RU2306566C1 - Method for predicting rapid disease progress in hiv-infected patients - Google Patents

Abstract

FIELD: medicine, laboratory diagnostics.

SUBSTANCE: in patients in the stages of generalized lymphoadenopathy (GLAP) or pre-AIDS it is necessary to sample venous blood to detect quantitative content of CD+-, CD8+-, CD16+-, CD20+-lymphocytes and circulating immune complexes (CIC). In case of detecting during GLAP stage the quantity of CD4+- being below 0.46x10*9/l, CD20+ - above 0.095x10*9/l and CIC being above 170 c.u. at probability of 99.0% one should predict rapid disease progress. In case of detecting during pre-AIDS stage the quantity of CD8+ - above 0.11x10*9/l at probability of 95.5% it is, also, possible to predict rapid disease progress. The innovation enables to develop simple and available method for predicting rapid flow of HIV-infection.

EFFECT: higher accuracy of prediction.

1 ex, 5 tbl

Description

The invention relates to medicine, namely to infectious diseases.

Despite the intensive study of HIV infection, which is among the most dangerous human diseases (Montagnier L., 1992; Sizyakina L.P., 1995, 1996, 2001), many aspects of its pathogenesis remain undecided (Cozzi Lepri A., 1995; Orlova V .M., 1996; Rosenberg ZF, Fauci AS, 1990; Shemshura A.B., 1997). This negatively affects the improvement of methods for the prevention, diagnosis and treatment of this disease (Vella et al., 1992; Pokrovsky VV, 2000; Fauci A.S., 1996). As for the available methods for predicting the adverse course of HIV infection, those have not been developed at all. Meanwhile, without them it is not possible to implement an individual, differentiated approach to the treatment of such patients (Khaitov P.M., Ignatyeva G.A., 1992; Sizyakina L.P., 2001; Denisenko V.B., 1997).

A known method for predicting the course of HIV infection, based on clinical signs, in particular on the characteristics of the IV-x stages and 6 phases (V.I. Pokrovsky, 1989).

The experience gained by clinicians allows us to make some predictions about the duration of these stages and thus predict the rate of infection and the need for therapeutic intervention. However, this method is subjective and does not always allow to justify the timely use of antiviral therapy.

There is also an immunological method for classifying HIV infection, based on the determination of the absolute content and ratio of CD4 + and CD8 + lymphocytes in peripheral blood (SJS / WHO, 1987). This method gives a clear idea of the degree of infection of the lymphocytes with the virus. However, the possibilities of this method with respect to predicting the course of HIV infection are more limited, since forecasting in this case is also based on empirical experience of the transition of one stage to another, and the prognosis is also not very accurate.

A known method for predicting the course of HIV infection (RF patent No. 2097766, MHK G01N 33/49, publication 11/27/1997), which is adopted as a prototype. The method consists in examining a patient’s peripheral blood, in which a lymphocytic fraction of blood is isolated, total DNA extraction is carried out in it, virus agents from the Herpesviridae group are isolated by the method of a DNA probe and, in the presence of two or more agents, a severe course of the disease is predicted.

The objective of the invention is the development of an affordable and simplified method for predicting the rapid progression of the disease in patients with HIV infection.

The objective is achieved in that patients with HIV infection in the stage of generalized lymphadenopathy (GLAP) or in the pre-AIDS stage take venous blood and determine the quantitative content of CD4 + -, CD8 + -, CD16 + -, CD20 + - lymphocytes and circulating immune complexes ( CEC). In the case of detecting in the GLAP stage the amount of CD4 + is less than 0.46 × 10 ⁹ / l, CD20 + is more than 0.095 × 10 ⁹ / l and the CEC is more than 170 c.u., and in the pre-AIDS stage, CD8 + is more than 28.4 % and CD16 + - more than 0.11 × 10 ⁹ / l with a probability of 99.0% and 95.5%, respectively, predict the rapid progression of the disease.

The inventive method for predicting the rapid progression of the disease is based on the results of a survey of 52 patients with HIV infection, among whom the stage of GLAP was qualified in 24 and the stage of pre-AIDS in 28 people.

The method is as follows.

All patients underwent immunological blood tests. In patients with HIV infection in the stage of GLAP or in the pre-AIDS stage, venous blood was taken and a number of immunological parameters were determined in it:

1) CD3 +, CD 4+, CD8 +, CD16 +, CD20 +, CD95 + - lymphocytes (by the method of A.V. Filatov et al., 1990);

2) serum immunoglobulins of classes A, M and G (according to Manchmi et al., 1965);

3) circulating immune complexes - CEC (according to the method of Haskova et al., 1978 as modified by Yu.A. Grinevich and A.I. Alferov, 1981).

