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PAST PROJECTS

A longitudinal cohort study of HIV-infected persons hospitalized with pneumonia in two settings: Mulago Hospital, Kampala and San Francisco General Hospital, San Francisco

Study period: October 2008 – December 2013. Brief description: Part of the Lung HIV Study, a network of 8 research programs and a central data coordinating center whose shared goal is to study the spectrum of HIV-associated lung disease and create a specimen bank and accompanying clinical database to catalyze future studies in the field. The MIND-IHOP study evaluates the diagnosis and epidemiology of HIV-associated pulmonary infections and the human responses to those infections. Collaborators: MU-UCSF Research Collaboration. Sponsored by: National Heart Lung and Blood Institute (NHLBI)

U01 Mulago III Parish Cohort Study: Longitudinal comparison of antimalarial treatment efficacy

Study period: November 2004 to December 2008. Brief description: This randomized, single-blinded, longitudinal clinical trial was designed to compare the safety, tolerability and efficacy of three different combination antimalarial regimens for the treatment of uncomplicated malaria. The study revealed that AL was superior to other anti-malarial combinations. Collaborators: MU-UCSF Research Collaboration. Sponsored by: The National Institutes of Health/Division of Microbiology and Infectious Diseases (NIH/DMID)

Pharmacokinetics of Antimalarial Medications in Ugandan Children

Study period: June 2007 to December 2008. Brief description: This study investigated the pharmacology of artemether/lumefantrine and artesunate/amodiaquine in HIV un-infected children in Kampala, Uganda.  The comparison to prior adult data suggests that LR exposure is lower in children and that AQ/DEAQ exposure is similar in children and adults.  For the artemisinin drugs, differences between exposure in children and adults vary depending on which artemisinin is administered. PK distinctions between children and adults should be considered to optimize dosing strategies for these widely utilized ACT regimens. Collaborators: MU-UCSF Research Collaboration. Sponsored by: CFAR, Drug Research Unit. (It is not clear whether the one who wrote this summary was reviewing past data or actually presenting what our study found. It needs to be edited by the author and he/she should include more of the findings.)

CHAMP: The Children with HIV and Malaria Project

Study period: October 2005 to May 2009. Brief description: The aim of this study was to study the interactions between Human Immunodeficiency Virus (HIV) infection and malaria in African children.  CHAMP has led to several important discoveries about malaria and HIV. In addition with such close clinical follow-up, CHAMP has also provided an opportunity to better understand other aspects of the disease HIV causes in African children. Collaborators: MU-UCSF Research Collaboration. Sponsored by:  National Institute of Health (NIH)(Even for CHAMP, we need to list the “several” important findings that we got.)

TB-VCT: HIV Voluntary Counseling and Testing for TB Evaluation Patients and their Family and Household Members in Kampala Uganda

Study period: August 2007 to March 2012. Brief description: The project aimed to determine the uptake of and barriers to HIV VCT among TB evaluation patients as well as comparing VCT uptake between Home-based VCT and TB Clinic-based VCT for family and household members of TB evaluation patients. This project has shown that it is feasible to carry HIV testing of households of subjects at high risk of testing HIV positive in this resource limited setting, although invariably showing that home HIV testing was superior to clinic based HIV testing  for successfully  testing household members. Predictors of successful Household Testing were, testing at Home Vs Clinic (aOR, 4.0, (1.6-6.2), higher household size and household member being female. The highest yield of HIV positive among household members was a spouse of an HIV positive TB evaluation subject. These results provide a working model of TB/HIV VCT that could be rapidly implemented across sub-Saharan Africa given the substantial pre-existing TB control infrastructure in the region. Collaborators: MU-UCSF Research Collaboration. Sponsored by: The National Institute of Health (NIH)

FRESH-AIR: The Impact of Household Ventilation on Transmission of Tuberculosis among Household Contacts of Active Tuberculosis Patients in Kampala, Uganda

Study period: July 2010 to December 2011. Brief description: This pilot study tested the feasibility of an in-home measurement of ventilation using a carbon dioxide (CO2) tracer gas decay technique, a low cost method, and evaluated if household ventilation is associated with TB in household contacts of adults with pulmonary TB (PTB) in Uganda. Findings indicated that Measuring household ventilation was feasible and Ventilation rates were lower (although not statistically significant) in homes with versus without co-prevalent TB in household contacts. Collaborators: MU-UCSF Research Collaboration. Sponsored by: UCSF Center for AIDS Research (CFAR)

TCC - Tororo Child Cohort: Interaction between HIV and malaria in African Children

