Peter T Frame

Pneumocystis carinii Pc remains a major cause of morbidity andoccasional mortality in HIV infected patients. Bronchoscopy withbronchoalveolar lavage BAL allows for studying the lung in symptomaticpatients. With lavage, the diagnosis of Pc is usually made. Inaddition, lavage provides a source of Pc specimen to be studied. Weplan to continue our policy of collecting and handling BAL specimens ina standardized fashion at our institution. This standard analysis hasprovided useful clinical information, and has been used to providesamples for research use. The proposed research will examine BALsamples in three areas: organism analysis including quantitation, viability, and molecular karyotyping, immunologic identificationevaluation of monoclonal and polyclonalantibodies against variousantigens of rat and human Pc, and immune response as assessed by theinflammatory nature of the lavage cells as well as systemic antibodies. These techniques, along with the clinical information obtained on thesepatients will allow to study these hypotheses: 1 BAL remains usefulin diagnosing Pc pneumonia in HIV infected patients; 2 Follow-up BALis useful in assessing response to therapy; 3 Analysis of local andsystemic immune response to Pc pneumonia provides diagnostic andprognostic information; 4 Recurrent Pc infection representsreinfection rather than reactivation of latent organisms; 5 Thecharacterization of the Pc isolates will predict virulence andantimicrobial sensitivity; 6 Characteristics of Pc isolates vary withgeographical and sociologic conditions.Plasma concentrations of zidovudine ZDV and other nucleoside analogdrugs have shown little correlation with clinical events. Because theymust be metabolized intracellularly to elicit a biological effect, intracellular concentrations of the phosphorylatedmetabolites ofnucleoside analogs might correlate with drug effects. The studiesherein propose to use a sensitive and reproducible radioimmunoassaymethod, suitable for routine monitoring of total phosphorylated ZDV inperipheral blood mononuclear cells PBMC, to define thepharmacokinetics of ZDV phosphorylation in PBMC from patients receivingZDV, and examine the relation between intracellular concentrations andcertain prognostic indicators of HIV disease. This includes a two armedstudy with a total of 40 patients. One arm will examine the rate of ZDVphosphorylation in ZDV-naive patients and the length of time required toreach steady-state concentrations while on standard dose ZDV 500mgday. The second arm will investigate the dose-response in patientson an escalating dose regimen. A two-year study combined both patientgroups, and investigates the effects of long-term ZDV therapy onintracellular pharmacokinetics, including clearance and phosphorylationupon re-introduction of drug. Concurrent measurements of the prognosticindicators will be made. This study may suggest that longer dosingintervals andor lower doses of ZDV are adequate to maintainintracellular concentrations. Additionally, an HPLCRIA method will bevalidated and used to determine pharmacokineticsof ZDV triphosphate this 10 patient study will be nested into the larger study because ofpractical limitations of the method, but the same parameters will beinvestigated. Similarly, a pilot study investigating thepharmacokinetic differences of ZDV phosphorylation in patients oncombination ZDVdideoxycytidine will also be performed in an effort toinvestigate synergistic efficacy. This study will be nested in sitepatients enrolled in ACTG 155. Finally, the development of new assaysfor measurement of intracellular nucleoside analog metabolites isplanned. Eventually, modifications of dose to maximize effect might bepossible through routine intracellular monitoring of nucleoside analogmetabolites.The goals of the Pediatric ACTU Subunit of the University of CincinnatiAdult ACTU are as follows: 1 study therapeutic drugs and treatmentstrategies in perinatal infection with the specific aim of preventingtransmi

Investigators:Frame, Peter 07-01-2002 -09-30-2002 Health Resources and Services Administration Great Lakes to Tennessee Valley AIDS Education & Training Center Role:PI $32,400.00 Closed Level:Federal

Investigators:Frame, Peter 10-01-2002 -06-30-2003 Health Resources and Services Administration Great Lakes to Tennessee Valley AIDS Education & Training Center Role:PI $38,787.00 Closed Level:Federal

Investigators:Frame, Peter 03-01-2003 -06-30-2003 Health Resources and Services Administration Pennsylvania/MidAtlantic AIDS Education & Training Center (AETC) Role:PI $37,038.00 Closed Level:Federal

Grant: #2-N01-CP-81017-02-A0-S0-E0 Investigators:Frame, Peter 12-09-1998 -02-08-2000 National Cancer Institute AIDS Related Cancer Cohort Study #5988-821 Role:PI $52,250.00 Closed Level:Federal

Grant: #RTI 5988-821-01-A0-S0-E0 Investigators:Frame, Peter 09-01-1997 -08-31-1999 Research Triangle Institute AIDS Related Cancer Cohort Study #5988-821 Role:PI $38,750.00 Closed Level:Private Non-Profit

Grant: #CHN-01-09-A0-S0-E0 Investigators:Frame, Peter 01-01-1998 -12-31-2000 Bureau of Primary Health Care Prevention and Primary Health Services HIV Infection and/or AIDS Role:PI $456,733.78 Closed Level:Federal

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