An International Research
Consortium to Maximise
Benefits & Equity of HIV
Treatment & Care Systems

Evidence for Action directly funds a number of small research initiatives:

Identifying and minimising the gap between knowledge, policy and practice in relation to use of Cotrimoxazole prophylaxis (CTX) in adult and paediatric HIV care

Countries: Malawi, Uganda and Zambia

Partners involved: LSHTM, MRC CTU, ZAMBART, MRC UVRI

Background

The concerted drive to establish increased access to antiretroviral treatment (ART) in resource-limited settings has seen a four-fold increase in the number of people living with HIV receiving ART since 2003 . However, many adults and children continue not to have access to ART.  Of the estimated 6.5million adults and children needing ART in low and middle income countries in 2005, an estimated 1.3million (20%) were receiving it.   Of the 2.3 million children under 15 years living with HIV requiring treatment, only 10% had access to ART . 
Opportunistic infections are a leading cause of death for people living with HIV in both developed and developing countries .  Of the 380,000 children who died from AIDS related causes in 2006, the majority will have died from treatable and preventable opportunistic infections .  The organisms causing opportunistic infections in HIV-infected individuals in the developing world include tuberculosis and bacterial and parasitic infections.  Exposure to common bacterial pathogens such as Pneumococcus, Staphylococcus, non-typhi Salmonellae and other gram-negative organisms is frequent.  For children, particularly those under 5 years who are unlikely to be immunised against Haemophilus, exposure to haemophilus influenzae pathogens remains.  Although seen infrequently after 12months of age in resource-limited settings, for infants, pneumocystis carinii pneumonia is an important cause of death .  In settings where access to ART is limited, preventing and treating infections is therefore imperative to improve survival. 
Cotrimoxazole (trimethoprim-sulphamethoxazole) is “a broad-spectrum antimicrobial agent that targets a range of aerobic gram-positive and gram-negative organisms, fungi and protozoa ” and there is wide-spread evidence to support its use as prophylaxis in HIV-exposed children, and HIV-infected children, adolescents and adults.
A three study meta-analysis examining the use of Cotrimoxazole prophylaxis for opportunistic infections in adults with HIV infection demonstrates an apparent beneficial effect with an estimated 31% reduction in mortality, 27% in morbid events and 55% in patients being hospitalised.  The meta-analysis compared Cotrimoxazole with placebo and demonstrated the relative risk for death in those taking Cotrimoxazole was 0.69 (95% confidence intervals 0.55 to 0.87), for morbid events was 0.76 (95%CI 0.64 to 0.9) and for hospitalisation was 0.66 (CI 0.48 to 0.92).  Cotrimoxazole was shown to significantly reduce the occurrence of bacterial infections (RR 0.48, 95% CI 0.37 to 0.62) and parasitic infections excluding toxoplasmosis (RR 0.37, 95% CI 0.24 to 0.58).
For children with HIV infection there is only one methodologically sound clinical trial evaluating the use of Cotrimoxazole prophylaxis in HIV infected children .  In a randomised trial (the CHAP trial) of once daily Cotrimoxazole prophylaxis in 534 HIV-infected Zambian children (Zambia is a country with high rates of bacterial resistance to Cotrimoxazole), mortality was reduced by 43% and hospital admission rates by 23% compared with matched placebo.  Mortality was improved in all ages, across the CD4 count range, and was sustained beyond at least 12months (median follow-up 22 months) .  A subsequent paper suggested that although cause of death was difficult to ascertain in many children, presumed bacterial sepsis appeared to be the cause of death most prevented by Cotrimoxazole prophylaxis. Cost-effectiveness analysis of data from this trial using Zambian costs has demonstrated Co-trimoxazole prophylaxis in HIV-infected children to be an inexpensive low technology intervention which has proved highly cost-effective in Zambia .   In 2004, guided by evidence from the CHAP trial in Zambia, WHO/UNAIDS/UNICEF issued a joint statement recommending the use of Co-trimoxazole as prophylaxis in HIV exposed and HIV infected children .
In 2006, the WHO issued further guidelines on Co-trimoxazole prophylaxis for HIV-related infection among children, adolescents and adults.  This states that “Co-trimoxazole prophylaxis is a simple, well-tolerated and cost-effective intervention for people living with HIV.  It should be implemented as an integral component of the HIV chronic care package and as a key element of pre-antiretroviral therapy care.  Co-trimoxazole prophylaxis needs to continue after antiretroviral therapy is initiated until there is evidence of immune recovery” .However, in 2006, it is estimated that globally only 4% of HIV-infected adults and 1% of children living with HIV were able to obtain Cotrimoxazole . 
CTX is a combination of generic drugs Sulfamethoxazole and Trimethoprim and is widely available in both syrup and solid formulations at low cost in most places, including resource limited settings ,  It is produced under brand names such as Bactrim, Bactrim DS, Bethaprim, Co-trimoxazole, Cotrim, Cotrim DS, Septra, Septra DS, Sulfatrim.  Anecdotal evidence suggests that despite high quality generics being produced in for example, India and Zambia, some vertically funded programmes insist that countries get their CTX from their supplier, often sidelining local generic companies .  Investigating the routes of supply chains may be of relevance to the issues around uptake of CTX in country.
In the revised guidelines the WHO acknowledged that countries and programmes in resource-limited settings have been slow in adopting Cotrimoxazole for the use of prophylaxis in HIV-exposed children, children living with HIV and adolescents and adults living with HIV .  It is important to understand why, despite the evidence from methodologically sound studies undertaken in resource limited settings and recommendations by WHO/UNAIDS/UNICEF, the use of Cotrimoxazole prophylaxis, a life-saving intervention, appears not to have rapidly translated from scientific studies to policy and practice.

