Use of Pharmacoepidemiology to Understand Predictors and Impact of Low-level Viremia in Persons with HIV in West Africa

利用药物流行病学了解西非艾滋病毒感染者低水平病毒血症的预测因子和影响

• 批准号: 10749658
• 负责人: Ebiere Clara HERBERTSON
• 金额: $ 6.54万
• 依托单位: NIGERIAN INSTITUTE OF MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-15 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10749658
• 关键词: Acquired Immunodeficiency Syndrome; Adherence; Adult; Africa; Africa South of the Sahara; African; Anti-Retroviral Agents; Antiretroviral drug resistance; Appointment; Award; Blood; Caring; Cells; Cessation of life; Chronic; Clinical; Clinical Pharmacology; Collection; Communicable Diseases; Country; Data; Data Analyses; Databases; Development Plans; Diphosphates; Drug Exposure; Drug resistance; Dryness; Epidemic; Epidemiologist; Epidemiology; Event; Failure; Funding; Future; Goals; Guidelines; HIV; HIV-1; HIV-2; Hair; Individual; Intake; International; Intervention; K-Series Research Career Programs; Knowledge; Learning; Literature; Measurement; Measures; Mentors; Methods; Monitor; Names; Nigeria; Outcome; Patient Self-Report; Patients; Persons; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacology; Pharmacy facility; Policies; Policy Maker; Predictive Value; Prevalence; Prospective cohort; Public Health; Records; Regimen; Reproductive Health; Research; Research Design; Research Personnel; Resistance; Resistance development; Resource-limited setting; Retrospective cohort; Scientist; Site; Source; Specialist; Spottings; Techniques; Tenofovir; Testing; Training; Treatment outcome; Urine; Viral; Viral Load result; Viral load measurement; Viral reservoir; Viremia; Virus Activation; Women' s Health; adolescent health; advanced analytics; antiretroviral therapy; biological sex; career; career development; clinical care; clinical prognosis; cohort; comorbidity; comparative; evidence base; experience; follow-up; improved; innovation; insight; longitudinal, prospective study; mathematical model; pharmacologic; pill; point of care; point of care testing; population health; prognostic value; scale up; skills; socioeconomics; statistics; study population; therapy outcome; translational physician; translational scientist; transmission process; treatment guidelines

PROJECT SUMMARY/ABSTRACT With this K43 Career Development Award, I will develop the skills necessary to reach my ultimate goal of becoming an independent investigator focused on the use of pharmacoepidemiology and experimental pharmacology to inform improved strategies for achieving sustained viral suppression in HIV treatment. Career Development Plan: My long-term career goal is to become an independently funded researcher with expertise in pharmacoepidemiology (epidemiology and clinical pharmacology) to inform improved strategies for achieving sustained viral suppression in HIV treatment. In the short-term during this K43 period, my goals are to Identify and characterize a retrospective cohort of PLWH in the IeDEA West Africa Database and determine the epidemiology and predictors of HIV-1, HIV-2 low-level viremia (LLV) in the cohort; and to determine the relationship between low-level viremia (LLV) and adherence to ART in a prospective cohort using 3 different adherence measures (pharmacy refill records (PRR), innovative urine-tenofovir POC test, and innovative TFV-DP in DBS). To attain these goals, I will be mentored during this K43 award period by a group of experienced career scientists: Dr. Cecile Lahiri, a clinician scientist whose focus is on HIV cure/eradication; Dr. Oliver Ezechi, a specialist in reproductive and population health whose focus is on the clinical impact of infectious diseases on women and adolescent health; Dr Antoine Jaquet, a clinician/epidemiologist with focus on the epidemiology of HIV and related chronic comorbidities; Dr. Igho Ofotokun an HIV translational clinician scientist with focus on women’s health and Dr. Castillo-Mancilla, a translational researcher focused on applied clinical pharmacology. For this K43 award, I will complete coursework and hands-on training in large data analysis and experimental pharmacology, I will also conduct research that exemplifies the undetectable = untransmissible (U=U) agenda with the goal of learning new ways of monitoring adherence to achieve effective HIV treatments that will stop transmission and eliminate HIV eventually. Merging my background in pharmacy practice in HIV care and infectious diseases, with advanced analytic skills, mathematical modelling, epidemiology, and experimental pharmacology from this K43, will give me the capacity for a career as an independent researcher. Research Plan: Emerging evidence suggests that persistent low-level viremia (LLV) in persons with HIV (PLWH) on antiretroviral therapy (ART) is a barrier to achieving the goal of zero transmission and eradication of HIV1-8, but not much is known about the impact of LLV on attaining the goal of viral suppression in West Africa; thus, this proposal aims to provide information vital to understand the impact of LLV in ART outcomes in West Africa. It will also be important to understand if differences exist between HIV-1 and HIV-2 treatment outcomes in the presence of LLV, since West Africa is one of the few regions in the world where HIV-2 is endemic. While literature is unanimous that sub-optimal adherence results in LLV, controversy surrounds the prognostic value of LLV for clinical outcomes. Some studies attribute the cause of LLV to drug resistance and reactivation of viral reservoirs, but other studies name these factors as consequences of LLV9-11. The ‘Undetectable=Untransmissible (U=U)’ concept is hinged on exploring pharmacologic, psycho- socio-economic, and other interventions to improve adherence and achieve undetectable viral load12,13. Individuals with LLV have been shown to be significantly less likely to subsequently achieve complete undetectable viral load. The upper limit of LLV (200-1000 copies/ml), has also been shown to be associated with virologic failure, development of resistance to ARVs, AIDS events and AIDS-related deaths1. Current WHO guidelines do not advise monitoring or treatment interventions even after repeated measurements of low-level viraemia. Consequently, patients are kept on failing ART regimens. Non-monitoring of LLV may result in an epidemic of resistance to currently used antiretrovirals and poor clinical prognosis in PLWH. Thus, it is vital to understand the predictors of LLV and its impact on PLWH, to inform improved clinical care of PLWH. Our proposed aims are: 1). To identify and characterize a cohort of from the IeDEA West Africa Database and determine the epidemiology and predictors of low-level viremia (LLV) in the cohort (for HIV-1 and HIV-2) and ii). Establish a prospective cohort of PLWH in Lagos, Nigeria, to estimate adherence to ART, using 3 different adherence measures (pharmacy refill records (PRR), innovative urine tenofovir POC test, and innovative TFV-DP in DBS). To accomplish this, We will assess the prevalence of LLV in a large West African database (IeDEA West Africa) and also determine the relationship between adherence with low-level viremia (LLV) in a cohort of 272 PLWH in Lagos, Nigeria and predict future LLV. This will be a 2-year follow-up prospective longitudinal study (3-monthly appointments for urine and DBS collection and 6- monthly viral load testing).

项目总结/文摘