Lessons Learned From Option B+ in the Evolution Toward "Test and Start" From Malawi, Cameroon, and the United Republic of Tanzania.

The acceleration of prevention of mother-to-child transmission (PMTCT) activities, coupled with the rollout of 2010 World Health Organization (WHO) guidelines, led to important discussions and innovations at global and country levels. One paradigm-shifting innovation was Option B+ in Malawi. It was later included in WHO guidelines and eventually adopted by all 22 Global Plan priority countries. This article presents Malawi's experience with designing and implementing Option B+ and provides complementary narratives from Cameroon and Tanzania. Malawi's HIV program started in 2002, but by 2009, the PMTCT program was lagging far behind the antiretroviral therapy (ART) program because of numerous health system challenges. When WHO recommended Option A and Option B for PMTCT in 2010, it was clear that Malawi's HIV program would not be able to successfully implement either option without increasing existing barriers to PMTCT services and potentially decreasing women's access to care. Subsequent stakeholder discussions led to the development of Option B+. Operationalizing Option B+ required several critical considerations, including the complete integration of ART and PMTCT programs, systematic reduction of barriers to facilitate doubling the number of ART sites in less than a year, building consensus with stakeholders, and securing additional resources for the new program. During the planning and implementation process, several lessons were learned which are considerations for countries transitioning to "treat-all": Comprehensive change requires effective government leadership and coordination; national clinical guidelines must accommodate health system limitations; ART services and commodities should be decentralized within facilities; the general public should be well informed about major changes in the national HIV program; and patients should be educated on clinic processes to improve program monitoring.

Scaling-up antiretroviral therapy in Malawi.

PROBLEM: In Malawi, health-system constraints meant that only a fraction of people infected with human immunodeficiency virus (HIV) and in immediate need of antiretroviral treatment (ART) received treatment. APPROACH: In 2004, the Malawian Ministry of Health launched plans to scale-up ART nationwide, adhering to the principle of equity to ensure fair geographical access to therapy. A public health approach was used with standardized training and treatment and regular supervision and monitoring of the programme. LOCAL SETTING: Before the scale-up, an estimated 930 000 people in Malawi were HIV-infected, with 170 000 in immediate need of ART. About 3000 patients were on ART in nine clinics. RELEVANT CHANGES: By December 2015, cumulatively 872 567 patients had been started on ART from 716 clinics, following national treatment protocols and using the standard monitoring system. LESSONS LEARNT: Strong national leadership allowed the ministry of health to implement a uniform system for scaling-up ART and provided benchmarks for implementation on the ground. New systems of training staff and accrediting health facilities enabled task-sharing and decentralization to peripheral health centres and a standardized approach to starting and monitoring ART. A system of quarterly supervision and monitoring, into which operational research was embedded, ensured stocks of drug supplies at facilities and adherence to national treatment guidelines.

Act local, think global: how the Malawi experience of scaling up antiretroviral treatment has informed global policy.

The scale-up of antiretroviral therapy (ART) in Malawi was based on a public health approach adapted to its resource-poor setting, with principles and practices borrowed from the successful tuberculosis control framework. From 2004 to 2015, the number of new patients started on ART increased from about 3000 to over 820,000. Despite being a small country, Malawi has made a significant contribution to the 15 million people globally on ART and has also contributed policy and service delivery innovations that have supported international guidelines and scale up in other countries. The first set of global guidelines for scaling up ART released by the World Health Organization (WHO) in 2002 focused on providing clinical guidance. In Malawi, the ART guidelines adopted from the outset a more operational and programmatic approach with recommendations on health systems and services that were needed to deliver HIV treatment to affected populations. Seven years after the start of national scale-up, Malawi launched a new strategy offering all HIV-infected pregnant women lifelong ART regardless of the CD4-cell count, named Option B+. This strategy was subsequently incorporated into a WHO programmatic guide in 2012 and WHO ART guidelines in 2013, and has since then been adopted by the majority of countries worldwide. In conclusion, the Malawi experience of ART scale-up has become a blueprint for a public health response to HIV and has informed international efforts to end the AIDS epidemic by 2030.

HIV and tuberculosis in prisons in sub-Saharan Africa.

