Volume 14 Supplement 1
The HIV/AIDS epidemic in sub-Saharan Africa: thinking ahead on programmatic tasks and related operational research
© Zachariah et al; licensee BioMed Central Ltd. 2011
Published: 6 July 2011
Until now, we have all been desperately trying to run behind the HIV/AIDS epidemic and catch up with it, but despite all our efforts, the epidemic remains well ahead of us. In 2010, the antiretroviral treatment (ART) gap was about 60%, AIDS-related deaths were almost two million a year, and on top of these figures, for every one person started on ART, there were two new HIV infections. What is needed to change this situation is to think ahead of the epidemic in terms of the programmatic tasks we will be faced with and try to act boldly in trying to implement those tasks. From a programmatic perspective, we: a) highlight what needs to fundamentally change in our thinking and overall approach to the epidemic; and b) outline a number of key task areas for implementation and related operational research.
Until now, we have all been desperately trying to run behind the HIV/AIDS epidemic and catch up with it, but despite all our efforts, the epidemic remains well ahead of us. The annual estimates of people living with HIV/AIDS, new HIV infections and AIDS-related deaths since the dawn of the epidemic three decades ago provide undeniable justification to this statement. Although we are beginning to see some encouraging trends  we remain far from any epidemiological ideal of control.
In 2009, there were 5.25 million people receiving anti-retroviral treatment (ART) in low- and middle-income countries, which is a 40% coverage of those estimated to be in need of treatment . However, with 2.6 million new HIV infections in 2009, for every person started on ART, there were two new infections, a sobering statistic that belies any claims that we are on top of this epidemic. AIDS continues to take its toll, with an estimated 1.8 million AIDS-related deaths in 2009 .
In summary, the backlog is high and the pipeline of new HIV/AIDS cases remains wide open. Given the enormity of the problem, it is not surprising that all the set implementation targets, such as the “3 by 5” Initiative  and “Universal ART access by 2010”  were not achieved. In the current state of affairs, the likelihood of achieving, by 2015, the United Nations Millennium Development Goal (MDG)  targets and the “Getting to Zero” target  (the three zeros: zero new HIV infections, zero discrimination and zero AIDS-related deaths) of the Joint United Nations Programme on HIV/AIDS (UNAIDS) seem highly unlikely.
What is needed is to look forward, think of appropriate strategies and follow these with bold action. Such action needs to be guided by embedding operational research into programmes. From a programme perspective, operational research has been defined as the search for knowledge on strategies, interventions or tools that can enhance the performance of health programmes in which the research is being conducted . The authors of this paper have been involved with HIV/AIDS and related operational research at the programme level in sub-Saharan Africa for many years.
From a programme perspective, we: a) highlight what needs to fundamentally change in our thinking and overall approach to the epidemic; and b) outline a number of key task areas for implementation and related operational research.
What needs to fundamentally change in our approach and thinking?
First, we need to imagine what the epidemic will look like in five to 10 years from now, as well as and the related programmatic challenges . In this light, UNAIDS’s new innovative Treatment 2.0  is one example of the kind of approach that is needed. This approach describes how ART and HIV/AIDS care delivery systems should evolve to become simpler and more accessible on a wider level so as to have a significant impact in closing the current treatment gap, as well as in preventing HIV infection. This approach could save up to 10 million lives and prevent millions of new infections .
Second, in light of the massive current gaps in both treatment and prevention, we must look beyond maintaining the status quo, which is not making an adequate “dent” in the epidemic.
Third, we need to overcome the current gaps of the traditional approach in documenting efficacy of new tools and strategies, such as randomized controlled trials, and the science of how to translate these into large-scale field implementation. Social science, in particular, is critical here and assists in contextual understanding of various issues. For example, randomized controlled trials have shown that circumcised adult men may have some protection against HIV infection [9, 10], and it is now recommended that this surgical intervention be scaled up .
What is missing is a careful assessment of the potential consequences of large-scale, male circumcision initiatives that are currently taking place in six African countries . It is quite possible that there are group or societal effects, including behavioural changes that may reduce, or enhance, the effect of male circumcision as a preventive strategy. The randomized controlled trial design avoids such contextual considerations, but in real life, these trials play an important role, especially when considering implementation on a large scale [13, 14]. In particular, social science research on context-specific and gendered understanding and community messaging is likely to be vital in large-scale roll out.
Another example is the history of prevention of mother to child transmission of HIV (PMTCT), for which evidence and international recommendations exist . However, contextual and feasibility challenges in sub-Saharan Africa have greatly affected uptake, with only about half of all HIV-infected pregnant mothers receiving antiretroviral drugs for PMTCT [1, 12]. It is clear that gendered power relations within and beyond the household are likely to have a key role in whether or not mothers decide to engage with PMTCT programmes .
Finally, there is a need for new tools and new innovative strategies – even daring and bold action, things that most people might simply dismiss as being unfeasible – in different contexts.
Thinking ahead on task areas for implementation and related operational research
Specific task areas related to the HIV/AIDS epidemic and related operational research issues
Task 1: Sustain long-term HIV/AIDS financing
Demonstrate how HIV/AIDS interventions contribute positively to improving healthcare services (directly or indirectly).
Move from vertical to more integrated primary care delivery models.
Show the positive impact of HIV/AIDS interventions at population level and clearly articulate how these link up with the achievement of the 2015 Millennium Development Goals and beyond.
Perform economic analysis to show the economic gains of HIV/AIDS interventions on health services and beyond (HIV/AIDS interventions are cost effective?).
Task 2: Think of how to offer care to the ever growing cohort on ART ahead of time
Enhance simplicity, efficiency and cost effectiveness of the delivery mechanism and adapt these to different contexts, for example:
Design simpler and cheaper ART protocols that are less toxic (safer) and easier for patients and health services (for both first-line and second-line treatment).
Pilot innovative models of delivery outside the health facilities (task shifting) and evaluate their effectiveness.
Expert patient-based models
Find tangible solutions to the human resources shortage for health in Africa.
Think of sustainable drug supply and commodity management chains that do not end up with drug stock outs
Conduct social science research to better understand contextual issues influencing uptake of specific interventions.
Task 3: Think of those still waiting to get onto ART
Offer ART earlier in line with revised WHO recommendations (41).
Radically simplify ART eligibility assessment for patients in WHO stage 1 and 2 with point-of-care CD4 testing.
Reduce high pre-ART attrition and test how to deliver specific packages of care (Cotrimoxazole preventive prophylaxis, , Isoniazid preventive therapy , Impregnated mosquito nets, nutritional support) that will support patients in pre-ART care and possibly keep them well and not yet needing ART.
Task 4: Monitor cohorts of people with HIV in care
Develop and assess how to set up simple and robust monitoring and reporting systems to follow retention and attrition (pre-ART and on ART) of thousands and eventually millions of patients.
Work out how to set quality indicators and acceptable quality thresholds for mass scale up.
Use point-of-care viral load tests for monitoring adherence, as well as deciding the optimal time to switch to second-line therapy.
Use available and new technology to boost adherence, e.g., telephones and online tools.
Task 5: Provision of HIV care that is associated with a minimal risk of tuberculosis
Determine how best to implement TB case finding, infection control (air ventilation and patient flow organization) and isoniazid preventive therapy.
Determine how to monitor these interventions.
Task 6: Invest in HIV prevention as this is a key to breaking the current epidemic
Find innovative ways of improving HIV testing and knowledge of HIV status.
Assess feasibility of male circumcision on a large scale:
Through simpler and safer techniques
Integrating circumcision into preventive services (e.g., WHO’s Expanded Programme on Immunization)
Enhancing community and civil society acceptance through partnerships.
Pilot the feasibility and effectiveness of ART for prevention in the general population and high-risk groups.
Radically simplify the PMTCT approach and protocol for health service providers and the mother (e.g., a one-pill-a-day standardized approach).
Assess feasibility of pre-exposure prophylaxis in high-risk groups and discordant couples.
Understand the societal factors influencing uptake through social science research in relevant areas.
Task 7: Build capacity for conducting operational research: testing out new models of training
Try out and assess different types of training models and curricula that are performance and/or output based.
Sustaining long-term HIV/AIDS funding
Over recent years, there has been growing evidence of donor fatigue and what seems like a retreat from HIV/ AIDS funding by major donors. In 2010, the Global Fund to Fight AIDS, Tuberculosis and Malaria received US$11.7 billion in pledges compared with the $20 billion it had said it needed to meet the target of Universal Access. The United States-funded US President’s Emergency Plan for AIDS Relief programme, which supports at least half of all people on HIV/AIDS treatment in developing countries, has flat-lined funding for the third year in a row .
These are worrying signs, and economic recession is not the only culprit. Although not formally stated, issues of concern to donors include the fact that HIV/AIDS interventions have predominantly been vertical, with limited evidence of wider benefits to health systems [18, 19]. There is some evidence demonstrating positive benefits of HIV/AIDS interventions . A few specific examples include: the impact of ART in keeping health workers alive, particularly in sub-Saharan Africa ; the positive population impact of HIV/AIDS interventions in reducing crude mortality ; and community-wide benefits in reducing the incidence of such diseases as TB [23–25] and malaria [26, 27]. More examples of this type of operational research are needed to provide evidence of a broader impact both within and outside of the health sector, and this should help convince donors to invest in HIV/AIDS as a integral and worthwhile strategy towards achieving the health-related MDG targets . In particular, operational research demonstrating a positive impact on maternal and child health services would be of great value .
How to offer care to the ever-growing cohort on ART?
More than five million people are on ART in low- and middle-income countries, and this case load is expected to double or triple in the next five to 10 years. The daunting challenges include: retaining and managing such patients ; providing an uninterrupted supply of drugs; ensuring adherence to medication; monitoring drug-related side effects; and detecting and managing drug resistance. The underlying problem is that the increase in case loads and the consequent challenges occur in situations where there are serious shortages of health workers and weak health infrastructure. Sub-Saharan Africa, for example, has a shortfall of almost five million health workers, more than double the numbers working today [30, 31].
An additional problem is that most delivery models of care are labour intensive, with doctors and nurses playing a central role in service delivery and healthcare management [32, 33]. In addition, most ART and support services are run from hospitals, but most of these hospitals are located in urban centres that patients from distant rural and semi-urban settings cannot access because of high transport and opportunity costs .
Encouraging evidence from decentralized, home-based models involving empowerment of non-clinical workers is emerging [35–37]. Importantly, a cluster randomized trial in Uganda demonstrated the cost effectiveness of home-based HIV care using non-clinical workers . Similarly, recent encouraging evidence from rural Mozambique showed that self-forming groups of patients successfully conducted four vital activities: they facilitated monthly ART distributions to their group members in the community; they provided adherence and social support; they monitored outcomes; and they ensured that each group member underwent a clinical consultation at least once every six months 
Several point-of-care CD4 and viral load tests are either on the market or in development, and offer an opportunity to decentralize monitoring to the patient level . For example, people with diabetes can check their blood glucose levels almost anywhere in the world with point-of-care tools. If a mother is worried that her child has a fever, she can use a thermometer to check if this is the case. Similarly, we need a simple test for monitoring viral load and CD4 counts that can be used at home, something akin to a “dipstick” that can be easily read and interpreted by lay people.
We already do have a single-tablet fixed-dose combination for first-line ART (Atripla), and this can help radically simplify the treatment protocol. If this can evolve further into a pill that has no side effects and that has a high barrier to the development of resistance, it would be ideal. Further simplification could also be achieved if new regimens could be developed that allow greater spacing, for example, once-a-week treatment. This could ease stock and supply management as well as may be more cost advantageous. A decreased frequency of interaction with healthcare providers will free up HIV/ AIDS-dedicated human resources, lower out-of-pocket costs, such as transport fees for the care seeker , and would bring obvious advantages to the task of simplifying drug and commodity management.
In terms of operational research, what is needed is to implement and assess the feasibility and effectiveness of delivery models for scale up of ART that move away from hospitals to communities and from clinical to non-clinical staff [32, 39, 40]. There is also a need to decentralize point-of-care tools, such as CD4 and viral load tests, to the patient level and assess if self-testing can be used responsibly. Finally, there is a need to find ways of radically simplifying treatment protocols and assessing the impact that this has on patient and programme outcomes.
Getting those still waiting for ART onto treatment
At present, about six out of every 10 persons who need ART fail to access treatment . When patients eventually get to the ART clinic, they are often weak, with advanced immune suppression, and despite treatment for opportunistic infections, a high proportion die early . Reducing the waiting list for ART will need fast tracking of patients with simpler and less labour-intensive models and starting patients on ART earlier (with CD4 counts equal to or less than 350 cells/mm3 or less), as has been recommended by the World Health Organization (WHO) .
For example, a randomized controlled trial in Haiti showed convincingly that early initiation of ART was associated with a lower risk of death and incident risk of TB . Operational evidence from Lesotho adds to this knowledge, showing that providing ART earlier leads to a 68% reduction in deaths, a 27% reduction in new opportunistic diseases, a 63% reduction in hospitalization, and a 39% reduction in people defaulting from care .
The use of WHO staging, as now recommended by WHO, avoids the need for CD4 tests to determine ART eligibility in those with advanced clinical disease (WHO stages 3 and 4) and thus shortens the road to ART. The challenge remains for patients in earlier clinical stages (WHO stages 1 and 2) who still need CD4 counts to assess their ART eligibility . Finally, early infant diagnosis remains problematic, and in 54 reporting countries, only 15% of children born to HIV-infected mothers were tested for HIV in the first two months of life .
In terms of operational research, interesting challenges would include assessing the feasibility and effectiveness of a point-of-care CD4 test at community or patient levels as a gateway to facilitate access to ART for patients in WHO stages 1 and 2 . Finding ways of delivering specific packages of care (e.g., cotrimoxazole prophylaxis, isoniazid preventive therapy, nutritional support) to support patients in pre-ART care and to prevent pre-ART attrition is required . Finally, there is a need to develop and assess the feasibility of simple-to-use and accurate HIV diagnostic tools for infants with the aim of improving early HIV diagnosis in this highly vulnerable group.
Monitoring cohorts in care
Current monitoring systems are geared towards following patients for retention and adherence over time. The sources of information for such monitoring are patient cards and registers. The work involves manual, labour-intensive reviews, which are unsustainable in the medium to longer term as reporting cohort outcomes involves hours of manual work, sifting through individual patient cards and registers of hundreds if not thousands of patients. Radical simplification is needed [45, 46].
Encouraging ways forward include, for example, the use of robust electronic touch screen systems with automated cohort reporting [47, 48]. The use of existing common technology, such as mobile phone messaging in Kenya to enhance adherence, reduced the need for patients to physically return to health facilities and proved effective in enhancing ART adherence and viral load suppression . In terms of operational research, there is a need to explore and further field test the potential of mobile phone technologies, including smart phones, and other innovative approaches linking the ever-expanding technology with healthcare interventions. Piloting new and effective ways of moving from district-level reporting to facility-based monitoring and reporting, so that individual health facilities are able to manage and use their data in an effective manner, is also much desired.
