Project Grant K43TW012350

VIRAL DIVERSITY AN INNOVATIVE BIOMARKER FOR REFINING ESTIMATES OF HIV INCIDENCE - PROJECT SUMMARY CANDIDATE: DR SIKHULILE MOYO IS UNWAVERINGLY COMMITTED TO AN OVERARCHING CAREER FOCUSED ON CONTRIBUTING TO ENDING THE HIV EPIDEMIC AND RELATED PUBLIC HEALTH EMERGENCIES. HE COMMITTED TO A CAREER FOCUSED ON FINDING COST-EFFECTIVE TOOLS FOR ESTIMATING THE IMPACT OF INTERVENTIONS AND TOWARDS HIV CURE RESEARCH. HE ENVISIONS HIMSELF AS A LEADER GLOBALLY, IN RESEARCH AIMED TOWARDS TRACKING AND ELIMINATING NEW HIV INFECTIONS & TOWARDS DEVELOPING AN HIV CURE, WORKING WITH RESEARCHERS, PROGRAM IMPLEMENTERS AND POLICY MAKERS FOR RAPID AND COST-EFFECTIVE EVALUATION OF INTERVENTIONS. DR MOYO'S 5-YEAR CAREER DEVELOPMENT PLAN IS FOCUSED ON THREE KEY AREAS: PHYLOGENETICS, EPIDEMIOLOGY AND BIOSTATISTICS; CROSS-SECTIONAL INCIDENCE AND IMPLEMENTATION; AND HIV CURE & CHARACTERIZATION OF EARLY FOUNDER VIRUSES, AND SARS-COV-2 GENOMICS. IN ORDER TO ACHIEVE HIS SHORT- AND MEDIUM-TERM CAREER OBJECTIVES HE SEEKS TO: A) DEVELOP ADVANCED METHODOLOGIC AND ANALYTIC SKILLS IN MOLECULAR EPIDEMIOLOGY, PHYLOGENETIC ANALYSIS AND BIOINFORMATICS; B) EXPAND LABORATORY EXPERTISE IN REAL-TIME HIGH-THROUGHPUT NEXT GENERATION SEQUENCING AND ACCURATE AND RELIABLE QUANTIFICATION OF PROVIRAL RESERVOIRS FOR ADVANCING HIV CURE STUDIES, AND C) STRENGTHEN LEADERSHIP ABILITIES PARTICULARLY IN MANAGING LARGE SCIENTIFIC PROJECTS, POPULATION-LEVEL SURVEYS, AND DIVERSE RESEARCH TEAMS WITH EXPERTISE IN DIFFERENT FIELDS, ORGANIZATIONAL LEADERSHIP AND STUDENT RESEARCH SUPERVISION. TRAINING ACTIVITIES WILL ENCOMPASS FORMAL TRAINING AND COURSEWORK, PRACTICAL APPLICATION THROUGH THE PROPOSED RESEARCH PROJECT, AND DIRECT MENTORSHIP FROM MY HIGHLY EXPERIENCED MENTORSHIP AND ADVISORY TEAM. THESE ACTIVITIES WILL DRAW ON THE STRENGTHS OF THE MENTORSHIP TEAM AND LEADING RESEARCH INSTITUTIONS WITH STRONG COLLABORATIVE TIES AND HAVE A RECORD OF MENTORING YOUNG INVESTIGATORS TO R01 AND INDEPENDENCE. RESEARCH: THE STUDY AIMS TO INTRODUCE AN INNOVATIVE APPROACH TO ESTIMATING HIV INCIDENCE, WHICH IS VERY IMPORTANT FOR NATIONAL HIV PROGRAMS / PUBLIC HEALTH, AND ALSO FOR HIV PREVENTION RESEARCH, BUT CAN BE EXPENSIVE AND CHALLENGING TO DO. THE SPECIFIC AIMS ARE: 1) TO ASSESS ADJUSTED VIRAL DIVERSITY AS A POTENTIAL BIOMARKER OF HIV INCIDENCE. 2) TO REFINE RESULTS OF SEROLOGICAL SCREENING IN SUBSETS OF TRUE- AND FALSE-RECENT CASES, AND PATIENTS WITH ESTABLISHED INFECTION (ART-NAIVE AND ON ART), BY ADJUSTED VIRAL DIVERSITY. WE WILL TEST WHETHER VIRAL DIVERSITY WITHIN THE MOST INFORMATIVE REGIONS ACROSS THE HIV-1C GENOME ADJUSTED FOR MULTIPLICITY OF TRANSMISSION, RECOMBINATION, AND LEVEL OF VIRAL REPLICATION COULD BE USED TO REFINE THE RESULTS OF SEROLOGICAL SCREENING AND IMPROVE SPECIFICITY AND SENSITIVITY. WE EXPECT THAT THE ADJUSTED VIRAL DIVERSITY WITHIN THE MOST INFORMATIVE REGIONS WILL INCREASE SPECIFICITY AND SENSITIVITY IN ESTIMATION OF HIV INCIDENCE WITHIN THE 4 SUBSETS OF INDIVIDUALS TARGETED IN THIS AIM TO =95%. ESTABLISHING A COST-EFFECTIVE ALGORITHM TO ESTIMATE INCIDENCE IS OF CRITICAL PUBLIC HEALTH IMPORTANCE IN LOW RESOURCE SETTINGS.