Mbarara University Grants Office

Mbarara University of Science and Technology
Grants Office

SOR

Info coming soon. You may check later

NCD R21

Info coming here soon. Check later

Non-communicable diseases (NCD) CFAR

Background

An estimated 8 million people living with HIV/AIDS (PLWHA) in Sub-Saharan Africa are taking antiretroviral therapy (ART). As a result, HIV-related mortality has declined, adult life expectancy has increased, and the public health paradigm of HIV-care is shifting from improving early survival to improving long-term health and quality of life. A rapidly growing literature from resource-rich settings describes increased rates of hypertension, diabetes mellitus, atherosclerosis, myocardial infarction, and stroke in HIVinfected versus HIV-uninfected persons. Root causes of the elevated risk in PLWHA are hypothesized to

result from a multi-factorial process involving traditional cardiovascular risk factors, altered immune function, toxicity of ART, and the elevated inflammatory state associated with HIV infection. However, similar data on cardiovascular risk factors and outcomes are largely lacking from Sub-Saharan Africa, which is home to 70% of HIV-infected persons globally. Thus, there is a critical need to collect non-communicable disease epidemiologic data on PLWHA on ART to guide public health prioritization for this population.

 Innovation

The diverse expertise within our collaboration is uniquely positioned to perform clinical study of HIV-infected individuals in a rural, sub-Saharan African setting and to utilize state-of-the-art technology, including carotid ultrasonography, RNA deep sequencing for microbiome speciation, and flow cytometry for immune activation testing, to advance our understanding of cardiovascular disease epidemiology among HIV-infected persons in sub-Saharan Africa.

 RELEVANCE

Data collected from this study will help will help serve multiple purposes, including: 1) identification of modifiable cardiovascular disease risk factors for PLWHA on ART in sub-Saharan Africa, 2) guidance of public health programs for monitoring and intervention on highest priority disease states, and 3) setting priorities for future areas of research for care of PLWHA in the region.

 

External PI: Mark Siedner

Internal PI:

Coordinator: Ruth Nakku

META

Info coming here soon. Check later

R01MH054907 - Uganda AIDS Rural Treatment Outcomes Cohort (UARTO)

Back Ground

The study follows a cohort of HIV infected adults to study antiretroviral adherence, resistance and Mortality in a poor resource setting.

Perceived relationships about adherence, risk of resistance, and clinical impact of resistance drive concerns about providing HIV therapy to impoverished populations. These debates first focused on drug users and the homeless[1-5]; now the focus is on resource-constrained countries[6-8]. These debates have rarely been evidence-based and have not considered critical determinants of drug resistance such as: adherence, genomic variability of drug metabolism and transport, immune activation, disease stage at treatment initiation, and viral subtype.  Discussions regarding the risk of resistance should start with population-specific distributions of these critical variables and their relationships to drug resistance and treatment outcome.  Over the past few years, we have been extending our successful studies of these issues in the REACH cohort in a cohort of Ugandans on antiretroviral therapy. We suggest that a combined behavioral and biologic approach is essential to understand treatment outcomes in resource-poor as in resource-rich settings.

Millions of sub-Saharan Africans lost their lives to HIV/AIDS.  Sub-Saharan Africa claimed nearly 75% of worldwide HIV/AIDS related deaths by December 2001[9]. Price reductions combined with multiple initiatives have increased access to antiretroviral treatment[9].  The annual price of combination antiretroviral therapy has declined from $12,000/year to $300 per year in Uganda [9]. The Presidential Emergency Plan For AIDS (PEPFAR) initiative has treated millions of people in 11 African countries including Uganda[10]. For instance, low-cost fixed dose combination therapy is becoming the mainstay of antiretroviral therapy in resource-constrained settings. Triomune (D4T/3TC/NVP) is produced by the generic manufacturer Cipla and is available in Uganda at 27USD/month.  We suggest that the causes of HIV drug resistance in HIV therapy in sub-Saharan Africa may be fundamentally different than in the US. Failure to identify how pathways to drug resistance differ between settings runs the risk of falsely attributing drug resistance to failure of medications, failure in adherence, or both. Full characterization of the biologic and behavioral causes of resistance to generic antiretroviral therapy in sub-Saharan Africa and how it compares to the US was the main objective of our earlier study in Mbarara, Uganda (Uganda Antiretroviral Treatment Outcomes Cohort Study).  With this new study, we will expand on this work and also define a strategy that uses wireless objective adherence measurement to limit HIV RNA monitoring for detection of treatment failure.  We will additionally lay the foundation for proactive prevention, versus reactive response, to viral rebound through real-time detection of adherence lapses.

Overview
The goal of the current award is to recruit an additional 350 individuals (previously approved for a downward revision from the initial goal of 500 individuals due to administrative delays and funding reductions) to the UARTO Cohort for a total of 850 individuals (approximately 700 in active follow-up due to mortality and loss) in Uganda with the aims to 1) to quantitatively test a social capital model of adherence, 2) to characterize the biologic consequences of interrupted adherence, and 3) to use real-time wireless adherence data to build a predictive model of virologic failure in order to develop a new paradigm in therapeutic monitoring. During the year 17, our group published 16 manuscripts for a total of 33 published or accepted manuscripts in year 16-17  in leading journals, including Science, Clinical Infectious Diseases, AIDS, Archives of Psychiatry, and Journal of Acquired Immune Deficiency Syndromes. An additional 6 manuscripts are currently in review.  See below for publication list.

Revision of data collection forms

Data collection forms were created for the new study design, including social support, food insecurity, HIV related stigma, and fertility desire.  Human subject’s documents were revised to accommodate these changes and approved by all relevant institutional review boards (Mbarara University of Science and Technology, Uganda National Council on Science and Technology, Partners HealthCare, and University of California San Francisco).

Recruitment

Recruitment began on June 6, 2011.  To date, we have transitioned 396 participants from the protocols associated with the previous UARTO grants to the protocols of the current grant.  The remaining participants have not been transitioned primarily because of problems with cellular network coverage and moving out of the now 60-kilometer catchment area.  We are actively developing the capacity to work with alternative network providers and anticipate being able to transition the majority of these participants in the coming months.  We have also recruited 168 research-naïve individuals to date, for a total of 564 participants followed per the new protocols.  We have been able to readily identify new participants, although network coverage and the catchment area are also barriers to recruiting new participants.

You are here: Home Projects