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 ave been shown to have anti-HIV activ ity in vitro. However, many of these compounds are not suited fos use in vivo because they present an increased risk oi bleeding or cannot b e administered chronically. We tested the ani-HIV effects of low molec ular weight heparin (LMW-heparin) (Enoxaparin) in vitro using a model system of HIV infectivity because LMW-heparin can be given to patients on a longterm basis with little risk. In vitro, LMW-heparin was shown to inhibit HIV-1 production from a T cell lymphoma line (H9) and phyt ohemagglutinin-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 prophylacti c doses, CD4 counts appeared to stabilize or increase in most patients during the first 3 months of treatment, then remained stable or decli ned after 6 months. There was no appreciable change in serum p24 level s. There was no evidence of drug toxicity and no bleeding episodes. Th ese findings demonstrated that a commercially available, relatively no n-toxic form of LMW-heparin is a potent inhibitor of HIV-I 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 L MW-heparins and related compounds as experimental anti-viral agents in patients with HIV infection are indicated.