[Reactogenicity, safety, immunogenicity and prophylactic effectiveness of polysaccharide pneumococcus vaccine during immunization of HIV-infected patients].

AIM: Study safety, reactogenicity, immunogenicity and prophylactic effectiveness of polysaccharide pneumococcus vaccines during immunization of adult HIV-infected patients. MATERIALS AND METHODS: 200 HIV-infected patients at stages 3 to 4A of the disease aged 20 to 50 years with the quantity of CD4+ T-lymphocytes in blood of no less than 500 microl(-1) took part in the study. 100 individuals immunized with polysaccharide 23-valent pneumococcus vaccine (Pneumo 23, Sanofi Pasteur, France) constituted the observation group. 100 individuals not immunized against pneumococcus infection constituted the comparison group. The groups were standardized by sex, age and disease stage. Vaccine reactogenicity was evaluated by detection of general and local postvaccination reactions, degree of their intensity and duration. Vaccine safety was evaluated based on comparative evaluation of results of general clinical and biochemical studies of blood, general urine analysis, determination of IgE in blood sera, CD4+ T-lymphocytes level, quantity of HIV RNA (viral load) before vaccination and 28 days after the immunization. Vaccine immunogenicity was evaluated by determination in blood sera of IgG against a mixture of Streptococcus pneumoniae polysaccharides comprising Pneumo 23. Prophylaxis effectiveness of the preparation was evaluated by juxtaposition of acute respiratory illness morbidity in observation and control groups. RESULTS: During immunization of HIV-infected patients against pneumococcus infection postvaccination complications, severe local and general postvaccination reactions were not detected, laboratory studies carried out before and after the immunization gave evidence on the lack of progression of the main disease and activization of the infectious process. After the immunization the geometric mean antibody titer against S. pneumoniae increased by 2 times and reached protective level. Index of prophylactic effectiveness of Pneumo 23 vaccines during immunization of HIV-positive patients was 5.6, and relative risk of the disease in the immunized group--0.07, in the control group--0.42. CONCLUSION: The data provided give evidence on the high prophylactic effect of vaccination of immune compromised HIV-positive patients with a lack of deterioration of the main disease course.

[Humoral response to hepatitis C virus antigens in coinfection with human immunodeficiency virus type 1].

A humoral immune response to individual hepatitis C virus (HCV) antigens was studied in 49 patients at the subclinical stage of HIV-1 infection. These patients, as compared with a group comprising 50 patients with chronic hepatitis C, showed statistically significant higher levels of HCV-specific immunoglobulins G to nucleocapsid protein and the antigens NS3, NS4ab, NS5a. The group of patients with coinfection did not differ from those with chronic HCV monoinfection in detection rates and anti-HCV IgM.

[The molecular epidemiological aspects of hiv-infection spreading in Perm region].

Retrospective analysis of HIV-infection spreading in Perm region in conjunction with the genetic characterization of viral subtypes circulated on this territory from 1988 (when 1st case of infection was detected) until 2005 was performed. Analysis of epidemic process allowed to determine three periods of its development basing on both epidemic intensity and nature of circulating HIV-1 subtypes. During 1988 - 1996 (first period), when viral population was heterogenous (simultaneous circulation of three HIV-1 subtypes) with multiple routes of transmission, the epidemic process was characterized by low intensity. High incidence of HIV-infection among injection drug users and high homogeneity of circulated HIV-1 variants (98% of isolated variants belonged to HIV-1 subtype A with low level of genetic variability) were characteristics of the second period lasted from 1997 to 2001. Decrease in HIV-infection incidence in 2002-2005 was accompanied by the increase of HIV-1 transmission through heterosexual contacts and continuation of subtype A predominance between isolates. However increase in heterogeneity of viral population during this period, which manifested as increase of env and pol genes polymorphism, was detected.

[Protease and reverse transcriptase genetic polymorphism in HIV type 1 subtype A variants predominating in cis countries].

To define frequencies of drug resistance mutations among HIV-1 variants circulating within the territory of Russia, subtype A HIV-1 nucleotide sequences encoding protease and reverse transcriptase were analyzed. The analysis was carried out in 141 antiretroviral-naive individuals. Low frequency (less than 1%) of primary drug resistance mutations was shown. However, high frequencies of secondary mutations V77I in protease and A62V in RT (67% H 63%, respectively) linked to each other in most cases were observed. The HIV-1 isolates bearing both substitutions (MutV77I/A62V) were also characterized by the presence of several synonymous mutations, suggesting common origin for these viruses. HIV Biochip Hybridization microarray and/or Restriction fragment-length polymorphism analyses were performed to characterize gene pol polymorphism in additional 178 subtype A HIV-1 isolates. Among total 319 samples studied, Mutv77IA62V variant accounted for 56%, and was found to predominate in Russia in terms of both its geographical distribution and number of cases caused. Moreover, these viruses were prevalent in the regions known to have highest incidence of HIV-1 infection (Irkutsk, Samara, and Moscow regions). In addition, three other variants were found: viruses not containing the substitutions V77I or A62V, and variants bearing only one of them. Evolutional relationships between all four HIV-1 variants, as well as potential impact of the gene pol polymorphism on HIV-1 replicative fitness and drug resistance development are discussed.