Aims and Objectives

Aim
-    To understand the processes and context affecting the adoption of CTX in national health policies in low income countries, as well as the processes involved in implementation of CTX prophylaxis policies.

Objectives
-    To identify the evidence to support the use of CTX prophylaxis
-    To identify the process by which the research evidence on CTX has translated into policy in three low income countries through:
o    Investigation of CTX policy development in Zambia, Uganda, and Malawi
o    Comparative analysis of the processes involved in taking up research findings and international recommendations in these three countries.
-    To investigate the process by which national policies and guidelines have translated into actual practice in the three countries through:
o    Mapping the implementation activities in key facilities, including identifying the sources of CTX supply
o    In-depth investigation in key facilities to understand how policies have been taken up or interpreted in particular ways
-    To feed-back findings into policy making and influencing bodies in EfA partner countries to attempt to improve the process by which evidence feeds into policy and practice.

Shifts in home-based care for PLHA in the era of ART

Country: Zambia

Partners involved: International HIV AIDS Alliance, LSHTM, ZAMBART

Background

In sub-Saharan Africa and in other low and middle-income countries, most community Home-Based Care (HBC) programmes were initially developed as unsystematic and need-based efforts when it became evident that other options of care were necessary to deal with the effects of HIV/AIDS (WHO 2002). HBC initiatives have since been formalized to some extent through their incorporation in national AIDS control policies, external funding, and the recognition that they may serve as crucial entry points to testing and treatment uptake.  Activities routinely performed as part of HBC include counseling and referral to HIV-testing sites, basic nursing care, palliative care, ART literacy and preparedness as well as treatment and adherence support.  As access to ART and to treatment for opportunistic infections increase, the paradigm of care in low income settings is gradually shifting from nursing to ambulatory services.  Given that ART is clearly having an effect on patients’ physical well-being, HBC interventions are increasingly moving towards providing support for HIV testing and counseling as well as treatment adherence.  Although a large number of studies and reports have focused on HBC interventions in relation to TB and HIV (Bond et al. 2005, Mwansa 1999, Chela 1991, Miti et al. 2003, etc.), HBC in the context of ART remains an area relatively under-researched in sub-Saharan Africa.  Apondi et al. (2007) suggest that HBC in Africa has expanded, but most social outcomes of home-based ART programmes are unknown.
The overall aim of the research is to understand current shifts in Home-Based Care in relation to the availability of ART in low income population groups, and to explore the consequences and costs of scaling up HBC for HIV/AIDS in the context of ART.  We will focus in particular on the situation in Zambia, one of the first countries in sub-Saharan Africa to have implemented HBC for HIV/AIDS, and work with selected local NGOs and CBOs that provide both counselling and care to PLHA via HBC.  The study can be considered pilot work that we hope to replicate in other EfA sites later.
Using qualitative methods, we will examine the current role and acceptability of HBC providers in the community and in relation to the public health system, and look at how HBC initiatives shape PLHA experiences of treatment.  A cost-analysis will be conducted to assess the operational costs for implementing these initiatives.  The data generated by these methods will a) enhance understanding of how HBC initiatives might influence the uptake of HIV-testing, treatment preparedness and treatment adherence and b) inform discussions on the potential benefits or drawbacks of scaling up ART-related HBC interventions.
