Awarded: Jan 01, 2007
$2,000,000 over 2 years
In 2007, 10 teams of researchers received two-year grants of $200,000 each to support operations research on AIDS care and treatment in Africa.
2007 ORACTA Grantees
Transport Support to Improve ARV Treatment Outcomes
Macronutrient Supplement for HIV-Infected Patients Initiating ART
Impact and Value of Improving TB Control in Africa
Combating MDR and XDR TB in Rural South Africa
Impact of Peer Educators and Mobile Phones on HIV Care
Trial of Strategies to Enroll Pregnant Women into ART
Evaluating Two Models of ART Delivery in Rural Rwanda
Mobile ARV Pharmacy at TREAT Sites in Rural Uganda
Improving TB Diagnosis in High HIV Primary Care Settings
Community-Based Case Finding of TB-HIV Patients
Transport Support to Improve ARV Treatment Outcomes
Principal Investigator:
David Bangsberg, M.D., Ph.D.,
University of California, San Francisco
Co-Investigators:
Winnie Muyindike, M.B.Ch.B., M.Med., Mbarara University of Science and Technology, Uganda
Harsha Thirumurthy, Ph.D., University of North Carolina, Chapel Hill
James Habyarimana, Ph.D., M.A., B.Sc., Georgetown University
Cristian Pop-Eleches, Ph.D., M.A., Columbia University
Irene Andia, M.B.Ch.B, M.Med., Mbarara University of Science and Technology, Uganda
Abstract:
Transportation challenges to pick up HIV medication is a major barrier to continued HIV treatment in resource-limited countries. Our data suggest that treatment interruptions due to transport barriers accessing medications account for 90% of missed doses, that these increase with distance to clinic, and are a major cause of ARV resistance. Nevirapine fixed-dose combination therapy is particularly vulnerable to treatment interruptions due to differing half-lives and a subsequent "nevirapine tail" during interruptions. We propose to determine the behavioral, biologic and economic impact of monthly transportation assistance over 12 months in a rural African HIV treatment setting. We will specifically look at how transportation assistance impacts the following:
Behavioral Outcomes. We will determine the impact of transportation assistance on reducing treatment interruptions.
Biologic Outcomes. We will determine the impact of transportation assistance on HIV viral suppression.
Economic Outcomes. We will determine the impact of transportation assistance on economic productivity.
We will conduct a randomized trial of monthly transportation to clinic concurrent with refill dates and physician visits compared to standard care (no transportation provided) among 200 people attending the Mbarara University HIV Clinic in rural southwestern Uganda. We will provide morning transportation from the participant's residence to clinic on the prearranged time and date each month to pick up refills and see a health care provider. We will coordinate with the clinic and pharmacy to schedule the same return dates for patients in a common geographic region. Participants will be given funds for return transportation via available mini-bus or bicycle taxi. The comparison group will arrange self transportation to clinic each month as is customary for the current standard of care in Mbarara, Uganda. Structured interviews regarding medication/health service use, functional health status, and economic variables will be conducted every 3 months. HIV viral load and CD4 cell count will be collected at baseline and 12 months.
To determine whether transportation assistance is associated with fewer treatment interruptions, we will compare total days of interrupted therapy, number of 48 hour treatment interruptions, and pharmacy refill behavior between the two groups. To determine whether transportation assistance is associated with HIV viral load suppression, we will compare HIV viral load between the two groups. To determine whether transportation assistance improves the economic output, we will examine the effects of transportation assistance on labor supply, household consumption, child labor and schooling hours, and loans received in order to determine the full benefit of transportation assistance.
Macronutrient Supplement for HIV-Infected Patients Initiating ART
Principal Investigator:
Wafaa El-Sadr, M.D., M.P.H., Mailman School of Public Health, Columbia University
Co-Investigators:
Stephen Arpadi, M.D., M.S., Columbia University
Richard Deckelbaum, M.D., Columbia University
Mark Hawken, M.D., M.S., Mailman School of Public Health, Columbia University
Pricilla Nyakundi, M.B., M.Med. Ped., M.Sc., Kenya Medical Research Institute
Abstract:
While the advent of effective antiretroviral therapy (ART) in resource limited settings holds promise of making a substantial impact on health and well-being, many HIV-infected persons suffer from lack of nutrition and develop weight loss and wasting, often with severe consequences including death. Background malnutrition in sub-Saharan Africa is very important in HIV given that over 30% of people have insufficient food intake and decrease in weight as measured by decrease in body mass index (BMI) to less than 18 is strongly predictive of death. Even with use of ART, weight loss during first 4 weeks of ART is also associated with death. Most studies to date have paid little attention to utilization of food (macronutrient) as a major tool for nutrition intervention. Thus, national guidelines, while acknowledging the importance of the patients’ nutritional status, do not provide specific recommendations due to the lack of rigorous evidence.
