IE63418B1 - Progression risk of HIV by assay of dehydroepiandrosterone in body fluid - Google Patents
Progression risk of HIV by assay of dehydroepiandrosterone in body fluidInfo
- Publication number
- IE63418B1 IE63418B1 IE326690A IE326690A IE63418B1 IE 63418 B1 IE63418 B1 IE 63418B1 IE 326690 A IE326690 A IE 326690A IE 326690 A IE326690 A IE 326690A IE 63418 B1 IE63418 B1 IE 63418B1
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- IE
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- Prior art keywords
- dhea
- body fluid
- amount
- sample
- hiv
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- FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 title claims abstract description 73
- 210000001124 body fluid Anatomy 0.000 title claims description 16
- 239000010839 body fluid Substances 0.000 title claims description 16
- FMGSKLZLMKYGDP-UHFFFAOYSA-N Dehydroepiandrosterone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CC=C21 FMGSKLZLMKYGDP-UHFFFAOYSA-N 0.000 title description 48
- 229960002847 prasterone Drugs 0.000 title description 48
- 238000003556 assay Methods 0.000 title description 8
- 238000000034 method Methods 0.000 claims abstract description 31
- 208000031886 HIV Infections Diseases 0.000 claims abstract description 13
- 208000037357 HIV infectious disease Diseases 0.000 claims abstract description 12
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims abstract description 12
- 230000028327 secretion Effects 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 4
- 238000003018 immunoassay Methods 0.000 claims description 11
- 210000002966 serum Anatomy 0.000 claims description 8
- 210000004369 blood Anatomy 0.000 claims description 6
- 239000008280 blood Substances 0.000 claims description 6
- 102000004190 Enzymes Human genes 0.000 claims description 5
- 108090000790 Enzymes Proteins 0.000 claims description 5
- 210000004027 cell Anatomy 0.000 claims description 5
- 238000001030 gas--liquid chromatography Methods 0.000 claims description 5
- 230000000984 immunochemical effect Effects 0.000 claims description 5
- 210000004698 lymphocyte Anatomy 0.000 claims description 4
- 238000003127 radioimmunoassay Methods 0.000 claims description 4
- 108060003951 Immunoglobulin Proteins 0.000 claims description 3
- 239000000427 antigen Substances 0.000 claims description 3
- 102000036639 antigens Human genes 0.000 claims description 3
- 108091007433 antigens Proteins 0.000 claims description 3
- 230000002255 enzymatic effect Effects 0.000 claims description 3
- 102000018358 immunoglobulin Human genes 0.000 claims description 3
- 238000012360 testing method Methods 0.000 claims description 3
- 238000001262 western blot Methods 0.000 claims description 2
- 208000024891 symptom Diseases 0.000 abstract 1
- 208000030507 AIDS Diseases 0.000 description 14
- 239000000523 sample Substances 0.000 description 11
- 241000725303 Human immunodeficiency virus Species 0.000 description 10
- 102000003992 Peroxidases Human genes 0.000 description 7
- 108040007629 peroxidase activity proteins Proteins 0.000 description 7
- 239000011324 bead Substances 0.000 description 5
- 238000005534 hematocrit Methods 0.000 description 5
- 208000035473 Communicable disease Diseases 0.000 description 3
- 229960002685 biotin Drugs 0.000 description 3
- 239000011616 biotin Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- CZWCKYRVOZZJNM-USOAJAOKSA-N dehydroepiandrosterone sulfate Chemical compound C1[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 CZWCKYRVOZZJNM-USOAJAOKSA-N 0.000 description 3
- 230000000652 homosexual effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 238000005497 microtitration Methods 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 229950009829 prasterone sulfate Drugs 0.000 description 3
- 208000010648 susceptibility to HIV infection Diseases 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 206010001513 AIDS related complex Diseases 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 108010027044 HIV Core Protein p24 Proteins 0.000 description 2
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- 102000004169 proteins and genes Human genes 0.000 description 2
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- 206010006187 Breast cancer Diseases 0.000 description 1
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- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
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- 206010038997 Retroviral infections Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
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- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
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- 238000000338 in vitro Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
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- 210000002540 macrophage Anatomy 0.000 description 1
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- 230000005184 men's health Effects 0.000 description 1
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- 238000012205 qualitative assay Methods 0.000 description 1
- 238000012206 semi-quantitative assay Methods 0.000 description 1
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- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
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- 231100000027 toxicology Toxicity 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56983—Viruses
- G01N33/56988—HIV or HTLV
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
- G01N33/743—Steroid hormones
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Cell Biology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Pathology (AREA)
- Biotechnology (AREA)
- Virology (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Endocrinology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
PURPOSE: To obtain the method which can be used to indicate the tendency of HIV infection progress or confirm the possibility of HIV infection progress and measure the concentration of DHEA of a patient who can possibly be reduced in symptoms by dosing DHEA or its salt or combined body. CONSTITUTION: This is the method which measure the degree of danger of the progress of HIV infection of an examinee who is independent in the degree of danger of HIV infection progress of other indexes, and DHEA concentration which is less than the lower limit of a contrast range of 180 to 1,250ng/d1 or a value less than the least value of the contrast range is measured as to a sample of the humor or a secretion of the examinee.