Current estimates state that 17% of adult Zambians are infected with HIV, with 84% of these between the ages of 20 and 29.  Although there were reportedly close to 400 sites offering VCT services nationwide by 2005, only 1 in 10 people have ever been tested for HIV and know their status. While there has been a massive scale-up of treatment services, with more than 109,000 people now on antiretroviral drugs, this represents only 20% of women and men who need them (UNAIDS Country Profile Zambia 2007, MoH Zambia 2007). 
Zambia was one of the first countries in sub-Saharan Africa to implement HBC for HIV/AIDS as of the early 1990s.  There is a wealth of experience in the country concerning the development and implementation of HBC programmes. While a number of faith and NGO-based organisations in Zambia providing counselling, nursing and palliative care predated the era of ART , it is clear that their role is evolving.  As treatment has become more widely available, HBC programmes are seen not only as an option to alleviate the burden of hospital care for PLHA, but as an effective entry point for promoting uptake of testing, partner notification and referrals as well as treatment preparedness and adherence support.
Despite their potentially crucial role, there is little documentation on how HBC programmes focused on access and adherence to ART are currently evolving, how they fit into public health systems, how best to monitor and evaluate their quality and impact on testing and adherence behaviours, and how to promote their sustainability given extensive reliance on donor funding and on voluntarism.  In their examination of two major Zambian home-based care programmes pre-ART, Nsutebu et al (2001) proposed a range of factors that appeared to affect the expansion and replication of these programmes.  They included the level of community participation as care-givers, the use of existing support groups, levels of government and foreign donor support as well as programme costs.   These remain useful system-related factors to consider in the era of ART. However, major limitations of their study include the lack of a systematic cost-analysis of the programmes as well as in-depth information on the relationship of HBC providers to the formal health system as well as on patient satisfaction with the services.  By patient satisfaction, we refer to the extent to which services provided corresponded to differential needs based on gender, age and stages of illness, and made a difference in terms of patient experience and outcomes.

Aim and Objectives

The overall aim of the research is to explore current shifts in HBC in the context of ART and understand how these interventions shape the perceptions and experiences of treatment and care for individuals living with HIV/AIDS and their families.  We focus in particular on home-based interventions that provide both counselling and care to PLHA in three districts of Zambia.  By examining shifts in perceived responsibility, tasks, and relationships among formal and informal care providers at the household level, the study will contribute to an assessment of community responsiveness to home-based care interventions and PLHA uptake of actions that support the continuity of HIV care (testing, disclosure and partner notification, adherence to treatment, food aid).  At the same time, by examining the operational costs and delivery of these services within the health system, the study will inform discussions on scaling up of home-based care interventions.

