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PACTG 353 A Phase I Study of Safety, Pharmacokinetics, and Antiviral Activity of Combination Nelfinavir (NFV), ZDV, and 3TC in HIV-Infected Pregnant Women and Their Infants Y. BRYSON, A. STEK, M. MIRICHNICK, J. CONNOR, S. HUANG, M. HUGHES, L. MOFENSON, M. CULANE, J. SNIDOW, and M. GERSTEN. Univ. of California at Los Angeles; Univ. of Southern California, Los Angeles; Boston Univ., MA; Univ. of California, San Diego; Harvard Univ., Boston MA; NIH, Bethesda, MD; Glaxo Wellcome, Res. Triangle Park, NC; and Agouron Pharmaceuticals, La Jolla, CA In order to assess safety, pharmacokinetics (pk) and antiviral activity of nelfinavir (NFV) in combination with ZDV and 3TC in HIV infected pregnant women and their infants 10 HIV infected pregnant women (14-34 weeks gestation) were enrolled and received oral (po) NFV (750mgtid), ZDV (200mgtid), 3TC (150 mg bid), during ges and postpartum (pp) and po NFV, 3TC, and IV ZDV in labor. Infants received 6 wks of po NFV (10mg/kg tid), ZDV (2.6mg/kg tid) and 3TC (2mg/kg bid). Viral load, CD4 count, NFV pk and clinical and lab toxicities were assessed. 8 of 10 women completed the study; 1 had a therapeutic abortion, 1 had a fetal demise due to obstetrical complications. Women tolerated the Rx without significant toxicity. There was a significant decrease in maternal plasma HIV RNA levels from baseline to del and pp (med -1.8, and -2.4 log, p=0.01) and 6/8 had plasma viremia of <400 HIV RNA cp/ml at del. CD4 count and % increased from baseline to del and pp (med CD4 cells/ml 220/ 308/ 415) (mean CD4% 20,23,30) rsp. (p= 0.005). 8 infants had a med ges age of 38 wks (range 35-40wks) and all were HIV uninfected. One infant who did not receive study drugs died with clinical sepsis and pulmonary hypertension (not study related). Transient grade 2/3 decreases in Hb and/or neutrophils occurred in 7 infants, which resolved with discontinuation of ZDV. Maternal NFV Pk during pregnancy and 6 wks pp was similar. The med maternal NFV plasma levels at del was 2 mg/ml. Cord blood levels were undetectable or low in all infants. At one week of life, the med NFV levels were low (pre-dose 0.74ug/ml, Cmax 1.23 ug/ml). Combination of NFV ZDV and 3TC was well tolerated in HIV infected pregnant women and their infants and resulted in significant decreases in maternal plasma viremia and increases in CD4 cells. Pregnancy had no effect on maternal NFV pk and placental transfer of NFV was poor. The initial dose of 10mg/kg NFV used in the infant was inadequate and further study of a higher dose (40 mg/kg bid) is underway. Key Words: Combination therapy, Pediatric, Pharmacokinetics |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |