Our group has recently reported a mean reduction in viral load of 2.1 logs in our series of 20 patients treated with the protease inhibitor ritonavir (ABT-538) in a dose range of 600 mg to 1200 mg daily. Durability of response appears to be dose related. Data recently presented by others were equally encouraging, with the most durable responses seen in the patients treated with 600 mg BID. Therefore, we have chosen the most active drugs available -- zidovudine (AZT) and lamivudine (3TC) and ritonavir -- to treat the acutely infected person, the host with the least genetic diversity, and therefore the one least likely to harbor multiply resistant viruses. We propose that achieving a four-to-five-log reduction in viral load, which would then be followed by the appearance of the immune response, should dramatically alter the natural history of HIV-1 infection. Ritonavir (ABT-538) will be administered at 300 mg orally BID on Day 1, 400 mg orally BID on days 2 and 3, 500 mg orally BID on day 4, and 600 mg orally BID on Day 5 and subsequently, provided the patient can tolerate the dose escalation without severe nausea and/or vomiting. If needed, the dose escalations may be delayed. AZT will be administered at 200 mg orally TID, and 3TC at 150 mg orally BID. Virologic studies will include plasma RNA determinations, quantitative plasma and cell culture for HIV-1, and quantitative DNA PCR on patient PBMC. In addition, frequent monitoring of T-cell subsets will be performed to assess the viral load in the cellular compartment using flow cytometric techniques. Pharmacokinetic studies will also be performed.

Project Start
2000-12-01
Project End
2001-11-30
Budget Start
Budget End
Support Year
37
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Rockefeller University
Department
Type
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Bagdade, John D; Jilma, Bernd; Hudgins, Lisa C et al. (2018) LpA-II:B:C:D:E: a new immunochemically-defined acute phase lipoprotein in humans. Lipids Health Dis 17:127
Butelman, Eduardo Roque; Bacciardi, Silvia; Maremmani, Angelo Giovanni Icro et al. (2017) Can a rapid measure of self-exposure to drugs of abuse provide dimensional information on depression comorbidity? Am J Addict 26:632-639
Ansar, Muhammad; Raza, Syed Irfan; Lee, Kwanghyuk et al. (2015) A homozygous missense variant in type I keratin KRT25 causes autosomal recessive woolly hair. J Med Genet 52:676-80
Rosenbaum, Michael; Leibel, Rudolph L (2014) 20 years of leptin: role of leptin in energy homeostasis in humans. J Endocrinol 223:T83-96
Ohmatsu, Hanako; Humme, Daniel; Gulati, Nicholas et al. (2014) IL32 is progressively expressed in mycosis fungoides independent of helper T-cell 2 and helper T-cell 9 polarization. Cancer Immunol Res 2:890-900
Alemán, José O; Eusebi, Leonardo H; Ricciardiello, Luigi et al. (2014) Mechanisms of obesity-induced gastrointestinal neoplasia. Gastroenterology 146:357-373
Barbuto, Scott; Idoyaga, Juliana; Vila-Perelló, Miquel et al. (2013) Induction of innate and adaptive immunity by delivery of poly dA:dT to dendritic cells. Nat Chem Biol 9:250-6
Butelman, Eduardo R; Yuferov, Vadim; Kreek, Mary Jeanne (2012) ?-opioid receptor/dynorphin system: genetic and pharmacotherapeutic implications for addiction. Trends Neurosci 35:587-96
Guo, Xiuyang; Dhodapkar, Kavita M (2012) Central and overlapping role of Cathepsin B and inflammasome adaptor ASC in antigen presenting function of human dendritic cells. Hum Immunol 73:871-8
Dustin, Lynn B; Charles, Edgar D (2012) Primary, post-primary and non-specific immunoglobulin M responses in HCV infection. Antivir Ther 17:1449-52

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