[Treatment of infection caused by human immunodeficiency virus in the Russian Federation].

AIM: To study efficacy and safety of highly active antiretrovirus treatment (HAAT) used in the Russian Federation for development of recommendations for HIV infection treatment. MATERIAL AND METHODS: A total of 285 patients with chronic HIV infection and 42 patients with acute HIV infection participated in investigation of efficacy and safety of different HAAT schemes in 1997-2008. Efficacy of the treatment was assessed by percentage of the patients who had HIV RNA undetectable by the test system (< 400 copy/ml) after 24-48 treatment weeks, by a mean reduction of HIV RNA in blood plasma and an increase in the number of CD4-lymphocytes in 1 mcl of blood. RESULTS: A 12-year experience in antiretrovirus therapy administration for management of HIV infection is reviewed. Efficacy and safety of Russian antiretrovirus drug Phosphaside in HAAT schemes are shown in patients with both chronic and acute HIV infection. The model of HIV patients consulting before the treatment, psychological support during the treatment, methods of individual and group consulting, conception of the school for patients on HAAT are presented. Recommendations are proposed for administration of antiretroviral therapy and a model of calculation of the number of HIV-infected patients in need of antiretroviral therapy in Russia. Basing on the results of investigations on efficacy and safety of HAAT schemes, the physicians of the National Anti-AIDS Center have developed clinical recommendations, guidelines on the treatment of HIV infection, standards of medical care for HIV-infected patients.

[Hemostatic disorders in patients with HIV infection]. / Narusheniia v sisteme gemostaza u bol'nykh s VICh-infektsiei.

Impaired hemostasis was studied in 50 adult patients with HIV infection. The blood coagulative potential, the number and functional activity of platelets were examined. Platelet aggregation and secretion were shown to change earlier than thrombocytopenia developed and clinical signs of HIV infection appeared. The disturbance in the plasma section of hemostasis are due to concurrent opportunistic diseases and infections.

[Clinical manifestations and the problems of classification of HIV infection]. / KLinicheskie proiavleniia i voprosy klassifikatsii VICh-infektsii.

The clinical manifestations and some immunological parameters (CD4 lymphocytes, CD4/CD8 ratio, IgM, IgA, IgG levels, skin test) were examined in 226 adult patients (148 males and 78 females) infected with HIV. These included 58 (26%) asymptomatic patients with seropositive test, 109 (48%) with the only clinical manifestation generalized lymphadenopathy; 54 (24%) with AIDS-related infections, 5 (2%) with AIDS. A subsequent follow-up of 3 months to 3 years demonstrated that AIDS developed in 7 patients, 9 died. The period of infection with HIV and death ranged from 1.5 to 9 years. The signs of cell immunodeficiency were found in 70% of the examinees. Recommendations are given on the classification of HIV infection.

[The characteristics of the HIV isolated from HIV-infected persons and AIDS patients on the territory of the CIS]. / Kharakteristika VICh, vydelennykh ot VICh-infitsirovannykh lits i bol'nykh SPIDom na territorii SNG.

HIV strains were isolated from HIV-infected patients and AIDS patients in CIS. A total of 81 HIV isolates were obtained. The isolates were identified by using immunofluorescence and enzyme immunoassay, by determining the activity of reverse transcriptase, immunoblot, electron microscopy, polymerase chain reaction. Of the 81 isolates 79 were HIV-1 and 2 HIV-2. The strains differed in their infectivity, the kinetics of virus antigen accumulation, and the spectrum of susceptible cell lines. The viruses isolated may be assigned as two groups: high and low infective. The biological properties of the national HIV isolates were shown to be similar to the prototype HIV strains isolated elsewhere.

[Replicative properties of HIV-1 strains, resistant to 3'-azido-2'3'-dideoxythymidine]. / Replikativnye svoistva shtammov VICh-1, rezistentnykh k 3'-azido-2',3'-didezoksitimidinu.

