoba F, et al
. Viral Rebound and Emergence of Drug Resistance in the Absence of Viral Load Testing: A Randomized Comparison between Zidovudine-Lamivudine plus Nevirapine and Zidovudine-Lamivudine plus Abacavir
. J Infect Dis
2009; Nov 25. [Epub ahead of print].
23. Global Fund against AIDS, TB & Malaria (GFATM). Report of the Executive Director.
Twentieth Board Meeting, Addis Ababa, Ethiopia 9–11 November 2009.
24. Walensky RP, Kuritzkes DR. The Impact of The President's Emergency Plan for AIDS Relief (PEPfAR) beyond HIV and Why It Remains Essential
. Clin Infect Dis
2009; Nov 30. [Epub ahead of print].