HIV Clinical Pharmacology and Implementation Research in YRG CARE, India S. Saravanan, PhD 4 th Annual Workshop on

YRGCARE Medical Center is a 20- bed clinical facility with an intensive care unit, an outpatient unit, counseling and nutritional services, a subsidized pharmacy with adherence program. YRGCARE has a well developed Hospital Management System (HMS) database which integrates the clinic, laboratory and pharmacy. The Natural History Database (NHD), a subset of the HMS, provides valuable insight about the progression of HIV disease in India. YR Gaitonde Centre for AIDS Research and Education (YRGCARE) in Chennai, India is a non-profit medical and research institution. Established in 1993, the activities are organized around four core areas - Education, Care & Support, Research and Training. Background

YRG CARE Infectious Diseases Laboratory is quality assured by the College of American Pathologists (USA) and UK-NEQAS (UK), quality controlled by the Johns Hopkins University, USA and Virology Quality Assurance Program, Rush, USA YRG CARE (Site ID: & Lab ID: 316) is one of the international multi site of NIH multi-centric clinical trials sponsored by DAIDS through HPTN and ACTG programs from the year YRG CARE performs all the protocol assays, which include HIV-RNA & DNA PCR, CD4, blood chemistries, CBC, infectious diseases serology, clinical pathology and diagnosis of opportunistic infections including TB.

Affiliated to the University of Madras, Chennai for conducting Ph.D. degree program in Medical Microbiology. Biochemistry, Clinical Pathology, HIV Genotyping Lab, Hematology & Immunology, Microbiology, Serology, Virology & Molecular biology Accredited by National Accreditation Board for Testing and Calibration Laboratories (NABL, New Delhi) and the NABL accreditation is assessed in accordance with ISO 15189:2007 standards for medical laboratories. YRG CARE Laboratory is the very first HIV specialty laboratory got accredited by the NABL in India.

Objectives Development and validation of analytical procedures forthe quantification of antiretroviral agents. Participation in the DAIDS HIV Clinical Pharmacology Quality Assurance (CPQA) program. Implementation of DAIDS mandated requirements eventually to become Pharmacology Specialty Laboratory to support the scientific agenda of the DAIDS. HIV Clinical Pharmacology and Implementation

Translational Pharmacology Research Core NYS Center of Excellence in Bioinformatics and Life Sciences 701 Ellicott Street Buffalo, NY Pharmacology lab visit

Orientation about Alliance e /PDA Preventive maintenance Priming the Solvent Management System Dry Priming & Wet Priming Priming the Needle-Wash Pump Priming the Plunger Seal-Wash Pump Purging the Injector

Priming Fixing column Conditioning the Column

Sample preparation Mobile phase preparation Loading Carousels Empower software & utility

1. Configure system 2. Creating instrument method 3. Creating method set 4. Processing method 5. Reporting format

NVP estimation using Xanthine as IS Reverse Phase HPLC Liquid Extraction – Ethyl Acetate Mobile Phase: KH2PO4:ACN(90:10)

Calibration Curve

Peak Summary Peak Summary Report Retention Time: 6.75 mins for Xanthine; 8.02 mins for NVP

Estimation of Stavudine and Lamivudine using Didanosine as the Internal Standard Solid Phase Extraction Method Oasis HLB cartridges 3TC : 8.30 mins DDI(IS): mins D4T : mins

Current Status Alliance e2695 /2998 PDA – Installed Completed Instrumentation & Application training Process of NIH Fogarty Application: UB AIDS Clinical Trials Group PSL & YRG CARE Planning Grant for Fogarty HIV Research Training Program for Low- and Middle- Income Country Institutions (D71)

Upon the completion of technology transfer from UB, the assays will be standardized and will complete the CPQA panels. Eventually the PSL would support the scientific agenda of the ACTG/HPTN. The established PSL would carry out protocol-required pharmacologic assays - analysis of PK/PD data from both primary protocols and sub- studies. Develop concept proposal and integrate pharmacologic research questions with the ACTG/HPTN scientific agenda. Anticipated contribution of establishing Clinical Pharmacology at YRG CARE:

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