The replicative activity of two strains of human immunodeficiency virus type I, 1974 and 1978, resistant to 3'-azido-2',3'-dideoxythymidine (AZT), was investigated. Assessment of AZT sensitivity by the standard method showed the 50% effective dose (ED50) for strain 1974 to be 0.1 mumole and for strain 1978, 1 mumole. Both strains had the slow/low. 3 phenotype. The level of virus-specific antigens in these strains was 3-7 times lower than in AZT-sensitive strain IIIB. In order to study the effects of AZT on virus replication, the strains were passaged in Jurkat-tat cells in the presence of 3.5 mumole of AZT. Virus activity was assessed from the level of intracellular (S-12) and extracellular (P-100) antigens, cell viability, and syncytium formation. Cell viability increased by 10%, syncytium formation dropped 5 times, and antigen accumulation increased 1.5-2 times in the culture with strain 1974. For strain 1978 these parameters were as follows: 17% decrease of cell viability, increase of syncytium formation by 1.7 times, and no changes in the level of viral antigen. After four serial passages in the presence of AZT ED50 for strain 1974 was 0.5 mumole and at least 1 mumole for strain 1978.

[Amplification of the activity of HIV-1 isolates purified from seropositive children after cryopreservation of persistently-infected cells]. / Usilenie aktivnosti izoliatov VICh-1, vydelennykh ot seropozitivnykh detei, posle kriokonservatsii persistentno infitsirovannykh kletok.

HIV-1 strains MC-1974 and MC-1978 were isolated from children infected in hospital. Both children presented with symptoms of HIV infection by the moment the blood samples for virus isolation were collected. In vitro the isolated strains showed weak infective activity and caused no cytopathic effect in sensitive cells. It may be explained by azidothymidine antiviral therapy or by initial immunodeficient status of both children not caused by HIV infection. Virus activity was enhanced in both cultures after reactivation of Jurkat-tat cells persistently infected with MC-1974 and MC-1978 strains after cryopreservation. Viruses isolated from culture fluid effectively infected Jurkat-tat cells. The infection was associated with formation of syncytia, accumulation of viral particles detected by electron microscopy and of intracellular antigens detected by fluorescent antibody technique and by immunoblotting. The results suggest the presence in the body of infected children and in Jurkat-tat-1974 and Jurkat-tat-1978 persistent lines of a viral genome containing all virusspecific genes necessary for productive expression of HIV-1.

[The characteristics of human immunodeficiency virus strains isolated from HIV-infected persons on the territory of the USSR]. / Kharakteristika shtammov virusa immunodefitsita cheloveka, vydelennykh ot VICh-infitsirovannykh lits na territorii SSSR.

Fifty-seven HIV-1 strains were isolated from peripheral blood lymphocytes of 102 HIV-infected persons involved in epidemic outbreaks in different cities of the USSR. The effectiveness of isolation was 29.1% in asymptomatic infection, 51.7% in cases with generalized lymphadenopathy, and 82.6% in persons with severe clinical manifestations. Identification of the isolates by indirect immunofluorescence, ELISA, reverse transcriptase activity, Western blot, electron microscopy, and polymerase chain reaction showed them to belong to HIV-1 type. Reproduction of the isolates in cell cultures was accompanied by cytopathic effect and syncytium formation. The isolated strains can be divided into two groups: (1) the poorly growing isolates with low or negative RT and ELISA results and (2) the isolates with high infectivity, broad spectrum of cell tropism, and high levels of RT and ELISA. These data show the correlation of biological properties of HIV-1 strains isolated in the USSR with those of HIV strains previously isolated in Europe, USA, and Africa.

[Genetic characteristics of variants of human immunodeficiency virus type 1, causing an epidemic among substance abusers in Commonwealth of Independent States countries]. / Geneticheskaia kharakteristika variantov virusa immunodefitsita cheloveka 1-go tipa, vyzvavshikh épidemiiu sredi narkomanov v stranakh SNG.

Gag/env nucleotide sequences of human immunodeficiency virus type 1 (HIV-1) variants detected in drug users in Russia, Ukraine, and Belarus are analyzed. Two HIV-1 subtypes A and B circulate in this risk group. Genetic variability within one subtype is no higher than 3.1 and 3.9% for gag and env genes, respectively, suggesting the same source of infection in populations of drug users infected with the same subtype. Recombinant viruses with gagAenvB genotype, genetically related to parental strains of subtypes A and B, circulate in this risk group. This is the first report about HIV-1 recombinant of the two subtypes, for which both parental strains are known, directly confirming the in vivo recombination between different subtypes.

[The structure of the secondary diseases in HIV-infected patients in Russia]. / Struktura vtorichnykh zabolevanii u bol'nykh VICh-infektsiei v Rossii.