Provision of HIV care that is associated with a minimal risk of tuberculosis
WHO recommends the implementation of a package of the Three “I”s (isoniazid preventive therapy, intensified case finding and infection control) as being essential to effective HIV and TB care that is safe from nosocomial TB transmission [50, 51]. Despite good evidence of the benefits of this package, we have been far too slow in the application of knowledge into practice. The implementation gaps remain wide, with only 2.5% of 1.9 million eligible individuals screened for TB and only 8.7% of 16 million people placed on isoniazid preventive therapy. There are no global data on infection control . Ways forward to enhance feasibility and uptake of each of these components are urgently needed [52, 53].
Investing in HIV prevention strategies as a key to breaking the current epidemic
Prevention is key to breaking the current epidemic as this will close the pipeline of new cases that adds to existing case loads and mortality. Simulations have consistently shown that in the longer term, the most important driver of HIV prevalence and HIV case load is present-day HIV incidence. Halving of HIV incidence leads, with a eight-to 10-year lag, to halving the number of people needing to start ART, and considerably lower overall HIV prevalence  The first challenge is that only about 40% of people living with HIV currently know their HIV status. Second, there is a need to find feasible and acceptable ways of rolling out biomedical interventions, such as male circumcision at the community level [11, 13, 14]
Third, there is the dramatic impact of ART on prevention through viral suppression [8, 55] A recent study showed that ART used in discordant couples reduces HIV transmission (between couples) by 92% . Mathematical modelling has also suggested the potential impact of offering annual universal voluntary HIV testing and counselling, followed by immediate ART, irrespective of clinical stage or CD4 counts. Such a strategy would reduce the transmission rate (Ro) to <1 (Ro being defined as the number of secondary infections resulting from one primary infection in an otherwise susceptible population). As a consequence, the incidence of HIV would be reduced to less than one case per thousand persons per year within 10 years of full implementation of the strategy and the prevalence of HIV to less than 1% within 50 years [57–59].
Fourth, PMTCT remains a major challenge and finding ways forward in increasing access and uptake is urgently needed. Even the current WHO protocol  is complicated; what is needed is a radical simplification of the PMTCT approach and protocol for both the provider and the mother. Finally, a randomized, double-blind multi-country trial among HIV-negative men and trans-gender women who have sex with men showed that pre-exposure prophylaxis with two oral ART drugs (tenofovir and emtrictabine) was associated with a 44% reduction in HIV incidence compared with placebo, the prophylactic effect being strongly correlated with detectable blood levels of the two drugs [60, 61]. The CAPRISA 004 trail also demonstrated the effectiveness and safety of a 1% vaginal gel formulation of tenofovir for the prevention of HIV acquisition in women .
In terms of operational research, there is an urgent need to find ways of increasing knowledge of HIV status by increasing the uptake of HIV testing and linkages to care  The feasibility and acceptability of integration of circumcision into routine preventive activities, such as WHO’s Expanded Programme on Immunization, or as stand-alone services needs to be explored. In terms of ART for prevention at the community level, there is an urgent need to think around the challenges of acceptability and feasibility of this approach in the general population and among high-risk groups [57–59]. For PMTCT, a one-pill-a-day ART, a standardized approach that covers both prevention of transmission and early treatment of the infected mother, should be tried. Finally, feasibility of implementing pre-exposure prophylaxis should be explored under operational conditions, and to save on costs, the efficacy of pre-exposure prophylaxis only at the time of sexual exposure should be examined. Combining implementation and social science research in all these areas is vital.
Building capacity for conducting operational research: testing out new models of training
Programmes in low-income countries and, particularly in sub-Saharan Africa, need to develop the capacity to conduct operational research [6, 30, 63]. Some of the programmatic challenges include inadequate or irrelevant research questions, lack of time and opportunity, lack of research infrastructure, and lack of knowledge about how to translate research findings into policy and practice . In particular, capacity to conduct and publish research is seriously lacking . Programme-embedded models with strong on-the-job mentorship are urgently needed. Training models will need to take programmatic hurdles into consideration, to be performance and output linked, and able to deliver in a relatively short time. Two examples of such approaches include the International Union Against Tuberculosis and Lung Disease-MSF approach to sustainable operational research and that offered by the US Centers for Disease Control and Prevention [65–67]. Operational research is also needed to evaluate the existing models and tailor them to ensure outputs.
Turning the tide of the devastating HIV/AIDS epidemic will require us to think ahead about the challenges with regards to policy, care and prevention that we will be facing in the years to come. It is beholden upon us both as implementers and researchers to act now through bold action and operational research so that will be able to face up to current and impending tasks related to the epidemic.
We are grateful to our many donors, who encourage and support operational research and the related training and capacity-building efforts in low-income countries.
This article has been published as part of Journal of the International AIDS Society Volume 14 Supplement 1, 2011: HIV/AIDS epidemic in sub-Saharan Africa: Facing up to programmatic and operational challenges. The full contents of the supplement are available online at http://www.jiasociety.org/supplements/14/S1. This supplement was financially supported by the Centre for Operational Research, International Union Against Tuberculosis and Lung Disease, Paris, France in collaboration with the Operational Research Unit, Médecins sans Frontières, Brussels Operational Centre, Luxembourg.
