NOVEL USE OF VITAMIN D COMPOUNDS TO INHIBIT REPLICATION OF THE AIDS VIRUS

Abstract: A novel use for the Vitamin D compound 1 alpha , 25-dihydroxycholecalciferol, and its related and derived analogs, to treat human acquired immunodeficiency syndrome, AIDS, inasmuch as these agents inhibit the replication in human cells of HIV, the human immunodeficiency virus that causes the acquired immunodeficiency syndrome, AIDS.

Description: NOVEL USE OP VITAMIN D COMPOUNDS TO INHIBIT REPLICATION OF THE AIDS VIRUS Background of the Invention The present invention relates to vitamin D compounds and more particularly to the use of vitamin D compounds to treat acquired immune deficiency syndrome (AIDS) inasmuch as they inhibit replication of the acquired immune deficiency syndrome (AIDS) virus. The effects of Vitamin D compounds on the immune system have only recently been recognized. Rigby, Immunology Today. Vol. 9, pages 54-57, 1988 and Manolagas et al Annals of Internal Medicine, Vol. 100, pages 144- 146, 1984. This group of compounds is best recognized for their use in disorders of calcium and skeletal metabolism. Manolagas et al, Annals of Internal Medicine. Vol. 100, pages 144-146, 1984 and Manolagas et al, Journal of Clinical Endocrinology and Metabolism. Vol. 63, pages 394-400, 1986. The active Vitamin D metabolite, lα,25-dihydroxycholecalciferol (1,25DHCC) supports immune function in many in vitro systems. Manolagas et al, Annals of Internal Medicine. Vol. 100, pages 144-146, 1984 and Prowedini et al, Bone. Vol. 7, pages 23-28, 1986. Its actions are pleiotropic, involving most types of immune cells and many of their immunoregulatory cytokines. Rigby, Immunology Today f Vol. 9, pages 54-57, 1988 and Prowedini et al, Bone. Vol. 7, pages 23-28, 1986. One action of 1,25DHCC is to promote the differentiation of monocytes to macrophages and, thus, increase their activity as effector cells of the immune system. Prowedini et al, Bone. Vol. 7, pages 23- 28, 1986. Other analogs of 1,25DHCC have similar effects. Zhou et al, Blood. Vol. 74, pages 82-93, 1989. Monocytes and macrophages constitute a reservoir for infection and are important participants in the development of human immunodeficiency virus (HIV) infection. Pauza, Cellular Immunology. Vol. 122, pages 414-424, 1988 and Pauza et al, Journal of Virology, Vol. 62, pages 3558-3564, 1988. Accordingly, a series of Vitamin D compounds should be evaluated for their effects on this virus in a human monocyte/macrophage cell line, the U937 cell line. This line responds to the pro- differentiation effects of certain Vitamin D metabolites and provides a human model for HIV infection. Pauza et al, Journal of Virology. Vol. 62, pages 3558-3564, 1988. Summary of the Invention The effects of Vitamin D compounds on the replication of human immunodeficiency virus (HIV) in human cells are described. The physiologically active metabolites, lα,25-dihydroxycholecalciferol (l,25DHCC), and two of its analogs, lα,25-dihydroxy-24,24- difluorocholecalciferol (1,25DHDFCC) and lα,25-dihydroxy- 26,27-hexadeuterocholecalciferol (1,25 DHHDCC) , inhibited viral replication in a dose-dependent manner. This action was accompanied by a pro-differentiation effect of the compounds on the phenotype and growth of the cells. The results indicate that these vitamin D compounds as well as others having cellular differentiation activity can be useful in treating the acquired immune deficiency syndrome (AIDS) . Accordingly, compositions containing one or more three vitamin D compounds having cell differentiation activity, preferably selected from the group consisting of lα-hydroxyvitamin D homolog compounds, 19-nor-vitamin D compounds and secosterol compounds, together with a suitable carrier useful in the treatment of human immunodeficiency virus infection and acquired immune deficiency syndrome (AIDS) are described. The treatment may be topical, oral or parenteral. Methods of employing the compositions are also disclosed. The compounds are present in the composition in an amount from about 0.01 μg/gm to about 100 μg/gm of the composition, and may be administered orally or parenterally in dosages of from about 0.01 μg/day to about 100 μg/day. In one aspect of the invention, compositions containing one or more side chain unsaturated lα- hydroxyvitamin D homolog compounds for the treatment of human immunodeficiency virus infection and acquired immune deficiency syndrome (AIDS) are provided. Methods employing these compositions are also provided. In another aspect of the invention, compositions containing one or more side chain saturated lα-hydroxyvitamin D homolog compounds for the treatment of human immunodeficiency virus infection and acquired immune deficiency syndrome (AIDS) are provided. Methods employing these compositions are also provided. In still another aspect of the invention, compositions containing one or more 19-nor-vitamin D compounds for the treatment of human immunodeficiency virus and acquired immune deficiency syndrome (AIDS) are provided. Methods employing these compositions are also provided. In yet another aspect of the invention, compositions containing one or more secosterol compounds for the treatment of human immunodeficiency virus and acquired immune deficiency syndrome (AIDS) are provided. Methods employing these compositions are also provided. The compounds disclosed herein unexpectedly provide highly effective treatments without producing unwanted systemic or local side effects. Brief Description of the Drawings Fig. 1 is a graph of reverse transcriptase activity of HIV infected U937 cells versus time for three different concentrations of 1,25-dihydroxyvitamin D 3 (1,25 DHCC) ; Fig. 2 is a graph of percent inhibition of HIV replication in U937 cells versus concentrations for six different vitamin D compounds; Fig. 3 is a graph of percent inhibition of HIV replication in U937 cells and percent cellular differentiation versus concentrations for three different vitamin D compounds; Fig. 4 illustrates hybridization analysis of viral RNA in vitamin D 3 treated U937 cells; and Fig. 5 is a graph of percent cellular differentiation versus concentration for l,25-(OH) 2 D 3 and three of its homologs. Fig. 6 illustrates various structures of the vitamin D metabolites and analogs tested. Fig. 7 illustrates the ability of OH analogs to induce HL-60 cell differentiation as assayed by nitroblue tetrazolium reduction. Fig. 8 illustrates the induction of phagocytic activity in HL-60 cells by a series of 25-OH- D 3 and 25-OH-D 2 metabolites and analogs. Fig. 9 illustrates the effect of side chain elongation and/or truncation and 5,6-isomerization on the ability of the l,25-(OH) 2 D 3 analog to induce nonspecific acid esterase activity in HL-60 cells. Fig. 10 illustrates the activity of short chain and primary alcohol analogs of l,25-(OH) 2 D 3 in inducing NBT reducing activity in HL-60 cells after a 4- day incubation. Fig. 11 illustrates the nonspecific acid esterase activity induced by l,24R,25-(OH) 3 D 3 and 1,25- (OH) 2 D 2 in HL-60 cells. Detailed Description of the Invention The following analogs of Vitamin D 3 (Myelodysplastic syndromes. Uchino et al, eds, Elsevier, pp. 133-138, 1988) were evaluated for their effect on HIV replication in infected U937 cell cultures. A: 1,25- dihydroxycholecalciferol (1,25DHCC) , B: 1,25-dihydroxy- 24,24 difluorocholecalciferol (1,25DHFCC), C: 1,25- dihydroxy-26,27-hexadeuterocholecalciferol (1,25 DHHDCC) , D: 25-hydroxycholecalciferol (25HCC) , E: 24R,25- dihydroxycholecalciferol (24R,25DHCC) , and F: 25S,26- dihydroxycholecalciferol (25S,25DHCC) . Cell free supernates were assayed for reverse transcriptase activity as a measure of virus replication. Figure 1 illustrates that 1,25-dihydroxycholecalciferol (1,25DHCC) inhibits HIV-1 replication in U937 cells. Growing U937 cells were infected with the LAV1 strain of HIV-l at a multiplicity of infection of 1.0 tissue culture infectious doses per cell as described previously in Pauza, Journal of Virology, Vol. 62, pages 3558-3564, 1988. After 2.5 hours exposure to HIV, the cells were washed to remove extracellular virus and then cultured in RPMI-1640 medium supplemented with 10% heat-inactivated fetal bovine serum and 1,25DHCC. Under these conditions of infection, approximately 70% of the cells were immunofluorescence-positive for viral gpl20 or p24 on day 3 post-infection in the absence of 1,25DHCC. Samples were removed after various intervals post-infection and the cell-free reverse transcriptase activity was determined as described in Pauza, Journal of Virology. Vol. 622, pages 3558-3564, 1988. After sampling on day 2, the cultures were supplemented with an equal volume of medium containing an appropriate concentration of 1,25DHCC. The filled circles represent data for untreated, control infections. Open circles correspond to 10 "10 M, filled triangles to lO "8 ^! and open triangles to 10 " °M 1,25DHCC respectively. These results represent the average of five independent determinations. As shown in Fig. 1, l,25DHCC inhibited viral replication at all doses tested. The effect was dose dependent and curves representing the time course of virus production shifted to the right (Figure 1) . At 10 * 9 M drug concentration, the peak of virus production was observed on day 3, compared to the peak on day 2 in untreated cultures and was reduced by approximately 3- fold. Little evidence for HIV production was observed in the 10 *9 M samples. At 10 "10 M virus replication became restricted on day 2, similar to control cultures, although the magnitude of this peak was reduced sharply. Accordingly, the dose-response relationship between 1,25DHCC treatment and HIV replication in U937 cells revealed two independent activities of this agent: a quantitative inhibition of virus growth and a qualitative change in the pattern of virus replication. Both of these features attest to the ability of 1,25DHCC to inhibit acute HIV infection of U937 cells. Based on this pattern of HIV replication in 1,25DHCC treated cultures, day 2 post-infection was used to compare the effects of Vitamin D compounds on HIV replication in U937 cells. Cells were infected in batches for 2.5 hours and then washed and distributed to individual flasks containing the appropriate concentration of drug. Figure 2 illustrates a comparison of the dose-response curves for six analogues of Vitamin D 3 , tested for their ability to inhibit HIV replication in U937 cells. In this case, samples were collected at day 2 post-infection. HIV infection and reverse transcriptase assays were as described in Fig. 1. Figure 2 shows that two 1,25DHCC analogues, namely, 1,25DHDFCC and 1,25DHHDCC, inhibited HIV replication more than 1,25DHCC, itself. Significant inhibition of HIV replication was still observed at concentrations as low as 10 "10 M of these compounds. The compounds 25HCC and 24R,25DHCC were only slightly effective at reducing HIV production, even at the highest concentrations tested. The 25S,26DHCC analog was marginally inhibitory, although its effective concentration was approximately two orders of magnitude higher than the effective concentration of 1,25 DHCC. Based on the comparison of these six analogues of Vitamin D, only the first three were believed to be sufficiently active for further investigation. Accordingly, the capacity of these analogues to induce differentiation of the U937 cells was examined and compared to the dose-response curves for inhibition of virus production. Figure 3 illustrates the effects of 1,25-dihydroxycholecalciferol (1,25DHCC), 1,25-dihydroxyhexadeuterocholecalciferol (1,25DHHDCC) and 1,25-dihydroxydifluorocholecalciferol (l,25DHDFCC) on U937 differentiation and HIV replication. Figure 3 illustrates the effect of these metabolites on two measures of cellular differentiation, i.e., the expression of tetrazolium reductase and inhibition of cellular proliferation. The results in Figure 3 represent the average of three independent experiments. The filled circles designate the capacity of these compounds to inhibit HIV replication as assessed by cell- free reverse transcriptase activity on day 2 post- infection. The filled squares show the percentage of cells positive for tetrazolium reductase activity as evaluated by in situ cytologic assay (See Prowedini et al, Bone, Vol. 7 pages 23-28, 1986). Cellular proliferation was also inhibited by these compounds. The extent of inhibition was roughly the same for each of the drugs. The data for 1,25DHCC are shown here and are representative of the effects cf the other two analogues. The drug concentrations giving half-maximal responses in these assays were assessed from this graph. The average of the maximum and minimum responses were calculated and the drug concentrations required to induce this effect were determined and tabulated in Table 1. These results demonstrate that the pro- differentiation effects of the Vitamin D compounds parallel their inhibition of HIV replication. However, the antiviral and pro-differentiation effects could be distinguished by calculating the half-maximal analog concentration necessary for each effect. Similar concentrations were required to affect HIV replication or cellular differentiation. It is thus likely that inhibition of HIV replication was achieved by a mechanism related to the effects on cellular differentiation. Table 1 Doses Required to Induce Half-Maximal Cellular Differentiation * or to Inhibit HIV Replication "1"* in U937 Cells Compound Reductase Growth Inhibition Activity Inhibition HIV 1,25-DHCC 1.4 X 10 "10 M 1.0 X 10 *10 M 5.4 X 10 '9 M 1,25-DHHDCC . 