In 95 patients with HIV infection (76 males and 19 females), observed in 1993-1997, the structure of secondary diseases was studied. During this period 58 patients (61.1%) died. In the structure of secondary diseases represented by 14 nosoforms prevailed cytomegalovirus and candidal infections, tuberculosis, Kaposi's sarcoma, rarely--pneumocystis pneumonia, cryptococcal meningitis and toxoplasmosis.

[The first case of HIV infection in a citizen of the USSR]. / Pervyi sluchai VICh-infektsii u grazhdanina SSSR.

The first AIDS patient was a homosexual male who contacted HIV infection in 1982 in Tanzania. In December 1985 the first sign of Kaposi's sarcoma was noted in this patient. HIV infection was diagnosed in him only in February 1987. He was treated with AZT, reaferon, immunoglobulin and underwent electronic therapy. His state of health was stable till February 1991. Then he got severe bacterial pneumonia, candidosis. Pancytopenia progressed. The dose of AZT (0.8 g daily) was increased and intensive antibiotic therapy and the course of diflucan were prescribed. In spite of this treatment the number of CD4 lymphocytes catastrophically decreased (CD4 = 0.01 x 10(9)/l) and the patient died. Thus, more than 63 months passed from the date of the appearance of the first symptoms of AIDS in the patient to his death.

[The effect of immunoglobulin on hemostatic function in patients with HIV infection]. / Vliianie immunoglobulina na sostoianie gemostaza u bol'nykh VICh-infektsiei.

The influence of immunoglobulin for intravenous injection on the state of cell- and plasma-mediated elements of hemostasis in patients with HIV infection, treated with immunoglobulin (Ig) in connection with the presence of secondary diseases of bacterial nature and having thrombocytopenia, was analyzed. After two injections of 50.0 ml of Ig to patients with HIV infection and thrombocytopenia a rise in the count of blood platelets in 80% of cases; this rise reached its maximum on day 7-10 after the beginning of treatment and was retained 1-3 months later in most patients on the level of healthy persons. Under the influence of Ig the aggregation capacity of thrombocytes increased mainly in persons with the initially low function of blood platelets. The introduction of Ig did not perceptibly influence the capacity of thrombocytes for endo-exocytosis, the aggregation activity of red blood cells, as well as the plasma-mediated element of hemostasis.

[The thrombocytic link in hemostasis and the immunity system of patients with HIV infection]. / Sostoianie trombotsitarnogo zvena gemostaza i sistemy immuniteta u bol'nykh VICh-infektsiei.

To find out possible relationships between disturbances in the thrombocytic element of hemostasis and in the immune system (the count of lymphocytes CD4, the concentration of IgG, the content of circulating immune complexes), 18 adult patients with HIV infection were examined, and in 8 of them thrombocytopenia was diagnosed. 10 patients without thrombocytopenia formed the control group. The study revealed that with the development of thrombocytopenia in patients with HIV infection the aggregation capacity of their blood platelets decreased, which correlated (p < 0.01) with a decrease in the count of lymphocytes CD4; this was indicative of the progress of immunodeficiency.

[Pyoderma vegetans as an early sign of HIV infection]. / Vegetiruiushchaia piodermiia kak rannii priznak VICh-infektsii.

Skin and mucosal lesions are described in a 40-year-old man who suffered from HIV infection in the stage of secondary diseases. The diagnosis was supported by demonstration of antibodies to HIV in the immune blotting test. The clinical manifestations were reduced to steady fever, generalized lymphadenopathy, pyoderma vegetans and chancriform pyoderma, candidiasis of the oral cavity, and seborrheic dermatitis, HIV infection was diagnosed 4 years after the appearance of pyoderma which initially was amenable by external antibacterial agents and then became resistant to them. Eruptions of pyoderma vegetans simulating wide condylomas were located in inguinal folds, on the internal surface of the thighs and scrotum; the chancriform focus was located in the internal preputial layer. The treatment with azothymidine combined with antibacterial and antimycotic agents led to the improvement of the patient's general status and to the reduction of local lesions. However, on recommendations of an unknown witch doctor who started treating him with the aid of reflexotherapy, phytotherapy and bioenergetic actions the patient stopped receiving the treatment prescribed and did not report for control examinations. After 5 months he died of brain edema.

[The prognostic significance of the clinical manifestations of HIV infection during seroconversion]. / Prognosticheskoe znachenie klinicheskikh proiavlenii VICh-infektsii v periode serokonversii.