Study period: August 2007 to March 2013. Brief description: The study was designed to; assess whether trimethoprim-sulfamethoxazole(TMP/SMX) prophylaxis is highly effective in preventing malaria in both HIV-infected and HIV-uninfected children, assess the effect of TMP/SMX prophylaxis on selection of malaria parasites containing mutations confering resistance to antifolate drugs,and  compare the efficacy, safety and tolerability of artemether-lumefantrine(AL) and dihydroartemisinin-piperaquine(DP) for the treatment of uncomplicated falciparum malaria among HIV-infected and uninfected children. The study demonstrated that TMP/SMX prophylaxis reduced the incidence of malaria by 39% and there was no difference in prevalence of markers of antifolate resistance in children who were on TMP/SMX prophylaxis compared to those who were not and that both DP and AL were equally efficacious and safe for treatment of uncomplicated malaria.Collaborators: MU-UCSF Research Collaboration.  Sponsored by: The Doris Duke Charitable Foundation, Center for Disease Control (CDC)

Access Bottlenecks Costs and Equity Study

Study period:  April 2012 to December 2012. Brief description: To understand the constraints to health service delivery, determinants of patient access and policies which affect both supply and demand of health care in Uganda. Collaborators: Institute of Health Metrics and Evaluation (IHME). Sponsored by: Bill and Melinda Gates Foundation

Serial HIV Testing Study: Acceptability and Feasibility of Serial HIV Antibody Testing to Detect Incident HIV Infection during Pregnancy and Lactation and Partner Testing in Tororo, Uganda

Study Period: January 2011 to December 2011. Brief description: To determine the proportion of women who complete serial HIV antibody testing. The integration of a serial HIV testing program into routine antenatal and postnatal health care visits was highly acceptable to pregnant women. However, the majority of women only partially completed the serial testing protocol.  Thus, a less intensive serial HIV testing protocol such as 1 repeat test in the 3rd trimester of pregnancy and 1 repeat test at 6 months postpartum may be more feasible.  Collaborators: MU-UCSF Research Collaboration. Sponsored by: UCSF Gladstone Institute for Virology and Immunology, Center for AIDS Research (CFAR)

A Programmatic Evaluation of Sulfadoxine-Pyrimethamine for Prevention of Placental Malaria in Uganda

Study period: February 2011 to July 2011. Brief description: To determine whether the current program of routine SP administration is effective in reducing placental malaria in Tororo, Uganda. Findings: In this area of Uganda with high malaria transmission intensity, use of > 2 doses of SP was not associated with protection against placental malaria and improved birth outcomes compared with < 2 doses of SP. These findings highlight the need for alternatives to SP for the protection against malaria in pregnant women in areas of moderate-to-high malaria transmission and with widespread SP resistance. Collaborators: MU-UCSF Research Collaboration and Uganda Malaria Surveillance Project (USMP). Sponsored by: USMP/CDC

Pharmacokinetics of Piperaquine and Lumefantrine in Young Children in Tororo Uganda

Study period: March 2008 to 2012. Brief description: The aim of this study is to provide information on drug disposition and the relationship between drug exposure and outcomes.  In addition, the impact of factors such as weight and concomitant medications on PK exposure will also be evaluated. Collaborators: MU-UCSF Research Collaboration. Sponsored by: Novartis, Inc., Holley-Cotec Pharmaceuticals

PROMOTE: Prevention of Malaria and HIV Disease in Tororo, Uganda

Study period: October 2009 – July 2013. Brief description: The PROMOTE program establishes new approaches to reduce HIV and malaria burdens in sub-Saharan Africa, and enhances the public health approach to both diseases. Three of the projects are interlinked hypothesis-based intervention cohort trials. The other 2 projects are linked to all of the clinical trials and utilize data and specimens from each of these trials to characterize nutrition and drug resistance. The program is being conducted in Tororo District, Uganda, a rural area with HIV seroprevalence of 8% and malaria transmission intensity of 562 infective bites per person year
Collaborators:  MU-UCSF Research Collaboration.  Sponsored by: The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD/NIH)

PROMOTE - Pediatrics

A randomized open label trial of HIV protease inhibitors for the prevention of malaria in HIV-infected children Study period: October 2009 to January 2013. Brief description: The aim of this study was to determine if the use of PI-based (LPV/r) ART versus NNRTI-based ART among HIV-infected children will reduce the incidence density of malaria in children. This study demonstrated that HIV infected children treated with LPV/r-based ART regimen had a significantly lower risk of malaria compared to those treated with an NNRTI-based regimen.

PROMOTE - PIs (Pregnant women and Infants): Protease inhibitors to reduce malaria morbidity in HIV-infected pregnant women

Study period: October 2009 to July 2013. Brief description: The aim of this study is to determine if the use of PI-based ART versus non-PI ART among HIV-infected pregnant women leads to reduced rates of placental malaria as measured by Giemsa-stained smear or polymerase chain reaction (PCR) of placental blood.