2.6 X 10 "10 M 2.3 X 10 "10 M 5.0 X 10 "9 M 1,25-DHDFCC 4.7 X 10 " ^ 7.6 X 10 "10 M 1.2 X 10 "9 M +Differentiation was measured as the acquisition of capacity to reduce tetrazolium dye in situ (as described in Prowedini et al, Bone, Vol. 7, pages 23-28, 1986) . The half-maximal concentration is determined to be that concentration of drug able to induce 50% of the difference between untreated and cells treated with lO "6 !! drug. The values for inhibition of cellular differentiation were calculated similarly. ++HIV replication was determined as described with respect to Figure 1. The 50% inhibitory dose was determined graphically as described above. To assess the extent of virus replication in acutely infected U937 cells, analysis of viral RNA accumulation in the cells was performed by Northern hybridization. Figure 4 illustrates hybridization analysis of viral RNA in Vitamin D 3 -treated U937 cells. Infections were performed as described with respect to Fig. 1. Time course analyses showed that the peak of viral RNA production occurred on day 2 post-infection; accordingly, this sampling interval was chosen. Total cellular RNA was prepared by guanidinium-isothiocyanate extraction and gradient purification. The purified samples were dissolved in water and the concentration of nucleic acid was determined from the optical density at 260 nm. Twenty micrograms of each RNA was loaded per lane. The 9.2, 4.3 and 2.0 kb HIV RNA species were detected by hybridization with a LTR-specific fragment, and their positions are indicated on Figure 4. After autoradiographic exposure to reveal the pattern of HIV-1 gene expression, the filters were stripped and rehybridized with a mouse 3-actin probe. The intensity of 3-actin mRNA serves as a control. The Vitamin D compounds thus tested produced a decrease in the HIV ribonucleic acid (RNA) of the treated cells, i.e. the intensity of hybridization in the Vitamin D-treated cultures was approximately one-half that observed in the untreated control culture. This value is consistent with the decreased virus production demonstrated in Figure 1. As a result of the above evaluations, and based upon the demonstrated relationship between cellular differentiation and inhibition of HIV replication, various other vitamin D compounds are expected to have the same or similar therapeutic activity. The vitamin D compounds useful in the compositions of the present invention and for the treatment of acquired immune deficiency syndrome (AIDS) are those which induce cellular differentiation, and preferrably those which induce cellular differentiation with minimal or no effect on either intestinal calcium absorption or bone calcium mobilization. Accordingly, specific preferred examples of vitamin D compounds defined by the above functions are those selected from the group consisting of lα- hydroxyvitamin D homolog compounds, 19-nor vitamin D compounds and secosterol compounds. The lα-hydroxyvitamin D homolog compounds useful in the present invention are characterized structurally as side chain unsaturated and side chain saturated homologs of vitamin D, and preferably of 1,25- (OH) 2 D 3 in which the side chain is elongated by insertion of one or more methylene units into the chain at the carbon 24 position. They may be represented, therefore, by the following general structure of formula I: where and R 5 represent hydrogen, deuterium, flourine or when taken together R 4 and R ς represent a carbon- carbon double bond or a carbon-carbon triple bond, R 13 represents hydrogen, deuterium, hydroxy, protected hydroxy, fluorine or an alkyl group, Z represents hydrogen, hydroxy or protected-hydroxy, R 3 represents hydrogen, hydroxy, protected hydroxy, fluorine or an alkyl group, X and Y which may be the same or different are hydrogen or a hydroxy-protecting group, R., represents the group -CF 3 , -CD 3 , or -(CH 2 ) -H and R 2 represents the group -CF 3 , -CD 3 , or -(CH 2 ) -H, and where n, q and p are integers having independently the values of 1 to 5, and R 1 and R 2 when taken together represent the group -(CH 2 ) m - where m is an integer having the value of 2 to 5. The 19-nor-vitamin D compounds referred to herein are a class of lα-hydroxylated vitamin D compounds in which the ring A exocyclic methylene group (carbon 19) typical of all vitamin D systems has been removed and replaced by two hydrogen atoms. Structurally these novel analogs are characterized by the general formula II shown below: where X 1 and Y 1 are each selected from the group consisting of hydrogen, acyl, alkylsilyl and alkoxyalkyl, and where the group U represents any of the typical side chains known for vitamin D compounds. Thus, U may be an alkyl, hydrogen, hydroxyalkyl or fluoroalkyl group, or U may represent the following side chain: wherein Z 1 represents hydrogen, hydroxy or O-acyl, R 6 and R 7 are each selected from the group consisting of alkyl, hydroxyalkyl and fluoroalkyl, deuteroalkyl or, when taken together represent the group — ( CH 2 ) m — where m is an integer having a value of from 2 to 5, R 8 is selected from the group consisting of hydrogen, deuterium, hydroxy, fluorine, O-acyl, alkyl, hydroxyalkyl and fluoroalkyl, , is selected from the group consisting of hydrogen, deuterium, fluorine, alkyl, hydroxyalkyl and fluoroalkyl, or, R 8 and H^ taken together represent double-bonded oxygen or double-bonded carbon, R 10 and Ή are each selected from the group consisting of hydrogen, deuterium, hydroxy, O-acyl, fluorine and alkyl, or, R 10 and R^ taken together form a carbon-carbon double bond or a carbon-carbon triple bond, and wherein n is an integer having a value of from 1 to 5, and wherein the carbon at any one of positions 20, 22, or 23 in the side chain may be replaced by an 0, S, or N atom. Specific important examples of side chains for the 19-nor compounds are the structures represented by formulas (a), (b) , (c) , (d) and (e) below, i.e. the side chain as it occurs in 25-hydroxyvitamin D 3 (a) ; vitamin D 3 (b) ; 25-hydroxyvitamin D 2 (c) ; vitamin D 2 (d) ; and the C-24-epimer of 25-hydroxyvitamin D 2 (e) . Purely structurally, the class of secosterol compounds referred to herein has a similarity with some of the known vitamin D compounds. Unlike the known vitamin D compounds, however, the secosterols used in the present invention do not express the classic vitamin D activities in vivo, i.e. stimulation of intestinal calcium transport, or the mobilization of bone calcium, and hence they cannot be classified as vitamin D derivatives from the functional point of view. In light of the prior art, it was all the more surprising and unexpected then, to find that these secosterols are remarkably effective in the treatment of AIDS. This finding provides an effective method for the treatment of AIDS, since the above described secosterols can be administered to subjects in doses sufficient to inhibit HIV replication, without producing simultaneously unphysiologically high and deleterious blood calcium levels. The group of secosterols exhibiting this unique and heretofore unrecognized activity pattern is characterized by the general structure III shown below: where R 12 is hydrogen, methyl, ethyl or propyl and where each of X 2 and Y 2 represent, independently, hydrogen, an acyl group, or a hydroxy-protecting group. As used in the description, and in the claims, the term "hydroxy-protecting group" refers to any group commonly used for the protection of hydroxy functions during subsequent reactions, including, for example, acyl or alkylsilyl groups such as trimethylsilyl, triethylsilyl, t-butyldimethylsilyl and analogous alkylated silyl radicals, or alkoxyalkyl groups such as methoxymethyl, ethoxymethyl, ethoxyethoxymethyl, tetrahydrofuranyl or tetrahydropyranyl. A "protecteά- hydroxy" is a hydroxy function derivatized by one of the above hydroxy-protecting groupings. "Alkyl" represents a straight-chain or branched hydrocarbon radical of 1 to 10 carbons in all its isomeric forms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, etc., and the terms "hydroxyalkyl" and "fluoroalkyl" refer to such an alkyl radical substituted by one or more hydroxy or fluoro groups respectively. An acyl group is an alkanoyl group of 1 to 6 carbons in all its isomeric forms, or an aroyl group, such as benzoyl, or halo-, nitro- or alkyl- substituted benzoyl groups, or a dicarboxylic acyl group such as oxalyl, malonyl, succinoyl, glutaroyl, or adipoyl. The term "aryl" signifies a phenyl-, cr an alkyl-, nitro- or halo-substituted phenyl group. It should be noted in this description that the term "24-dihomo" refers to the addition of two methylene groups at the carbon 24 position in the side chain, and the term "trihomo" refers to the addition of three methylene groups at the same position so that both additions have the effect of extending the length of the side chain. Also, the term "26,27-dimethyl" refers to the addition of a methyl group at the carbon 26 and 27 positions so that for example R 1 and R 2 are ethyl groups. Likewise, the term "26,27-diethyl" refers to the addition of an ethyl group at the 26 and 27 positions so that R., and R 2 are propyl groups. Specific and preferred examples of these compounds when the side chain is unsaturated (i.e. R 4 and ς represent a double bond) are: 24-dihomo-l,25- dihydroxy-22-dehydrovitamin D 3 , i.e. the compound shown above, where X and Y are hydrogen, Z is hydroxy, n equals 3, and R., and R 2 are each a methyl group; 26,27-dimethyl- 24-dihomo-l,25-dihydroxy-22-dehydrovitamin D 3 , i.e. the compound shown above where X and Y are hydrogen, Z is hydroxy, n equals 3, and R 1 and R 2 are each an ethyl group; 24-trihomo-l,25-dihydroxy-22-dehydrovitamin D 3 , i.e. the compound having the structure shown above, where X and Y are hydrogen, Z is hydroxy, n equals 4, and R, and R 2 are each a methyl group; 26,27-dimethyl-24- trihomo-l,25-dihydroxy-22-dehydrovitamin D 3 , i.e. the compound shown above where X and Y are hydrogen, Z is hydroxy, n equals 4, and R 1 and R 2 are each an ethyl group; 26,27-diethyl-2 -dihomo-l,25-dihydroxy-22- dehydrovitamin D 3 , i.e. the compound shown above where X and Y are hydrogen, Z is hydroxy, n equals 3, and R., and R 2 are each a propyl group; 26,27-diethyl-24-trihomo- l,25-dihydroxy-22-dehydrovitamin D 3 , i.e. the compound shown above where X and Y are hydrogen, Z is hydroxy, n equals 4, and R 1 and R 2 are each a propyl group, 26,27- diprop l-24-dihomo-l,25-dihydroxy-22-dehydrovitamin D 3 , i.e. the compound shown above where X and Y are hydrogen, Z is hydroxy, n equals 3, and R, and R 2 are each a butyl group; and 26,27-dipropyl-24-trihomo-l,25-dihydroxy-22- dehydrovitamin D 3 , i.e. the compound shown above where X and Y are hydrogen, Z is hydroxy, n equals 4, and R 1 and R 2 are each a butyl group. Specific and preferred examples of these compounds when the side chain is saturated (i.e. R and R 5 each represent hydrogen) are: 24-dihomo-l,25- dihydroxy-vitamin D 3 , i.e. the compound shown above, where X and Y are hydrogen, Z is hydroxy, n equals 3, and R 1 and 2 are each a methyl group; 26,27-dimethyl-24- dihomo-l,25-dihydroxy-vitamin D 3 , i.e. the compound shown above where X and Y are hydrogen, Z is hydroxy, n equals 3, and R 1 and R 2 are each an ethyl group; 24-trihomo-l, 25-dihydroxy-vitamin D 3 , i.e. the compound having the structure shown above, where X and Y are hydrogen, Z is hydroxy, n equals 4, and R 1 and R 2 are each a methyl group; 26,27-dimethyl-24-trihomo-l,25-dihydroxy-vitamin D 3 , the compound shown above where X and Y are hydrogen, Z is hydroxy, n equals 4, and R 1 and R 2 are each an ethyl group; 26,27-diethyl-24-dihomo-l,25-dihydroxy-vitamin D 3 , i.e. the compound shown above where X and Y are hydrogen, Z is hydroxy, n equals 3, and R 1 and R 2 are each a propyl group; 26, 27-diethyl-24-trihomo-l,25-dihydroxy-vitamin D 3 , i.e. the compound shown above where X and Y are hydrogen, Z is hydroxy, n equals 4, and R 1 and R 2 are each a propyl group; 26,27-dipropyl-24-dihomo-l,25- dihydroxy-vitamin D 3 , i.e. the compound shown above where X and Y are hydrogen, Z is hydroxy, n equals 3, and R, and R 2 are each a butyl group; and 26,27-dipropyl-24- trihomo-1,25-dihydroxy-vitamin D 3 , i.e. the compound shown above where X and Y are hydrogen, Z is hydroxy, n equals 4, and R, and R 2 are each a butyl group. Preparation of Homologated Saturated And Unsaturated Side Chain Compounds: Examples of the compounds of this invention wherein the side chain is saturated can be prepared according to the general process illustrated and described in U. S. Patent No. 4,927,815 issued May 22, 1990 entitled "Compounds Effective In Inducing Cell differentiation And Process For Preparing Same," the description of which is specifically incorporated herein by reference. Examples of the compounds of this invention wherein the side chain is unsaturated can be prepared according to the general process illustrated and described in U. S. Patent No. 4,847,012 issued July 11, 1989 entitled "Vitamin D Related Compounds And Processes For Their Preparation," the description of which is specifically incorporated herein by reference. Examples of the compounds of this invention wherein R, and R 2 together represent a cyclopentano group can be prepared according to the general process illustrated and described in U. S. Patent No. 4,851,401 issued July 25, 1989 entitled "Novel Cyclopentano-Vitamin D Analogs," the description of which is specifically incorporated herein by reference. Another synthetic strategy for the preparation of side-chain-modified analogues of lα,25- dihydroxyergocalciferol is disclosed in Kutner et al, The Journal of Organic Chemistry, 1988, Vol. 53, pages 3450- 3457. In addition, the preparation of 24-homo and 26- homo vitamin D analogs are disclosed in U. S. Patent No. 4,717,721 issued January 5, 1988 entitled "Sidechain Homo-Vitamin D Compourds With Preferential Anti-Cancer Activity" the description of which is specifically incorporated herein by reference. Preparation of 19-Nor-Vitamin D Compounds The preparation of lα-hydroxy-19-nor-vitamin D compounds having the basic structure shown above in formula II can be accomplished by a common general method, using known vitamin D compounds as starting materials. For the synthesis of lα,25-dihydroxy-19-nor- vitamin D 3 , reference is made to Perlman et al. Tetrahedron Letters, 1990, Vol. 31, No. 13, pages 1823- 1824. Suitable starting materials are, for example, the vitamin D compounds of the general structure IV: where U is any of the side chains as defined above. These vitamin D starting materials are known compounds, or compounds that can be prepared by known methods. Using the procedure of DeLuca et al U.S. Patent 4,195,027, the starting material is converted to the corresponding lα-hydroxy-3,5-cyclovitamin D derivative, having the general structure V below, where X 3 represents hydrogen and Q represents an alkyl, preferably methyl: So as to preclude undesired reaction of the lα-hydroxy group in subsequent steps, the hydroxy group is converted to the corresponding acyl derivative, i.e. the compound V shown above, where X 3 represents an acyl group, using standard acylation procedures, such as treatment with an acyl anhydride or acyl halide in pyridine at room temperature or slightly elevated temperature (30-70°C) . It should be understood also that whereas the process of this invention is illustrated here with acyl protection of hydroxy functions, alternative standard hydroxy- protecting groups can also be used, such as, for example, alkylsilyl or alkoxyalkyl groups. Such protecting groups are well-known in the art (e.g. trimethylsilyl, triethylsilyl, t.-butyldimethylsilyl, or tetrahydrofurany1, methoxymethyl) , and their use is considered a routine modification of experimental detail within the scope of the process of this invention. The derivative as obtained above is then reacted with osmium tetroxide, to produce the 10,19- dihydroxy analog, VI (where X 3 is acyl) , which is subjected to diol cleavage using sodium metaperiodate or similar vicinal diol cleavage reagents (e.g. lead tetraacetate) to obtain the 10-oxo-intermediate, having the structure VII below (where X 3 is acyl) : VI VII These two consecutive steps can be carried out according to the procedures given by Paaren et al. (J. Org. Chem. 48, 3819 (1983)). If the side chain unit, U carries vicinal diols (e.g. 24,25-dihydroxy- or 25,26-dihydroxy, etc.), these, of course, also need to be protected, e.g. via acylation, silylation, or as the isopropylidene derivative prior to the periodate cleavage reactions. In most cases, the acylation of the lα- hydroxy group as mentioned above will simultaneously effect the acylation of side chain hydroxy functions, and these acylation conditions can, of course, be appropriately adjusted (e.g. elevated temperatures, longer reaction times) so as to assure complete protection of side chain vicinal diol groupings. The next step of the process comprises the reduction of the 10-oxo-group to the corresponding 10- alcohol having the structure VIII shown below (where X 3 is acyl and Y 3 represents hydroxy) . When X 3 is acyl, this reduction is carried out conveniently in an organic solvent at from about 0°C to about room temperature, using NaBH 4 or equivalen t hydride reducing agents, se.1active for the reduct.__.on of carbonyl groups without cleaving ester functions. Obviously, when X 3 is a hydroxy-protecting group that is stable to reducing agents, any of the other hydride reducing agents (e.g. LiAlH 4 , or analogous reagents) may be employed also. The 10-hydroxy intermediate is then treated with an alkyl-or arylsulfonylhalide (e.g. methanesulfonylchloride) in a suitable solvent (e.g. pyridine) to obtain the corresponding 10-0-alkyl-or arylsulfonyl derivative (the compound having the structure shown VIII above, where Y 3 is alkyl-S0 2 0-, or aryl-S0 2 0-, and this sulfonate intermediate is then directly reduced, with lithium aluminum hydride, or the analogous known lithium aluminum alkyl hydride reagents in an ether solvent, at a temperature ranging from 0°C to the boiling temperature of the solvent, thereby displacing the sulfonate group and obtaining the 10-deoxy derivative, represented by the structure VIII above, where X 3 and Y 3 are both hydrogen. As shown by the above structure, a 1-0-acyl function in the precursor compound VII is also cleaved in this reduction step to produce the free lα-hydroxy function, and any O-acyl protecting group in the side chain would, of course, likewise be reduced to the corresponding free alcohol function, as is well understood in the art. If desired, the hydroxy groups at C-l (or hydroxy groups in the side chain) can be reprotected by acylation or silylation or ether formation to the corresponding acyl, alkylsilyl or alkoxyalkyl derivative, but such protection is not required. Alternative hydroxy-protecting groups, such as alkylsilyl or alkoxyalkyl groups would be retained in this reduction step, but can be removed, as desired, at this or later stages in the process by standard methods known in the art. εtructure shown VIII above, where Y 3 is alkyl-S0 2 0-, or aryl-S0 2 0-, and this sulfonate intermediate is then directly reduced, with lithium aluminum hydride, or the analogous known lithium aluminum alkyl hydride reagents in an ether solvent, at a temperature ranging from 0"C to the boiling temperature of the solvent, thereby displacing the sulfonate group and obtaining the 10-deoxy derivative, represented by the structure VIII above, where X 3 and Y 3 are both hydrogen. As shown by the above structure, a 1-0-acyl function in the precursor compound VII is also cleaved in this reduction step to produce the free lα-hydroxy function, and any O-acyl protecting group in the side chain would, of course, likewise be reduced to the corresponding free alcohol function, as is well understood in the art. If desired, the hydroxy groups at C-l (or hydroxy groups in the side chain) can be reprotected by acylation or silylation or ether formation to the corresponding acyl, alkylsilyl or alkoxyalkyl derivative, but such protection is not required. Alternative hydroxy-protecting groups, such as alkylsilyl or alkoxyalkyl groups would be retained in this reduction step, but can be removed, as desired, at this or later stages in the process by standard methods known in the art. The above lα-hydroxy-10-deoxy cyclovitamin D intermediate is next solvolyzed in the presence of a low- molecular weight organic acid, using the conditions of DeLuca et al U.S. Patents 4,195,027 and 4,260,549. When the solvolysis is carried out in acetic acid, for example, there is obtained a mixture of lα-hydroxy-19- nor-vitamin D 3-acetate and lα-hydroxy-19-nor-vitamin D l-acetate (compounds IX and X, below) , and the analogous 1- and 3-acylates are produced, when alternative acids are used for solvolysis. The above lα-hydroxy-10-deoxy cyclovitamin D intermediate is next solvolyzed in the presence of a low- molecular weight organic acid, using the conditions of DeLuca et al U.S. Patents 4,195,027 and 4,260,549. When the solvolysis is carried out in acetic acid, for example, there is obtained a mixture of lα-hydroxy-19- nor-vitamin D 3-acetate and lα-hydroxy-19-nor-vitamin D 1-acetate (compounds IX and X, below) , and the analogous 1- and 3-acylates are produced, when alternative acids are used for solvolysis. IX X Direct basic hydrolysis of this mixture under standard conditions then produces the desired lα-hydroxy-19-nor- vitamin D compounds of structure II above (where X 1 and Y 1 are both hydrogen) . Alternatively, the above mixture of monoacetates may also be separated (e.g. by high pressure liquid chromatography) and the resulting 1- acetate and 3-acetate isomers may be subjected separately to hydroxysis to obtain the same final product from each, namely the lα-hydroxy-19-nor-vitamin D compounds of structure II. Also the separated monoacetates of structure IX or X or the free 1,3-dihydroxy compound can, of course, be reacylated according to standard procedures with any desired acyl group, so as to produce the product of structure II above, where X 1 and Y 1 represent acyl groups which may be the same or different. The 19-nor-vitamin D compounds useful in this invention are more specifically described by the following illustrative examples. In these examples specific products identified by Roman numerals and letters, i.e. Ila, lib, ..., etc. refer to the specific structures and side chain combinations identified in the preceding description. Example 1 Preparation of lα,25-dihydroxy-19-nor-vitamin D 3 (Ila) (a) lα, 25-Dihvdroxy-3 ,5-cvclovitamin D, 1-acetate, 6- methyl ether: Using 25-hydroxyvitamin D 3 (IVa) as starting material, the known lα,25-dihydroxy-3,5- cyclovitamin derivative Va (X 3 =H) was prepared according to published procedures (DeLuca et al . . , U. S. Patent 4,195,027 and Paaren et al . , J. Org. Chem. 4.5, 3252 (1980)). This product was then acylated under standard conditions to obtain the corresponding 1-acetate derivative Va (X 3 =Ac) . (b) 10,19-Dihydro-lα,10.19 ,25-tetrahydroxy-3 ,5- cyclovitamin D 3 l-acetate, 6-methyl ether (Via) : Intermediate Va (X 3 =Ac) was treated with a slight molar excess of osmium tetroxide in pyridine according to the general procedure described by Paaren et a_l. (J. Org. Chem. 48 . , 3819 (1983)) to obtain the 10,19-dihydroxylated derivative Via. Mass spectrum m/z (relative intensity) , 506 (M*, 1), 488 (2), 474 (40), 425 (45), 396 (15) , 285 (5), 229 (30) , 133 (45), 59 (80j , 43 (100). 1 H, NMR (CDC1 3 ) δ 0.52 (3H, s, 18-CH 3 , 0.58 (1H, , 3-H) , 0.93 (3H, d, J=6.1 Hz, 21-CH 3 , 1.22 (6H, s, 26-CH 3 and 27-CH 3 ) , 2.10 (3H, s, COCH 3 ) , 3.25 (3H, s, 6-OCH 3 3.63 (2H, m, 19- CH 2 ) , 4.60 (1H, d, J=9.2 Hz, 6-H) , 4.63 (1H, dd, 1/3-H) , 4.78 (1H, d, J=9.2 Hz, 7-H) . (c) lα,25-Dihvdroxy-10-oxo-3 ,5-cvclo-19-nor-vitamin D, 1-acetate, 6-methyl ether (Vila) : The 10,19- dihydroxylated intermediate Via was treated with a solution of sodium metaperiodate according to the procedure given by Paaren et a_l. (J. Org. Chem. 4_8, 3819, 1983) to produce the 10-oxo-cyclovitamin D derivative (Vila, X 3 =Ac) . Mass spectrum m/z (relative intensity) 442 (M * -MeOH) (18), 424 (8), 382 (15), 364 (35), 253 (55), 225 (25), 197 (53), 155 (85), 137 (100). 1 H NMR (CDC1 3 ) δ 0.58 (3H, S, I8-CH 3 ) , 0.93 (3H, d, J=6.6 Hz, 21-CH 3 ) , 1.22 (6H, s, 26-CH 3 and 27-CH 3 ) , 2.15 (s, 3- OCOCH 3 ) , 3.30 (3H, s, 6-OCH 3 ) , 4.61 (1H, d, J=9.1 Hz, 6- H) , 4.71 (1H, d, J=9.6 Hz, 7-H) , 5.18 (lH,m, 1/3-H) . It has been found also that this diol cleavage reaction does not require elevated temperatures, and it is, indeed, generally preferable to conduct the reaction at approximately room temperature, (d) lα-Acetoxy-10,25-dihvdroxy-3,5-cyclo-l9-nor-vitamin D, 6-methyl ether (Villa, X 3 =Ac, Y 3 =OH : The 10-oxo derivative Vila (X 3 =Ac) (2.2 mg, 4.6 μmol) was dissolved in 0.5 ml of ethanol and to this solution 50 μl (5.3 μmol) of a NaBH 4 solution (prepared from 20 mg of NaBH 4 , 4.5 ml water and 0.5 ml of 0.01 N NaOH solution) was added and the mixture stirred at 0°C for ca. 1.5 h, and then kept at 0°C for 16 h. To the mixture ether was added and the organic phase washed with brine, dried over MgS0 4 , filtered and evaporated. The crude product was purified by column chromatography on a 15 x 1 cm silica gel column and the alcohol Villa (X 3 =Ac, Y 3 =0H) was eluted with ethyl acetate hexane mixtures to give 1.4 mg (3 μmol) of product. Mass spectrum m/z (relative intensity) 476 (M * ) (1), 444 (85), 426 (18), 384 (30), 366 (48), 351 (21), 255 (35), 237 (48), 199 (100), 139 (51), 59 (58). (e) lα,25-Dihvdroxy-19-nor-vitamin D ; (Ila, X 1 = Y 1 =H) : The 10-alcohol (Villa, X 3 =Ac, Y 3 =0H) (1.4 mg) was dissolved in 100 μl anhydrous CH 2 C1 2 and 10 μl (14 μmol) triethylamine solution (prepared from 12 mg (16 μl) triethylamine in 100 μl anhydrous CH 2 C1 2 ) , followed by 7 μl (5.6 μmol) methyl chloride solution (9 mg mesyl chloride, 6.1 μl, in 100 μl anhydrous CH 2 C1 2 ) added at 0°C. The mixture was stirred at 0°C for 2 h. The solvents were removed with a stream of argon and the residue (comprising compound Villa, X 3 =Ac, Y 3 =CH 3 S0 2 0-) dissolved in 0.5 ml of anhydrous tetrahydrofuran; 5 mg of LiAlH 4 was added at 0°C and the mixture kept at 0°C for 16 h. Excess LiAlH 4 was decomposed with wet ether, the ether phase was washed with water and dried over MgS0 4 , filtered and evaporated to give the 19-nor product Villa (X 3 =γ 3 =H) # This product was dissolved in 0.5 ml of acetic acid and stirred at 55°C for 20 min. The mixture was cooled, ice water added and extracted with ether. The other phase was washed with cold 10% sodium bicarbonate solution, brine, dried over MgS0 4 , filtered and evaporated to give the expected mixture of 3-acetoxy- 1-α-hydroxy- and lα-acetoxy-3-hydroxy isomers, which were separated and purified by HPLC (Zorbax Sil column, 6.4 x 25 cm, 2-propanol in hexane) to give about 70 μg each of compounds IXa and Xa. UV (in EtOH) λ mχ 242.5 (OD 0.72), 251.5 (OD 0.86), 260 (OD 0.57). Both 19-nor-l,25-dihydroxyvitamin D 3 acetates IXa and Xa were hydrolyzed in the same manner. Each of the monoacetates was dissolved in 0.5 ml of ether and 0.5 ml 0.1 N KOH in methanol was added. The mixture was stirred under argon atmosphere for 2 h. More ether was added and the organic phase washed with brine, dried over anhydrous MgS0 4 , filtered and evaporated. The residue was dissolved in a 1:1 mixture of 2-propanol and hexane and passed through a Sep Pak column and washed with the same solvent. The solvents were evaporated and the residue purified by HPLC (Zorbax Sil, 6.4 x 25 cm, 10% 2- propanol in hexane) . The hydrolysis products of IXa and Xa were identical and gave 66 μg of Ila (X 1 =Y 1 =H) . Mass spectrum (mz relative intensity) 404 (M * ) (100) , 386 (41), 371 (20), 275 (53), 245 (51), 180 (43), 135 (72), 133 (72), 95 (82), 59 (18), exact mass calcd. for C 26 H 44 0 3 404.3290, found 404.3272. 1 H NMR (CDCl 3 ) δ 0.52 (3H, ε, 18-CH 3 ) , 0.92 (3H, d, J=6.9 Hz, 21-CH 3 ) , 1.21 (6H, S, 26- CH 3 and 27-CH 3 ) , 4.02 (1H, m, 3αH) , 4.06 (1H, m, 13-H) , 5.83 (1H, d, J=11.6 HZ, 7-H) , 6.29 (1H, d, J=10.7Hz, 6-H) . UV (in EtOH) , A^ 243 (OD 0.725), 251.5 (OD 0.823) , 261 (OD 0.598) . Example 2 Preparation of lα-hydroxy-19-nor-vitamin D 3 (IIb) : (a) With vitamin D 3 (IVb) as starting material, and utilizing the conditions of Example la, there is obtained known lα-hydroxy-3,5-cyclovitamin D 3 1-acetate, 6-methyl ether, compound Vb (X 3 =Ac) . (b) By subjecting intermediate Vb (X 3 =Ac) , as obtained in Example 2a above to the conditions of Example lb, there is obtained 10,19-dihydro-lα,10-l9-trihydroxy-3,5- cyclovitamin D 3 1-acetate, 6-methyl ether VIb (X 3 =Ac) . (c) By treatment of intermediate VIb (X 3 =Ac) with sodium metaperiodate according to Example lc above, there is obtained lα-hydroxy-10-oxo-3,5-cyclo-19-nor-vitamin D 3 l- acetate, 6-methyl ether Vllb (X 3 =Ac) . (d) Upon reduction of the 10-oxo-intermediate Vllb (X 3 =Ac) under the conditions of Example Id above, there is obtained lα-acetoxy-10-hydroxy-3,5-cyclo-19-nor- vitamin D 3 6-methyl ether Vlllb (X 3 =Ac, Y 3 =OH) . (e) Upon processing intermediate Vlllb (X 3 =Ac, Y 3 =OH) through the procedure given in Example le above, there is obtained lα-hydroxy-19-nor-vitamin D 3 (lib, X^Y^H) . Example 3 Preparation of lα,25-dihydroxy-19-nor-vitamin D 2 : (a) Utilizing 25-hydroxyvitamin D 2 (IVc) as starting material and experimental conditions analogous to those of Example la, there is obtained lα,25-dihydroxy-3,5- cyclovitamin D 2 1-acetate, 6-methyl ether, compound Vc (X 3 =Ac) . (b) Subjecting intermediate Vc (X 3 =Ac) , as obtained in Example 3a above, to the reaction conditions of Example lb, provides 10,19-dihydro-lα,10,19,25-tetrahydroxy-3,5- cyclovitamin D 2 1-acetate, 6-methyl ether, Vic (X 3 =Ac) . (c) By treatment of intermediate Vic (X 3 =Ac) with sodium metaperiodate according to general procedures of Example lc above, there is obtained lα,25-dihydroxy-10-oxo-3,5- cyclo-19-nor-vitamin D 2 1 acetate, 6-methyl ether VIIc (X 3 =Ac) . (d) Upon reduction of the 10-oxo-intermediate VIIc (X 3 =Ac) under conditions analogous to those of Example Id above, there is obtained lα-acetoxy-10,25-dihydroxy-3,5- cyclo-19-nor-vitamin D 2 6-methyl ether VIIIc (X 3 =Ac, Y 3 =0H) . (e) Upon processing intermediate VIIIc (X 3 =Ac, Y 3 =OH) through the procedural steps given in Example le above, there is obtained lα,25-dihydroxy-19-nor-vitamin D 2 (He, X 1 =Y 1 =H) . Example 4 Preparation of lα-hydroxy-19-nor-vitamin D 2 : (a) With vitamin D 2 (IVd) as starting material, and utilizing the conditions of Example la, there is obtained known lα-hydroxy-3,5-cyclovitamin D 2 1-acetate, 6-methyl ether, compound Vd (X 3 =Ac) . (b) By subjecting intermediate Vd (X 3 =Ac) , as obtained in Example 4a above to the conditions of Example lb, there is obtained 10,19-dihydro-lα,10,19-trihydroxy-3,5- cyclovitamin D 2 1-acetate, 6-methyl ether, Vld (X 3 =Ac) . (c) By treatment of intermediate Vld (X 3 =Ac) with sodium metaperiodate according to Example lc above, there is obtained lα-hydroxy-10-oxo-3,5-cyclo-19-nor-vitamin D 2 1- acetate, 6-methyl ether, Vlld (X 3 =Ac) . (d) Upon reduction of the 10-oxo-intermediate Vlld (X 3 =Ac) under the conditions of Example Id above, there is obtained lα-acetoxy-10-hydroxy-3,5-cyclo-19-nor- vitamin D 2 6-methyl ether, VIIId (X 3 =Ac, Y 3 =OH) . (e) Upon processing intermediate Vllld (X 3 =Ac, Y 3 =OH) through the procedure given in Example le above, there is obtained lα-hydroxy-19-nor-vitamin D 2 (lid, X 1 =Y 1 =H) . -28- Preparation of Secosterol Compounds: The secosterol of structure III where R 12 is hydrogen can be prepared according to the method of Lam et al as published in Steroids 2j5, 422 (1975) , the description of which is specifically incorporated herein by reference. The secosterols of structure III, where R 12 is methyl, ethyl or propyl, can be prepared according to the general process illustrated and described in U. S. Patent No. 4,800,198 issued January 24, 1989 entitled "Method of Inducing the Differentiation of Malignant Cells With Secosterol", the description of which is specifically incorporated herein by reference. Compositions for use in the above-mentioned treatment of AIDS comprise an effective amount of one or more vitamin D compounds as defined by the above formulae, and a suitable carrier. The preferred compounds are one or more side chain unsaturated or side chain saturated lα-hydroxyvitamin D homolog compound, one or more 19-nor-vitamin D compound, or one or more secosterol compound as the active ingredient. An effective amount of such compounds for use in accordance with this invention is from about 0.001 μg to about 10.0 μg per gm of composition, and may be administered topically, orally or parenterally in dosages of from about 0.1 μg/day to about 100 μg/day. A concentration of 0.01 μg per gm of the composition is preferred. The compounds may be formulated as creams, lotions, ointments, topical patches, pills, capsules or tablets, or in liquid form as solutions, emulsions, dispersions or suspensions in pharmaceutically innocuous and acceptable solvent or oils, and such preparations may contain in addition other pharmaceutically innocuous or beneficial components, such as antioxidantε, emulsifiers, coloring agents, binders or coating materials. The compounds may be administered topically, as oral doses, or parenterally by injection or infusion of suitable sterile solutions. The compounds are advantageouεly administered in amounts sufficient to effect the differentiation of Promyelocytes to normal macrophages. Dosages as described above are suitable, it being understood that the amounts given are to be adjusted in accordance with the severity of the disease, and the condition and response of the subject as iε well understood in the art. Biological Activity of lα-Hvdroxyvitamin D Homolog Compounds: Four different 24-homologated compounds having structures falling within formula I were tested for both differentiation activity and calce ic activity, using established assays known in the art. Differentiation activity was asseεsed by nonεpecific acid esterase (NSE) activity, nitroblue tetrazolium (NBT) reducing activity and phagocytic capacity in HL60 cells. Calcium mobilizing activity was assessed by intestinal calcium transport data and serum calcium data. Abbreviations: 1,25-(OH) 2 D 3 , 1,25- dihydroxyvitamin D 3 ; A 22 -24,24-dihomo-l,25-(OH) 2 D 3 , (22E)- 22-dehydro-24,24-dihomo-l,25-dihydroxyvitamin D 3 ; A 22 - 24,24,24-trihomo-l,25-(OH) 2 D 3 , (22E)-22-dehydro-24,24,24- trihomo-1,25-dihydroxyvitamin D 3 ; 24-homo-l,25-(OH) 2 D 3 , 24-homo-1,25-dihydroxyvitamin D 3 . Test Results. Data is presented in Table 2 as the percent of differentiated cells resulting from treatment with various concentrations of l,25-(OH) 2 D 3 (used as comparison standard) or one of the four homologated vitamin D test compounds. The data in Table 2 is also shown in Figure 5. Calcemic activity of the compounds is presented in Table 3 and expresεed in terms of intestinal calcium transport data and serum calcium data. Table 2: HL-60 Differentiating Activity of 24-Homologues of l ,25-(OH) 2 D 3 ° concn NSE NBT phagocytosis compound (M) (%) ( ) (%) " Results arc expressed as percent of total cells counted that have differentiated. " Vitamin D deficient rats were fed a low-calcium diet and given the indicated daily dose of compound in propylene glycol intraperitoneally or by Alzet minipump (experiment I) for 7 days. Controls received the vehicle. At 7 days the rats were killed for the determinations. There were at least six rats per group. Statistical analysis was done by Stu¬ dent's i test. Experiment 1, Ca transport: b 1 , b 2 , b 3 from a, p < 0.025; c 1 , c 2 from a, NS; c 3 from a, p = 0.025; c'c 2 , c 3 from b\ b 2 , b\ NS; b 3 from b 1 , b 2 , NS. Experiment 1, serum Ca: b 3 from a, p < 0.01 ; b 2 from a, NS. Experiment II, Ca transport: b\ b 2 from a, p < 0.001 ; c from ~ , p < 0.001 ; d from a, p < 0.001 ; c from b p < 0.05; c from b : , p = 0.01 ; d from b b p < 0.001 ; d from c, p = 0.01 ; b 1 from b 2 , NS. Experiment II, serum Ca: b\ b 2 from a, p < 0.005; c 2-4 , d 1-5 from a, NS; b\ b 2 from c ^, p < 0.001 ; b 1 , b 2 from ά ]~ p < 0.001 ; d 1"5 from a 1 and a, NS. Experiment III, Ca transport: b from a, p = 0.001 ; c 2 from a, p < 0.05; c 3 and c from a, NS; c 2 " 4 from b, p < 0.01. Exper¬ iment III, serum Ca: b from a, p < 0.001 ; c 1 " 4 from a, NS; b from c' p < 0.001. As shown in Figure 5, 24,24-dihomo-l,25- (OH) 2 D 3 and 24-homo-l,25-(OH) 2 D 3 are approximately 10 times more active than the native hormone in causing differentiation of HL-60 cells. Thus, the addition of more than one carbon at the carbon 24 position does not increase differentiative activity further. The addition of an additional carbon at the carbon 24 position as in Δ 22 -24,24,24-trihomo-l,25-(OH) 2 D 3 resultε in differentiative activity half that of the native hormone. Table 2 illustrates that other measurements of differentiation activity gave the same result. The results presented in Table 2 clearly indicate that the four 24-homologated compounds tested are potent in inducing the differentiation of leukemic cells to normal monocyte cells. For example, at a concentration of 1 x 10 "8 molar, l,25-(OH) 2 D 3 produces 60- 62% differentiated cells, whereas 24,24-dihomo-l,25- (OH) 2 D 3 at the same concentration gives 80-83% differentiation. Considering that a concentration of 1 x 10 "7 molar of l,25-(OH) 2 D 3 is required to achieve about the same degree of differentiation as produced by a concentration of 1 x 10 "8 molar of the dihomo analog, one can conclude that this analog is in the order of 10 times more potent than l,25-(OH) 2 D 3 as a differentiation agent. In sharp contrast, the four 24-homologated compounds show very low calcemic activity compared to l,25-(OH) 2 D 3 . This conclusion iε εupported by the results of Tables 2 and 3. The intestinal calcium transport asεay, repreεented by Table 3, for example, shows the known active metabolite, l,25-(OH) 2 D 3 to elicit, as expected, very pronounced responses (compared to control) when administered. There is no doubt that l,25-(OH) 2 D 3 is the superior compound in terms of mobilizing calcium from the skeleton. 