Then, over the next four years, these patients underwent dynamic monitoring, at the end of which two groups were identified: 1) with relatively fast and 2) relatively slow progression of the disease.

The timing of the transition of HIV infection from one stage to the next stage was taken as the main criterion for this division. If they turned out to be less than one year, the rapid progression of the disease qualified, otherwise - slow.

The group of patients with the rapidly progressing course of HIV infection included 30 people, of whom 10 - the disease passed from the GLAP stage to the pre-AIDS stage, and 20 - from the pre-AIDS stage to the AIDS stage. In the group of patients with relatively slow progression of HIV infection, 22 people were found, including - 14, in which the disease was transformed from the GLAP stage to the pre-AIDS stage, and in 8 - from the pre-AIDS stage to the AIDS stage.

After that, the immunity indicators studied four years ago were compared in each of these two groups of patients with HIV infection (with a relatively fast and slow progression of the disease). The analysis was carried out separately: at the GLAP stage and at the pre-AIDS stage.

As can be seen from Table 1, with the rapid progression of HIV infection in the stage of GLAP, in contrast to the relatively favorable course, lower indices of the number of CD3 + -, CD4 + -, and CB8 + cells were noted. At the same time, the absolute content of CD20 + - lymphocytes and CEC was significantly higher.

At the pre-AIDS stage, differences were also found in the quantitative level of a number of indicators of the immune system (Table 2). So, with subsequent adverse development of the disease, the quantitative blood count of CD8 + and CD16 + lymphocytes in patients with HIV infection was higher than in the other group.

To develop a forecast method, a Wald method of sequential alternative analysis was used, in accordance with the principles of which, in the presence of two states (conditionally “A” and “B”), characterized by the same, but with different frequencies, occurring signs, by sequentially summing the logarithms of the relations the frequency of each individual characteristic in state “A” to its frequency in state “B”, it is possible to gradually accumulate statistically significant information that allows a sufficiently reliable distribution chenie these states. If we take “α” for the error value in recognizing the state “A”, and “β” for recognizing the state “B”, then with the sum of the logarithms (Σ lg) of these relations in each case

with the selected level of reliability (> 95.5%;> 99% or 99.9%), we can state state “A”, and at

и

, то накопленной информации может оказаться недостаточно для разграничения указанных состояний с заданным уровнем надежности.- state "B". If the quantity Σ lg is in the interval between

and

, then the accumulated information may not be enough to distinguish between these states with a given level of reliability.

In the claimed method, state “A” was identified with the rapidly progressing course of HIV infection, state “B” - with a relatively slow one.

The calculation of the values of prognostic coefficients that can have either a positive or negative sign (the latter indicates the development of the state “B”) was carried out according to the formula: PC = 10 × log (A: B), where PC is the prognostic coefficient, (A: B ) - the ratio of the frequencies of the sign under conditions "A" and "B".

Upon reaching the threshold sum of 13 points as a result of sequential addition of PC values, the procedure was terminated and a rapidly progressing course of HIV infection was predicted with a reliability level of 95.5%. With negative values of the algebraic sum of PK (-13 points and below), a relatively slow progression of the disease was assumed.

If, upon completion of a sequential alternative analysis, the accumulated sum of personal computers did not reach the required level of reliability, being in the range from +13 to 13 points, the forecast qualified as uncertain.

Based on the materials of the studies, the most prognostically significant immunological indicators were selected, which had significant differences in frequency.

In accordance with the principles of Wald's alternative analysis, the prognosis procedure is carried out in practice by summing the PC of each of the signs identified in the subject in a sequence determined by the degree of their information content (from greater to lesser), calculated using the Kullback measure by the formula: MK = (A-B )% × EPK, where MK is the Kullback measure; (A-B)% - the absolute value of the difference in the frequencies of the characteristic in the compared groups; YPC - the sum of the absolute values of the PC of each of the sign variants.

Based on the obtained data, two scales were constructed to determine criteria for predicting the course of the disease in the stages of GLAP and pre-AIDS in specific patients with HIV infection (Tables 3, 4).

The use of the method is illustrated by a clinical example.

Case history No. 485.

Patient V., 34 years old.