We propose a study to determine whether HIV-infected patients with BMI <18.5 who are initiating ART and multiple micronutrient supplements (MMS) as per national guidelines will have improved nutritional, clinical, immunologic outcomes as well as improvement in performance status and quality of life measures with specific food supplementation. The study will be conducted at two health facilities in Central Province in Kenya. One site will receive ART, the food supplement and MMS while the other will receive standard of care (ART play MMS). The primary outcome will be change in BMI from baseline to 12 months i.e. 6 months after completion of nutrition supplementation to determine durability of any effect. Secondary outcomes will include change in measures of body composition, mortality, clinical outcomes, CD4 cell count, performance status, quality of life and changes in nutritional blood parameters.
There is an urgent need to define the influence of nutritional status on patient outcomes in the context of use of ART in resource-limited settings. Findings from the proposed study can have a substantial impact on the management of individual patients and can serve to guide national policy.
Impact and Value of Improving TB Control in Africa
Principal Investigator:
Kenneth A. Freedberg, M.D., M.Sc., Massachusetts General Hospital
Co-Investigators:
Robin Wood, B.M., B.Ch., M.Med., University of Cape Town, South Africa
Linda-Gail Bekker, M.B.Ch.B., F.C.P., University of Cape Town, South Africa
Melissa Bender, M.D., Massachusetts General Hospital
Abstract:
HIV and tuberculosis (TB) coinfection in Africa represent a public health emergency, requiring urgent decisions by health care providers and policymakers. AIDS is the leading cause of death in sub-Saharan Africa, and TB is the region’s leading cause of HIV-related morbidity and mortality. Despite numerous studies over many years, there is no consensus regarding the best way to diagnose and prevent TB in HIV-infected people. The rising incidence of TB and the recent emergence of a highly lethal strain of extensively drug resistant (XDR) TB, together with concerns about its transmission in the hospital, magnify the urgency of these questions. Early, rapid TB case detection is essential to stem the trajectory of these XDR outbreaks, but current diagnostic methods used in resource-limited settings lack both sensitivity and speed.
This project will examine the value and impact of improving TB case detection and implementing measures to reduce transmission. We will use a state-transition, computer simulation model to project the clinical impact, costs, and cost-effectiveness of improving TB infection control in an area of high HIV prevalence with the following 3 aims:
- To examine the cost-effectiveness of introducing TB screening at HIV voluntary counseling and testing (VCT) sites;
- To evaluate the cost-effectiveness of standard TB case detection compared with routine sputum culture or rapid TB detection techniques in areas of high XDR prevalence; and
- To assess the cost-effectiveness of implementing TB infection control procedures in resource-limited health care settings with high HIV prevalence.
To carry out these aims, we will use data from the South African PEPFAR site in Cape Town to inform the analysis using the “Cost-Effectiveness of Preventing AIDS Complications” (CEPAC) International model, a widely published, detailed state-transition model of HIV infection. This proposal will benefit from the rich collaborative ties established between investigators in Cape Town and in Boston in addressing the value of rapid TB detection and control in the context of the dual epidemics of HIV and TB disease.