24-Homo-l,25- (OH) 2 D 3 showed no calcium mobilizing activity from the skeleton when provided at 65 pmol/day, whereas 1,25- (OH) 2 D 3 elicited calcium mobilizing activity at 65 pmol/day. When provided at as much as 2280 pmol/day, neither of the dihomo compounds elicited a bone calcium mobilization response, whereas significant bone mobilizing response was found with l,25-(OH) 2 D 3 provided at 32 pmol/day. These results suggest that the dihomo compounds are approximately 1000 times less active in mobilizing skeletal calcium than is l,25-(OH) 2 D 3 . Not surprisingly, therefore, no bone calcium mobilization was found with A 22 -24,24,24-trihomo-l,25-(OH) 2 D 3 . In the case of intestinal calcium transport, 6.5-32.5 pmol/day of l,25-(OH) 2 D 3 appears to saturate this system. The 24-homo-l,25-(OH) 2 D 3 compound is less active than l,25-(OH) 2 D 3 in this test. However, the dihomo compounds do not saturate even when provided at 285 pmol and thus are at least 10 times less active than l,25-(OH) 2 D 3 . The trihomo compound shows little or no activity at even 1096 pmol/day. Although exact estimates of activity in this εyεtem are not possible from the data available, it is clear that the dihomo and trihomo compounds are at least 10 times less active in inteεtinal calcium tranεport than iε l,25-(OH) 2 D 3 . In εummary, it is evident from Figure 5 and the data in Tables 2 and 3 that A 22 -24,24,24-trihomo- l,25-(OH) 2 D 3 retains almost full activity (i.e. half that of l,25-(OH) 2 D 3 ) in causing differentiation of HL-60 cells into monocyteε, whereas it has lost most of its calcium mobilizing activity. Because some intestinal calcium transport activity is noted at high doεes of the dihomo compounds, these compounds should increase serum calcium slightly when calcium is present in the intestine. The 24,24-dihomo-l,25-(OH) 2 D 3 compounds, whether saturated in the 22-position or unsaturated, have 10-fold higher HL-60 differentiative activity than 1,25- (OH) 2 D 3 but have markedly diminished calcium mobilizing activity. The 24-homo-l,25-(OH) 2 D 3 shows a 10-fold increase in the HL-60 activity and a 5-10 fold decrease in calcium mobilizing activity. If the differentiative activity is of thereapeutic importance in the treatment of AIDS as the data presented herein indicates, then the 24-homologated l,25-(OH) 2 D 3 compounds may be very effective. Biological Activity of lα-Hvdroxy-19-Nor-Vitamin D Compounds The 19-nor compounds of this invention also exhibit a pattern of biological activity similar to the above homologated compounds, namely, high potency in promoting the differentiation of malignant cells and little or no activity in calcifying bone tissue. This is illustrated by the biological assay results obtained for lα,25-dihydroxy-19-nor-vitamin D 3 which are summarized in Tables 4 and 5, respectively. Table 4 showε a comparison of the activity of the known active metabolite lα,25- dihydroxyvitamin D 3 and the 19-nor analog lα,25- dihydroxy-19-nor-vitamin D 3 in inducing the differentiation of human leukemia cells (HL-60 cells) in culture to normal cells (monocytes) . Differentiation activity was assesεed by three εtandard differentiation assays, abbreviated in Table 4 as NBT (nitroblue tetrazolium reduction) , NSE (non-specific esterase activity) , and PHAGO (phagocytosis activity) . The assays were conducted according to known procedures, as given, for example, by DeLuca et aJL. (U.S. Patent 4,717,721 and Ostrem et al.. , J. Biol. Chem. 262, 14164, 1987). For each assay, the differentiation activity of the test compounds is expresεed in termε of the percent of HL-60 cellε having differentiated to normal cells in reεponεe to a given concentration of test compound. The results summarized in Table 4 clearly show that the analog, lα,25-dihydroxy-l9-nor-vitamin D 3 iε aε potent aε lα,25-dihydroxyvitamin D 3 in promoting the differentiation of leukemia cellε. Thuε in all three assayε close to 90% of the cells are induced to differentiate by lα,25-dihydroxy-vitamin D 3 at a concentration of 1 x 10 "7 molar, and the εame degree of differentiation (i.e. 90, 84 and 90%) iε achieved by the 19-nor analog. Table Differentiation of HL-60 Cells lα , 2 -5-dihv ■ croxwi -t —aι_. ■ in D 3 A Differentiated Cells ( moles/liter) (mean _+ SEM) HI USE PHΛC0 1 x 10 -7 86 +_ 2 89 +_ 1 87 ■*- 3 1 x 10 " 60 +_ 2 60 _+ 3 64 - 2 1 x 10 -9 33 _+ 2 31 + 2 34 + 1 lα , 25-Dihy rox7-19- nor _ vitamin D (moles/liter) 2 x 10~ 7 ~ 7 1 x 10 -8 In contrast to the preceding results, the 19- nor analog exhibits no activity in an assay measuring the calcification of bone, a typical reεponεe elicited by vitamin D compounds. Relevant data, representing the results of an asεay comparing the bone calcification activity in ratε of lα,25-dihydrox vitamin D 3 and lα,25- dihydroxy-19-nor vitamin D 3 are summarized in Table 5. Thiε aεεay was conducted according to the procedure described by Tanaka et al. , Endocrinology £2., 417 (1973). The results presented in Table 5 show the expected bone calcification activity of lα,25- dihydroxyvitamin D 3 as reflected by the increase in percent bone aεh, and in total aεh at all doεe levelε. In contrast, the 19-nor analog exhibits no activity at all three dose levels, when compared to the vitamin D- deficient (-D) control group. Table 5 Calcification Activicy Compound Amount Administered 'J. Ash (pmoles/day/7 days) (mean _+ SEH) (πeεπ -_ SEM) -D (control) 0 19 + 0.8 23 + 1.2 lα,25-dihydroxy- 32.5 23 +_ 0.5 34 +_ 1.6 vitanin D„ 65.0 26 +_ 0.7 36 +_ 1.1 325.0 28 + 0.9 40 + 1.9 lα,25-dihydroxy-19- 32.5 22 +_ 0.9 28 +_ 1.6 nor-vitamin D„ 65.0 19 + 1.5 28 +_ 3.4 325.0 19 + 1.2 30 + 2.4 Each assay group comprised 6 rats, receiving the indicated amount of test compound by intraperitoncal injection daily for a period of seven days. Thus the 19-nor analog shows a selective activity profile combining high potency in inducing the differentiation of malignant cells with very low or no bone calcification activity. The compounds of this novel structural claεε, therefore, can be useful as therapeutic agents for the treatment of AIDS. Biological Propertieε of Secoεterol Compoundε Biological activity of compoundε of εtructure III in the differentiation of human leukemia cellε. Two different secosterol compounds having structures falling within formula III were tested for both differentiation activity and calcemic activity using established assays known in the art. The differentiation results are reported in Table 6. Table 6 Percent differentiation of HL-60 cells induced by seco-sterols or by known lα-hydroxyvitamin D compounds administered at various concentrations as measured by NBT-reduction, rosette formation and esterase activity assays Compound NBT Rosette Esterase Administered Concentration Reduction Formation Activity (M) (%) (%) (%) EtOH Control 4.5 9 3.5 Secosterol m 1 x 10 9 9 2 5 x 10~ 6 59 68 69 Secosterol m 1 x 10 15 23 30 1 x 10~ 5 69 70 91 lα-0H-D 3 1 x 10 "7 10 44 12 1 x 10~ 6 39 61 90 1 x 10~ 5 85 79 100 lα,25-(0H) 2 D 1 x 10~ 8 39 44 65 The above results illustrate the efficacy of the seco-sterols of general s ruc ureHEas agents for the .differentiation of human leukemia cells to macrophages (monocytes) . The compounds show highly significant activity in all three of the differentiation assays used; 50% differentiation is achieved at concentrations of about 10 M. For comparative purposes, the table above also includes the cell differentiation activity exhibited by lα-hydroxyvitamin D_ (lα-OH-D.,) and lα,25-dihydroxyvitamin D. (1,25-(0H)„D.) , two known vitamin D derivatives with potent antileukemic action. The tabulated data show that the level of activity of the seco sterols is lower than that shown by 1,25-(0H)_D_ (the most potent vitamin D-derived agent for differentiation of leukemia cells) , but is approximately equivalent to that shown by lα-hydroxyvitamin D_, a compound known to be effective in the treatment of human leukemoid diseases (Suda _et_ aJL., U.S. Patent 4,391,802). Assay of secosterols of structure IUfor bone calcium mobiliza¬ tion and calcium transport. Male weanling rats, purchased from the Holtzman Co., Madison, WI, were fed the low calcium, vitamin D-deficient diet described by Suda et_ al. [J. Nutr. 100, 1049 (1970)] ad libitum for 3 weeks. The rats were then divided into 4 groups of 6 animals each. The first group (control group) received 0.05 ml of 951 EtOH by intrajugular injection. The second and third groups were dosed by the same route with 625 picomoles and 6250 picomoles, respectively, of secosterol HI dissolved in 0.05 ml of EtOH, and the fourth group received an intrajugular injection of 625 picomole of lα,25-dihydroxyvitamin D (in 0.05 ml of EtOH). Seven hours after dosing, the rats were killed by decapitation and their blood was collected and centrifuged to obtain serum. Serum calcium concentration was determined with an atomic absorption spectrometer according to the conventional protocol. Results are listed in Table 7 below. The small intestines of these same rats were removed, rinsed and everted for measurement of calcium transport activity according to the technique of Martin and DeLuca [Am. J. Physiol. 216, 1351 (1969)]. The measured intestinal calcium transport activity data, expressed as the ratio of serosal/mucosal calcium concentration, are -also listed in Table 7. Table 7 Serum Calcium Intestinal Compound Administered Amount Concentration Ca-transport (pmole) (mg/100 ml) [Ca-serosal]/ mean +_ S.D. [Ca-mucosal] mean + S.D. EtOH (control) 2.6 + 0.1 3.6 + 0.1 Secosterol III 625 2.9 + 0.1 3.4 + 0.1 (R 12 =CH 3 , y 2 =X 2 =H) Secosterol III 6250 3.0 + 0.1 3.4 + 0.1 (R 12 =CH 3 , y 2 =X 2 =H) 1,25-(0H) 2 D 3 625 3.8 + 0.2 6.7 + 0.8 ~> ~> The above results show that secosterol III ( i2 =< -^3' v = = H) expresses no significant calcemic activity even at high doses. The compound does not elevate serum calcium levels and thus is devoid of significant bone calcium mobilization activity. Further, the compound does not stimulate calcium transport in the intestine at a dose level of 6250 picomole per animal. Under the same conditions, the known active vitamin D metabolite, 1,25-(0H) ? D„ , is, as expected, fully active at 10 times lower dose levels. It can be concluded, therefore, that these seco steroidε of general structure III (where R 12 is hydrogen, methyl, ethyl, propyl) do not carry out the classical vitamin D functions in vivo,, since they elicit no significant jin vivo biological response with respect to bone mineral mobilization, and intestinal calcium transport activation. The above data establish that the seco¬ sterols of this invention possess an unusual and unexpected spectrum of activities. They exhibit highly significant cell differentiation activity, like some of the known vitamin D-related compounds, but do not express the calcemic activity typical of vitamin D-derivatives. Thus, in being devoid of the undesired calcemic action of the known antileukemic vitamin D-compounds, the seco- steroids of this invention provide a novel and preferred method for the treatment of viral diseases such as AIDS. Bone calcium mobilization activity of lα,25-(OH)..