Serpin drugs for treatment of HIV infection and method of use thereof

Abstract

The invention includes compositions comprising substantially purified serpin that are useful in methods for the treatment and prevention of HIV infection. The invention also includes methods for the treatment and prevention of HIV infection comprising contacting a composition of the invention with a human patient or treating HIV infection by introducing into a cell susceptible to HIV infection a DNA molecule encoding a serpin. Additionally, the invention includes antibodies and kits useful in the detection, treatment, and prevention of HIV infection.

Description

RELATED APPLICATIONS[0001] This application claims priority from U.S. Ser. No. 60 / 264,338, filed Jan. 26, 2001, which is incorporated herein by reference in its entirety.FIELD OF THE INVENTION[0002] The present invention relates to a method of antiviral treatment using a serpin that inhibits serine protease and binds heparin.BACKGROUND OF THE INVENTION[0003] The human retrovirus, human immunodeficiency virus (HIV) causes Acquired Immunodeficiency Syndrome (AIDS), an incurable disease in which the body's immune system breaks down leaving the victim vulnerable to opportunistic infections, e.g., pneumonia, and certain cancers, e.g., Karposis Sarcoma. AIDS is major global health problem. The Joint United Nations Programme on HIV / AIDS (UNAIDS) estimates that there are now over 34 million people living with HIV or AIDS worldwide, some 28.1 million of those infected individuals reside in impoverished sub-Saharan Africa. In the United States, one out of every 250 people are infected with HI...

AI Technical Summary

Benefits of technology

0009] The invention provides compositions comprising substantially purified serpin which are useful in methods for the treatment and prevention of HIV infection. The invention also includes methods for the treatment and prevention of HIV infection comprising contacting a composition of the invention with a human patient or treating HIV infection by introducing into a cell susceptible to HIV infection a DNA molecule encoding a serpin. Additionally, the invention provides antibodies and kits useful in the detection, treatment, and prevention of HIV infection.

0010] The present invention provides a method of inhibiting the infectivity of HIV by contacting an HIV virion with a composition comprising a substantially purified preparation of a serpin, or analog thereof. The composition is incubated with the virion for a period of time sufficient to inhibit the infectivity of HIV. The serpin may be selected from, but is not limited to, a group consisting of antithrombin (ATIII), protein C-inhibitor, activated protein C, plasminogen activator inhibitor, and alpha-1-antitrypsin A and may be pretreated chemically or enzymatically, e.g., elastase pretreatment. The serpin may be either bovine-originated or human-originated. In a preferred embodiment, the serpin, or analog thereof, inhibits serine protease and binds heparin. In a more preferred embodiment, a 43 kDa modified form of antithrombin III (hereinafter, mATIII) from activated CD8.sup.+ T-cell supernatants is used as an HIV inhibitory factor capable of inhibiting the replication of both R5 and X4 HIV. In a most preferred embodiment, the composition is comprised of 43 kDa ATIII (hereinafter mATIII), R-ATIII, S-ATIII, or a combination thereof.

0011] The serpin composition may be used in a method of decreasing the infectivity of HIV, if any is present, in a biological sample by contacting the biological sample with an amount of serpin sufficient to decrease the infectivity of HIV in the biological sample. In a preferred embodiment, biological samples are contacted with serpin at a concentration of at least about 2 U/ml final biological sample volume. Biological samples which may treated for HIV infection include, but are not limited to, blood, plasma, serum, semen, cervical secre

Problems solved by technology

AIDS is major global health problem.

There is still no cure for AIDS.

The persistence of latent HIV in the body, however, has been underestimated.

Such combination therapy is often only partially effective, and it is unknown how much viral suppression is required to achieve durable virologic, immunologic, and clinical benefit (Deeks, JAMA, 286: 224-6 (2001)).

Anti-HIV drugs are highly toxic and can cause serious side effects, including heart damage, kidney failure, and osteoporosis.

Long-term use of protease inhibitors has been linked to peripheral wasting accompanied by abnormal deposits of body fat.

The efficacy of current anti-HIV therapy is further limited by the complexity of regimens, pill burden, and drug-drug interactions.

Compliance with the toxic effects of antiretroviral drugs make a lifetime of combination therapy a difficult prospect and many patients cannot tolerate long-term treatment with HAART.

There is an urgent need for other antiviral therapies due to poor adherence to combination therapy regimes, which has led to the emergence of drug-resistant strains of HIV.

These CC-chemokines, however, do not account for all CAF antiviral activity released from these cells, particularly since CAF can inhibit the replication of X4 HIV strains that use CXCR4 and not CCR5 as a coreceptor.

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