Inhibition of HIV-1 infectivity by low molecular weight heparin. Results of in vitro studies and a pilot clinical trial in patients with advanced AIDS.
Several sulfated polysaccharides have been shown to have anti-HIV activity in vitro. However, many of these compounds are not suited for use in vivo because they present an increased risk of bleeding or cannot be administered chronically. We tested the anti-HIV effects of low molecular weight heparin (LMW-heparin) (Enoxaparin) in vitro using a model system of HIV infectivity because LMW-heparin can be given to patients on a long-term basis with little risk. In vitro, LMW-heparin was shown to inhibit HIV-1 production from a T cell lymphoma line (H9) and phytohemagglutinin-stimulated lymphoblasts. Inhibition of infectivity was dose dependent at concentrations achievable in vivo. We then performed a pilot clinical trial in 13 patients with advanced AIDS of 6 months of chronic, self-administered Enoxaparin given in standard prophylactic doses. CD4 counts appeared to stabilize or increase in most patients during the first 3 months of treatment, then remained stable or declined after 6 months. There was no appreciable change in serum p24 levels. There was no evidence of drug toxicity and no bleeding episodes. These findings demonstrate that a commercially available, relatively non-toxic form of LMW-heparin is a potent inhibitor of HIV-1 production in cultured cells and that it is feasible to treat patients with AIDS with LMW-heparin on a long-term basis. Definitive clinical trials of LMW-heparins and related compounds as experimental anti-viral agents in patients with HIV infection are indicated.
Howell
A L
AL
Veterans Administration Medical Center, White River Junction, VT 05009, USA.
Taylor
T H
TH
Miller
J D
JD
Groveman
D S
DS
Eccles
E H
EH
Zacharski
L R
LR
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D005260:Female; D015497:HIV-1 / Q000187:drug effects*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010865:Pilot Projects; D019233:Retreatment; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D006495:Heparin, Low-Molecular-Weight