Description
Progression risk of HIV by assay of dehydroepiandrosterone in body fluid This invention relates to a method of determining risk of progression of human immunodeficiency virus (HIV) infection in a subject based on serum hormone levels.
UK-A 2 204 237 describes the use of certain 17-ketosteroids, including dehydroepiandrosterone (DHEA), in the prophylaxis and therapy of retroviral infections including HIV infection, Acquired ImmunoDeficiency Syndrome (AIDS) and AIDS related complex (ARC). More specifically, UK-A 2 204 237 describes the inhibition of HIV p24 antigen production in HIV-infected macrophages.
Bricaire, F. et al. (La Press Medicale Sept. 1988 17 No. 30) have determined the hormonal profile (viz sex hormones and cortisol) in twelve persons presenting with AIDS and twenty eight persons presenting with ARC. All forty persons were homosexual men with a mean age of thirty seven years. Overall levels of the sex hormones, including dehydroepiandrosterone sulphate (DHEA-S), were found to be significantly decreased in AIDS and ARC patients, whereas levels of cortisol were unchanged.
Jacobson, M.A. et al. (Abstracts of the 5th International Conference on AIDS Montreal, June 1989) reported a fifty percent inhibition of macrophage HIV p24 expression at DHEA concentrations of 3-30qg/ml. They also observed that at-risk HIV seronegative homosexual men had a significantly higher serum DHEA-S level than age-matched HIV positive men or healthy HIV negative blood donors. They concluded that DHEA/DHEA-S may have a protective effect in HIV infection.
Wisniewski, T. et al. (Abstracts of the 7th International Conference on AIDS, Florence, June 1991) investigated the relationship between the levels of DHEA and cortisol, absolute T4 levels and clinical stage of disease of HIV positive individuals. Ninety eight adults 6341 6 with HIV infection had plasma cortisol and DHEA levels determined, sixty seven of whom also had simultaneous absolute T4 levels estimated; clinical stage was determined by history and physical examination. The authors found a significant relationship between DHEA levels and absolute T4 levels, but not between absolute T4 levels and cortisol or cortisol/DHEA ratios. They concluded that a positive relationship exists between immune status and DHEA levels.
Mulder, J.H. et al. (Abstracts of the 7th International Conference on AIDS, Florence, June 1991) prospectively followed a cohort of homosexual, initially asymptomatic, HTV-I infected men. Serum DHEA levels were determined in forty one subjects who progressed to AIDS during a five year period, the initial measurement being carried out on a serum sample from 1985 and the final measurement on a serum sample taken fom- months before the diagnosis of AIDS. Forty one age- matched HIV infected subjects who remained asymptomatic during follow-up acted as control subjects. CD4+ counts and HIV p24 antigenaemia had also been determined. Subjects who progressed to AIDS showed a significant decline in DHEA levels while controls did not. DHEA levels, CD4+ counts and HIV p24 antigen status were found to be independent predictors of disease progression. The authors concluded that in asymptomatic HIV-I infected subjects, a decline in DHEA levels is seen before AIDS develops.
