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The following DAIDS-sponsored contract resources are available to assist investigators in the evaluation of novel anti-HIV therapies.

Biochemical Assays

A variety of virus-specific biochemical assays (e.g. , reverse transcriptase, protease, integrase) are available for the evaluation of compounds and to aid in mechanism of action studies.

In Vitro Efficacy Evaluations

Agents can be evaluated for efficacy against HIV-1 and HIV-2 in established T-cell lines and in primary human peripheral blood mononuclear cells and macrophages. These resources are not available for the screening of previously untested compounds (with the exception noted below), nor for the evaluation of multi-component natural product extracts, but instead are dedicated to confirming and extending preliminary findings of anti-HIV activity generated elsewhere.

• Potential therapeutic agents can be evaluated for cytotoxicity and for efficacy against HIV-1 and HIV-2 in several established human T-cell lines, peripheral blood mononuclear cells, and macrophages.
  
• Capabilities include evaluation against drug resistant virus isolates, studies of molecular mechanisms of action, and other specialized investigations examining a variety of viral parameters.
  
• Therapeutic agents can be evaluated either alone or in combination with other agents.
  
• Compounds with potential as topical microbicides can be evaluated in cell-free and cell-associated HIV transmission blocking assays. Limited screening of previously untested compounds for this specific task sometimes can be accommodated.

In Vivo Efficacy Evaluations

• A model utilizing HIV infection of SCID-hu mice implanted with human fetal thymus and liver tissue is available. Antiviral efficacy is demonstrated by a reduction in virus load (p24 and RNA) and protection of CD4+ cells from virus-induced depletion.
  
• Therapeutic agents can be evaluated either alone or in combination with other agents.
  
• Both anti-HIV and immune-based therapies can be evaluated.
  
• Compounds are evaluated for in vitro efficacy against the virus strains used in the model prior to initiating in vivo studies.
  
• Limited pharmacokinetic and toxicology evaluations and studies to determine optimal routes and schedules of administration can be performed.

Sample Contractor Publications

• S.M. Halliday, et al. 1996. Inhibition of human immunodeficiency virus replication by the sulfonated dye resobene. Antiviral Research 33:41-53.
  
• L. Rabin, et al. 1996. Use of standardized SCID-hu thy/liv mouse model for preclinical efficacy testing of anti-human immunodeficiency virus type 1 compounds. Antimicrob. Agents Chemother. 40:755-762.

Accessing These Resources

• For further information regarding biochemical assays and specialized in vitro efficacy evaluations please contact Dr. Roger Miller (phone: 301-496-8197; e-mail: rm42i@nih.gov).
  
• For further information regarding general in vitro efficacy evaluations please contact Dr. Steven Turk (phone: 301-435-3771; e-mail: st15m@nih.gov).
  
• For further information regarding in vivo efficacy evaluations contact Dr. Paul Black (phone: 301-402-2970; e-mail: pblack@niaid.nih.gov).