-26 -homo-D, compounds Male weanling rats were purchased from Holtzman Co., Madison, is. and fed ad libitum a low calcium, vitamin D deficient diet aε deεcribed by Suda et al (J. Nutrition 100: 1049, 1970) and water for 3 weekε. The ratε were then divided into 4 groups of 6 each and were intrajugularly given respectively 650 pmole of either lα,25-(OH) 2 -26-homo-D 3 , lα,25-(OH) 2 -(22E)Δ 22 -26-hαιo-D 3 or lα,25-(OH) ^ dissolved in 0.05 ml of 95% ethanol 7 hrs. prior to sacrifice. The rats in the control group were given 0.05 ml of 95% ethanol 7 hrs. prior to sacrifice. The rats in the control group were given 0.05 ml of ethanol vehicle in the same manner. They were killed by decapitation, the blood was collected and centrifuged to obtain serum. Serum calcium concentration was determined with an atonic absorption spectrophotcπεter (Perkin-El er Model 214) in presence of 0.1% lanthanum chloride. Results are shown in the table belcw: Table 8 Serum Calcium Concentration Cαnpσund Administered (mj/100 ml) a) ethanol 3.4 + 0.3 b) lα,25-(OH) 2 -26-h to-D 3 4.6 j 1 0.2 b) lα,25-(OH) 2 -(22E)Δ 22 -26-hcπo-D 3 4.6 + 0.3 b) lα,25-(OH) 2 D 3 4.5 + 0.2 *standard deviation frcm the mean b) is significantly different from a) P 0.001 It can be concluded frcm the foregoing data that in the vitamin D responsive systems of vitamin D-deficient animals the ccπpσunds of this invention exhibited the same activity as lα,25-hydroxyvitamin D.,, the circulating hormonal form of the vitamin. It has recently been discovered that lα,25-dihydroxy- vitamin D- (lα,25-(0H)„D_) and its structural analog lα-hydroxyvitamin D 3 (lα-OH-D. , in addition to their well-established calcemic action referred to above, also express potent anti-cancer activity. Specifically, it was shewn that the above-named compounds were e fective in causing differentiation of malignant human cells, such as leukemia cells in culture, to non-malignant macrophages, and the anti-cancer activity on cells in vitro could be correlated with beneficial effects in vivo by showing that the administration of these compounds extended the life span of leukemic mice (compared to controls) and markedly improved the condition of human leukemia patients. Based on these observations, lα-hydroxylated vitamin D compounds have been proposed as therapeutic.agents for the treatment of leukemoid diseases (Suda et al. , U.S. Patent No. 4,391,802). Although these kncwn lα-hydroxyvitamin D compounds tested by Suda et al. (supra) , namely lα-hydroxyvitamin D., (lα-OH-D 3 ) and lα,25-dihydroxyvit_amin D-. (lα,25-(0H) _D_ , are indeed highly effective in causing differentiation of leukemic cells, a serious disadvantage to their use as antileukemic agents is the inherent, and hence unavoidable high calcemic activity of . these substances. Thus, lα,25-(0H) „D_, the most potent vitamin-derived antileukemic agent known thus far, is also the most potent calcemic agent, and the antileukemic potency of lα-OH-D_ is likewise correlated with high calcemic activity. The administration of these compounds, at the dosage level where they are effective as antileukemic drugs (e.g. 1 μg/day as specified in the examples of the Suda et al_. patent) , would necessarily produce elevated, potentially excessive, calcium levels with attendant serious medical complications, particularly in patients already suffering from debilitating disease. Because of the high intrinsic potency of the known lα-hydrσxyvitamin D ocmpσunds in raising calcium levels, their use as antileukemic agents may be precluded. A preferred method of treatment of viral diseases clearly would be the administration of ccmpcunds characterized by a high antileukemic to calcemic activity ratio, that is, of cαipσunds exhibiting an enhanced potency in causing differentiation of leukemic cells as compared to their potency in raising serum calcium levels. The ccπr unds of this invention are also preferentially active in inducing the differentiation of malignant cells to non-malignant cells, i.e. in antineσplastic activity as measured by leukemia cell differentiation, while being no more active than lα,25-d___hydroxyvitamin D., in their effect on calcium metabolism. Because of this unique and unexpected combination of properties, the novel side-chain hcmovitamin D cσπroσunds of this invention represent superior and preferred agents for the treattrent of leukemias, and viral diseases, such as AIDS. When administered to human prcmyelccytic leukemia cells (KL-60 cells) grcwn in culture, the side-chain hατσvitamin D compounds of this invention induce the differentiation of these cells to macrophages (πonocytes) . In several standard assays for measuring differentiation activity, these ccmpσunds were shewn to be more effective than lα,25- (OH) -D_, the most active vitamin D derivative kncwn thus far. The extent of differentiation induced by the tes_ed vitamin D derivatives was expressed as the percentage of cells that exhibitfunctional and enzymatic markers characteristic of ironocytes. The two markers assayed were a) the ability of the cells to phagocytize dead yeast, and b) the ability of the cells to produce superoxide (reduce nitro- tetrazalium blue) when stimulated with phorbol esters. This "% phagocytic cells" indicates the percent of differentjatjcn induced by the test ccπpσundε. Results are summarized in Table 9 belcw. Table 9 Percent phagocytic (differentiated) cells produced in HL-60 cell cultures treated with vitamin D compounds at various concentrations Compound Concentration (moles/liter) Administered 0 (a,b) 3xl0- 10 5xlO- 10 lxl0- 9(b) lxlθ "8 (b) lxlO _7 (b) 3xlO -7 l,25- (OH) 2 D 3 10+1.5 17 hαmo-cpd I* 10+1.5 28 hαnra-cpd II** 10+1.5 22 a Control level; cell cultures were treated with solvent ethanol only. Results tabulated in these columns represent the mean +_ SEM of three different experiments, each done in duplicate. *lα, 25-d_Uιydroxy-26-hcrrιovitamin D_ **lα, 25-dihydroxy-22E-dehydro-26-homovitamin D_ The results in Table 9 show that the homo compounds are significantly more potent than 1,25- (OH) 2 D 3 . At all concentrations, the homo compounds achieve a greater degree of differentiation of the leukemia cellε than lα,25-(OH) 2 D 3 , the most active compound known thus far. For example, at a concentration of 10 "8 molar the homo compounds achieve a differentiation of 70%, whereas l,25-(OH) 2 D 3 at the same concentration gives only about 47% differentiated cells. To achieve 50% differentiation requires a concentration of 1 x 10 " M of the homo compounds, but about 1 x 10 " ° of lα,25-(OH) 2 D 3 , i.e. a difference in potence of about 10- fold. The results of the NBT assay are shown in Table 10 below. Table 10 Percent of cells in HL-60 cell cultures exhibiting nitroblue tetrazolium (NBT) reduction activity after treatment with Vitamin D Compounds at various concentrations "d 1 Control level; cell cultures treated with solvent ethanol only. Data represent the mean +_ SEM of three separate experiments, each assayed in duplicate. *lα,25-d_Uιydroxy-26-homovitamin D^ **lα,25-^ihyά^oxy-22E-^ehydro-26-homovitamin D^ VO T t~ © ON The results shown in Table 10 again establish that the homo compounds tested are more active than lα,25-(OH) 2 D 3 in inducing the differentiation of human mycloid leukemia cells to normal cells, in vitro. To achieve 60% differentiation of the leukemic cells as measured by this NBT reduction assay, requires a concentration of 2 x 10 "9 M of the homo compounds; to achieve the same degree of differentiation with lα,25- (OH) 2 D 3 requires a concentration of 3.5 x 10 " ^—a 17-fold difference in potency. Thus, both of the above asεays confirm the high potency of the homovitamin D compoundε in inducing the differentiation of leukemic cellε. In addition, the above results show that in this differentiation activity these homovitamin D compounds are significantly more potent than lα,25-(OH) 2 D 3 . Since this differentiating activity is expreεεed in the caεe of human leukemia cells (HL-60) , it iε clear that theεe novel homovitamin D compoundε can be uεed effectively against leukemiaε in human subjects. At the same time, these compounds do not exhibit enhanced calcemic activity, but are about as active as lα,25- (OH) 2 D 3 . Thus, theεe homovitamin D compoundε are characterized by a high antineoplastic to calcemic activity ratio. By virtue of this novel and desirable biological property, theεe εide-chain homo compounds would function as superior thereapeutic agents for the treatment of AIDS. For the treatment of human leukemia or AIDS, the homovitamin D compounds of this invention are administered to subjects in dosageε εufficient to induce the differentiation of myeloid cellε to macrophageε. Suitable doεage amountε are as described above, it being understood that doεageε can be adjusted according to the severity of the disease or the response or the condition of subject as is well-understood in the art. Biological Activity of Cyclopentano Vitamin D Analogs The vitamin D analogs, cyclopentano-l, 25- dihydroxy-vitamin D 3 and cyclopentano-l, 25-dihydroxy-22E- dehydro-vitamin D 3 were assayed for both calcemic activity and differentiation activity, using established procedures known in the art. The assay procedures and results obtained are described in the following examples. Intestinal calcium transport activity and bone calcium mobilization activity of compounds. Male weanling rats (obtained from Harlan- Sprague Dawley Co., Madison, WI) were fed a low calcium, vitamin D-deficient diet (0.22% Ca, 0.3% P) as described by Suda et al. (J. Nutr. 100, 1049-1052, 1970), for a total of 4 weeks ad libitum. At the end of the third week, the animals were divided randomly into groups of 6 rats each. One group (the control group) received a daily dose of solvent vehicle (0.1 mL of 95% propylene glycol/5% ethanol) by interperitoneal (i.p.) injection for a total of 7 days. The other groups received the amounts of test compound (i.e. 1,25-(0H) D , compound I, or compound II) as indicated in Table ii, dissolved in the same amount of solvent vehicle by daily injection over a period of 7 days. The animals were killed 24 hours after the last injection, their intestines were removed for intestinal calcium transport measurements, and their blood was collected for the assay of bone calcium mobilization (measurement of serum calcium levels). Intestinal calcium transport was measured by the everted gut sac technique [Martin DeLuca, Am. J. Physiol. 216, 1351 (1969)] as described by Halloran and DeLuca [Arch. Biochem. Biophys. 208, 477-486 (1981)]. The results, expressed in the usual fashion as a ratio of serosal/mucosal calcium concentrations, are given in Table 11 below. Bone calcium mobilization was assayed by measuring serum calcium levels, using the standard procedures: 0.1 raL aliquots of serum were diluted with 1.9 mL of a 0.12 aqueous solution of LaCl. and calcium concentrations were then determined directly by atomic absorption spectroscopy. Results, expressed as mg Z calciur., are also presented in TableH below. Table 11 Intestinal Calcium Transport and Bone Calcium Mobilization (Serum Calcium Levels) Activity of the Cyclopentano- Vitamin D Analogs Ca Transport Compound Amount [Ca serosa'l]/ Serum Calcium Administered ng/day [Ca ucosal] mgZ mean + S.E.M. mean + S.E.M. none (control) 2.4 + 0.22 3.7 + 0.06 1,25-(0H) 2 D 3 50 8.3 + 0.43 4.6 + 0.10 Cyclopentano- 25 7.7 +_ 0.37 5.5 +_ 0.31 1,25-(OH) D 125 10.4 + 0.10 7.4 + 0.06 Cyclopentano- 50 8.3 + 0.81 5.9 + 0.14 l,25-(0H) 2 -22- dehydro-D Differentiation activity of gyclopentano Compounds. Degree of differentiation of HL-60 cells (human leukemia cells) in response to test compounds was assessed by three different assays: NBT reduction, esterase activity, and phagocytosis activity. The NBT reduction and phagocytosis assays were carried out as described by DeLuca et al. in U.S. Patent 4,717,721. The third assay, measuring nonspecific acid esterase as a marker for degree of differentiation was conducted according to the method given in Sigma Kit No. 90, available from Sigma Chemical Corp., St. Louis, MO [see also, Ostrem _et_ al. , Proc. Natl. Acad. Sci. USA _84_, 2610 (1987); Ostre et_ al. , J. Biol. Chem. 262, 14164 (1987)). Results are shown in Table 12 below. The data for the three assays are presented as the percent of differentiated cells resulting from treatment with various concentrations of l,25-(OH)_D, (used as comparison standard) or the cyclopentano-vitamin D analogs. Table 12 Differentiation Activity of Cyclopentano-l , 25-(0H) _D_ and Cyclopentano-l , 25- (OH) -22-dehydro-D. in HL-60 Cell Cultures The preceding test results establish that the new cyclopentano analogs possess high calcemic and differentiation activity. Indeed, the assay results listed in Table H and Table 12 show that, with respect to calcemic activity and differentiation activity, the two cyclopentano vitamin D analogε are more potent than the natural hormone, l,25-(OH) 2 D 3 . Thuε, the calcium tranεport reεponεe elicited by the cyclopentano analogε (εee Table 11) iε approximately the εame aε that given by l,25-(OH) 2 D 3 in their effect on calcium mobilization from bone (Table 11) . Similarly, the data in Table 12 εhow that the cyclopentano analogs are approximately five times more active than l,25-(OH) 2 D 3 in inducing the differentiation of leukemic cells. This is evident, for example, from the entries showing that both cyclopentano compounds achieve 90% differentiation at a concentration of 5 x 10 " , whereas a five-fold higher concentration (1 x 10 "7 M) of l,25-(OH) 2 D 3 is required to produce the same degree of differentiation. Based on these results, one can conclude that both of the cyclopentano analogs can be uεed effectively aε calcium regulating agents or as differentiation-inducing