Combating MDR and XDR TB in Rural South Africa
Principal Investigator:
Gerald Friedland, M.D., Yale University
Co-Investigators:
Neel Gandhi, M.D., Albert Einstein College of Medicine
Anthony Moll, M.Sc., M.B.Ch.B., Church of Scotland Hospital, South Africa
N. Sarita Shah, M.D., M.P.H., Albert Einstein College of Medicine
Adriaan Willem Sturm, M.D., Ph.D., University of KwaZulu-Natal, South Africa
Umesh Lalloo, M.D., M.B.Ch.B., University of KwaZulu-Natal, South Africa
Abstract:
The global HIV epidemic is fuelling an extraordinary increase in tuberculosis (TB) cases, and in the number of patients co-infected with both diseases. This has most heavily impacted sub-Saharan Africa where the rates of both TB and HIV are highest in the world. We have been performing operations research studies aimed at integrating the care and treatment of TB and HIV in a rural area of the province of KwaZuluNatal, South Africa. Using innovative patient and community support, this strategy has been highly successful in improving the outcome of both diseases. In the course of this work, however, we have recently uncovered and provided the first clinical, epidemiologic and microbiologic reports regarding the presence of a highly prevalent strain of multiple drug resistant tuberculosis (MDR TB) and extensively drug resistant tuberculosis (XDR TB) among HIV co-infected patients. We have found that infection with these organisms is associated with extremely high and rapid mortality. In addition, our studies indicate that there has been recent transmission of these dangerous organisms in both community and hospital settings. Our report of these findings (Lancet 2006) has resulted in widespread and appropriate concern in both the medical and lay communities. Subsequent information has indicated that MDR and XDR TB is widespread in this and other provinces in South Africa and likely in other sub-Saharan African countries. The presence of this and other resistant strains of tuberculosis threaten to further undermine already overwhelmed TB control programs, to blunt the benefit of the introduction of antiretroviral therapy to HIV/TB co-infected populations and to limit the needed integration of HIV/TB diagnosis and treatment.
We propose in this project to develop and evaluate a three part strategy to reduce the prevalence, transmission and consequences of drug resistant tuberculosis among HIV co-infected patients in rural South Africa:
- Earlier diagnosis of MDR and XDR TB, using innovative clinical evaluation and laboratory testing;
- Strengthening and monitoring of infection control practices to reduce hospital associated transmission; and
- Inaugurating community based treatment of drug resistant TB.
This project is based upon and will expand our success in introducing antiretroviral therapy to HIV/TB co-infected patients, and will be undertaken by an established collaborative US and South African research team with investigators at Yale University and Albert Einstein College of Medicine and at a district hospital and NGO, Philanjalo, in rural KwaZulu-Natal, province, the Nelson R. Mandela School of Medicine and Doris Duke Medical Research Institute in Durban and with the support of the KwaZulu-Natal Department of Health. The proposed project has potential for benefit both at the local level in KwaZulu-Natal and in the many resource limited settings worldwide where TB and HIV are highly prevalent.
Impact of Peer Educators and Mobile Phones on HIV Care
Principal Investigator:
Ronald H. Gray, M.D., M.Sc., Johns Hopkins University, Bloomberg School of Public Health
Co-Investigators:
Larry Chang, M.D., M.P.H., Johns Hopkins University
Joseph Kagaayi, M.B.Ch.B., M.P.H., Rakai Health Sciences Program, Uganda
Steven Reynolds, M.D., M.P.H., National Institutes of Health
David Serwadda, M.B.Ch.B., M.Sc., M.Med, M.P.H., Makerere University Institute of Public Health, Uganda
Abstract:
The provision of antiretroviral therapy (ART) in rural, resource-limited settings entails substantial challenges due to limitations in the health service infrastructure and human resources. With PEPFAR funding, the Rakai Health Sciences Program (RHSP) has screened 4,397 HIV+ persons and initiated ART for over 900 patients with CD4 counts <250 in a rural area of southwestern Uganda using an innovative strategy of mobile clinics and home-based care. However, long distances between providers, care facilities and patients are barriers to appropriate and timely care. To overcome these constraints, we conducted a pilot study of the use of peer educators as frontline patient adherence supporters. Under this pilot study, we have also assessed use of mobile phones to improve peer educator access to health care providers, and have established a "Warmline" (staffed during clinic hours) to provide clinical advice to peer educators and patients. The pilot study demonstrated the feasibility of the peer educator/mobile phone approach, but data are insufficient to assess the impact on treatment and compliance.