PROMOTE – Chemoprevention: A randomized trial of monthly dihydroartemisinin-piperaquine versus monthly sulfadoxine-pyrimethamine versus daily trimethoprim-sulfamethoxazole versus no therapy for the prevention of malaria

Study period: October 2012 to July 2014. Brief description: The aim of this study to compare the incidence of malaria among infants enrolled at 4-5 months of age and randomized to one of the four arms until they reach the age of 24 months. This study demonstrated that the incidence of malaria was extremely high in the no chemo-prevention arm despite the use of ITNs and increased with age. In addition, monthly SP was not effective for the prevention of malaria. In this study population, daily TS was associated with a modest protection against malaria, and monthly DP was associated with good protection against malaria.

PROMOTE – Drug Resistance: This program includes Pediatrics, PIs and Chemoprevention

Study period: October 2012 to July 2013 Brief description: The aim of this study is to test whether long-term use of chemopreventive antimalarial therapies in children or of antiretroviral protease inhibitors in children or pregnant women will decrease the incidence of malaria and related malarial morbidity.

PROMOTE - Nutrition

Study period: October 2009 to July 2013. Brief description: This project evaluates the nutritional status of PROMOTE program participants, identifying factors which increase the risk of nutritional deficiency and subsequent poor clinical outcomes, correlating levels of malnutrition and ART pharmacokinetic exposure and response, and pilots a nutritional supplementation strategy tailored to routine practice in resource limited settings.

EARLI: Early Antiretroviral Therapy in Resource Limited Settings in Patients with High CD4+ Cell Counts

Study period: November 2011 to March 2015. Brief description: To assesses efficacy and adherence to ART, and answer implementation science questions of delivering ART to high CD4 patients using a streamlined model. Preliminary findings suggest high ART acceptability among patients with high CD4 counts. Collaborators: MU-UCSF Research Collaboration, Mbarara University Joint Program (MJAP), Infectious Diseases Research Collaboration (IDRC). Sponsored by: NIH / Gilead Scineces

Supporting the Implementation of Malaria Prevention and Control Strategies Relevant Ancillary Activities in the Republic of Uganda

Study period: September 2008 to September 2013. Brief description: The purpose of this project is to support the implementation of strategies to prevent and control malaria, and relevant ancillary activities in the Republic of Uganda as part of the President’s Malaria Initiative (PMI). Collaborators: Uganda Malaria Surveillance Program (UMSP), Uganda National Malaria Control Program, Center for Disease Control (CDC) Sponsored by: DHHS/CDC.

Pharmacokinetic Interactions between Antiretroviral Agents, Lopinavir/Ritonavir and Efavirenz and Antimalarial Drug Combinations, Artesunate/ Amodiaquine and Artemether/Lumefantrine

Study period: June 2006 – March 2013. Brief description: This study includes three (3) components for evaluating potential drug-drug interactions in healthy HIV sero-negative volunteers. The first component evaluated the impact of efavirenz on amodiaquine/artesunate but was discontinued early due to unexpected hepatic toxicity in the first two subjects.  The second component revealed that lumefantrine exposure increases 200% in the context of lopinavir/ritonavir co-administration. However, due to the excellent safety profile for artemether/lumefantrine, dosage adjustment is not recommended but increased safety monitoring is warranted.  The third study is nearing completion and is evaluating the effect of efavirenz on the pharmacokinetics of artemether/lumefantrine.  It is expected that efavirenz will lower lumefantrine exposure significantly due to its CYP3A4 induction effects. Collaborators: MU-UCSF Research Collaboration. Sponsored by: CFAR, Drug Research Unit, Novartis, Inc.

HIV VCT and Linkage to Care in Uganda

Study Period: September 2007 to August 2012. Brief description: To compare the efficacy of routine counseling and testing for HIV among hospitalized adults to traditional counseling and testing in reducing HIV risk behavior among inpatients after discharge 2) To compare the effectiveness of Enhanced Linkage to Care model of post-disclosure referral to HIV-specific medical care with Usual Referral in receipt of opportunistic infection prophylaxis, antiretroviral therapy, and reducing mortality. Collaborators:  Sponsored by: NIH (NIMH).

ACT PRIME: Comparing the impact of enhanced health facility-based care on malaria and febrile illnesses in children in Tororo, Uganda

Study period: December 2009 to April 2013. The major goals of this study are to compare the impact of enhanced health facility based care on key population-based indicators, including the prevalence of anemia in children under five, on key longitudinal indicators, including treatment incidence density, in a prospectively followed cohort of children under five and on key indicators of case management for malaria and other illnesses, including the risk of inappropriate anti-malarial treatment, in children under five treated at health facilities. Collaborators: Infectious Diseases Research Collaboration (IDRC), London School of Hygiene and Tropical Medicine (LSHTM), UCSF. Sponsored by: Bill and Melinda Gates Foundation.