Clinical diagnosis: HIV infection, stage of primary manifestations, phase 11B (GLAP). Generalized lymphadenopathy, acute pneumonia.

Infected with blood transfusion 5 years ago. Over the past year, she suffered from ARVI, acute acute pneumonia 4 times. At the age of 34 years, the patient in the blood found AT against HIV (ELISA) and its proteins ("Westem-blot").

Received in the infectious ward with complaints of fever, cough, general weakness. General condition of moderate severity. Body temperature - 38.1 ° C. The correct physique. Satisfactory nutrition. The skin is pale, clean. The occipital lymph nodes are enlarged to 1.1 cm in diameter, the cervical and inguinal - up to 1.0-1.5 cm, the submandibular axillary - up to 1.0-2.0 cm. In the lungs, hard breathing is heard on the right, on the left - in the lower sections weakened, single crepitating rales. NPV - 20 per min. Heart sounds are muffled, rhythmic. Heart rate - 100 per minute. The abdomen is soft, painless. Liver - at the edge of the costal arch on the right. The spleen is not palpable. Chair and diuresis - without features.

In the general analysis of blood: leukocytosis with a neutrophilic shift, accelerated ESR.

Indicators of the patient's immune status upon admission to the hospital are presented in table 5. Using the scale for determining the prognosis of HIV infection, a total of 14 points was obtained, which made it possible to predict the rapid progression of the disease with a reliability of 95.5%.

Indeed, after 3 months in a patient with HIV infection, the disease passed from the stage of GLAP to the stage of pre-AIDS. Subsequently, due to the progression of the disease, AIDS developed, which led to a fatal outcome.

Table 3
The scale for determining the prognosis of fast (PD) and slow (MP) disease progression in patients with HIV infection in the stage of GLAP No. / No. Defined attribute Feature Characteristic BUT AT PC (in conventional points) BP (+) MP (-) one. CD4 + (10 ⁹ / L) <0.46 80.0 35.7 +4 ≥0.46 20,0 64.3 -5 2. CD20 + (10 ⁹ / L) > 0,095 60.0 14.3 +6 ≤0.095 40,0 85.7 -3 3. CEC (c.u.) > 170 60.0 14.3 +6 ≤170 40,0 85.7 -3 four. CD8 + (10 ⁹ / L) <0.56 70.0 28.6 +4 ≥0.56 30,0 71,4 -four

Table 4
The scale for determining the prognosis of fast (PD) and slow (MP) disease progression in patients with HIV infection in the pre-AIDS stage No. / No. Defined attribute Feature Characteristic BUT (%) AT (%) PC (in conventional points) BP (+) MP (-) one. CD8 + (%) > 28.4 65.0 12.5 +7 ≤28.4 35.0 87.5 -four 2. CD16 + (10 ⁹ / L) > 0.11 60.0 12.5 +7 ≤0.11 40,0 87.5 -3

Table 5
Indicators of immune status in patient B. Indicators Patient B. CD3 + (%) 77.0 CD3 + (10 ⁹ / L) 1.44 CD4 + (%) thirty CD4 + (10 ⁹ / L) 0.41 CD8 + (%) 29th CD8 + (10 ⁹ / L) 0.5 CD16 + (%) 6.5 CD16 + (10 ⁹ / L) 0.12 CD4 + / CD8 + 1,03 CD20 + (%) 7 CD20 + (10 ⁹ / L) 0.13 CD95 + (%) 7 CD95 + (10 ⁹ / L) 0.12 IgA (g / l) 1.8 IgM (g / l) 1,0 IgG (g / l) 11.71 CEC (c.u.) 134 HCT spont. (cu) 83 HCT Steam (cu) 134 K.st. (cu) 1,6

Claims (1)

A method for predicting the rapid progression of the disease in patients with HIV infection by immunological blood testing, characterized in that in patients with stages of the disease of generalized lymphadenopathy (GLAP) or pre-AIDS, venous blood is taken and the quantitative content of CD4 + -, CD8 + -, CD16 + - is determined in it , CD20 + - of lymphocytes and circulating immune complexes (CEC), and if CD4 + amounts of less than 0.46 · 10 ⁹ / l are detected in the GLAP stage, CD20 + - more than 0.095 · 10 ⁹ / l and CEC more than 170 c.u., and in the pre-AIDS stage - CD8 + - more than 28.4% and CD16 + - more than 0.11 · 10 ⁹ / l with a probability of corresponding About 99.0 and 95.5% predict a rapid progression of the disease.