Jacobson, M.A. et al. (Journal of Infectious Diseases, In Press) reported a study on serum DHEA and DHEA-S levels and subsequent progression to AIDS, in HIV infected homosexual males participating in the San Francisco Men's Health Study followed prospectively since 1984. Among one hundred and eight men seropositive for HIV at study entry, and with a CD4 lymphocyte count in the 200-500 cells/μΐ range, DHEA levels below the lower limit of normal (< 180 ng/dl) were predictive of subsequent progression to AIDS, after controlling for hematocrit, age and absolute CD4 cell numbers. The authors concluded that DHEA may have a protective effect in HIV infection.
DHEA and its interconvertible sulphate DHEA-S have been reported to inhibit viral expression and have been associated with a decreased risk of cancer (Schwartz, A.G. et al., Toxicologic Pathology 1986 14, No. 3). Increased DHEA-S levels have been associated with reduced breast cancer incidence (Schwartz, A.G. et al., Nutrition and Cancer 1981 3, No. 1).
According to the invention there is provided a method of determining risk of progression of HIV infection in a subject infected with HIV which is independent of other indices of risk of such progression, which method comprises measuring the level of DHEA in a sample of a body fluid or secretion from said subject and comparing said DHEA level with a reference range for DHEA of 180-1250 ng/dl, wherein a level of DHEA which is at the lower end of, or lower than the lowest value on, said reference range is indicative of risk of progression of HIV infection in said subject.
The reference range for DHEA used herein is the reference range of the Nichol's Institute, San Francisco, U.S.A.
It has been determined that low DHEA levels i.e. < 180ng/dl in HIV seropositive subjects appear to be associated with disease progression independent of factors such as age, CD4 count and hematocrit (Jacobson, M.A. et al. (Journal of Infectious Diseases, In Press) which is incorporated herein by reference).
Preferably, the sample of body fluid or secretion is obtained from a subject with a CD4 lymphocyte count of 200-500 cells/μΐ.
Further, preferably, the sample used for the determination of DHEA in accordance with the invention is a body fluid. The body fluid is suitably blood or a blood fraction. The blood fraction is preferably plasma or serum.
The amount of DHEA may be measured in various ways secundem artem. Thus the DHEA may be measured by gas liquid chromatography (GLC).
However, clinical laboratories or, indeed, medical practitioners' surgeries will not normally be equipped with the necessary apparatus for carrying out GLC. Thus, preferably, the determination of DHEA in accordance with the invention would be carried out by immunoassay.
Accordingly, the DHEA may be determined by radio immunoassay or enzyme immunoassay. As with GLC, clinical laboratories may not, and medical practitioners' surgeries, will be unlikely to have the facilities and expertise for carrying out radio immunoassays.
Thus the immunoassay for DHEA determination according to the invention is preferably carried out by enzyme immunoassay.
Thus in one embodiment of the invention there is provided an immunoassay method for the determination of the DHEA antigen component of the DHEA antigen-antibody reaction which comprises: a) adding a sample of a body fluid or secretion containing DHEA to an amount of anti-DHEA in an insolubilised form; b) allowing the immunochemical reaction to take place; and c) estimating the amount of DHEA bound to said insolubilised antiDHEA.
The amount of bound DHEA may be determined by Western Blotting in a manner known per se.
However, equally the amount of bound DHEA may be determined enzymatically in a manner known per se.
Thus an immunoassay method according to the invention may comprise: a) adding a sample of a body fluid or secretion containing DHEA to an amount of anti-DHEA in an insolubilised form; b) allowing the immunochemical reaction to take place, while simultaneously or subsequently adding a predetermined amount of labelled anti-DHEA; and c) estimating the amount of DHEA by determining the amount of free or bound labelled anti-DHEA in a manner known per se.
The bound anti-DHEA may be contacted with anti-mammahan immunoglobulin prior to the enzymatic determination.
The insolubilised antibody may be polyclonal antibody or monoclonal antibody.
The monoclonal antibody if used, may suitably be human, mouse or rat monoclonal antibody prepared by conventional methods, including those methods currently available for producing monoclonal antibody on a commercial scale, genetically engineered monoclonal antibody or antibody fragments or antibody produced by in vitro immunisation of suitable cells.