agents. Thus, the new analogs can be employed in the prophylaxis or treatment of calcium metabolism disorders such as renal osteodystrophy, vitamin D-resiεtant ricketε, osteoporosis and related diseases. Likewise, their high potency in inducing the differentiation of analogs can be used in place of such known compounds as l,25-(OH) 2 D 3 for the treatment of neoplastic diεease, especially leukemias, and now AIDS. Biological Activity of Other Vitamin D Analogs: 1,25-Dihydroxyvitamin D 3 , the hormonal form of vitamin D, induces differentiation of HL-60 human promyelocytes into monocyte-like cells in vitro. The relative activity of 30 analogs of 1,25-dihydroxyvitamin D 3 in inducing development of monocytic markers in HL-60 cells waε assesεed. The three differentiation markerε assayed were nonspecific acid esterase activity, nitroblue tetrazolium reducing activity, and phagocytic capacity. Activity Ratio (AR^ — The data from each assay was used to construct 3 log dose-response curves for each analog. The ED 50 , i.e. the concentration WO _/0324<; - - PCT/US . required to achieve 50X differentiation after 4 days, was obtained directly from each curve. An average ED 5 _ was calculated from the 3 assays for each analog. Relative activity (AR) is the ratio of the average ED n of the analog —8 to the ED 5Q of l,25-(OH)_D (i.e. 10 M). The AR value, therefore, expresses 5 the potency of an analog to induce maturation of HL-60 cells under the above mentioned conditions, relative to that of the natural hormone. .Figure 6 shows the structures__fif_most of the analogs studied. Figures 7 0 through11.are representative log dose-response curves for the various analogs. Steroidal side-chain structures are shown above each curve, and each figure provides the curves for one of the assays used. Similar curves were prepared for the other 2 assays and were used to calculate the ED- ^ s for each analog. Table 13 provides the ED,- 0 s determined by each of the 3 assays for most of the - ~ * analogs as well as the calculated activity ratios (AR). Figure 7 shows the activity of five lα-hydroxylated analogs that do not contain- side-chain hydroxyl groups. lα-OH-D, (1;J) is 100 times less active ...than.1,25-(OH) 2 D 3 (la) (ED 50 s=10~ 6 M and lθ "8 M, respectively; Table13), • indicating that loss of the 25-hydroxyl group diminishes potency by two order 20 .of magnitude. In contrast, methylation of the 25-hydroxy group to produce th methyl ether of the natural hormone (In) results in only a 6-7-fold decrease activity. Introduction of a Δ 22-trans double bond improves the activity of 1-OH-D, 2-fold: Δ 22 -trans-l-OH-D, (Ik) induces 50% differentiation at 5 x 10 -6 M, compared to the 10 M required for the saturated 1-OH-D.. Isomerization 25 2° ~~ 2 the Δ -trans to Δ " -cis (lm) as well as epimerization of the lα-OH to lβ-OH practically eliminates all activity: Even at 10~ M, these compounds induce only 10-20X differentiation. Figure 8 compares the activity of a series of 25-0H analogs having no lα-hydroxyl group (2a-2f). As seen with 25-0H-D- (2a) , loss of the lα-OH leads to an 80-fold reduction in activity. 25-0H-D (2b) and 24-epi-25-OH-D (2c) -7 -7 can induce 50Z differentiation at 4 x 10 M and 3 x 10 M, respectively, 5 being approximately 2-fold more active than 25-0H-D,. This observation agrees with the result in Figure 7 that introduction of a trans double bond at C-22 improves the activity 2-fold. Both 25-0H-D„ isomers have approximately the same activity in this system indicating a tolerance for either R- or S-methyl stereochemistry at C-24. Introduction of fluorine groups in the side chain as 0 in 26,27-F 6 -25-0H-D 2 (2e) improves the activity of 25-0H-D 2 two-fold. This agrees with previous observations of Shiina et al. and Koeffler et al. that fluorination either in the 24-posϊtion or 26,27-position improves ability of 1,25-(0H)_D 3 to induce myeloid cell maturation 4 to 7-fold. 22 23 Isomerization of the side-chain double bond from Δ to Δ -position (2d) which - • ' creates an sp2 planar center at C-24 decreases the activity of 25-0H-D„ two-fold. 2 R,25-(0H) 2 D 3 (2f) Is less active than 25-QH-D.,, suggesting that the 24-hydroxyl group in the presence of a 25-hydroxyl function slightly reduces activity in this system. Similarly, 24-hydroxylation of 1,25-(0H) 2 D„ . reduces its activity in HL-60 cells. 20 The effect of side chain elongation and truncation as well as the effect of isomerization of the triene system from 5,6-cis to 5,6-trans are examined in Figure 9. Generally, elongation by one carbon improves the activity of the natural hormone by one order of magnitude, while truncation of the side-chain by each carbon removed diminishes activity by one order of magnitude. 25 24-Homo-l,25-(0H)_D (lb) and 26-homo-l,25-(0H)_D, (lc) are 8-fold more active than the natural hormone since they can induce 50Z maturation of the HL-60 —9 8 cells at 1.3 x 10 M compared to the 10 M required for 1,25-(0H) 2 D 3 . WO 9./032 * - 57- PCTΛW Introduction of unsaturation at C-22 resulted in analogs that retained the 8-fold improved potency These results cannot be explained on the basis of the affinity of the homoanalogs for the 1,25-(0H) D, receptor. Competition studies show these compounds to have equivalent ability with 1,25-(0H) < ,D_ in displacing the natural hormone from its binding site in chick and rat intestin as well as HL-60 cells Deletion of one carbon (24-nor-l,25-(0H) 2 D 3 ) (Id or two carbons (23,24-nor-l,25-(0H)„D ) (le) from the steroid side-chain results in a 13- and 220-fold reduction in activity, respectively. The bindin affinity of these truncated analogs, as determined by displacement studies using the chick intestinal 1,25-(0H),D 3 receptor, closely parallels their activity in the HL-60 system: Id and le have 10-fold and 160-fold lower affinity, respectively, for the 1,25-(0H),D« receptor (S. Lee, H. K. Schnoes, and H. F. DeLuca, unpublished results). A derivative with a 5,6-trans-triene modification is only 7 times less effective than the 5,6-cis compound (Figure 9) . Thus, 7 x 10~ M concentrati of the 5,6-trans isomer of 24-nor-l,25-(0H)„D, is required to achieve 50% -7 differentiation compared to 1.3 X 10 M needed of the 5,6-cis derivative (Id) Recognizing the importance of the lα-hydroxy group for effectiveness in the •HL-60 system, this relative high.activity of the 5,6-trans derivative is probably a result of the transposition of the 3β-hydroxy group into a pseudo-lα-hydroxy position. Similarly, 25-0H-6,19-epoxyvitamin D„, which lac an lα-hydroxyl, shows unexpected high activity in the HL-60 system Figureιo presents the activity of primary alcohol side chains of various lengths as well as short chain analogs (compounds . 26,27-bis-nor-l,25 ~t (0H) D_ (lo) differs from the natural hormone only in its lack of the two methyl groups flanking the 25-hydroxy substituent. Yet, this compound is two orders of magnitude less effective than 1,25-(OH)_D . Sequential deletion of one carbon from the side chain of lo represented by analogs lp-lr has no further effect in decreasing the activity: 23,24,25,26,2 -pentanor-l,22- (OH)„D_ (lr) is also two orders of magnitude less effective than 1,25-(OH)_D,. Oxidation of the C-22-hydroxyl to a less bulky and less polar aldehyde (Is) 5 improves the activity two-fold; AR iε reduced from 170 to 80-fold lower than the natural hormone. Removal of the oxygen substituent from C-22 results in a dramatic improvement in activity: lα-OH-bishomopregna- (It) and lα-OH-homopregnacholecalciferol (lu) are only 20-fold less active than 1,25-(0H) 2 D 3 . In view of the fact that lα-0H-D_, an analog that has lost the 10 25-hydroxyl substituent while retaining the original length of the steroidal side chain is 100-fold less active than 1,25-(0H) 2 D 3 , these results are remarkable. The high activity of It and lu.can be explained in terms of their surprising high affinity for the 1,25-(0H)„D_ receptor. lα-OH-homopregnachole- calciferol and lα-OH-bishomopregnacholecalciferol are only 4- and 11-fold less 1 ~s effective than l,25-(OH) 2 D in displacing the natural ligand from its binding site on the chick intestinal receptor (22) . 1,24R-(0H)„D„ (If) has equivalent activity with the natural hormone, while its stereoisomer, l,2 S- OH) 2 D 3 (lg) is half as active (Table 13) . In vivo, .1,24S-(0H) 2 D 3 is less active in stimulating calcium transport and bone calcium 20 mobilization and has equal affinity for the receptor compared to 1,25-(0H) 2 D 3 Matsui et al. have also shown that 1,24R-(0H) 2 D shows the same potency as 1,25-(0H)„D_ in inducing monocyte/granulocyte associated plasma membrane antigens, and 1,24S-(0H) 2 D is only slightly less active. This Indicates a small discrimination against the 24S- stereoisomer which could be 25 due to a steric effect of the C-24S-substituenf since 1,25-(0H) 2 D (li) that has a methyl group in the C-24S-ρosition is also 2-fold less active than 1,25-(0H),D (Table 13). In fact, l,25-(0H) D (li) and 1,24R,25-(0H),D, (lh) uniquely produce unexpected and highly reproducible biphasic log doεe-response curves (Figure 11) with 2 ED 50 s at 2-3 x 10 " °M and 9 x 10 " °M. In summary, of the known metabolites of vitamin D, 1,25-dihydroxyvitamin D 3 is the most active; fifty percent of the cells exhibit the mature phenotype following a 4-day treatment with lO "6 ^.1,25- dihydroxyvitamin D 3 . Removal of either the C-l or C-25- hydroxyl group reduces activity by two orders of magnitude, while epimerization of the lα- to 1/3-hydroxyl group virtually abolisheε activity. Elongation of the steroidal side chain of 1,25-dihydroxyvitamin D 3 by addition of one carbon at C-24 or C-26 improveε the potency by an order of magnitude. Truncation of the εteroidal εide chain leads to a ten-fold reduction in activity for each carbon removed. Elimination of the C- 26 and C-27 athylk groups reduces activity 100-fold. Analogs with short aliphatic side chains as lα-hydroxy- homo- and bishomopregnacholecalciferol have surprisingly high activity, being only 20-fold lesε potent than the natural hormone. The activity of moεt analogε in the HL- 60 εyεtem parallelε their known relative affinities for the well characterized 1,25-dihydroxyvitamin D 3 receptor in chick intestine, providing further evidence that this function of 1,25-dihydroxyvitamin D 3 is receptor- mediated. It should be specifically noted that lα- hydroxyvitamin D 3 is leεε than 100 timeε aε active aε lα,25-dihydroxyvitamin D 3 (see Table 13) in causing differentiation of HL60 cells in vitro. However, jLn vivo it is well established that lα-hydroxyvitamin D 3 is rapidly converted to lα,25-dihydroxyvitamin D 3 , Hollick et al, Science, Vol. 190, pages 576-578 (1975) and Hollick et al, Journal of Clinical Endocrinology & Metabolism, Vol. 44, pages 595-598 (1977), which compound as shown herein is highly potent in cell differentiation. Thus, it is clear that the human body can rapidly convert the relatively inactive lα-hydroxylated vitamin D compounds to metabolites highly active in causing cell differentiation. This jln vivo capability makes possible the treatment of malignancies and viral diseases such as AIDS with lα-hydroxylated vitamin D compounds that do not initially have a hydroxyl group at the 24 or 25 carbon position in the side chain. In addition, the present invention provideε compositions and methods for treating lentivirus infections, and attendant immune and infectious disorders. With respect to lentiviruses, thiε iε accompliεhed by administering an effective amount of a vitamin D compound which compound when tested in vitro is capable of inhibiting the replication of the lentiviruε. Lentiviruεeε are well known, and in general termε can be deεcribed aε retro viruses having a relatively slow pathology with a genetic structure common to this group of viruseε. For example, lentiviruεeε include human immunodeficiency virus type 1 (HIV-l) , human immunodeficiency virus type 2 (HIV-2) , simian immunodeficiency virus (SIV) , equine encephalitis- arthritis virus (CAEV) , visna-naedi virus, bovine leukosis virus (BLV) , and feline immunodeficiency virus (FIV) . TABLE 13 Relative activities of 1,25-(0H) ,D analogs in inducing HL-60 differentiation These compounds gave a biphasic response. The values represent the ED derived from the dose response curve at the lower concentration of analog. HL-60 cells were cultured for four days in the presence of the indicated concentration of 1,25-(0H)_D 3 analogs. The analog concentration capable of inducing 50% maturation by the three assays was derived from log dose-response curves. AR is the ratio of the analog average ED to the ED^ for —8 1,25-(0H) 2 " D 3 (10 M) and relates the activity of the analog to that of the natural hormone. Untreated cultures consistently show 5-7% monocytic cells by the above three assays.