ACT PROCESS

Study period: December 2009 to April 2013. Brief description: Involves a comprehensive evaluation framework implemented in parallel with ACT PRIME. The major goal is to evaluate the process, context and impact of the intervention implemented in the ACT PRIME study in order to further our understanding about why the HFI was effective, or not.

Malaria Control Policy Assessment - Uganda

Study period: March 2012 to Feb 2014. Brief description: Evaluating the impact of malaria control interventions on child mortality in Uganda. Collaborators: Infectious Diseases Research Collaboration (IDRC), University of Washington, Institute for Health Metrics and Evaluation (IHME). Sponsored by: Bill and Melinda Gates Foundation.

TET: Therapeutic Efficacy Trial- Efficacy of artemether-lumefantrine and amodiaquine + artesunate for treatment of uncomplicated malaria in children in Uganda

Study period: 2013. Brief description: To compare the efficacy and safety of 2 artemisinin-based combination therapies (ACT), amodiaquine-artesunate (AQ+AS), and artemether-lumefantrine (AL) for treatment of uncomplicated malaria in children in Uganda. The study is being conducted at 3 Uganda Malaria Surveillance Project (UMSP), sentinel health centers, Aduku, Mubende and Kihihi. Collaborators: UMSP, IDRC, MoH, CDC, USAID, PMI, WHO, UCSF. Sponsored by: PMI and WHO.

R01 Parasitology: Resistance of Malaria Parasites to Artemisinin-Based Combination Therapies

Study period: July 2009 to June 2014. Brief description: The study is three fold. 1. To identify genotypes associated with decreased responses to ACTs in Africa. 2. To assess molecular mechanisms and parasitological consequences of increasing resistance to ACTs. 3. To characterize the specific impacts of parasite polymorphisms on drug sensitivity and fitness. Collaborators: MU-UCSF Research Collaboration.  Sponsored by: NIH/NIAID.

RO1 Immunology: Impact of Chemoprevention on Humoral Antimalarial Immunity

Study period: July 2011 to July 2014. Brief description: To assess the impact of blood stage P. falciparum infection and chemoprevention on humoral antimalarial immunity. Collaborators: UCSF, IDRC, UC Irvine. Sponsored by: The Doris Duke Charitable Foundation

The PQ Study

Study period: December 2011 – December 2013. Brief description: An evaluation of the efficacy and safety of single-dose primaquine for the clearance of gametocytes in children with uncomplicated malaria in Uganda. The goal of the study is to evaluate the efficacy and safety of lower doses of primaquine than the dose (0.75mg primaquine base/kg) recommended in the WHO 2010 malaria treatment guidelines. Collaborators: Infectious Diseases Research Collaboration (IDRC), London School of Hygiene and Tropical Medicine (LSHTM) and the Mahidol Oxford Research Unit (MORU). Sponsored by: Wellcome Trust of Great Britain, Bill and Melinda Gates Foundation.

START-ART: Streamlined ART Initiation Strategy

Study period: July 2012 to June 2014. Brief description: The project will test our Streamlined ART Initiation Strategy in a randomized, controlled trial, in 24 clinics in Uganda.The overall goal of START is to initiate ART among the greatest number of eligible patients in the shortest amount of time possible while maintaining safety, efficacy and cost effectiveness. Collaborators: MU-UCSF Research Collaboration.  Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID).

Tuberculosis Acquisition in Early Childhood in Uganda: Influence of HIV exposure and malnutrition

Study period: February 2013 to February 2014. Brief description: To elucidate the epidemiology of the LTBI reservoir in early childhood and the influence of HIV-exposure on LTBI and we will test the hypotheses that (1) the prevalence of LTBI increases with age within the 5 and under age group,  (2) HIV-exposed, un-infected children have a higher prevalence of LTBI compared to HIV-unexposed children.  In addition to characterizing TB acquisition in early childhood, we will utilize existing HIV clinical and nutritional data from established MU-UCSF cohorts to test the hypothesis that HIV-exposed, un-infected children have an increased risk for LTBI infection relative to HIV-unexposed children. Collaborators: MU-UCSF Research Collaboration.  Sponsored by: NIAID.

SEARCH Community Campaign, Linkage and Household Survey Protocol

Study period: December 2010 to December 2012. Brief description: The Mbarara Community Campaign Pilot was designed to test and refine the methodology for a high-throughput community campaign in a rural, east African setting. Collaborators: MU-UCSF Research Collaboration.  Sponsored by: NIH/NIAID

TRAP-TB: The Transmission and Pathogenesis of TB - Molecular Epidemiology and Geospatial Analysis of TB Transmission in Tororo Uganda

Study period: June 2011 to June 2016. Brief description: Characterizing recent TB transmission networks, identifying sites of ongoing TB transmission, and understanding how HIV influences TB transmission to develop novel strategic intensified TB case-finding approaches in Africa. Collaborators: MU-UCSF Research Collaboration.  Sponsored by: NIAID