- UNAIDS: UNAIDS report on the global AIDS epidemic 2010. UNAIDS/10.11E/ JC1958E. 2010, [http://www.unaids.org/documents/20101123_GlobalReport_em.pdf]Google Scholar
- WHO: Towards Universal Access;: scaling up priority HIV/AIDS interventions in the health sector. 2010, [http://www.who.int/hiv/pub/2009progressreport/en/index.html]Google Scholar
- WHO: The 3 by 5 Initiative. Treat three million people with HIV/AIDS by 2005. 2002, [http://www.who.int/3by5/en/]Google Scholar
- United Nations: Millennium Development Goals. Traget 6. 2000, [http://www.un.org/millenniumgoals/aids.shtml]Google Scholar
- UNAIDS: Getting to Zero. 2011-2015 strategy. 2011, [http://www.unaids.org/en/media/unaids/contentassets/documents/unaidspublication/2010/JC2034_UNAIDS_Strategy_en.pdf]Google Scholar
- Zachariah R, Harries AD, Ishikawa N, Rieder HL, Bissell K, Laserson K, Massaquoi M, Van Herp M, Reid T: Operational research in low-income countries: what, why, and how?. Lancet Infect Dis. 2009, 9 (11): 711-717. 10.1016/S1473-3099(09)70229-4.View ArticlePubMedGoogle Scholar
- UNAIDS: Taking long term-view. 2010, [http://www.ftpress.com/store/product.aspx?isbn=0132614146]Google Scholar
- UNAIDS: Treatment 2.0. Is this the future of treatment?. 2009, [http://data.unaids.org/pub/Outlook/2010/20100713_outlook_treatment2_0_en.pdf]Google Scholar
- Mills E, Cooper C, Anema A, Guyatt G: Male circumcision for the prevention of heterosexually acquired HIV infection: a meta-analysis of randomized trials involving 11,050 men. HIV Med. 2008, 9 (6): 332-335. 10.1111/j.1468-1293.2008.00596.x.View ArticlePubMedGoogle Scholar
- Mattson CL, Campbell RT, Bailey RC, Agot K, Ndinya-Achola JO, Moses S: Risk compensation is not associated with male circumcision in Kisumu, Kenya: a multi-faceted assessment of men enrolled in a randomized controlled trial. PLoS One. 2008, 3 (6): e2443.Google Scholar
- WHO: Male circumcision for HIV prevention. 2007, [http://www.who.int/hiv/topics/malecircumcision/en/index.html]Google Scholar
- WHO, UNAIDS, UNICEF: Towards Universal Access. Scaling up priority HIV/AIDS interventions in the health sector. Progress report. 2010, [http://www.who.int/hiv/pub/2010progressreport/summary_en.pdf]Google Scholar
- Weiss HA, Dickson KE, Agot K, Hankins CA: Male circumcision for HIV prevention: current research and programmatic issues. AIDS. 2010, 24 (Suppl 4): S61-69. 10.1097/01.aids.0000390708.66136.f4.PubMed CentralView ArticlePubMedGoogle Scholar
- Fox M, Thomson M: HIV/AIDS and circumcision: lost in translation. J Med Ethics. 2010, 36 (12): 798-801. 10.1136/jme.2010.038695.View ArticlePubMedGoogle Scholar
- WHO: Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants. 2009, [http://www.who.int/hiv/pub/mtct/antiretroviral2010/en/index.html]Google Scholar
- WHiPT: (Womens HIV Prevention Tracking Project). Making Medical Male Circumcision Work for Women. 2010, [http://www.avac.org/ht/a/GetDocumentAction/i/28715]Google Scholar
- MSF: HIV/AIDS Progress Under Siege Double Blow of Reduced Funding and High Drug Prices Blocks Impact of Latest Science and Treatment Recommendations for People Living With HIV/AIDS. 2010, [http://www.doctorswithoutborders.com/oublications/article.cfm?id=489O&cat=special-report]Google Scholar
- Levine R, Oomman N: Global HIV/AIDS funding and health systems: Searching for the win-win. J Acquir Immune Defic Syndr. 2009, 52 (Suppl 1): S3-5.View ArticlePubMedGoogle Scholar
- El-Sadr WM, De Cock KM: Health systems exist for real people. J Acquir Immune Defic Syndr. 2009, 52 (Suppl 1): S1-2.View ArticlePubMedGoogle Scholar
- Sherr K, Pfeiffer J, Mussa A, Vio F, Gimbel S, Micek M, Gloyd S: The role of nonphysician clinicians in the rapid expansion of HIV care in Mozambique. J Acquit Immune Defic Syndr. 2009, 52 (Suppl 1): S20-23.View ArticleGoogle Scholar
- Makombe SD, Jahn A, Tweya H, Chuka S, Yu JK, Hochgesang M, Aberle-Grasse J, Pasulani O, Schouten EJ, Kamoto K, Harries AD: A national survey of the impact of rapid scale-up of antiretroviral therapy on health-care workers in Malawi: effects on human resources and survival. Bull World Health Organ. 2007, 85: 851-857.PubMed CentralPubMedGoogle Scholar