Building on this initial experience, we will conduct a three arm, cluster-randomized trial of the impact on HIV care of peer educators, with and without mobile phones (intervention arms A and B), compared to a control arm in rural Rakai District, Uganda. The peer educators will be supported with a Warmline toll-free service staffed by clinicians experienced in HIV care. The primary endpoints will be virologic treatment failure and antiretroviral (ARV) adherence over one year. The hypotheses are that compared to control communities, peer educators will reduce treatment failures and improve ARV adherence, and mobile phones used by peer educators will more rapidly address adherence and clinical problems, resulting in lower treatment failures. If, as is anticipated, the peer educator/mobile phone interventions reduce treatment failure and improve adherence, during the second year of the proposed project we will scale up these interventions in all communities while maintaining post-trial monitoring to evaluate effectiveness.
Trial of Strategies to Enroll Pregnant Women into ART
Principal Investigator:
William P. Killam, M.D., M.P.H., University of Alabama at Birmingham, School of Medicine
Co-Investigators:
Moses Sinkala, M.B.Ch.B., M.P.H, Zambian Ministry of Health
Dwight Rouse, M.D., University of Alabama at Birmingham, School of Medicine
Jeffrey Stringer, M.D., University of Alabama at Birmingham, School of Medicine
Namwinga Chintu, M.D., M.Med, M.Trop.Paed., Centre for Infectious Disease Research in Zambia
Abstract:
In resource-constrained settings, HIV-infected pregnant women should be evaluated for treatment eligibility and offered highly active antiretroviral therapy (HAART) if eligible. The benefits to both mother and infant are substantial and include reduced HIV transmission to the infant and reduced maternal and infant mortality. However, programs have had limited success to date in identifying all eligible pregnant women and getting most to start HAART during pregnancy.
The urban district of Lusaka, Zambia has large, well-established programs for the prevention of mother-to-child HIV transmission (PMTCT) and for HIV care and treatment. All pregnant women are routinely offered HIV testing in antenatal care, with an option to opt out of testing. In our setting, pregnant women identified as HIV-positive are offered routine CD4 count screening and assessed for clinical signs of treatment eligibility. Those who are identified as eligible for treatment according to national guidelines are then brought by peer educators to the HIV care clinic. To date, this strategy has succeeded in starting HAART in pregnancy in approximately 21% of women identified as treatment-eligible.
In order to increase the number of eligible pregnant women who start HAART in pregnancy, the Lusaka District has decided to begin providing HIV care within the antenatal clinics. This service will be rolled out in phases. Through the Doris Duke Charitable Foundation's ORACTA grant, we will be able to evaluate the effectiveness of integrated HIV care in the antenatal clinic as a strategy for starting treatment-eligible pregnant women on HAART.
Our primary aim is to evaluate whether providing HIV care in the antenatal clinic increases the percentage of treatment-eligible pregnant women initiating HAART during pregnancy. HIV care will be introduced in eight antenatal clinics in a phased roll out over a 10 month period. We will determine the percentage of treatment eligible women initiating HAART in all antenatal clinics at baseline and after introduction of integrated HIV care. Because antenatal clinics will initiate integrated HIV care at different time points, we will be able to account for whether enrollment into care is improving over time. The secondary aims of this study are to evaluate whether women initiate HAART earlier in pregnancy when it is provided in the antenatal clinic; to evaluate adherence to therapy for each strategy by measuring patient retention in the program and timeliness of pharmacy pick-ups; and to evaluate the incremental cost per patient commenced on therapy with the antenatal HIV care strategy.
Evaluating Two Models of ART Delivery in Rural Rwanda
Principal Investigator:
Michael L. Rich, M.D., M.P.H., Brigham and Women's Hospital; Partners in Health, Rwanda
Co-Investigators:
Henry Epino, M.D., Partners in Health
Paul Farmer, M.D., Ph.D, Brigham and Women's Hospital; Partners in Health
Molly Franke, B.A., Partners in Health
Felix Kaigamba Rubagumya, M.D., Ruhengeri Hospital, Rwanda
Pierre Niyigena, Rwanda Ministry of Health; Partners in Health
Abstract:
Antiretroviral therapy (ART) has proven effective in decreasing mortality in both high- and low- resource settings; however, malnourished patients, those with low levels of adherence, and those who lack psychosocial resources are at higher risk for poor outcomes. Maintaining high levels of adherence to ART can be challenging in resource-poor settings for a multitude of reasons. First, ART can cause disruptive side effects, and the cost of ancillary medications to treat these symptoms is often prohibitive. Second, the need to assuage competing hardships, such as food and water insecurity, may prevail over the need for prompt and consistent pill taking. Third, limited financial income, particularly in rural areas where the principal activity is subsistence farming, limits available financial resources for ART-related expenses, such as user fees and the costs of travel to and from the local health clinic. Fourth, because literacy and education rates are often low in resource-poor settings, effective education regarding HIV disease and the importance of ART adherence requires numerous interactions with trained healthcare personnel.
We hypothesize that the application of a comprehensive model of ART care in rural Rwanda will eliminate many of the barriers described above and will improve patient outcomes while offering indirect benefits to the patient, family, and community. The objective of this project is to comprehensively study and compare the direct and indirect benefits conferred by two models of rural ART care: the standard model of care in Rwanda, which includes the provision of ART, routine clinical visits and laboratory testing, and a more comprehensive model of care that also includes universal nutritional support, daily home visits, and social support.
We will pursue the following primary aims:
- To compare clinical outcomes, including viral load after one year of ART and changes in CD4 count and weight, among patients receiving each model of ART care in two rural districts of Rwanda;
- To compare psychosocial outcomes, including depression, social support, stigma, and quality of life, among patients receiving each model of ART care;
- To assess adherence among patients receiving each model of care and examine factors related to non-adherence;
- To evaluate potential indirect benefits associated with each model of care.
A prospective observational cohort of patients initiating ART in two rural areas, one that utilizes the standard model of ART care in Rwanda and one that uses the more comprehensive model of care, will be defined and longitudinally followed. Patients at both sites will undergo standardized clinical, laboratory, adherence and psychosocial evaluations. Adherence will be assessed via unannounced pill counts and self-reports after three, six, and twelve months of ART. Indirect benefits, such as changes in work and school attendance, and changes in health seeking behavior, will be measured through standardized questionnaires administered at six-month intervals.
Mobile ARV Pharmacy at TREAT Sites in Rural Uganda
Principal Investigator:
Ajay K. Sethi, Ph.D., M.H.S., Case Western Reserve University School of Medicine
Co-Investigators:
Peter Mugyenyi, M.D., F.R.C.P., D.C.H., Joint Clinical Research Center, Uganda
Cissy Kityo Mutuluuza, M.D., M.Sc., Joint Clinical Research Center, Uganda
Francis Bajunirwe, M.B.Ch.B., M.S., Mbarara University of Science and Technology, Uganda
Edgar Mugema Mulogo, B.D.S., M.P.H., M.S., Mbarara University of Science and Technology, Uganda
Abstract:
In Uganda, the Joint Clinical Research Center (JCRC) has built a network of HIV clinics with the capacity to deliver antiretroviral therapy (ARV) safely and effectively through its TREAT program (Timetable for Regional Expansion of Antiretroviral Therapy). In rural areas, patients tend to live far from the clinic and distance is a barrier to picking up HIV medication refills on time. The result is unintended non-adherence to ARVs and the potential for patients to develop resistance to ARVs. To address this problem, we will integrate a mobile ARV pharmacy into HIV care at three rural TREAT sites. After identifying patients who would benefit from receiving ARVs via this strategy, we will synchronize their monthly refill dates so that we can operate the mobile pharmacy on as few days as possible and minimize costs. We will implement the strategy, determine its feasibility, and estimate its effectiveness in improving adherence. We hope to recruit 700 patients at three hospitals to formally evaluate the mobile ARV pharmacy. We believe that the mobile pharmacy will improve adherence to ARVs and HIV care and decrease the occurrence of treatment failure. We will also determine whether the intervention decreases overcrowding at the clinic and patient wait time and increases doctor-patient time. If the intervention is satisfying to patients and physicians, effective in improving ARV adherence, and affordable, we will recommend use of this strategy country-wide and possibly in other rural settings where distance is a barrier for HIV-infected patients.
Improving TB Diagnosis in High HIV Primary Care Settings
Principal Investigator:
Kwonjune J. Seung, M.D., Brigham and Women's Hospital
Co-Investigators:
Jennifer Furin, M.D., Ph.D., Brigham and Women's Hospital
Hind Satti, M.D., Cure Medical Center, Lesotho
Salmaan Keshavjee, M.D., Ph.D., Brigham and Women's Hospital
Abstract:
The goal of this research project is to improve the diagnosis of Tuberculosis (TB) and other common respiratory illnesses in primary care settings. In most primary care clinics, nurses and other non-physician health workers do not have access to complicated laboratory tests. They must use simple laboratory tests and physical examination skills to determine if the patient has a life-threatening condition or just a simple cold.
This research project will assess the effectiveness of a standardized diagnostic algorithm to evaluate a patient with cough or difficulty breathing. The algorithm uses simple laboratory tests commonly available in primary health centers and basic physical examination skills, and can be performed by a nurse. Study patients will be recruited from the outpatient clinic of a busy district hospital in Lesotho, where much of the patient population has HIV, TB and other respiratory illnesses. The patients will first be assessed by a nurse who will use the algorithm to make a diagnosis. The results of this algorithm will then be compared to a "gold standard" of a physician using a full set of diagnostic tests, including chest x-ray and TB culture.
The results of this study are expected to be relevant to the many thousands of primary health centers in sub-Saharan Africa.
Community-Based Case Finding of TB-HIV Patients
Principal Investigator:
Christopher C. Whalen, M.D., M.S., Case Western Reserve University
Co-Investigators:
Juliet Sekandi, M.B.Ch.B., M.S., Makerere University, Uganda
Alphonse Okwera, M.B.Ch.B., M.Sc., Mulago Hospital Complex, Uganda
Henry Luzze, M.B.Ch.B., M.S., Mulago Hospital Complex, Uganda
Abstract:
Tuberculosis is an ancient disease that continues to plague humans. Although tuberculosis is contained in many industrialized countries, it remains a threat to both individual and public health in developing countries, especially in sub-Saharan Africa. In Africa, tuberculosis has re-emerged as a threat because of the contemporary epidemic of the human immunodeficiency virus type-1 (HIV). Indeed, HIV and tuberculosis are tightly linked and are often referred to as sister epidemics.
Before 2003, the management of HIV-infected patients with tuberculosis was simply to treat the tuberculosis because effective ways to treat HIV were not yet widely available in Africa. After 2003, with the financial commitments from the Presidential Emergency Plan for AIDS Relief (PEPfAR) and the Global Fund of the World Bank, there has been a rapid expansion of services to provide life-saving antiretroviral medicines to treat HIV. Health care professionals in Africa now have the means to treat their HIV-infected patients with tuberculosis.
The ability to treat HIV and tuberculosis together requires a proper diagnosis of both diseases. Early diagnosis of patients with both HIV and tuberculosis is imperative for it can reduce mortality and prevent further spread of these diseases to other people. Currently, most tuberculosis control programs around the world rely on passive case finding to detect new cases of tuberculosis. In passive case finding, tuberculosis patients are identified at clinics or hospitals after the patient has decided to seek care. Our preliminary research in Kampala, Uganda, has shown that passive case finding is associated with unnecessary delays in the diagnosis and treatment of HIV and tuberculosis.
The premise of our proposal is that active case finding will improve case detection of tuberculosis, identify cases at an earlier point in their disease, and will enhance detection of HIV-infected cases because of the tight link between HIV and tuberculosis. But active case finding can take many forms. Since the optimal form for accessing HIV-associated tuberculosis is unknown, we will evaluate two innovative community-based approaches to enhance early entry into an integrated care program for HIV and tuberculosis. In one approach, we will look for tuberculosis and HIV infection in the household contacts of infectious tuberculosis cases; in the other approach, we will look for tuberculosis and HIV infection in people with a cough lasting more than two weeks, identified in a door-to-door survey. With this information, we will be able to compare the effectiveness of each method to identify early tuberculosis cases and to compare the cost(s) of detecting one case of HIV and tuberculosis in the community. The findings of this study will inform policy about the effectiveness of active case finding in national tuberculosis programs where HIV is common.
These aims will be achieved through a longstanding collaboration between Case Western Reserve University and Makerere University. The program will be built upon capacity already supported by federally funded research on tuberculosis and HIV and by the PEPfAR program entitled 'Provision of Routine HIV Testing, Counseling, Basic Care and Antiretroviral Therapy at Teaching Hospitals in the Republic of Uganda.'