Antiretroviral therapy (ART) has enormous benefits for HIV-infected persons, including improved morbidity and mortality and reduced secondary transmissions. In sub-Saharan Africa, rapid scale-up of ART has allowed over four million persons to receive therapy. Maximizing treatment outcomes in these persons requires sufficient adherence and appropriate regimen selection. Viral load (VL) monitoring is one approach that has been underutilized in Africa, but has the potential to enhance long-term outcomes. Expanded monitoring may be critical to improving adherence, maintaining treatment efficacy, preserving therapeutic options, and controlling emerging resistant strains. Behaviorally, VL monitoring may be a potent motivator to improve adherence. The VL communicates important information to the patient regarding the threat of increasing severity of disease. Knowledge of an increased VL is a warning sign that may improve a patient's adherence behavior. For persons with resistance mutations, simple algorithms are needed to guide decisions and ensure prompt conversion to second-line therapy to minimize poor outcomes and transmission of resistant virus. Cost-effective interventions to maximize ART effects must consider the role of adherence and resistance in driving outcomes. Comprehensive cost-effectiveness analyses provide insight for policymakers considering implementation of monitoring strategies, addressing the consequences of early initiation of ART on a larger scale. The overall objective of this Kirschstein-NRSA individual fellowship (F30) proposal is to identify the clinical and policy implications of VL monitoring in sub-Saharan Africa, facilitating the development of sustainable, cost-effective ART monitoring to maximize treatment outcomes.
The specific aims of this proposal are: 1) To evaluate the effect of providing VL information on ART adherence;2) To develop a predictive model to identify persons with resistance from a single elevated VL;and 3) To develop a generalizable cost-effectiveness model to a) compare point-of-care, DBS, and conventional VL monitoring to current standard of care, and b) conduct optimization evaluation for design and pricing of forthcoming point-of-care tests. The proposed research includes an ancillary study of a prospective cohort study designed to examine the effect of VL information on ART adherence (Aim 1);a retrospective analysis of RCT data to improve efficiency in identifying treatment failure (Aim 2);and a generalizable cost-effectiveness analysis to inform VL monitoring policy (Aim 3). Through this research project and a carefully constructed training plan, the trainee will achieve the following fellowship goals: 1) develop advanced skills in econometric, clinical, and behavioral research methods;2) acquire clinical and translational research skills;and 3) develop professional skills necessary to foster a successful academic career.

Public Health Relevance

Maximizing the potential benefits of HIV medicine is critical to improve long-term outcomes for HIV-infected patients on treatment. Monitoring the amount of virus in an HIV patient's blood provides vital information about a person's response to therapy, but only a fraction of the four million persons on HIV treatment in sub-Saharan Africa have routine monitoring. This study will evaluate the impact of viral monitoring on adherence to HIV medicines in sub-Saharan Africa and examine the cost-effectiveness of widespread implementation to inform evidence-based HIV-therapy monitoring guidelines in sub-Saharan Africa.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30MH098731-02
Application #
8528384
Study Section
Special Emphasis Panel (ZRG1-AARR-C (22))
Program Officer
Stoff, David M
Project Start
2012-07-17
Project End
2017-07-16
Budget Start
2013-07-17
Budget End
2014-07-16
Support Year
2
Fiscal Year
2013
Total Cost
$37,314
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Rutstein, Sarah E; Siedhoff, Matthew T; Geller, Elizabeth J et al. (2016) Cost-Effectiveness of Laparoscopic Hysterectomy With Morcellation Compared With Abdominal Hysterectomy for Presumed Myomas. J Minim Invasive Gynecol 23:223-33
Rutstein, Sarah E; Hosseinipour, Mina C; Weinberger, Morris et al. (2016) Predicting resistance as indicator for need to switch from first-line antiretroviral therapy among patients with elevated viral loads: development of a risk score algorithm. BMC Infect Dis 16:280
Rutstein, S E; Golin, C E; Wheeler, S B et al. (2016) On the front line of HIV virological monitoring: barriers and facilitators from a provider perspective in resource-limited settings. AIDS Care 28:1-10
Rutstein, Sarah E; Pettifor, Audrey E; Phiri, Sam et al. (2016) Incorporating Acute HIV Screening into Routine HIV Testing at Sexually Transmitted Infection Clinics, and HIV Testing and Counseling Centers in Lilongwe, Malawi. J Acquir Immune Defic Syndr 71:272-80
Rutstein, Sarah E; Hosseinipour, Mina C; Kamwendo, Deborah et al. (2015) Dried blood spots for viral load monitoring in Malawi: feasible and effective. PLoS One 10:e0124748
Barber, Emma L; Rutstein, Sarah; Miller, William C et al. (2015) A preoperative personalized risk assessment calculator for elderly ovarian cancer patients undergoing primary cytoreductive surgery. Gynecol Oncol 139:401-6
Rutstein, Sarah E; Sellers, Christopher J; Ananworanich, Jintanat et al. (2015) The HIV treatment cascade in acutely infected people: informing global guidelines. Curr Opin HIV AIDS 10:395-402
Rosenberg, Nora E; Kamanga, Gift; Pettifor, Audrey E et al. (2014) STI patients are effective recruiters of undiagnosed cases of HIV: results of a social contact recruitment study in Malawi. J Acquir Immune Defic Syndr 65:e162-9
Rutstein, Sarah E; Kamwendo, Deborah; Lugali, Lebah et al. (2014) Measures of viral load using Abbott RealTime HIV-1 Assay on venous and fingerstick dried blood spots from provider-collected specimens in Malawian District Hospitals. J Clin Virol 60:392-8
Rutstein, Sarah E; Brown, Lillian B; Biddle, Andrea K et al. (2014) Cost-effectiveness of provider-based HIV partner notification in urban Malawi. Health Policy Plan 29:115-26

Showing the most recent 10 out of 11 publications