[Anti-CD4 autoimmunity in HIV-infected persons in Russia].

The frequency of anti-CD4 antibodies was determined in the sera or plasma derived from the patients infected with HIV-1 belonging to different genetic subgroups. The anti-CD4-antibodies in a dilution of > or = 1:1000 were found in 14% of the patients infected with the gagA/envA virus characteristic for injectable drug users in East Europe. The frequency of autoimmune antibodies among the HIV-infected patients with envB virus was substantially less (4.4%). Competitive ELISA using monoclonal antibodies to different CD4 domains demonstrated that irrespective of the viral genotype, the autoimmune epitope is located within the D4 or D3/D4 domains of CD4 receptor.

[Biological properties of HIV-1 variants circulating among drug users in Russia].

Human immunodeficiency virus type 1 variants belonging to subtype A, as well as recombinant gaga/engvB variants, derived from HIV-infected patients living in the Moscow and Perm Regions, were isolated and characterized. Intravenous administration of psychoactive drugs was a major risk factor of the infection for all the patients. All the examined isolates of HIV-1 types A and A/B were shown to be characterized by a low virus-specific activity and to be used as secondary CCR5 and CXCR4 protein receptors. The findings suggest that the domination of subtype A variant in this risk group is unassociated with fundamental differences in biological properties between the isolates of this subtype and recombinant viruses.

[Effect of home-made narcotics on infectious activity of HIV-1]. / Vliianie narkoticheskikh veshchestv, izgotavlivaemykh kustarnym sposobom, na infektsionnuiu aktivnost' VICh-1.

The stability of human immunodeficiency virus, type 1 (HIV-1), strain IIIB, was studied in liquid preparations of homemade drugs. The "Vint" preparation (containing Methamphetamine and obtained from Ephedrine) as well as "Khanka" (a liquid surrogate opiate made from poppy straw) were analyzed within the case study. HIV-1/IIIB was shown to maintain its infectious activity in "Khanka" at room temperature for least 7 days. The HIV-1 activity in neutralized "Vint" did not essentially change after a 30-minute incubation at pH 7.0. While an incubation in the acid "Vint" solution entailed a more rapidly decreasing activity. However, the virus infection ability preserved during the entire time period, during which the drug was fit for injections, i.e. for 30 minutes at room temperature or for 20 hours at 4 degrees C. Therefore, the infection virus could well preserve in the "Khanka" and "Vint" solutions after its entry, with infected blood, of large volumes of the discussed drugs. The mentioned big volumes of HIV-1 contaminated drugs, shared later into ready-to-use portions, could be the cause for HIV-1 dissemination among those who practice the parenteral administration of these substances. Besides, "Khanka" was shown to have little or no effect on the virus replication to cell culture MT-4. Its presence brought about an insignificant 1.5-fold increase in the viral stock (observed on days 2 and 3 after contamination) only when 2 x 10(5) MT-4 cells per ml and HIV-1/IIIB TCID 50 0.005 were used.

[The HIV-infection outbreak in the town Lys'va (Perm region): homozygote genotype CCR5 delta32/CCR5 delta32 provides the high level of the persistence in the parenteral transmission of the virus]. / Vspyshka VICH-infektsii b g. Lys'va Permskoi oblasti: gomozigotnyi genotip CCR5 delta32/CCR5 delta32 obespechivaet vysokii uroven' ustoichivosti pri parenteral'noi peredache virusa.

Specific features of human immunodeficiency virus type 1 (HIV-1) transmission among injecting drug users were studied on HIV infection outbreak in Lysva, the Perm region. During the period from November 1998 to March 2000, 32 injecting drug users infected with the subtype A HIV-1 variant originating from the same source, were found in this town. To understand the role of the CCR5 delta 32 mutation in parenteral transmission of HIV-1 the distribution of the mutant CCR5 delta 32 allele in HIV-infected and in non-infected but HIV-exposed drug users (n = 74) was analysed. The percentage of the homozygous CCR5 delta 32 genotype among HIV-exposed individuals (4/74, 5.4%) was significantly (p < 0.05) higher than the analogous rate for healthy blood donors in Russia (1/163, 0.6%). Thus, the homozygosity for this mutant allele confers a high resistance level to HIV even in parenteral transmission.