Preferably, the monoclonal antibody is of class IgG.
The immunoassay methods in accordance with the invention may be carried out using any known format, using for example, beads, dipsticks, membranes, particles, plates, rods, strips, etc. For example, insolubibsed or sobd phase antibody as used in accordance with the invention is suitably bound to a bead, dipstick, membrane, particle, plate, rod, strip, tube, well or the bke of plastics material or glass in a manner known per se. Beads of latex, nylon or other suitable material may also be used according to methods known per se.
More specifically, the insolubilised form of the antibody 4 5 comprises said antibody adsorbed on a surface adapted for protein adsorption. Said surface may be a bead, liposome, membrane, particle, plate, rod, tube, well or the like and of a material as hereinbefore specified. 10 Under laboratory conditions suitably the surface comprises a plastics microtitration plate or strip adapted for protein adsorption wherein the immunochemical reaction and the estimation of the DHEA can take place. The microtitration plates are suitably flat-well polystyrene microtitration plates marketed by Dynatech under the Trade Mark of MICROELISA. Examples of strips are strips marketed by Dynatech under the Trade Mark REMOVAWELL. 15 The relevant surface may be coated directly with an optimum dilution of polyclonal antibody prepared by separating the relevant immunoglobulin fraction of antiserum or, alternatively, monoclonal antibody. 20 The estimation of the bound DHEA in the sample can be carried out by enzymatic, fluorometric, luminometric or radiometric assay, using enzymes, fluorochromes, light-emitting probes or radio labels, respectively in qualitative and semiquantitative assays. The estimation may be carried out visually, for example, when the assay involves the use of coloured beads or the like in a manner known per se such as the methodology described in EP-A 0 154 749. 25 The labelled agents for use in the assays according to the invention are prepared in conventional manner or are purchased from f appropriate suppliers. Such labelled agents are normally in the form of conjugates such as enzyme-labelled antibodies for use in competitive / 30 binding assays. The labelled agent may be an antibody covalently linked to a radio label for use in a radiometric assay, when the assays are carried out under laboratory conditions provided with the necessary equipment and expertise.
Under laboratory conditions the estimation of the bound DHEA may be carried out by enzyme immunoassay, for example by using a suitable peroxidase labelled antibody or other suitable peroxidase conjugate. A suitable peroxidase is horseradish peroxidase. One such other suitable peroxidase conjugate is an avidin-biotin peroxidase complex, which may be used with an antibody biotin conjugate to amplify the enzyme assay in conventional manner. In such an enzyme assay antigen insolubilised on solid phase antibody binds to the antibody-biotin complex which in turn binds to the avidin/streptavidinbiotin peroxidase complex, whereupon the peroxidase activity is measured.
The methods hereinbefore specified can be used to determine levels of DHEA in a subject indicative of a predisposition to, or confirming the likelihood of, progression of HIV infection and which can be alleviated by administration of DHEA or a salt or conjugate thereof.
The invention also provides various test kits or packs containing the necessary components/ingredients for carrying out the diagnostic methods according to the invention. Such a test kit or pack may include antibody coated tubes containing all of the necessary components for carrying out the diagnostic methods according to the invention when a sample of a body fluid is added thereto.
It is also possible to provide a strip containing all of the necessary components/ingredients for carrying out a rapid, one-step assay in accordance with the invention when a sample of a body fluid is applied thereto in a manner known per se.
Further support for the invention is based on the following study as reported by Jacobson et al. (Journal of Infectious Diseases, In Press) supra.
The subjects, participants in a San Francisco Health Study originating in 1984, were evaluated at six month intervals, referred to as cycles, at which time serum samples were obtained and frozen at -70°C. The sera from 108 HIV seropositive homosexual males participating in this ongoing study were tested to determine the association between DHEA levels and AIDS progression. At examination cycle 5, when each of the subjects had a CD4 count in the range 200-500 cells/μΐ, DHEA levels were determined by radio immunoassay. DHEA levels were thus measured at each follow-up examination cycle and the subjects divided into two groups depending on whether their plasma DHEA levels were (i) < 180ng/dl or (ii) > 180ng/dl. The two groups were further subdivided into those subjects who had developed full blown AIDS and those who had not. During a median 37 month follow-up period, 16 of 27 individuals with subnormal DHEA levels (< 180ng/dl) progressed to AIDS compared to 22 of 81 with normal DHEA levels.