The specific objectives of the research are:

The role of Global Health Initiatives in the implementation of ARV roll-out in Copperbelt province in Zambia – twinning of UK and Zambian researcher

Country: Zambia

Partners involved: ZAMBART, LSHTM

Background

There is little understanding of processes governing implementation, particularly in developing countries (Saetren 2005). Where studies have been conducted these have primarily focused on national level implementation of global guidelines, (for example Schneider et al 2006), rather than on the iterative processes of implementation from national, provincial to district level.
At the same time health policies, particularly in developing countries, are increasingly guided by global guidelines, often implemented and financed through Global Health Initiatives (Boerema et al 2006). Often GHI’s are focused on HIV/AIDS. In Zambia the World Bank Multi-country AIDS Programme (MAP), the Global Fund to Fight AIDS, TB and Malaria, and the US President’s Emergency Plan for AIDS Relief (PEPFAR) have provided resources for the roll-out of anti-retroviral treatment (Hanefeld et al 2007). Research findings will be immediately relevant to policymakers implementing such initiatives, especially where these are aimed at rolling–out ARVs. Knowledge gained through this research will assist better policy implementation in the future.
The Zambian researcher will be recruited and employed by the EFA partner Zambart and continue working for ZAMBART on EFA activities, financed through ZAMBART’s existing EFA funds. This project aims to build capacity for the EFA network within ZAMBART, beyond the cycle of this specific project.
This proposal is to support research on factors governing national to district level implementation of ARV roll-out in the Copperbelt Province, Zambia. The project proposed will enable a ZAMBART based researcher, employed under the EFA project remit, to participate in this study - focusing specifically on the impact of GHI’s. It will allow them to work closely with and learn from a PhD candidate/researcher (Johanna Hanefeld) from the London School of Hygiene and Tropical Medicine (LSHTM). This aims to build longer-term capacity in qualitative research on health policy analysis for EFA, while conducting the research, and to work towards a joint publication of findings.
The research on the impact of GHI’s in policy implementation is envisaged as a pilot study, with possible further research next year either in one additional Zambian province, or in Malawi depending on interest by EFA partners. This proposal has been designed in collaboration with the Global Health Initiative’s Network (GHIN) at LSHTM.
Following this project, the Zambian researcher will continue working on the EFA project in ZAMBART, assist with further research as well as the adoption of the methodology to a further region/country at a later stage. 

Aims and Objectives

Assessment of the frequency, distribution and predictors of health-care service use of patients initiating ART in Goa, India and Uganda  

Countries: India and Uganda

Partners involved: MRC CTU, MRC UVRI, NARI

Background

Despite the scale-up of the provision of antiretroviral therapy (ART) in countries where HIV is a significant burden on the healthcare system, literature about the impact of ART provision on healthcare utilisation remains limited .
Anecdotal evidence from EfA partners in Malawi suggests a continued high utilisation of scarce clinical services by patients who have been initiated on ART .  However, this observation has not yet been substantiated by quantitative data analysis.  The reason for this potential increased service utilisation is unknown. 
The commonly used theoretical framework for understanding acute health service usage  describes three determinant factors: 1) characteristics of the health services delivery system, 2) changes in medical technology and social norms relating to the definition and treatment of illness, and 3) individual determinants of utilization.  This framework is enhanced to guide understanding of health service usage in relation to long-term care by identifying a set of psychosocial factors .
When patients are on effective treatment for HIV, the number of illness events necessitating attendance at a clinic is expected to decrease.  It is hypothesised that if this observed high utilisation of clinical services is a true representation of visit frequency, the morbidity associated with the increase in health care utilisation may be psychological in origin. Because, poor mental health (depression and lack of perceived social support  and loss of motivation, hopelessness, and avoidant coping strategies ) has been shown to predict poor adherence to antiretroviral therapy, being able to recognise and integrate services for mental illness is important .
To facilitate better planning of scarce resources it is vital to obtain quantitative data on the actual frequency of patient visits relative to the expected frequency.  Once a frequency distribution of health-care utilisation can be identified, it is important to determine the correlates of any health-care service use that is unexpected.

Aim and Objectives

Aim

To assess the frequency distribution and correlates of health-care service utilisation among HIV patients in Uganda and India.