Given the dual epidemics of HIV and tuberculosis in sub-Saharan Africa and evidence suggesting a disproportionate burden of these diseases among detainees in the region, we aimed to investigate the epidemiology of HIV and tuberculosis in prison populations, describe services available and challenges to service delivery, and identify priority areas for programmatically relevant research in sub-Saharan African prisons. To this end, we reviewed literature on HIV and tuberculosis in sub-Saharan African prisons published between 2011 and 2015, and identified data from only 24 of the 49 countries in the region. Where data were available, they were frequently of poor quality and rarely nationally representative. Prevalence of HIV infection ranged from 2·3% to 34·9%, and of tuberculosis from 0·4 to 16·3%; detainees nearly always had a higher prevalence of both diseases than did the non-incarcerated population in the same country. We identified barriers to prevention, treatment, and care services in published work and through five case studies of prison health policies and services in Zambia, South Africa, Malawi, Nigeria, and Benin. These barriers included severe financial and human-resource limitations and fragmented referral systems that prevent continuity of care when detainees cycle into and out of prison, or move between prisons. These challenges are set against the backdrop of weak health and criminal-justice systems, high rates of pre-trial detention, and overcrowding. A few examples of promising practices exist, including routine voluntary testing for HIV and screening for tuberculosis upon entry to South African and the largest Zambian prisons, reforms to pre-trial detention in South Africa, integration of mental health services into a health package in selected Malawian prisons, and task sharing to include detainees in care provision through peer-educator programmes in Rwanda, Zimbabwe, Zambia, and South Africa. However, substantial additional investments are required throughout sub-Saharan Africa to develop country-level policy guidance, build human-resource capacity, and strengthen prison health systems to ensure universal access to HIV and tuberculsosis prevention, treatment, and care of a standard that meets international goals and human rights obligations.

Evaluating the impact of prevention of mother-to-child transmission of HIV in Malawi through immunization clinic-based surveillance.

BACKGROUND: Prevention of mother-to-child transmission of HIV (PMTCT) programs can greatly reduce the vertical transmission rate (VTR) of HIV, and Malawi is expanding PMTCT access by offering HIV-infected pregnant women life-long antiretroviral therapy (Option B+). There is currently no empirical data on the effectiveness of Malawian PMTCT programs. This study describes a surveillance approach to obtain population-based estimates of the VTR of infants <3 months of age in Malawi immediately after the adoption of Option B+. METHODS AND FINDINGS: A sample of caregivers and infants <3 months from 53 randomly chosen immunization clinics in 4 districts were enrolled. Infant dried blood spot (DBS) samples were tested for HIV exposure with an antibody test to determine maternal seropositivity. Positive samples were further tested using DNA PCR to determine infant infection status and VTR. Caregivers were surveyed about maternal receipt of PMTCT services. Of the 5,068 DBS samples, 764 were ELISA positive indicating 15.1% (14.1-16.1%) of mothers were HIV-infected and passed antibodies to their infant. Sixty-five of the ELISA-positive samples tested positive by DNA PCR, indicating a vertical transmission rate of 8.5% (6.6-10.7%). Survey data indicates 64.8% of HIV-infected mothers and 46.9% of HIV-exposed infants received some form of antiretroviral prophylaxis. Results do not include the entire breastfeeding period which extends to almost 2 years in Malawi. CONCLUSIONS: The observed VTR was lower than expected given earlier modeled estimates, suggesting that Malawi's PMTCT program has been successful at averting perinatal HIV transmission. Challenges to full implementation of PMTCT remain, particularly around low reported antiretroviral prophylaxis. This approach is a useful surveillance tool to assess changes in PMTCT effectiveness as Option B+ is scaled-up, and can be expanded to track programming effectiveness for young infants over time in Malawi and elsewhere.

Mortality and health outcomes of HIV-exposed and unexposed children in a PMTCT cohort in Malawi.