- Mwagomba B, Zachariah R, Massaguoi M, Misindi D, Manzi M, Mandere BC, Bemelmans M, Philips M, Kamoto K, Schouten EJ, Harries AD: Mortality reduction associated with HIV/AIDS care and antiretroviral treatment in rural Malawi: evidence from registers, coffin sales and funerals. PLoS One. 2010, 5 (5): e10452-10.1371/journal.pone.0010452.PubMed CentralView ArticlePubMedGoogle Scholar
- Badri M, Wilson D, Wood R: Effect of highly active antiretroviral therapy on incidence of tuberculosis in South Africa: a cohort study. Lancet. 2002, 359: 2059-2064. 10.1016/S0140-6736(02)08904-3.View ArticlePubMedGoogle Scholar
- Lawn SD, Wood R: Antiretroviral therapy for control of the HIV-associated MDR and XDR tuberculosis epidemic in South Africa. Am J Respir Crit Care Med. 2010, 182: 1567-author reply 8-9View ArticlePubMedGoogle Scholar
- Lawn SD, Badri M, Wood R: Tuberculosis among HIV-infected patients receiving HAART: long term incidence and risk factors in a South African cohort. AIDS. 2005, 19: 2109-2116. 10.1097/01.aids.0000194808.20035.c1.View ArticlePubMedGoogle Scholar
- Nakanjako D, Kiragga AN, Castelnuovo B, Kyabayinze DJ, Kamya MR: Low prevalence of Plasmodium falciparum antigenaemia among asymptomatic HAART-treated adults in an urban cohort in Uganda. Malar J. 2011, 10: 66-10.1186/1475-2875-10-66.PubMed CentralView ArticlePubMedGoogle Scholar
- Mermin J, Ekwaru JP, Liechty CA, Were W, Downing R, Ransom R, Weidle P, Lule J, Coutinho A, Solberg P: Effect of co-trimoxazole prophylaxis, antiretroviral therapy, and insecticide-treated bednets on the frequency of malaria in HIV-1-infected adults in Uganda: a prospective cohort study. Lancet. 2006, 367: 1256-1261. 10.1016/S0140-6736(06)68541-3.View ArticlePubMedGoogle Scholar
- Myer L, Akugizibwe P: Impact of HIV treatment scale-up on women's reproductive health care and reproductive rights in Southern Africa. J Acquir Immune Defic Syndr. 2009, 52 (Suppl 1): S52-53.View ArticlePubMedGoogle Scholar
- Harries AD, Zachariah R, Lawn SD, Rosen S: Strategies to improve patient retention on antiretroviral therapy in sub-Saharan Africa. Trop Med Int Health. 2010, 52 (Suppl 1): 70-75.View ArticleGoogle Scholar
- Jaffar S, Lazarus JV, Onyebujoh P, Chakaya J, Garrib A, Mwaba P, Mboup S, Bellis K, Egwaga S, Corrah T, Coutinho A: Health services strengthening in Africa-research is a key component. Trop Med Int Health. 2010, 15: 1270-1273. 10.1111/j.1365-3156.2010.02626.x.View ArticlePubMedGoogle Scholar
- Anyangwe SC, Mtonga C: Inequities in the global health workforce: the greatest impediment to health in sub-Saharan Africa. Int J Environ Res Public Health. 2007, 4 (2): 93-100. 10.3390/ijerph2007040002.PubMed CentralView ArticlePubMedGoogle Scholar
- Van Damme W, Kober K, Kegels G: Scaling-up antiretroviral treatment in Southern African countries with human resource shortage: how will health systems adapt?. Soc Sci Med. 2008, 66 (10): 2108-2121. 10.1016/j.socscimed.2008.01.043.View ArticlePubMedGoogle Scholar
- Van Damme W, Kheang ST, Janssens B, Kober K: How labour intensive is a doctor-based delivery model for antiretroviral treatment (ART)? Evidence from an observational study in Siem Reap, Cambodia. Hum Resour Health. 2007, 5: 12-10.1186/1478-4491-5-12.PubMed CentralView ArticlePubMedGoogle Scholar
- Hardon AP, Akurut D, Comoro C, Ekezie C, Irunde HF, Gerrits T, Kglatwane J, Kinsman J, Kwasa R, Maridadi J, Moroka TM, Moyo S, Nakiyemba A, Nsimba S, Ogenyi R, Oyabba T, Temu F, Laing R: Hunger, waiting time and transport costs: time to confront challenges to ART adherence in Africa. AIDS Care. 2007, 19: 658-665. 10.1080/09540120701244943.View ArticlePubMedGoogle Scholar
- Wools-Kaloustian KK, Sidle JE, Selke HM, Vedanthan R, Kemboi EK, Boit LJ, Jebet VT, Carroll AE, Tierney WM, Kimaiyo S: A model for extending antiretroviral care beyond the rural health centre. J Int AIDS Soc. 2009, 12 (1): 22-10.1186/1758-2652-12-22.PubMed CentralView ArticlePubMedGoogle Scholar
- Jaffar S, Amuron B, Fosters S, Birungi J, Levin J, Namara G, Nabiryo C, Ndembi M, Kyomuhangi R, Opio A, Bunnell R, Tappero JW, Mermin J, Coutinho A, Grosskurth H: 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. Lancet. 2009, 374 (9707): 2080-2089. 10.1016/S0140-6736(09)61674-3.PubMed CentralView ArticlePubMedGoogle Scholar