Claims: We claim: 1. A method for treating human immunodeficiency virus infection and acquired immune deficiency syndrome which comprises administering to a patient an effective amount of a compound of the formula: where R 4 and R j represent hydrogen, deuterium, or when taken together R 4 and R j represent a carbon-carbon double bond or a carbon-carbon triple bond, R 13 represents hydrogen, hydroxy, protected hydroxy, fluorine, deuterium or an alkyl group, Z represents hydrogen, hydroxy, protected-hydroxy, R 3 represents hydrogen, deuterium, hydroxy, protected-hydroxy, fluorine or an alkyl group, X and Y which may be the same or different, are hydrogen or a hydroxy-protecting group, R, represents the group -CF 3 , -CD 3 , or -(CH 2 ) -H and R 2 represents the group -CF 3 , -CD 3 , or -(CH 2 ) -H, and where n, q and p are integers having independently the values of l to 5, and R 1 and R 2 when taken together represent the group -(CH 2 ) m - where m is an integer having the value of 2 to 5. 2. The method of claim 1 wherein said compound is lα,25-dihydroxy-vitamin D 3 . 3. The method of claim 1 wherein said compound is lα,25-dihydroxy-24,24-difluoro-vitamin D 3 . 4. The method of claim 1 wherein said compound is lα,25-dihydroxy-26,27-hexadeutero-vitamin D 3 . 5. The method of claim 1 wherein said compound is lα,25-dihydroxy-26,27-hexafluorovitamin D 3 . 6. The method of claim 1 wherein said compound is lα-hydroxyvitamin D 3 . 7. The method of claim 1 wherein the compound is 24-homo-lα,25-dihydroxy-22-dehydrovitamin D 3 . 8. The method of claim 1 wherein the compound is 24-dihomo-lα,25-dihydroxy~22-dehydrovitamin D 3 . 9. The method of claim 1 wherein the compound is 24-trihomo-lα,25-dihydroxy-22-dehydrovitamin D 3 . 10. The method of claim 1 wherein the compound is 26,27-dimethyl-24-dihomo-lα,25-dihydroxy-22- dehydrovitamin D 3 . 11. The method of claim 1 wherein the compound is 26,27-dimethyl-24-trihomo-lα,25-dihydroxy-22- dehydrovitamin D 3 . 12. The method of claim 1 wherein the compound is 26,27-diethyl-24-dihomo-lα,25-dihydroxy-22- dehydrovitamin D 3 . 13. The method of claim 1 wherein the compound is 26,27-diethyl-24-trihomo-lα,25-dihydroxy-22- dehydrovitamin D 3 . 14. The method of claim 1 wherein the compound is 26,27-dipropyl-24-dihomo-lα,25-dihydroxy-22- dehydrovitamin D 3 . 15. The method of claim 1 wherein the compound is 26,27-dipropyl-24-trihomo-lα,25-dihydroxy-22- dehydrovitamin D 3 . 16. The method of claim 1 wherein the compound is 24-homo-lα,25-dihydroxyvitamin D 3 . 17. The method of claim 1 wherein the compound is 24-dihomo-lα,25-dihydroxyvitamin D 3 . 18. The method of claim 1 wherein the compound is 24-trihomo-lα,25-dihydroxyvitamin D 3 . 19. The method of claim 1 wherein the compound is 26,27-dimethyl-24-dihomo-lα,25- dihydroxyvitamin D 3 . 20. The method of claim 1 wherein the compound is 26,27-dimethyl-24-trihomo-lα,25- dihydroxyvitamin D 3 . 21. The method of claim 1 wherein the compound is 26,27-diethyl-24-dihomo-lα,25- dihydroxyvitamin D 3 . 22. The method of claim 1 wherein the compound iε 26,27-diethyl-24-trihomo-lα,25- dihydroxyvitamin D 3 . 23. The method of claim 1 wherein the compound is 26,27-dipropyl-24-dihomo-lα,25- dihydroxyvitamin D 3 . 24. The method of claim 1 wherein the compound is 26,27-dipropyl-24-trihomo-lα,25- dihydroxyvitamin D 3 . 25. A method for treating human immunodeficiency virus infection and acquired immune deficiency syndrome which comprises administering to a patient an effective amount of a compound of the formula: where X 1 and Y 1 are each selected from the group consisting of hydrogen, acyl, alkylsilyl and alkoxyalkyl, and where U is selected from the group consisting of alkyl, hydrogen, hydroxyalkyl, fluoroalkyl and a side chain of the formula wherein Z 1 represents hydrogen, hydroxy or O-acyl, R 6 and R 7 are each selected from the group consisting of alkyl, deuteroalkyl, hydroxyalkyl and fluoroalkyl, or, when taken together represent the group — (CH 2 ) m — where m is an integer having a value of from 2 to 5, R 8 is selected from the group consiεting of hydrogen, deuterium, hydroxy, fluorine, O-acyl, alkyl, hydroxyalkyl and fluoroalkyl, ~ Rr, is selected from the group conεisting of hydrogen, deuterium, fluorine, alkyl, hydroxyalkyl and fluoroalkyl, or, R 8 and R g taken together represent double-bonded oxygen or double-bonded carbon, R 10 and R are each selected from the group consisting of hydrogen, deuterium, hydroxy, O-acyl, fluorine and alkyl, or, R 10 and R taken together form a carbon-carbon double bond or a carbon-carbon triple bond, and wherein n is an integer having a value of from 1 to 5 and wherein the carbon at any one of positions 20, 22, or 23 in the side chain may be replaced by an 0, S, or N atom. 26. The method of claim 25 wherein the compound iε lα,25-dihydroxy-19-nor-vitamin D 3 . 27. The method of claim 25 wherein the compound iε lα-hydroxy-19-nor-vitamin D 3 . 28. The method of claim 25 wherein the compound is lα,25-dihydroxy-19-nor-vitamin D 2 . 29. The method of claim 25 wherein the compound is lα-hydroxy-19-nor-vitamin D 2 . 30. The method of claim 25 wherein the compound is lα-hydroxy-19-nor-24 epi-vitamin D 2 . 31. The method of claim 25 wherein the compound is lα,25-dihydroxy-19-nor-24 epi-vitamin D 2 . 32. A method for treating human immunodeficiency virus infection and acquired immune deficiency syndrome which comprises administering to a patient an effective amount of a compound of the formula: where R 12 iε hydrogen, methyl, ethyl or propyl and where each of X 2 and Y 2 represent, independently, hydrogen, an acyl group, or a hydroxy- protecting group. 33. The method of claim 32 wherein R 12 is hydrogen. 34. The method of claim 32 wherein R 12 is methyl. 35. The method of claim 32 wherein R 12 is ethyl. 36. The method of claim 32 wherein R 12 iε propyl. 37. The method of claim 1 wherein said effective amount compriεes about 0.01 μg/day to about 100 μg/day of sεid compound. 38. The method of claim 25 wherein said effective amount comprises about 0.01 μg/day to about 100 μg/day of said compound. 39. The method of claim 32 wherein said effective amount comprises about 0.01 μg/day to about 100 μg/day of said compound. 40. A composition for use in the treatment of human immunodeficiency virus infection and acquired immune deficiency syndrome which comprises an effective amount of a compound of the formula where R 4 and R 5 represent hydrogen, deuterium, or when taken together R 4 and g represent a carbon-carbon double bond or a carbon-carbon triple bond, R 13 represents hydrogen, hydroxy, protected-hydroxy, fluorine, deuterium, or an alkyl group, Z represents hydrogen, hydroxy or protected-hydroxy, R 3 represents hydrogen, deuterium, hydroxy, protected-hydroxy, fluorine or an alkyl group, X and Y which may be the same or different, are hydrogen or a hydroxy-protecting group, R t representε the group -CF 3 , -CD 3 , or -(CH 2 ) -H and R 2 represents the group -CF 3 , -CD 3 , or -(CH 2 ) -H, and where n, q and p are integers having independently the values of 1 to 5, and R 1 and R 2 when taken together represent the group -(CH 2 ) m - where m is an integer having the value of 2 to 5; and a suitable carrier. 41. The composition of claim 40 wherein said compound is lα,25-dihydroxy-vitamin D 3 . 42. The composition of claim 40 wherein said compound is lα,25-dihydroxy-24,24-difluoro-vitamin D 3 . 43. The composition of claim 40 wherein said compound iε lα,25-dihydroxy-26,27-hexadeutero-vitamin D 3 . 44. The compoεition of claim 40 wherein εaid compound is lα,25-dihydroxy-26,27-hexafluorovitamin D 3 . 45. The composition of claim 40 wherein said compound iε lα-hydroxyvitamin D 3 . 46. The composition of claim 40 wherein the compound is 24-homo-lα,25-dihydroxy-22-dehydrovitamin D 3 . 47. The compoεition of claim 40 wherein the compound is 24-dihomo-lα,25-dihydroxy-22-dehydrovitamin D 3 . 48. The composition of claim 40 wherein the compound is 24-trihomo-lα,25-dihydroxy-22-dehydrovitamin D 3 . 49. The composition of claim 40 wherein the compound is 26,27-dimethyl-24-dihomo-lα,25-dihydroxy-22- dehydrovitamin D 3 . 50. The composition of claim 40 wherein the compound is 26,27-dimethyl-24-trihomo-lα,25-dihydroxy-22- dehydrovitamin D 3 . 51. The composition of claim 40 wherein the compound is 26,27-diethyl-24-dihomo-lα,25-dihydroxy-22- dehydrovitamin D 3 . 52. The composition of claim 40 wherein the compound is 26,27-diethyl-24-trihomo-lα,25-dihydroxy-22- dehydrovitamin D 3 . 53. The composition of claim 40 wherein the compound is 26,27-dipropyl-24-dihomo-lα,25-dihydroxy-22- dehydrovitamin D 3 . 54. The composition of claim 40 wherein the compound is 26,27-dipropyl-24-trihomo-lα,25-dihydroxy-22- dehydrovitamin D 3 . 55. The composition of claim 40 wherein the compound is 24-homo-lα,25-dihydroxyvitamin D 3 . 56. The composition of claim 40 wherein the compound iε 24-dihomo-lα,25-dihydroxyvitamin D 3 . 57. The compoεition of claim 40 wherein the compound iε 24-trihomo-lα,25-dihydroxyvitamin D 3 . 58. The composition of claim 40 wherein the compound is 26,27-dimethyl-24-dihomo-lα,25- dihydroxyvitamin D 3 . 59. The compoεition of claim 40 wherein the compound iε 26,27-dimethyl-24-trihomo-lα,25- dihydroxyvitamin D 3 . 60. The composition of claim 40 wherein the compound iε 26,27-diethyl-24-dihomo-lα,25- dihydroxyvitamin D 3 . 61. The composition of claim 40 wherein the compound is 26,27-diethyl-24-trihomo-lα,25- dihydroxyvitamin D 3 . 62. The composition of claim 40 wherein the compound is 26,27-dipropyl-24-dihomo-lα,25- dihydroxyvitamin D 3 . 63. The composition of claim 40 wherein the compound is 26,27-dipropyl-24-trihomo-lα,25- dihydroxyvitamin D 3 . 64. A composition for use in the treatment of human immunodeficiency virus infection and acquired immune deficiency syndrome which comprises an effective amount of a compound of the formula: where X 1 and Y 1 are each selected from the group consisting of hydrogen, acyl, alkylsilyl and alkoxyalkyl, and where U is selected from the group consiεting of alkyl, hydrogen, hydroxyalkyl, fluoroalkyl and a εide chain of the formula: wherein Z 1 represents hydrogen, hydroxy or O-acyl, R 6 and R 7 are each selected from the group consisting of alkyl, deuteroalkyl, hydroxyalkyl and fluoroalkyl, or, when taken together represent the group — ( CH 2^m — where m is an integer having a value of from 2 to 5, R 8 is selected from the group consisting of hydrogen, deuterium, hydroxy, fluorine, O-acyl, alkyl, hydroxyalkyl and fluoroalkyl, R p is selected from the group consisting of hydrogen, deuterium, fluorine, alkyl, hydroxyalkyl and fluoroalkyl, or, R 8 and 1^ taken together represent double-bonded oxygen or double-bonded carbon, R 10 and ,_, are each selected from the group consisting of hydrogen, deuterium, hydroxy, O-acyl, fluorine and alkyl, or, R 10 and R^ taken together form a carbon-carbon double bond or a carbon-carbon triple bond, and wherein n is an integer having a value of from 1 to 5 and wherein the carbon at any one of positions 20, 22, or 23 in the side chain may be replaced by an 0, S, or N atom; and a suitable carrier. 65. The composition of claim 64 wherein the compound iε lα,25-dihydroxy-19-nor-vitamin D 3 . 66. The compoεition of claim 64 wherein the compound iε lα-hydroxy-19-nor-vitamin D 3 . 67. The compoεition of claim 64 wherein the compound is lα,25-dihydroxy-19-nor-vitamin D 2 . 68. The composition of claim 64 wherein the compound is lα-hydroxy-19-nor-vitamin D 2 . 69. The composition of claim 64 wherein the compound iε lα-hydroxy-19-nor-24 epi-vitamin D 2 . 70. The compoεition of claim 64 wherein the compound iε lα,25-dihydroxy-19-nor-24 epi-vitamin D 2 . 71. A compoεition for uεe in the treatment of human immunodeficiency viruε infection and acquired immune deficiency εyndrome which compriεeε an effective amount of a compound of the formula: x a o where R 12 is hydrogen, methyl, ethyl or propyl and where each of X 2 and Y 2 represent, independently, hydrogen, an acyl group, or a hydroxy- protecting group; and a suitable carrier. 72. The composition of claim 71 wherein R 12 is hydrogen. 73. The composition of claim 71 wherein R 12 is methyl, 74. The compoεition of claim 71 wherein R 12 is ethyl. 75. The composition of claim 71 wherein R 12 is propyl. 76. The composition of claim 40 wherein said effective amount is between about 0.01 μg to about 100 μg per gram of the composition. 77. The composition of claim 64 wherein said effective amount is between about 0.01 μg to about 100 μg per gram of the composition. 78. The composition of claim 71 wherein said effective amount is between about 0.01 μg to about 100 μg per gram of the composition. 79. A method of treating human immunodeficiency virus infection and acquired immune deficiency syndrome which comprises administering to a patient an effective amount of a vitamin D compound which compound when tested in vitro is capable of stimulating the differentiation of a human cell line. 80. The method of claim 79 wherein said cell line is a U937 cell line. 81. The method of claim 79 wherein said cell line is a HL60 cell line. 82. The method of claim 79 wherein εaid cell line iε a Ml cell line. 83. A method of treating human immunodeficiency viruε infection and acquired immune deficiency εyndrome which compriεes administering to a patient an effective amount of a lα-hydroxylated vitamin D compound which compound upon administration to humans is converted to a metabolite and said metabolite in vitro will cause differentiation in a human cell line. 84. The method of claim 83 wherein said cell line is a U937 cell line. 85. The method of claim 83 wherein said cell line is a HL60 cell line. 86. The method of claim 83 wherein said cell line is a Ml cell line. 87. A method of treating lentiviruε infections and attendant immune and infectious disorders which comprises administering to a patient an effective amount of a vitamin D compound which compound when tested in vitro is capable of inhibiting the replication of the lentivirus. 88. The method of claim 87 wherein said lentivirus is human immunodeficiency virus type 1. 89. The method of claim 87 wherein said lentivirus is human immunodeficiency virus type 2. 90. The method of claim 87 wherein said lentivirus is εimian immunodeficiency virus. 91. the method of claim 87 wherein said lentivirus is equine infectious anemia virus. 92. The method of claim 87 wherein said lentivirus is caprine encephalitis-arthritis virus. 93. The method of claim 87 wherein said lentivirus is visna-naedi virus. 94. The method of claim 87 wherein said lentivirus is bovine leukosis virus. 95. The method of claim 87 wherein said lentivirus is feline immunodeficiency virus.

Inventors: DEFTOS LEONARD JOHN, DELUCA HECTOR FLOYD, PAUZA CHARLES DAVID, DEFTOS, LEONARD, JOHN, DELUCA, HECTOR, FLOYD, PAUZA, CHARLES, DAVID
Applicants: WISCONSIN ALUMNI RES FOUND, WISCONSIN ALUMNI RESEARCH FOUNDATION
Application year: 1990
Main classification: A61K31
IPC codes: A61K31, A61P31, A61P37