How to Apply for PIF

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How to Apply for PIF?
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Specialty Lab Proposals

• 1-2 pages
• Rationale
• Design
• Possible trial integration
• Deliverables
• Timeline
• Budget
• Due Monday August 28
• Reviewed by ILSC 1st/2nd week of Sept
• To SOC/NEC

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Specialty Lab Projects
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Virology

• Use of OLA in international trials P1032, P1064
• Breast milk
• What is transmitted?
• Homogeneous vs heterogeneous
• Subtype differences
• Co-receptor
• Other characteristics
• Pathogenesis related to weaning
• In house resistance and entry assays

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Virology

• NVP resistance
• Simpler, cheaper diagnostics for infants
• Point of care tests
• Latency culture assays
• Early emergence of resistance using DBS
• Minority variant assays K65R
• Gp 41 sequencing

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Pharmacology

• Amniotic fluid, breast milk, and cervical-vaginal
  secretion PK UAB, UCSD
• DBS PK - UCSD
• Intracellular PK for NRTI (need 10ml) Colo
• Bound/unbound assays

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Pharmacology

• New ARVs
• TPV (UCSD/UAB)
• TNC-278
• Merck integrase inhibitor
• Darunavir
• CCR-5 antagonist
• Other drugs
• Anti-TB
• Anti-malaria

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Immunology

• Pathogenesis of infection process in women and
  infants
• Transmitting virus characteristics
• Correlates of protection
• What immune response do you target with a vaccine
• Immune response in women and infants
• What is baseline immune response in breastfed
  babies?
• What about continuous exposure to virus thru BM?
• Ad5 seroprevalence

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Immunology

• Mechanisms of CD4 depletion
• Immune preservation vs immune reconstitution
• Protective immunity to childhood vaccines and
  better understanding of morbidity and mortality
• Reservoirs and ongoing viral replication
• Neutralizing antibody assays develop a panel of
  infant pseudotyped viruses from our sites
• Regulatory T cells
• Innate immunity need fresh samples
• P1015 analyses
• P1049 immune responses
• Cultured ELISPOT assay
• NWCS from 326 and 230 cytokine and Ab responses
• P1047 CMI to HPV vaccine
• Rotavirus vaccine study
• Substudies to vaccine studies

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Immunology

• Apoptosis and tat different subtypes
• HIV and down regulation of autophagy
• Improved TREC assays in some studies already
• Cytokine and chemokine assays
• Receptor-receptor interactions
• Gut immunology stool specimens to look for
  depletion and viral replication
• Probiotics

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Microbiology

• Diarrheal diseases
• Pneumonia
• Malaria speciation, resistance
• TB detection, drug resistance
• HPV
• PCP

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Genomics

• Role of host genetics in
• MTCT (incl breastfeeding, NVP resistance)
• Disease progression
• Pharmacogenetics
• Pharmacokinetics
• Risk for OIs
• Neurocognitive impairment
• Response to vaccines

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DNA Repository

• Process, store and ship DNA (pellets or DBS vs
  DNA?) from specimens from high interest studies
• Meet all OHRP guidelines
• Mechanism for access to specimens including
  documentation of IRB approval by testing lab
• Develop protocols that include genetic analyses
• Single large study
• Targeted studies
• Combination of both

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Cross Disciplines

• DBS
• PK, virology, genomics, immunology
• Neutralizing antibody assays- breast milk may be
  a problem
• Pharmacogenomics

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Cross Networks

• Minority variant assays - AACTG
• DBS HVTN, HPTN
• PK assays AACTG, MTN
• Immunology HVTN, CHAVI, IAVI, VRC, Gates, etc
• ELISPOT
• Neutralizing antibody assay
• Regional vaccine immunology labs -HVTN