- Decroo T, Telfer B, Biot M, Maikere J, Dezembro S, Cumba LI, Dores CD, Chu K, Ford N: Distribution of antiretroviral treatment through self-forming groups of patients in Tete province, Mozambique. J Acquir Immune Defic Syndr. 2010,Google Scholar
- Zachariah R, Reid SD, Chaillet P, Massaguoi M, Schouten EJ, Harries AD: Why do we need a point-of-care CD4 test for low-income countries?. Trop Med Int Health. 2011, 16: 37-41. 10.1111/j.1365-3156.2010.02669.x.View ArticlePubMedGoogle Scholar
- Zachariah R, Ford N, Philips M, Lynch S, Massaguoi M, Janssens V, Harries AD: Task shifting in HIV/AIDS: opportunities, challenges and proposed actions for sub-Saharan Africa. Trans R Soc Trop Med Hyg. 2009, 103 (6): 549-558. 10.1016/j.trstmh.2008.09.019.View ArticlePubMedGoogle Scholar
- Harrington M: Community involvement in HIV and tuberculosis research. J Acquir Immune Defic Syndr. 2009, 52 (Suppl 1): S63-66.View ArticlePubMedGoogle Scholar
- WHO: Antiretroviral therapy for HIV infection in adults and adolescents: Recommendations for a public health approach. 2010, [http://www.who.int/hiv/pub/arv/adult2010/en/index.htm]Google Scholar
- Severe P, Juste MA, Ambroise A, Eliacin L, Marchand C, Apollon S, Edwards A, Bang H, Nicotera J, Godfrey C, Gulick RM, Johnson WD, Pape JW, Fitzgeralc DW: Early versus standard antiretroviral therapy for HIV-infected adults in Haiti. N Eng J Med. 2010, 363 (3): 257-265. 10.1056/NEJMoa0910370.View ArticleGoogle Scholar
- Ford N, Kranzer K, Hilderbrand K, Jouquet G, Goemaere E, Vlahakis N, Trivino L, Makakole L, Bygrave H: Early initiation of antiretroviral therapy and associated reduction in mortality, morbidity and defaulting in a nurse-managed, community cohort in Lesotho. AIDS. 2010, 24 (17): 2645-2650. 10.1097/QAD.0b013e32833ec5b2.View ArticlePubMedGoogle Scholar
- Tayler-Smith K, Zachariah R, Massaquoi M, Manzi M, Pasulani O, van den Akker T, Bemelmans M, Bauernfeind A, Mwagomba B, Harries AD: Unacceptable attrition among WHO stages 1 and 2 patients in a hospital-based setting in rural Malawi: can we retain such patients within the general health system?. Trans R Soc Trop Med Hyg. 2010, 104 (5): 313-319. 10.1016/j.trstmh.2010.01.007.View ArticlePubMedGoogle Scholar
- Braitstein P, Einterz RM, Sidle JE, Kimaiyo S, Tierney W: "Talkin' about a revolution": How electronic health records can facilitate the scale-up of HIV care and treatment and catalyze primary care in resource-constrained settings. J Acquir Immune Defic Syndr. 2009, 52 (Suppl 1): S54-57.View ArticlePubMedGoogle Scholar
- Nash D, Elul B, Rabkin M, Tun M, Saito S, Becker M, Nuwagaba-Biribonwoha H: Strategies for more effective monitoring and evaluation systems in HIV programmatic scale-up in resource-limited settings: Implications for health systems strengthening. J Acquir Immune Defic Syndr. 2009, 52 (Supp 1): S58-62.View ArticlePubMedGoogle Scholar
- Douglas GP, Gadabu OJ, Joukes S, Mumba S, McKay MV, Ben-Smith A, Jahn A, Schouten EJ, Landis Lewis Z, van Oosterhout JJ, AIlain TJ, Zachariah R, Berger SD, Harries AD, Chimbwandira F: Using touchscreen electronic medical record systems to support and monitor national scale-up of antiretroviral therapy in Malawi. PLoS Med. 2010, 7 (8):Google Scholar
- Siika AM, Rotich JK, Simiyu CJ, Kigotho EM, Smith FE, Sidle JE, Wools-Kaloustian K, Kimaiyo SN, Nyandiko WM, Hannan TJ, Tierney WM: An electronic medical record system for ambulatory care of HIV-infected patients in Kenya. Int J Med Inform. 2005, 74 (5): 345-355. 10.1016/j.ijmedinf.2005.03.002.View ArticlePubMedGoogle Scholar
- Lester RT, Ritvo P, Mills EJ, Kariri A, Karanja S, Chung MH, Jack W, Habyarimana J, Sadatsafavi M, Najafzadeh M, Marra CA, Estambale B, Ngugi E, Ball TB, Thabane L, Gelmon LJ, Kimani J, Ackers M, Plummer FA: Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenyal): a randomised trial. Lancet. 2010, 376 (9755): 1838-1845. 10.1016/S0140-6736(10)61997-6.View ArticlePubMedGoogle Scholar
- WHO: Accelerating the implementation of the Three I's for HIV/TB and earlier initiation of ART in Southern African countries Johannesburg, South Africa, Workshop Report. 2011, [http://www.stoptb.org/wg/tb_hiv/assets/documents/Workshop%20report.pdf]Google Scholar
- WHO: Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings. 2011, [http://whqlibdoc.who.int/publications/2011/9789241500708_eng.pdf]Google Scholar