For the period 1990-1993, HIV infection in seroconversion was diagnosed in Russia in 21 cases. Of them, 16 patients had acute symptoms. Follow-up results are available for 12 patients in seroconversion who had either typical or obscure symptoms (6 and 6 patients, respectively). It is found that the disease progresses more rapidly in patients with the history of acute HIV infection in seroconversion manifesting with clear-cut typical symptoms of 4-week duration, at least. One patient from this group 3 years and 7 months after seroconversion developed Kaposi's sarcoma and candidiasis esophagitis which indicates the occurrence of AIDS stage IIIB.

[Disorders in the plasma and cellular hemostatic components of patients with HIV infection]. / Narusheniia v plazmennom i kletochnom zvene gemostaza bol'nykh s VICh-infektsiei.

Plasmic and platelet components of hemostasis were investigated in 100 HIV-infected subjects. Its degree depended on the infection stage and associated opportunistic infections. The key factor in pathogenesis of hemocoagulatory disorders is reduced count, abnormal function and morphology of platelets. A direct relationship exists between the number of CD4-lymphocytes, a decline in the number and functional activity of platelets. Intravenous injection of immunoglobulin made in Russia as an adjuvant to combined therapy of HIV-infected subjects contributes to recovery of platelet count and aggregation.

[The clinical manifestations of HIV infection during seroconversion]. / Klinicheskie proiavleniia VICh-infektsii v periode serokonversii.

21 seroconversion HIV-infected subjects have been examined. 16 of them presented with acute symptoms. The disease in the period of seroconversion manifested with fever, weakness, headache, pain in the throat, enlargement of peripheral lymph nodes, polymorphous eruption. Typical mononucleosis-like syndrome occurred in 3 patients only. Half of the patients had subclinical disease, no eruption was seen. Because of clinical indications only 8 of 21 patients were examined for HIV infection. One-third of the patients in seroconversion had moderate thrombocytopenia, probably of autoimmune nature. Autoimmune disorder of the thyroid was registered in 1 patient. The diagnosis of acute HIV infection is not easy in view of rare occurrence of immunodeficiency typical for this infection. Candidiasis of the mucosa was seen in 37.5%, low levels of CD4-lymphocytes in 66.7% of the cases.

[The diagnosis and clinical characteristics of cytomegalovirus infection in HIV-infected subjects]. / Diagnostika i klinicheskaia kharakteristika tsitomegalovirusnoi infektsii u VICh-infitsirovannykh lits.

Out of 180 HIV carriers active cytomegalovirus (CMV) infection was found in 30 patients, in 16 cases the infection manifested clinically. Most of the latter were patients with HIV infection IIIb or IIIc stage against persistent lowering of CD4-lymphocyte count under 100/mm3. Active CMV infection may be determined most significantly by the following criteria: high or moderate concentrations of CMV DNA in the blood, low concentrations of blood CMV DNA in the presence of long-term (at least 3 months) persistence of anti-CMV IgM and isolation of urinary CMV. CMV infection manifested usually as a generalized disease with typical signs of retinitis, myelitis, erosive-ulcerative colitis. Most patients had thrombocytopenia, functionally defective platelets. CNS involvement predicts poor prognosis in CMV-infected HIV carriers.

[Tuberculosis in patients with HIV infection]. / Tuberkulez u bol'nykh s VICh-infektsiei.

Within 1987-1995 the authors observed 16 cases of tuberculosis in HIV-infected patients which accounted for 26.7% of AIDS patients treated by them. 14 cases were diagnosed intravitally, 2 postmortem. Infiltrative, generalized, cavernous, intrathoracic lymph node, intraabdominal lymph node tuberculosis and tuberculous pleurisy were identified in 5, 6, 2, 1, 1 and 1 patients, respectively. 6 patients from the above are still alive and are receiving treatment (5 of them with infiltrative tuberculosis), 10 died. Tuberculosis course and outcomes in HIV-infected subjects depended on the stage of their immunodeficiency. In moderate immunodeficiency (CD4-lymphocyte > 200/mm3) tuberculosis ran, as a rule, as local and infiltrative, sensitive to specific therapy. In severe damage to immune system (CD4 < 100/mm3) tuberculosis acquired a generalized course, sometimes fulminant, resistant to treatment. It is inferred that HIV-infected subjects with immunodeficiency need tuberculosis prophylaxis with isoniazide or rifampicin.