Impact of Malnutrition on HIV Treatment Failure in Resource-Limited Settings

Dates

Start Date: 04/01/2009
End Date: 03/31/2013

Highly active antiretroviral therapy (HAART) has reduced morbidity and mortality in HIV-infected persons worldwide. However, early treatment failure (i.e. WHO stage 3 or 4 illnesses or death during the first 12 months of HAART) is >3-fold higher in resource limited settings (RLS) than in resource-rich settings. Early treatment failure is associated with low CD4 count, low body mass index, and anemia, but these markers are nonspecific and could reflect advanced HIV, co-infections, and/or malnutrition. The relative contribution of malnutrition to early treatment failure in RLS is unknown. Up to 40% of adults in RLS are malnourished due to protein-energy, iron or iron-deficiency anemia, or other micronutrient deficiencies, which are associated with immune dysfunction and increased morbidity and mortality. However, the significance of this malnutrition in HIV-infected persons initiating HAART in RLS is unclear. In addition to immune dysfunction, this malnutrition has been associated with impaired gut integrity, increased microbial translocation and immune activation. Recently, chronic HIV infection has also been associated with a "leaky gut" and systemic immune activation. High levels of immune activation result in impaired immune restoration with HAART and HIV disease progression. Therefore, we hypothesize that baseline malnutrition is predictive of early treatment failure among HIV-infected adults in RLS and that early treatment failure is related to the synergistic deleterious effects of HIV and malnutrition on gut mucosal integrity leading to increased systemic immune activation. To address our hypotheses, we will utilize data and cryopreserved samples collected as part of an ongoing trial conducted by the Adults AIDS Clinical Trial Group (ACTG 5175). This NIH-funded study is evaluating the efficacy of HAART among 1571 HIV-infected adults in 8 RLS countries (Africa-3, Asia-2, Americas-3) and the United States. We propose three specific aims:1) To characterize baseline micronutrient status and assess its relationship to baseline disease stage, demographics and simple-to-measure nutritional indices among treatment-nave HIV-infected adults initiating HAART; 2) To assess whether specific measures of baseline malnutrition are independent predictors of early treatment failure. 3) To determine whether malnutrition and treatment failure are associated with microbial translocation, immune activation, and reduced immune restoration. Our study has a high likelihood of success because our international team includes leaders in HIV, immunology, statistics and nutrition research. Data and specimens for our study come from a NIH-funded trial that is ongoing but has completed enrolment.

Lilongwe
Harare
Port-au-Prince
Pune, India
Johannesburg
Porto Alegre, Brazil

People

Noreen Hynes, MD MPH

Director, Geographic Medicine Center of the Division of Infectious Diseases

Joanne Katz, ScD MS,BSc

Associate Chair, Director of Academic Programs

Caitlin Kennedy, PhD MPH,BA

Co-Director, MPH concentration in Social and Behavioral Sciences in Public Health; Associate Director, Center for Qualitative...

Stefan Baral, MD MPH,MBA,MSc

Director, Key Populations Program

Yukari C. Manabe, MD

Associate Director of Global Health Research and Innovation

Robert Bollinger Jr., MD MPH

Director, Johns Hopkins Center for Clinical Global Health Education (CCGHE); Associate Director, Johns Hopkins Center for Global...
«

April 2019

»
S
M
T
W
T
F
S
·
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
·
·
·
·

Projects

Building an Enabling Environment for Vaccines in India...

This project, now in its second phase, aims to create an enabling environment for vaccines in India and contribute to...

Read More

Nutrition Innovation Lab

"Poshan", which means good nutrition in Nepali is ongoing research that involves two interlinked large-scale research studies...

Read More

Mpilonhle

Mpilonhle brings multi-dimensional services to adolescents in rural South Africa. Its objective is to reduce the very high...

Read More

Identification and Enumeration of Pathogens in Drinking...

CWH researchers are using polymerase chain reaction and mass spectrometry technologies to develop a microbial isolation and...

Read More