[Genetic variants of hepatitis C virus in HIV-infected drug users]. / Geneticheskie varianty virusa gepatita C u VICh-infitsirovannykh narkomanov.

The prevalence of genetic variants (subtypes) of hepatitis C virus (HCV) among HIV-infected and noninfected intravenous drug users (IDU) in Russia is studied. HIV and HCV infections spread in the population of IDUs in Russia irrespective of each other. HCV subtypes 1b, 2a, and 3a (35.2, 18.3, and 29.6%, respectively) are the most prevalent in Russia. The profile of HCV subtype distribution in Russia differs from that in Europe; a "domestic" origin of HCV infection among IDUs is suggested. The authors conclude that identification of HCV subtype should be included in the protocol of examination of HIV-infected patients.

[Effect of heroin-containing substances on the infectivity of the human immunodeficiency virus type 1 in vitro]. / Vliianie preparata, soderzhashchego geroin, na infektsionnost' virusa immunodefitsita cheloveka tipa 1 in vitro.

At room temperature, HIV-1 IIIB is shown to remain infectious in a dose of 25 mg/ml of heroin solution for more than 8 days. The large batch of HIV-1-contaminated heroin solution may therefore remain infectious for a long period sufficient for transportation, packing, and sale in any area of Russia. At the same time 41-day incubation under the same conditions caused a complete loss of viral infectivity. Under certain conditions (the concentration of MT-4 cells being less than 2 x 105 cells/ml and the multiplicity of infection, less than 0.01 ID50/cell), heroin was demonstrated to be able to increase HIV-1 replication at the early stages of its life cycle. The findings should be borne in mind in elaborating measures to prevent the spread of HIV-1 among intravenous psychoactive drug users.

[Epidemiological and genetical characteristics of first forty cases of HIV infection in Perm region]. / Epidemiologicheskaia i geneticheskaia kharakteristika pervykh soroka sluchaev VICh-infektsii na territorii Permskoi oblasti.

The paper sums up molecular epidemiological data on all variants of human immunodeficiency virus type 1 (HIV-1) isolated in the Perm region in August 1988-March 1998. A total of 24 foci (40 cases) of HIV infection were detected; 20 of these were imported from other regions (Russian Federation, Ukraine, Belarus, Bulgaria, Poland, Uzbekistan, Yugoslavia). In August 1988-September 1996 viruses of 3 env subtypes (B, D, and G) were isolated in the region, and the virus was mainly sexually transmitted. All cases of HIV infection recorded in September 1996-March 1998 were detected in intravenous drug users and subjects who had sexual intercourse with HIV-infected drug users. The same 3 variants of HIV-1 with genotypes gagAenvA, gagBenvB, and gagAenvB were isolated in the Perm region during this period as in other regions of Russia.

[Presence of HTLV-I antibodies in patients with sexually transmitted diseases]. / Nalichie antitel k HTLV-I u patsientov s zabolevaniiami, peredaiushchimisia polovym putem.

The prevalence of human T-lymphotropic type I virus (HTLV-I) among patients with sexually-transmitted diseases is studied in Russia. Primary screening of antibodies to HTLV-I in the sera was carried out by enzyme immunoassay with recombinant gag and env HTLV-I-specific antigens synthesized in Escherichia coli. For secondary screening, Serodia HTLV-I and Vironostika Microelisa System kits were used. None of the 1271 serum samples collected in the towns of Perm and Ekaterinburg was HTLV-I-positive. This indicates a lower, in comparison with other European countries, level of infection with this virus, at least in this region of Russia. Testing of sera from 79 HIV-infected patients revealed none infected with HTLV-I.

[The use of the vif gene expression product of HIV-1 in bacteria for detecting specific antibodies in the sera of infected persons]. / Ispol'zovanie produkta ékspressii gena vif VICh-1 v bakteriiakh dlia obnaruzeniia spetsificheskikh antitel v syvorotkakh infitsirovannykh.

A fragment of the genome of human immunodeficiency virus type 1 (HIV-1) coding for p23 protein, the product of vif gene, was cloned in a plasmid vector pUR291. The resulting recombinant plasmid pLacVif1 was conducive in E. coli cells to the synthesis of a hybrid polypeptide with molecular weight of 136 kDa containing antigenic determinants of p23 protein of HIV-1. The employment of this polypeptide for analysis of HIV-1-positive sera by indirect enzyme immunoassay showed that vif-specific antibodies were found in 53% of the cases and their appearance was not related to the stage of the disease.