The development and evaluation of effective therapies for HIV-1 infection is limited by the long time interval to clinical endpoints and the relatively poor correlation or absence of virological markers for disease progression. Scientific investigation and treatment of infants with potentially toxic antiviral drugs are complicated by the fact that there is a lack of reliable methods to diagnose HIV-1 infection within the first several months of life due to passive transfer of maternal HIV-1 antibodies. Virological assays are needed that can 1) quantify HIV-1 load in the blood of patients on experimental antiviral drug therapies thereby providing an earlier assessment of drug efficacy and 2) accurately detect HIV-1 infection in infants. The proposed study has the following aims: 1. Standardize and validate the sensitivity, specificity, and reproducibility of commercial polymerase chain reaction (PCR) assays for the nonisotopic detection of HIV-1 sequences. 2. Correlate quantitative changes in HIV-1 proviral DNA and cell free HIV-1 RNA levels in plasma, as measured by PCR, with other virological assays, CD4 counts, clinical stage of disease, and clinical outcomes in patients on ACTG protocols. 3. Develop and evaluate specimen processing procedures and HIV-1 PCR assays for the nonisotopic detection of HIV-1 proviral DNA sequences in peripheral blood mononuclear cells (PBMC), cord blood mononuclear cells (CBMC) and dried blood spots of newborns of HIV-1 seropositive mothers. In order to achieve these aims, blood specimens from HIV-1 seropositive adults and newborns will be collected from one or several ACTU sites, and processed prospectively for HIV-1 PCR detection and quantitative endpoint dilution assays. HIV-1 PCR batch testing will be performed using the Perkin-Elmer/Gen-Probe HIV-1 PCR detection assays and/or the Roche HIV-1 PCR detection assay. After the initial evaluation of HIV-1 PCR sensitivity and specificity, the ability of qualitative and quantitative HIV-1 PCR to correlate with clinical outcome, CD4 counts, and other virological assays (HIV-1 culture, serum p24 antigen levels), will be evaluated prospectively within specific pediatric and adult ACTG protocols.

Project Start
1998-01-01
Project End
1998-12-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
11
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
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