Objectives

Constructing an analytical framework to map the level of integration of ART programmes in country health systems

Countries: Malawi, Zambia

Partners: LSHTM, Lighthouse, ZAMBART (TBC)

Background

The number of people receiving antiretroviral treatment (ART) has increased from about 400,000 at the end of 2003 to more than 3 million at the end of 2007.  This rapid scale up has been made possible by massive international resources being mobilised for HIV treatment programmes by the Global Fund, PEPFAR, other bilateral donors and public-private initiatives.  In most low income countries, ART programmes were developed vertically because of the new skills and equipment needed, and the imperative to scale up quickly.  However, as programmes start to stabilise and move from an emergency scale up phase to long-term chronic care, there is growing debate about if, when and how they should be integrated into existing health systems. 

Although some still believe that there is an ideological schism between vertical and horizontal programming, many see the progression from vertical to horizontal programmes as a dynamic equilibrium.  From this perspective, the establishment of a vertical programme may be justified in emergency health situations for priority interventions, for new health problems requiring new technologies and infrastructure, or for a time-bound intervention.  Vertical programmes may be attractive to donors because they are easier to monitor, and their impact is easier to measure.  However, many believe that for cost, sustainability and access issues, vertical programmes should eventually be integrated into existing health systems.  In the worst case scenario, the objectives of a vertical programme would not align with the government’s health priorities, and might even clash with them. In such cases they would be ‘owned’ by international development agencies and local NGOs rather than governments, potentially resulting in duplication, fragmentation and diversion of resources away from national priorities. 

With inadequate evidence to judge whether HIV treatment programmes are moving towards a best or worst case scenario, a first step in moving forward the current debate is to ascertain the extent to which HIV programmes have been integrated into existing health systems at present.  This would be followed by an examination of the possible effects that integration or lack thereof of different programme components may be having on effectiveness, efficiency and equity of HIV treatment.  Malawi and Zambia are interesting countries for an initial comparative study because of the similarities in the two countries with regards to the structure of the HIV epidemic, but the differences in terms of the funding and development of HIV treatment programmes. 

Aims and Objectives

Aims 

1. To develop and refine an analytical framework for mapping integration of the various components of HIV treatment programmes within national health systems over time;
2. To map the level and progression of integration of HIV treatment programmes into the national health systems in Malawi and Zambia.

Objectives

1. To develop an analytical framework for mapping the level of integration of a public sector HIV treatment programme with the existing health system over time, and refine the framework based on objective 2.
   
2. To map the structure and evolution of HIV treatment programmes in Malawi and Zambia, establishing the degree and type of integration of different programme components
   
3. To identify possible impacts of integration or lack thereof on effectiveness, efficiency and equity of HIV treatment to inform the development of more substantial follow up research in this area.

Preliminary Phase of the study ‘Evaluating outcome indicators used to assess the performance of HIV programmes of treatment and care in resource-limited countries’

Countries: Malawi, Uganda, India, Ukraine

Partners: MRC CTU, UCL, Lighthouse, MRC UVRI, NARI, International HIV AIDS Alliance, PPAI

Background

Aim

The main aim is to undertake the preparatory work necessary to establish the baseline site selection, data collection, methods of calculations and format so that once funding is secured we are in a good position to initiate data pooling immediately within countries.

A case study of the changing World Bank Multi-country AIDS Programme (MAP) in Zambia

Country: Zambia

Partners: LSHTM, ZAMBART

This new detailed, evidence will provide insights and explore the concerns around the sustainability of ART programmes that depend on external funding, including through Global Health Initiatives. Research findings will provide recommendations on how to minimise negative impact on programmes in cases where external resources stop or change, and ensure greater sustainability of ART programmes.

Background

The World Bank MAP is a Global Health Initiative launched by the Bank in 2000, with a commitment to run for fifteen years, focusing mainly on providing grants, including for the roll-out of ART. In 2002 Zambia received a MAP grant of USD 42 million over five years for its response to HIV/AIDS, the grant was entitled ZANARA (Zambia National Response to HIV/AIDS) and had five components, one of which was funding to the Ministry of Health for support to ART roll-out.

