A pilot study of the use of mycophenolate mofetil as a component of therapy for multidrug-resistant HIV-1 infection

被引:0
作者
Coull, JJ
Turner, D
Melby, T
Betts, MR
Lanier, R
Margolis, DM
机构
[1] Univ Texas, SW Med Ctr, Div Infect Dis, Dallas, TX 75390 USA
[2] Glaxo Wellcome Inc, Dept Virol, Res Triangle Pk, NC 27709 USA
关键词
mycophenolate mofetil; mycophenolic acid; HIV-1; antiretroviral resistance;
D O I
暂无
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mycophenolic acid (MPA) increases the activity of both abacavir (ABC) and didanosine (ddI) in vitro against wild-type and multinucleoside-resistant HIV. We treated 7 patients with diagnosed AIDS who did not respond to eight or more antiretroviral therapies in an open label pilot study with mycophenolate mofetil (MMF), ABC, ddI, amprenavir (APV), and ritonavir (RTV), with or without efavirenz (EFV). Therapy was well tolerated despite the patients' advanced disease states. No significant decline in lymphocyte or other blood counts was observed. Median HIV RNA was 5.26 log(10) copies/ml at entry, 4.53 log(10) copies/ml at 4 weeks, and 5.13 log(10) copies/ml at 16 weeks. Median CD4(+) count was 34 cells/mul at entry and 39 cells/mul at 16 weeks of therapy. CD4(+) counts increased further in five study subjects on extended therapy to 25 weeks (median 27 cells/mul at entry, 66 cells/mul at close), despite loss of virologic suppression in 4 of 5 cases. MPA can induce apoptosis in lymphocytes in vitro. However despite viral rebound, cell surface markers of apoptosis and activation declined in total CD3(+) cells and CD3(+)/CD4(+) cells twofold to foul fold in 4 of 5 adherent study subjects at 16 weeks, reaching levels comparable with those found in seronegative donors. Although low-dose MMF appears safe in late-stage HIV disease, this study did not demonstrate virologic efficacy. Higher doses of MMF may be more effective. With careful monitoring of toxicities and pharmacokinetics. MMF deserves further testing in HIV therapy.
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页码:423 / 434
页数:12
相关论文
共 39 条
[1]  
ALLISON AC, 1991, TRANSPL P, V23, P10
[2]  
ALLISON AC, 1993, ANN NY ACAD SCI, V696, P63
[3]  
Allison AC, 1996, CLIN TRANSPLANT, V10, P77
[4]  
ALLOON J, 2000, CLIN INFECT DIS, V30, P313
[5]   Pharmacokinetics and bioavailability of mycophenolate mofetil in healthy subjects after single-dose oral and intravenous administration [J].
Bullingham, R ;
Monroe, S ;
Nicholls, A ;
Hale, M .
JOURNAL OF CLINICAL PHARMACOLOGY, 1996, 36 (04) :315-324
[6]  
Bullingham RES, 1996, TRANSPLANT P, V28, P925
[7]  
CARR SF, 1993, J BIOL CHEM, V268, P27286
[8]   Effects of mycophenolic acid on human immunodeficiency virus infection in vitro and in vivo [J].
Chapuis, AG ;
Rizzardi, GP ;
D'Agostino, C ;
Attinger, A ;
Knabenhans, C ;
Fleury, S ;
Acha-Orbea, H ;
Pantaleo, G .
NATURE MEDICINE, 2000, 6 (07) :762-768
[9]   Mycophenolic acid increases apoptosis, lysosomes and lipid droplets in human lymphoid and monocytic cell lines [J].
Cohn, RG ;
Mirkovich, A ;
Dunlap, B ;
Burton, P ;
Chiu, SH ;
Eugui, E ;
Caulfield, JP .
TRANSPLANTATION, 1999, 68 (03) :411-418
[10]   Sustained CD4+ T cell response after virologic failure of protease inhibitor-based regimens in patients with human immunodeficiency virus infection [J].
Deeks, SG ;
Barbour, JD ;
Martin, JN ;
Swanson, MS ;
Grant, RM .
JOURNAL OF INFECTIOUS DISEASES, 2000, 181 (03) :946-953