BACKGROUND: Mortality and morbidity among HIV-exposed children are thought to be high in Malawi. We sought to determine mortality and health outcomes of HIV-exposed and unexposed infants within a PMTCT program. METHOD: Data were collected as part of a retrospective cohort study in Zomba District, Malawi. HIV-infected mothers were identified via antenatal, delivery and postpartum records with a delivery date 18-20 months prior; the next registered HIV-uninfected mother was identified as a control. By interview and health record review, data on socio-demographic characteristics, service uptake, and health outcomes were collected. HIV-testing was offered to all exposed children. RESULTS: 173 HIV-infected and 214 uninfected mothers were included. 4 stillbirths (1.0%) occurred; among the 383 livebirths, 41 (10.7%) children died by 20 months (32 (18.7%) HIV-exposed and 9 unexposed children (4.3%; p<0.0001)). Risk factors for child death included: HIV-exposure [adjOR2.9(95%CI 1.1-7.2)], low birthweight [adjOR2.5(1.0-6.3)], previous child death (adjOR25.1(6.5-97.5)] and maternal death [adjOR5.3(11.4-20.5)]. At 20 months, HIV-infected children had significantly poorer health outcomes than HIV-unexposed children and HIV-exposed but uninfected children (HIV-EU), including: hospital admissions, delayed development, undernutrition and restrictions in function (Lansky scale); no significant differences were seen between HIV-EU and HIV-unexposed children. Overall, no difference was seen at 20 months among HIV-infected, HIV-EU and HIV-unexposed groups in Z-scores (%<-2.0) for weight, height and BMI. Risk factors for poor functional health status at 20 months included: HIV-infection [adjOR8.9(2.4-32.6)], maternal illness [adjOR2.8(1.5-5.0)] and low birthweight [adjOR2.0(1.0-4.1)]. CONCLUSION: Child mortality remains high within this context and could be reduced through more effective PMTCT including prioritizing the treatment of maternal HIV infection to address the effect of maternal health and survival on infant health and survival. HIV-infected children demonstrated developmental delays, functional health and nutritional deficits that underscore the need for increased uptake of early infant diagnosis and institution of ART for all infected infants.

Improving data quality and supervision of antiretroviral therapy sites in Malawi: an application of Lot Quality Assurance Sampling.

BACKGROUND: High quality program data is critical for managing, monitoring, and evaluating national HIV treatment programs. By 2009, the Malawi Ministry of Health had initiated more than 270,000 patients on HIV treatment at 377 sites. Quarterly supervision of these antiretroviral therapy (ART) sites ensures high quality care, but the time currently dedicated to exhaustive record review and data cleaning detracts from other critical components. The exhaustive record review is unlikely to be sustainable long term because of the resources required and increasing number of patients on ART. This study quantifies the current levels of data quality and evaluates Lot Quality Assurance Sampling (LQAS) as a tool to prioritize sites with low data quality, thus lowering costs while maintaining sufficient quality for program monitoring and patient care. METHODS: In January 2010, a study team joined supervision teams at 19 sites purposely selected to reflect the variety of ART sites. During the exhaustive data review, the time allocated to data cleaning and data discrepancies were documented. The team then randomly sampled 76 records from each site, recording secondary outcomes and the time required for sampling. RESULTS: At the 19 sites, only 1.2% of records had discrepancies in patient outcomes and 0.4% in treatment regimen. However, data cleaning took 28.5 hours in total, suggesting that data cleaning for all 377 ART sites would require over 350 supervision-hours quarterly. The LQAS tool accurately identified the sites with the low data quality, reduced the time for data cleaning by 70%, and allowed for reporting on secondary outcomes. CONCLUSIONS: Most sites maintained high quality records. In spite of this, data cleaning required significant amounts of time with little effect on program estimates of patient outcomes. LQAS conserves resources while maintaining sufficient data quality for program assessment and management to allow for quality patient care.

How operational research influenced the scale up of antiretroviral therapy in Malawi.

The national scale up of antiretroviral therapy in Malawi is based on a public health approach, with principles and practices borrowed from the successful World Health Organization "DOTS" tuberculosis control framework. The scale up of antiretroviral therapy was under-pinned by a very strong monitoring and evaluation system, which was used to audit the scale up approach and conduct operational research to answer relevant questions. Examples of research included:- i) access to antiretroviral therapy, populations and social groups served, and how the different groups fared with regard to outcomes; ii) determining whether the quality of data at antiretroviral therapy sites was adequate and whether external supervision was needed; iii) finding feasible ways of reducing the high early mortality in patients starting treatment in both Malawi and the sub-Saharan African region; iv) the causes of loss-to-follow-up, what happened to patients who transferred out of sites and whether transfer-out patients had outcomes comparable to those who did not transfer; and v) the important question of whether antiretroviral therapy scale up reduced population mortality. The answers to these questions had an important influence on how treatment was delivered in the country, and show the value of this work within a programme setting. Key generic lessons include the importance of i) research questions being relevant to programme needs, ii) studies being coordinated, designed and undertaken within a programme, iii) study findings being disseminated at national stakeholder meetings and through publications in peer-reviewed journals and iv) research being used to influence policy and practice, improve programme performance and ultimately patient treatment outcomes.

Positive spill-over effects of ART scale up on wider health systems development: evidence from Ethiopia and Malawi.

BACKGROUND: Global health initiatives have enabled the scale up of antiretroviral treatment (ART) over recent years. The impact of HIV-specific funds and programmes on non-HIV-related health services and health systems in genera has been debated extensively. Drawing on evidence from Malawi and Ethiopia, this article analyses the effects of ART scale-up interventions on human resources policies, service delivery and general health outcomes, and explores how synergies can be maximized. METHODS: Data from Malawi and Ethiopia were compiled between 2004 and 2009 and between 2005 and 2009, respectively. We developed a conceptual health systems framework for the analysis. We used the major changes in human resources policies as an entry point to explore the wider health systems changes. RESULTS: In both countries, the need for an HIV response triggered an overhaul of human resources policies. As a result, the health workforce at health facility and community level was reinforced. The impact of this human resources trend was felt beyond the scale up of ART services; it also contributed to an overall increase in functional health facilities providing curative, mother and child health, and ART services. In addition to a significant increase in ART coverage, we observed a remarkable rise in user rates of non-HIV health services and an improvement in overall health outcomes. CONCLUSIONS: Interventions aimed at the expansion of ART services and improvement of long-term retention of patients in ART care can have positive spill-over effects on the health system. The responses of Malawi and Ethiopia to their human resources crises was exceptional in many respects, and some of the lessons learnt can be useful in other contexts. The case studies show the feasibility of obtaining improved health outcomes beyond HIV through scaled-up ART interventions when these are part of a long-term, system-wide health plan supported by all decision makers and funders.

Antiretroviral drug supply challenges in the era of scaling up ART in Malawi.

The number of people receiving antiretroviral treatment (ART) has increased considerably in recent years and is expected to continue to grow in the coming years. A major challenge is to maintain uninterrupted supplies of antiretroviral (ARV) drugs and prevent stock outs. This article discusses issues around the management of ARVs and prevention of stock outs in Malawi, a low-income country with a high HIV/AIDS burden, and a weak procurement and supply chain management system. This system for ARVs, paid for by the Global Fund to Fight AIDS, Tuberculosis and Malaria, and bypassing the government Central Medical Stores, is in place, using the United Nations Children's Fund's (UNICEF's) procurement services. The system, managed by a handful of people who spend limited time on supply management, is characterized by a centrally coordinated quantification based on verified data from all national ART clinics, parallel procurement through UNICEF, and direct distribution to ART clinics. The model worked well in the first years of the ART programme with a single first-line ARV regimen, but with more regimens becoming available (e.g., alternative first-line, second-line and paediatric regimens), it has become more difficult to administer. Managing supplies through a parallel system has the advantage that weaknesses in the national system have limited influence on the ARV procurement and supply chain management system. However, as the current system operates without a central warehouse and national buffer stock capacity, it diminishes the ability to prevent ARV stock outs. The process of ordering ARVs, from the time that estimates are made to the arrival of supplies in health facilities, takes approximately one year. Addressing the challenges involved in maintaining ARVs through an efficient procurement and supply chain management system that prevents ARV stock outs through the establishment of a dedicated procurement team, a central warehouse and/or national buffer stock is a priority.

Why did the scale-up of HIV treatment work? A case example from Malawi.

The national scale-up of antiretroviral therapy (ART) in Malawi is based on a public health approach, with principles and practices borrowed from the successful DOTS (directly observed treatment short course-the system used to successfully deliver antituberculosis treatment to people in some of the poorest countries of the world) tuberculosis control framework. During the first 6 years, the number of patients registered on treatment increased from 3000 to >350,000 in both the public and private sectors. The most important reasons for this success have been strong international and national leadership combined with adequate funds, a standardized approach to ART with practical guidelines, an approved national scale-up plan with clear, time-bound milestones; investment in an intensive program of training and accreditation of ART sites, quarterly supervision and monitoring of ART and operational research, rational drug forecasting and no stock-outs of drugs during the first few years, and involvement of the private sector. The looming challenges of human resources, guaranteed financial support, better but also more expensive ART regimens, use of electronic medical records to monitor response to therapy, and attention to HIV prevention need to be met head-on and solved if the momentum of the earlier years is to be maintained.

Operational research in Malawi: making a difference with cotrimoxazole preventive therapy in patients with tuberculosis and HIV.