The grant and programme end in February 2008. In August 2007, the Bank published its revised strategy for fighting HIV/AIDS – its Agenda for Action. This presents a substantial change in the MAP strategy, including a shift from providing grants, to using its institutional expertise to build countries’ capacity to respond to HIV. In practice this means technical assistance will be provided instead of direct financial support. In addition, all countries that have reached HIPC completion point (including Zambia), and achieved debt relief, now qualify only for loans - no longer for grants.

Current Challenges and Opportunities for the Integration of TB and HIV services for Co-Infected Patients: A Pilot Study in Pune, India

Country: India

Partners: LSHTM, NARI, MAAS

Background

India was one of the first countries in the world to bring out TB/HIV management guidelines jointly prepared by the National TB and HIV/AIDS programmes in 2001, almost as soon as the two programmes recognised co-infection to be a major problem.  Coordination activities were launched in the same year in the six high prevalence states and extended to a further eight states in 2004.  While there is on-going operational revision of the systems for delivery, referrals and documentation of care in response to initial challenges faced, there is not much evidence to demonstrate how the coordination of programme activities impacts on health seeking and care outcomes for co-infected patients in the public sector.  The presence of a large private sector, which plays a major role in the management of TB and HIV, further complicates the health-seeking pathways of co-infected patients.

Aim

This project aims to give us a better understanding of the current situation and prospects for integrating TB and HIV care from a programme manager, a provider, and a patient perspective, in the city of Pune, Maharashtra.  To this purpose, we will conduct qualitative health systems research in two phases over a six-month period.  In the first phase, interviews will be conducted with key informants in the public, private and NGO sector and with health providers to identify challenges and opportunities for HIV and TB programme collaboration.  In the second phase, we will conduct in-depth interviews with known co-infected patients under care in the public, private and NGO sectors, in order to identify key issues in their awareness, decision-making and experiences of care-seeking for TB and HIV. 

Preliminary Studies on Referral and Uptake of HIV Care and Treatment Services among HIV-positive Women Identified Through Prevention of Mother-to-Child Transmission of HIV Programme in Mwanza Municipality, Tanzania

Country: Tanzania

Partners: LSHTM, NIMR Mwanza

Background

In Africa more than 70% of pregnant women attend antenatal care (ANC) services at least once during pregnancy 1. ANC clinics are recognized as an excellent entry point for the provision of health interventions to pregnant women, particularly prevention of mother-to-child transmission of HIV (PMTCT) and syphilis screening and treatment.

In Tanzania PMTCT was introduced to selected sites in 2002 and now is being scaled-up. According to a recent UNGASS country progress report it is estimated that only 12% of the health facilities in Tanzania provide PMTCT and only 28% of HIV-positive pregnant women received ART for PMTCT between Jan 2007 and Dec 2007 2. 

Although ARV medication decreases HIV viral load, which reduces an infant’s exposure to HIV during pregnancy and breastfeeding3-6 and despite the potential for using PMTCT services as a referral mechanism for adult pregnant women to enter appropriate care and treatment centres (CTCs) in Tanzania, little is known about whether HIV-positive pregnant women, identified through PMTCT, receive proper counselling and timely referrals to HIV CTCs for their own care and treatment before and after delivery, whether they attend these services and whether they receive adequate assessment of their infection, including a CD4 count.

Aim and Objectives

The aim of this study is to determine whether pregnant women attending antenatal clinics that offer PMTCT services accept VCT and whether these services act as an appropriate entry point for onward referral of HIV-positive women to receive assessment of their own eligibility for highly active antiretroviral therapy (HAART) and other HIV care services (e.g. cotrimoxazole prophylaxis, support groups, etc).

The specific objectives are to-

1. Determine the uptake of PMTCT at the ANC /RCH over the previous 12 months.
2. Establish the proportion of HIV-positive pregnant women identified through PMTCT who were referred to HIV care and treatment clinic (CTC) and the proportion who attended the CTC and received adequate assessment of their HIV infection, including CD4 counts during pregnancy.
3. Determine the proportion of HIV-positive pregnant women identified through PMTCT who received referral to any support groups and who disclosed their HIV status to their partner or other persons.
4. Explore potential client and provider factors that are likely to influence women’s attendance at the CTC before delivery.