This Developmental Pharmacology Research application is composed of two component parts: 1) PK/PD response surface for antiretrovirals and 2) intracellular dideoxynucleoside analogues in target cells. Dr. Sheiner's section proposes three activities: (i) Simulation studies of pharmacokinetic (PK) monitoring of antiviral therapy. Cost effective use of (clinical) PK measurements requires that errors in timing of dose or blood sample acquisition not result in a """"""""noisier"""""""" relationship between """"""""exposure"""""""" and PK observation than between exposure and dose. This has not been adequately investigated for anti-HIV drugs. (ii) Development of population-based response-surface methods for interpreting PK and Pharmacodynamics (PD) of anti-HIV (especially combination) drug trials. Modern methods of population analysis and PK/PD modeling may allow more efficient use of data, dosage optimization, and improvements in trial designs. (iii) Collaboration with other ACTG investigators on population analysis of PK/PD data. Altered response in special groups (e.g. blacks, women, etc.) may depend on PK differences that can be discovered by analysis of PK data gathered during efficacy trials. Dr. Gambertoglio's section of the proposal will focus on two activities: (i) Develop methods for measurement of intracellular concentrations of zidovudine and its monophosphate, diphosphate and active triphosphate and lymphocytes and determine what relationship exists with extracellular plasma zidovudine concentrations. (ii) Determine the effect of granulocyte-macrophage colony stimulating factor (GM-CSF) on intracellular concentrations of zidovudine and formation of the active triphosphate anabolite in peripheral blood monocytes/macrophages from patients with HIV infection receiving both drugs.

Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
1996
Total Cost
Indirect Cost
Kempen, John H; Sugar, Elizabeth A; Varma, Rohit et al. (2014) Risk of cataract among subjects with acquired immune deficiency syndrome free of ocular opportunistic infections. Ophthalmology 121:2317-24
Kozak, Igor; Vaidya, Vijay; Van Natta, Mark L et al. (2014) The prevalence and incidence of epiretinal membranes in eyes with inactive extramacular CMV retinitis. Invest Ophthalmol Vis Sci 55:4304-12
Amorosa, Valerianna K; Luetkemeyer, Anne; Kang, Minhee et al. (2013) Addition of nitazoxanide to PEG-IFN and ribavirin to improve HCV treatment response in HIV-1 and HCV genotype 1 coinfected persons naïve to HCV therapy: results of the ACTG A5269 trial. HIV Clin Trials 14:274-83
Jabs, Douglas A; Ahuja, Alka; Van Natta, Mark et al. (2013) Comparison of treatment regimens for cytomegalovirus retinitis in patients with AIDS in the era of highly active antiretroviral therapy. Ophthalmology 120:1262-70
Gangaputra, Sapna; Drye, Lea; Vaidya, Vijay et al. (2013) Non-cytomegalovirus ocular opportunistic infections in patients with acquired immunodeficiency syndrome. Am J Ophthalmol 155:206-212.e5
Gangaputra, Sapna; Kalyani, Partho S; Fawzi, Amani A et al. (2012) Retinal vessel caliber among people with acquired immunodeficiency syndrome: relationships with disease-associated factors and mortality. Am J Ophthalmol 153:434-444.e1
Kalyani, Partho S; Fawzi, Amani A; Gangaputra, Sapna et al. (2012) Retinal vessel caliber among people with acquired immunodeficiency syndrome: relationships with visual function. Am J Ophthalmol 153:428-433.e1
Kempen, John H; Sugar, Elizabeth A; Lyon, Alice T et al. (2012) Risk of cataract in persons with cytomegalovirus retinitis and the acquired immune deficiency syndrome. Ophthalmology 119:2343-50
Sezgin, Efe; van Natta, Mark L; Ahuja, Alka et al. (2011) Association of host genetic risk factors with the course of cytomegalovirus retinitis in patients infected with human immunodeficiency virus. Am J Ophthalmol 151:999-1006.e4
Puhan, Milo A; Ahuja, Alka; Van Natta, Mark L et al. (2011) Interviewer versus self-administered health-related quality of life questionnaires - does it matter? Health Qual Life Outcomes 9:30

Showing the most recent 10 out of 82 publications