BACKGROUND: In Malawi, high case fatality rates in patients with tuberculosis, who were also co-infected with HIV, and high early death rates in people living with HIV during the initiation of antiretroviral treatment (ART) adversely impacted on treatment outcomes for the national tuberculosis and ART programmes respectively. This article i) discusses the operational research that was conducted in the country on cotrimoxazole preventive therapy, ii) outlines the steps that were taken to translate these findings into national policy and practice, iii) shows how the implementation of cotrimoxazole preventive therapy for both TB patients and HIV-infected patients starting ART was associated with reduced death rates, and iv) highlights lessons that can be learnt for other settings and interventions. DISCUSSION: District and facility-based operational research was undertaken between 1999 and 2005 to assess the effectiveness of cotrimoxazole preventive therapy in reducing death rates in TB patients and subsequently in patients starting ART under routine programme conditions. Studies demonstrated significant reductions in case fatality in HIV-infected TB patients receiving cotrimoxazole and in HIV-infected patients about to start ART. Following the completion of research, the findings were rapidly disseminated nationally at stakeholder meetings convened by the Ministry of Health and internationally through conferences and peer-reviewed scientific publications. The Ministry of Health made policy changes based on the available evidence, following which there was countrywide distribution of the updated policy and guidelines. Policy was rapidly moved to practice with the development of monitoring tools, drug procurement and training packages. National programme performance improved which showed a significant decrease in case fatality rates in TB patients as well as a reduction in early death in people with HIV starting ART. SUMMARY: Key lessons for moving this research endeavour through to policy and practice were the importance of placing operational research within the programme, defining relevant questions, obtaining "buy-in" from national programme staff at the beginning of projects and having key actors or "policy entrepreneurs" to push forward the policy-making process. Ultimately, any change in policy and practice has to benefit patients, and the ultimate judge of success is whether treatment outcomes improve or not.

Keeping health facilities safe: one way of strengthening the interaction between disease-specific programmes and health systems.

The debate on the interaction between disease-specific programmes and health system strengthening in the last few years has intensified as experts seek to tease out common ground and find solutions and synergies to bridge the divide. Unfortunately, the debate continues to be largely academic and devoid of specificity, resulting in the issues being irrelevant to health care workers on the ground. Taking the theme 'What would entice HIV- and tuberculosis (TB)-programme managers to sit around the table on a Monday morning with health system experts', this viewpoint focuses on infection control and health facility safety as an important and highly relevant practical topic for both disease-specific programmes and health system strengthening. Our attentions, and the examples and lessons we draw on, are largely aimed at sub-Saharan Africa where the great burden of TB and HIV / AIDS resides, although the principles we outline would apply to other parts of the world as well. Health care infections, caused for example by poor hand hygiene, inadequate testing of donated blood, unsafe disposal of needles and syringes, poorly sterilized medical and surgical equipment and lack of adequate airborne infection control procedures, are responsible for a considerable burden of illness amongst patients and health care personnel, especially in resource-poor countries. Effective infection control in a district hospital requires that all the components of a health system function well: governance and stewardship, financing,infrastructure, procurement and supply chain management, human resources, health information systems, service delivery and finally supervision. We argue in this article that proper attention to infection control and an emphasis on safe health facilities is a concrete first step towards strengthening the interaction between disease-specific programmes and health systems where it really matters ­ for patients who are sick and for the health care workforce who provide the care and treatment.

Diagnosis and management of antiretroviral-therapy failure in resource-limited settings in sub-Saharan Africa: challenges and perspectives.

Despite the enormous progress made in scaling up antiretroviral therapy (ART) in sub-Saharan Africa, many challenges remain, not least of which are the identification and management of patients who have failed first-line therapy. Less than 3% of patients are receiving second-line treatment at present, whereas 15-25% of patients have detectable viral loads 12 months or more into treatment, of whom a substantial proportion might have virological failure. We discuss the reasons why virological ART failure is likely to be under-diagnosed in the routine health system, and address the current difficulties with standard recommended second-line ART regimens. The development of new diagnostic tools for ART failure, in particular a point-of-care HIV viral-load test, combined with simple and inexpensive second-line therapy, such as boosted protease-inhibitor monotherapy, could revolutionise the management of ART failure in resource-limited settings.

Scaling up antiretroviral therapy in Malawi-implications for managing other chronic diseases in resource-limited countries.

The national scale-up of antiretroviral therapy (ART) in Malawi is based on the public health approach, with principles and practices borrowed from the successful DOTS (directly observed treatment, short course) tuberculosis control framework. The key principles include political commitment, free care, and standardized systems for case finding, treatment, recording and reporting, and drug procurement. Scale-up of ART started in June 2004, and by December 2008, 223,437 patients were registered for treatment within a health system that is severely underresourced. The Malawi model for delivering lifelong ART can be adapted and used for managing patients with chronic noncommunicable diseases, the burden of which is already high and continues to grow in low-income and middle-income countries. This article discusses how the principles behind the successful Malawi model of ART delivery can be applied to the management of other chronic diseases in resource-limited settings and how this paradigm can be used for health systems strengthening.