The follow-up study demonstrated an association between low DHEA levels in the subjects involved in the study and progression to full blown AIDS independent of age, CD4 count and hematocrit of the subjects as hereinafter demonstrated.
In evaluating the data, a series of Cox proportional hazards regression models were fitted to estimate the relative hazard of developing AIDS associated with subnormal DHEA levels both alone and adjusted for the levels of other covariates.
The relative hazards of developing AIDS associated with subnormal DHEA levels alone and adjusted for the influence of other covariates measured at cycle 5 are summarized in Table 1.
TABLE 1 RELATIVE HAZARDS OF DEVELOPING AIDS.
Predictor Relative Hazard p-value DHEA < 180 (alone) 2.38 <0.01 DHEA <180 (adjusted) 2.34 0.02 Age/10 2.18 <0.01 Hematocrit < 40 4.57 <0.01 CD4 Cells/10 0.99 0.71 The present invention is thus supported by the above analyses which 5 confirm a significant association between DHEA levels < 180ng/dl and an increased risk of progression to AIDS. This association was shown to persist even after adjusting for hematocrit and CD4 lymphocyte counts, which are known to be independent predictors of HIV disease progression,
Claims (22)
1. A method of determining risk of progression of HIV infection in a subject infected with HIV which is independent of other indices of risk of such progression, which method comprises measuring the level of DHEA in a sample of a body fluid or secretion from said subject and comparing said DHEA level with a reference range for DHEA of 1801250 ng/dl, wherein a level of DHEA which is at the lower end of, or lower than the lowest value on, said reference range is indicative of risk of progression of HIV infection in said subject.
2. A method according to Claim 1, wherein the sample of body fluid or secretion is obtained from a subject with a CD4 lymphocyte count of 200-500 cells/μΐ.
3. A method according to Claim 1 or 2, wherein the level of DHEA is < 180ng/dl.
4. A method according to any one of Claims 1 to 3, wherein the sample is a body fluid.
5. A method according to Claim 4, wherein the body fluid is blood or a blood fraction.
6. A method according to Claim 5, wherein the blood fraction is plasma or serum.
7. A method according to any preceding claim, wherein the DHEA is determined by gas liquid chromatography.
8. A method according to any one of Claims 1-6, wherein the determination of DHEA is carried out by immunoassay.
9. A method according to Claim 8, wherein the determination of DHEA is carried out by radio immunoassay.
10. A method according to Claim 8, wherein the determination of DHEA is carried out by enzyme immunoassay.
11. A method according to any one of Claims 1-6, wherein the DHEA is measured by immunoassay by determining the DHEA antigen component of the DHEA antigen-antibody reaction which comprises: a) adding a sample of a body fluid or secretion containing DHEA to an amount of anti-DHEA in an insolubilised form; b) allowing the immunochemical reaction to take place; and c) estimating the amount of DHEA bound to said insolubilised antiDHEA.
12. A method according to Claim 11, wherein the amount of bound DHEA is determined by Western Blotting in a manner known per se.
13. A method according to Claim 11, wherein the amount of bound DHEA is determined enzymatically in a manner known per se.
14. A method according to Claim 11, which comprises: a) adding a sample of a body fluid or secretion containing DHEA to an amount of anti-DHEA in an insolubilised form; b) allowing the immunochemical reaction to take place, while simultaneously or subsequently adding a predetermined amount of labelled anti-DHEA; and c) estimating the amount of DHEA by determining the amount of free or bound labelled anti-DHEA in a manner known per se.
15. A method according to Claim 14, wherein said bound anti-DHEA is contacted with anti-mammalian immunoglobulin prior to the enzymatic determination.