- Harries AD, Zachariah R, Corbett EL, Lawn SD, Santos-Filho ET, Chimzizi R, Harrington M, Maher D, Williams BG, De Cock KM: The HIV-associated tuberculosis epidemic--when will we act?. Lancet. 2010, 375 (9729): 1906-1919. 10.1016/S0140-6736(10)60409-6.View ArticlePubMedGoogle Scholar
- Harries AD, Zachariah R, Tayler-Smith K, Schouten EJ, Chimbwandira F, Van Damme W, EI-Sadr WM: Keeping health facilities safe: one way of strengthening the interaction between disease-specific programmes and health systems. Trop Med Int Health. 2010, 15 (12): 1407-1412. 10.1111/j.1365-3156.2010.02662.x.View ArticlePubMedGoogle Scholar
- Van Damme W, Kober K, Kegels G, Laga M: Scaling'3 by 5' to Universal Access requires enhanced prevention. Real Health News. 2006, 5: 29-32.Google Scholar
- Montaner JS, Hogg R, Wood E, Kerr T, Tyndall M, Levy AR, Harrigan PR: The case for expanding access to highly active antiretroviral therapy to curb the growth of the HIV epidemic. Lancet. 2006, 368 (9534): 531-536. 10.1016/S0140-6736(06)69162-9.View ArticlePubMedGoogle Scholar
- Donnell D, Baeten JM, Kiarie J, Thomas KK, Stevens W, Cohen CR, McIntyre J, Lingappa JR, Celum C: Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet. 2010, 375 (9731): 2092-2098. 10.1016/S0140-6736(10)60705-2.PubMed CentralView ArticlePubMedGoogle Scholar
- Fox W: Realistic Chemotherapeutic Policies for Tuberculosis in the Developing Countries. Br Med J. 1964, 1 (5376): 135-142. 10.1136/bmj.1.5376.135.PubMed CentralView ArticlePubMedGoogle Scholar
- Zachariah R, Harries AD, Philips M, Arnould L, Sabapathy K, O’Brien DP, Ferreyra C, Balkan S: Antiretroviral therapy for HIV prevention: many concerns and challenges, but are there ways forward in sub-Saharan Africa?. Trans R Soc Trop Med Hyg. 2010, 104 (6): 387-391. 10.1016/j.trstmh.2010.01.004.View ArticlePubMedGoogle Scholar
- Fendall NR: Auxiliaries and primary medical care. Bull N Y Acad Med. 1972, 48 (10): 1291-1300.PubMed CentralPubMedGoogle Scholar
- Grant RM: Antiretroviral agents used by HIV-uninfected persons for prevention: pre- and postexposure prophylaxis. Clin Infect Dis. 2010, 50 (Suppl 3): S96-101.PubMed CentralView ArticlePubMedGoogle Scholar
- Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, Goicochea P, Casapia M, Guanira-Carranza JV, Ramirez-Cardich ME, Montoya-Herrera O, Fernandez T, Veloso VG, Buchbinder SP, Chariyalertsak S, Schechter M, Bekker LG, Mayer KH, Kallas EG, Amico KR, Mulligan K, Bushman LR, Hance RJ, Ganoza C, Defechereux P: Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010, 363 (27): 2587-2599. 10.1056/NEJMoa1011205.PubMed CentralView ArticlePubMedGoogle Scholar
- Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, Kharsany AB, Sibeko S, Mlisana KP, Omar Z, Gengiah TN, Maarschalk S, Arulappan N, Mlotshwa M, Morris L, Taylor D: Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010, 329 (5996): 1168-1174. 10.1126/science.1193748.PubMed CentralView ArticlePubMedGoogle Scholar
- Mgone C, Volmink J, Coles D, Makanga M, Jaffar S, Sewankambo N: Linking research and development to strengthen health systems in Africa. Trop Med Int Health. 2010, 15 (12): 1404-1406. 10.1111/j.1365-3156.2010.02661.x.View ArticlePubMedGoogle Scholar
- Zachariah R, Tayler-Smith K, Ngamvithayapong-Yana J, Ota M, Murakami K, Ohkado A, Yamada N, Van Den Boogard W, Draguez B, Ishikawa N, Harries AD: The published research paper: is it an important indicator of successful operational research at programme level?. Trop Med Int Health. 2010, 15 (11): 1274-1277. 10.1111/j.1365-3156.2010.02630.x.View ArticlePubMedGoogle Scholar
- CDC: Field Epidemiology Training Program. 2010, [http://www.cdc.gov.tw/ct.asp?xItem=7726&CtNode=2488&mp=5]Google Scholar
- Harries AD, Rusen ID, Reid T, Detjen AK, Berger SD, Bissell K, Hinderaker SG, Edington M, Fussell M, Fujiwara PI, Zachariah R: The Union and Médecins Sans Frontières approach to operational research. Int J Tuberc Lung Dis. 2011, 15 (2): 144-154.PubMedGoogle Scholar
- Thacker SB, Dannenberg AL, Hamilton DH: Epidemic intelligence service of the Centers for Disease Control and Prevention: 50 years of training and service in applied epidemiology. Am J Epidemiol. 2001, 154 (11): 985-992. 10.1093/aje/154.11.985.View ArticlePubMedGoogle Scholar
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