With escalating global access to HIV antiretroviral (ARV) therapy, treatment failure is inevitable and must be anticipated. Correct and early diagnosis of treatment failure is essential for cost savings, durable response to therapy and prevention of morbidity and mortality. Most HIV treatment programs in the developing world either do not have access to viral load (VL) testing, the gold-standard treatment monitoring modality, or can apply it only on a limited basis. Other monitoring technologies such as drug resistance testing are even less common for financial and infrastructure constraints. In this proposal we will develop, evaluate and implement methods to optimize monitoring of ARV therapy in resource limited settings (RLS) that have diverse VL availability. Though several recent studies have proposed and evaluated lower-cost markers as VL surrogates and strategies for selective VL use, they generally are not based on a formal, decision theoretic framework that allows discovery of strategies with optimality properties that can be expressed in terms of misclassification rate, cost, and other clinically relevant parameters. We propose to develop the statistical framework, theory and methods required to discover optimal diagnostic algorithms for monitoring treatment failure with limited or no VL availability; to use cohort data from both the US and Kenya to derive, calibrate and cross-validate the algorithms; to use extant plasma samples from patients in a PEPFAR-funded HIV care program to design and cross-validate a new diagnostic algorithm that includes implementation of pooled assays; and to develop usable software that will enable programs to design their own protocols based on the characteristics of their patient population and local capacity for viral load testing.
Effective use of antiretroviral therapy is critical for managing and preventing the spread of HIV in the developing world. This proposal develops methods that make optimal use of diagnostic tests having limited availability to monitor the effectiveness of therapy and to prompt a change in regimen when it is warranted. Successful implementation will improve patient outcomes and help to prevent the spread of treatment-resistant strains of HIV.
|Paredes, Roger; Tzou, Philip L; van Zyl, Gert et al. (2017) Collaborative update of a rule-based expert system for HIV-1 genotypic resistance test interpretation. PLoS One 12:e0181357|
|Rhee, Soo-Yon; Varghese, Vici; Holmes, Susan P et al. (2017) Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. EBioMedicine 18:225-235|
|Gregson, John; Kaleebu, Pontiano; Marconi, Vincent C et al. (2017) Occult HIV-1 drug resistance to thymidine analogues following failure of first-line tenofovir combined with a cytosine analogue and nevirapine or efavirenz in sub Saharan Africa: a retrospective multi-centre cohort study. Lancet Infect Dis 17:296-304|
|Hu, Liangyuan; Hogan, Joseph W; Mwangi, Ann W et al. (2017) Modeling the causal effect of treatment initiation time on survival: Application to HIV/TB co-infection. Biometrics :|
|Kahler, Christopher W; Liu, Tao; Cioe, Patricia A et al. (2017) Direct and Indirect Effects of Heavy Alcohol Use on Clinical Outcomes in a Longitudinal Study of HIV Patients on ART. AIDS Behav 21:1825-1835|
|Saravanan, Shanmugam; Kausalya, Bagavathi; Gomathi, Selvamurthi et al. (2017) Etravirine and Rilpivirine Drug Resistance Among HIV-1 Subtype C Infected Children Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens in South India. AIDS Res Hum Retroviruses 33:567-574|
|Liu, Tao; Hogan, Joseph W; Daniels, Michael J et al. (2017) Improved HIV-1 Viral Load Monitoring Capacity Using Pooled Testing With Marker-Assisted Deconvolution. J Acquir Immune Defic Syndr 75:580-587|
|Brooks, K; DeLong, A; Balamane, M et al. (2016) HemaSpot, a Novel Blood Storage Device for HIV-1 Drug Resistance Testing. J Clin Microbiol 54:223-5|
|Dufort, Elizabeth M; DeLong, Allison K; Mann, Marita et al. (2016) Misclassification of Antiretroviral Treatment Failure Using WHO 2006 and 2010/2013 Immunologic Criteria in HIV-Infected Children and Adolescents in Western Kenya. J Pediatric Infect Dis Soc :|
|Sempa, Joseph B; Dushoff, Jonathan; Daniels, Michael J et al. (2016) Reevaluating Cumulative HIV-1 Viral Load as a Prognostic Predictor: Predicting Opportunistic Infection Incidence and Mortality in a Ugandan Cohort. Am J Epidemiol 184:67-77|
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