The overall goal of this research proposal is to study the emergence of HIV drug resistance (HIVDR) in a population beginning first-line antiretroviral therapy (ART) and assess potentially related factors at one ART roll-out site in Hanoi, Vietnam: The National Institute of Infection and Tropical Disease (NIITD). Importantly, the project will lead to the development of new allele-specific PCR assays for the detection of important HIVDR mutations present at low frequency prior to the start of ART and will develop a powerful model to define the virologic impact of low level HIVDR mutations in individuals starting first-line ART. To achieve these goals, I will use a newly established cohort of HIV infected adults in Hanoi, Vietnam. In 2005, my mentor Dr. Christine Wanke of Tufts University along with her collaborator Dr. Nguyen Due Hien from the National Institute of Infection and Tropical Disease (NIITD) in Hanoi, Vietnam established a cohort of 300 HIV-1 seropositive individuals. Dr. Wanke's project, entitled """"""""Nutritional Status of HIV-positive and HIV- negative drug users (IDUs) in Hanoi, Vietnam"""""""" [Center for Metabolic Research on HIV and Drug Use;NIH grant 1 P30 DA 13868] is a prospective cohort study that will follow subjects over a period of two years with study visits at six-month intervals. My proposal provides a critically important translational virology component to the existing study and is embedded in the parent study. The study will provide new and important insight into the emergence of HIVDR and will serve to identify factors associated with the emergence of HIVDR at this Vietnamese ART delivery site. Although the results will be site-specific, factors identified to be associated with the emergence of HIVDR at this site may be qualitatively generalized to other ART delivery sites. Additionally, this project will lead to the development of new allele-specific PCR assays for the detection of low-frequency HIVDR mutations and will develop a model to study the impact of these mutations on viral suppression after 12-months of first line ART. The results of this model are anticipated to be of importance in advancing the understanding of the development of HIVDR and in understanding the impact of low-frequency HIVDR mutations present at baseline on successful treatment outcomes. Importantly, the model developed as part of this study may be applied to other populations both in developed and resource-limited countries to understand the impact of low-frequency HIVDR mutations on successful ART treatment outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
3K23AI074423-03S1
Application #
7922996
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
Fitzgibbon, Joseph E
Project Start
2009-09-22
Project End
2011-08-31
Budget Start
2009-09-22
Budget End
2011-08-31
Support Year
3
Fiscal Year
2009
Total Cost
$50,000
Indirect Cost
Name
Tufts University
Department
Type
DUNS #
079532263
City
Boston
State
MA
Country
United States
Zip Code
02111
Hong, Steven Y; Jonas, Anna; DeKlerk, Michael et al. (2015) Population-based surveillance of HIV drug resistance emerging on treatment and associated factors at sentinel antiretroviral therapy sites in Namibia. J Acquir Immune Defic Syndr 68:463-71
Sluis-Cremer, Nicolas; Jordan, Michael R; Huber, Kelly et al. (2014) E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. Antiviral Res 107:31-4
Hong, Steven Y; Fanelli, Theresa J; Jonas, Anna et al. (2014) Household food insecurity associated with antiretroviral therapy adherence among HIV-infected patients in Windhoek, Namibia. J Acquir Immune Defic Syndr 67:e115-22
Jonas, Anna; Sumbi, Victor; Mwinga, Samson et al. (2014) HIV drug resistance early warning indicators in namibia with updated World Health Organization guidance. PLoS One 9:e100539
Nichols, Brooke E; Sigaloff, Kim C E; Kityo, Cissy et al. (2014) Averted HIV infections due to expanded antiretroviral treatment eligibility offsets risk of transmitted drug resistance: a modeling study. AIDS 28:73-83
Jordan, M R; Obeng-Aduasare, Y; Sheehan, H et al. (2014) Correlates of non-adherence to antiretroviral therapy in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam. Int J STD AIDS 25:662-668
Andersson, Emmi; Shao, Wei; Bontell, Irene et al. (2013) Evaluation of sequence ambiguities of the HIV-1 pol gene as a method to identify recent HIV-1 infection in transmitted drug resistance surveys. Infect Genet Evol 18:125-31
McMahon, James H; Elliott, Julian H; Hong, Steven Y et al. (2013) Effects of physical tracing on estimates of loss to follow-up, mortality and retention in low and middle income country antiretroviral therapy programs: a systematic review. PLoS One 8:e56047
McMahon, James H; Manoharan, Anand; Wanke, Christine A et al. (2013) Pharmacy and self-report adherence measures to predict virological outcomes for patients on free antiretroviral therapy in Tamil Nadu, India. AIDS Behav 17:2253-9
Jordan, Michael R; Winsett, Julie; Tiro, Aileen et al. (2013) HIV Drug Resistance Profiles and Clinical Outcomes in Patients with Viremia Maintained at Very Low Levels. World J AIDS 3:71-78

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