16. A method according to any one of Claims 11-15, wherein the insolubilised antibody is monoclonal antibody.
17. A method according to any one of Claims 11-16, wherein the insolubilised antibody is located on a dipstick. 5
18. A method according to any one of Claims 1-17, for determining levels of DHEA in a subject indicative of a predisposition to, or confirming the likelihood of, progression of HIV infection and which can be alleviated by administration of DHEA or a salt or conjugate thereof. 10
19. A method according to Claim 18, wherein the DHEA or salt or conjugate thereof is administered orally.
20. A test kit containing one or more component(s) for carrying out a method according to any one of Claims 1-19.
21. A method according to Claim 1, substantially as hereinbefore 15 described.
22. A test kit according to Claim 20, substantially as hereinbefore described.
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE326690A IE63418B1 (en) | 1990-09-10 | 1990-09-10 | Progression risk of HIV by assay of dehydroepiandrosterone in body fluid |
| JP3307281A JPH04351964A (en) | 1990-09-10 | 1991-09-09 | Screening method and application method thereof |
| ITMI912378A IT1255009B (en) | 1990-09-10 | 1991-09-09 | METHOD FOR DETERMINING THE RISK OF PROGRESS OF HIV INFECTION AND RELATED DIAGNOSTIC KIT |
| DE4129932A DE4129932A1 (en) | 1990-09-10 | 1991-09-09 | SCREENING PROCESS AND ITS APPLICATION |
| GB9119256A GB2249833B (en) | 1990-09-10 | 1991-09-09 | Progression risk of HIV by assay of dehydroepiandrosterone in body fluid |
| FR9111118A FR2666657A1 (en) | 1990-09-10 | 1991-09-09 | METHOD FOR DETERMINING THE RISK OF EVOLUTION OF INFECTION CAUSED BY HIV AND ITS IMPLEMENTATION |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE326690A IE63418B1 (en) | 1990-09-10 | 1990-09-10 | Progression risk of HIV by assay of dehydroepiandrosterone in body fluid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IE63418B1 true IE63418B1 (en) | 1995-04-19 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE326690A IE63418B1 (en) | 1990-09-10 | 1990-09-10 | Progression risk of HIV by assay of dehydroepiandrosterone in body fluid |
Country Status (6)
| Country | Link |
|---|---|
| JP (1) | JPH04351964A (en) |
| DE (1) | DE4129932A1 (en) |
| FR (1) | FR2666657A1 (en) |
| GB (1) | GB2249833B (en) |
| IE (1) | IE63418B1 (en) |
| IT (1) | IT1255009B (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4230684A (en) * | 1978-03-16 | 1980-10-28 | Cornell Research Foundation, Inc. | Method for determining steroids in human body liquids |
| NL194728C (en) * | 1987-04-16 | 2003-01-07 | Hollis Eden Pharmaceuticals | Pharmaceutical preparation suitable for the prophylaxis or therapy of a retroviral infection or a complication or consequence thereof. |
| EP0456753B1 (en) * | 1989-02-01 | 1994-05-04 | E.I. Du Pont De Nemours And Company | HIV p17 ASSAYS FOR MONITORING DEVELOPMENT OF AIDS |
| JPH02213766A (en) * | 1989-02-15 | 1990-08-24 | Mochida Pharmaceut Co Ltd | Reagent and implement for immunoassay |
-
1990
- 1990-09-10 IE IE326690A patent/IE63418B1/en not_active IP Right Cessation
-
1991
- 1991-09-09 FR FR9111118A patent/FR2666657A1/en active Granted
- 1991-09-09 DE DE4129932A patent/DE4129932A1/en not_active Withdrawn
- 1991-09-09 IT ITMI912378A patent/IT1255009B/en active IP Right Grant
- 1991-09-09 GB GB9119256A patent/GB2249833B/en not_active Expired - Lifetime
- 1991-09-09 JP JP3307281A patent/JPH04351964A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| FR2666657B1 (en) | 1997-02-21 |
| FR2666657A1 (en) | 1992-03-13 |
| GB2249833B (en) | 1994-09-07 |
| ITMI912378A0 (en) | 1991-09-09 |
| IT1255009B (en) | 1995-10-11 |
| DE4129932A1 (en) | 1992-03-12 |
| ITMI912378A1 (en) | 1993-03-09 |
| GB9119256D0 (en) | 1991-10-23 |
| JPH04351964A (en) | 1992-12-07 |
| GB2249833A (en) | 1992-05-20 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed |