[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.

[Variants of human immunodeficiency virus type 1, detected in Russia among those infected by the sexual route]. / Varianty virusa immunodefitsita cheloveka tipa 1, obnaruzhivaemye v Rossii sredi infitsirovannykh polovym putem.

We analyzed 52 blood samples obtained independently from among individuals, who had never practiced the intravenous administration of drugs, for the purpose of detecting the subtypes of HIV-1 that circulated during 1999-2002. The study materials were analyzed by the methods of gag/env heteroduplex mobility assay and by env gp120 C2-V3 sequencing. Four viral subtypes (A,B,C and G) and a recombinant gagA/envB were detected in subjects contaminated through heterosexual contacts. Noteworthily, HIV-1 variations of subtype A, which were found in 22 (73.3%) of 30 analyzed samples, were predominant in this risk group. An analysis of nucleotide sequences exposed a high degree of homology between the viruses, detected previously among drug-addicts, and the isolates detected by us in subjects contaminated heterosexually. However, HIV-1, subtype B, detected by us in all 16 studied cases, still continue to circulate among the males infected through homosexual contacts with men.

[Decrease of HIV-1 replicative capacity after serial passage in MT-4 cells under conditions of the combined antiretroviral therapy]. / Snizhenie replikativnoi sposobnosti VICh-1 posle passirovaniia v kletkakh MT-4 v usloviiakh kombinirovannoi antiretrovirusnoi terapii.

The replicative activity of HIV-1/IIIB was determined in MT-4 cells under conditions of combined HIV reverse transcriptase and protease inhibitors in the presence of four different drug cocktails: (1) phosphazide, didanosine, nevirapine; (2) stavudine, didanosine, nevirapine; (3) phosphazide, didanosine, nevirapine, indinavir; (4) stavudine, didanosine, nevirapine, indinavir. The concentration of every inhibitor was 10 times higher than the 50% effective concentration. Alpha interferon was used as a natural antiretroviral agent in addition. The virus was subjected to 5 serial passages in the presence of the drug cocktails and then to 5 serial passages without the agents using cocultivation of infected and uninfected cells at ratio 1:5 to increase virus activity. Virus replication in the presence of all the drug combinations resulted in the appearance of HIV-1 variants with low replicative activity that was insignificantly increased during further passages even without the antiretroviral agents. If extrapolated to the clinical practice, these results indicate that all the drug cocktails were effective inhibitors of HIV-1 replication because the virus variants with high replicative activity did not emerge. Moreover, the results showed that the clinical use of the drug cocktails was promising.

[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.

[Molecular genetic characteristics of HIV-1 in Russia]. / Molekuliarno-geneticheskaia kharakteristika VICh-1 na territorii Rossii.

The paper presents data on the variants of human immunodefficiency virus type 1 (HIV-1) currently circulating in Russia. The subtype A HIV-1 variant dominating is shown to be most widespread among drug-injected users in the most regions under study. By using the results of an analysis of 1,464 blood samples taken in the past 4 years in 69 subjects of the Russian Federation, the authors have estimated that this HIV-1 variant is responsible for 93% of all HIV-infection cases in the country. The greatest regional genetic diversity was observed in Moscow and its mean (2.35(1.59) was found to be comparable to that (2.41(1.85) in the whole country. Penetration of the subtype A IV-1 variant early detectable among drug-users into other risk groups was noted.

[Anti-interferon activity of peripheral blood leukocytes in patients infected with HIV-1]. / Antiinterferonovaia aktivnost' leikotsitov perifericheskoi krovi patsientov, infitsirovannykh VICh-1.

The study was aimed at anti-interferon activity of different components of the in vitro system cells MT-4--HIV-1 as well as the culture fluid of peripheral blood leukocytes from patients at different stages of HIV infection and from patients with mixed infection (HIV and chronic hepatitis C) in comparison with patients infected with hepatitis C virus alone and healthy persons. Anti-interferon activity was detected in all groups of patients, its detection rate varying within 33% and 68%. The tendency towards increased detection rate of anti-interferon activity in HIV-infected patients in parallel with decreased number of CD4+ lymphocytes was noted. These data made it possible to suggest that increased detection rate of anti-interferon activity in the culture fluid of peripheral blood leukocytes from HIV-infected patients in parallel with decreased number of CD4+ lymphocytes could result from pathogenetic processes in the body, leading to a decrease in therapy effectiveness of HIV-infected patients with the preparations of alpha-interferon, especially in patients with a low content of CD4+ cells.

[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.

[Molecular and epidemiologic characteristics of HIV-infection outbreak in the Irkutsk region]. / Molekuliarno-épidemiologicheskaia kharakteristika vspyshki VICh-infektsii v Irkutskoi oblasti.

The genetic analysis of the variants of human immunodeficiency virus of type 1 (HIV-I) circulating among drug addicts in the Irkutsk region was carried out. The results of serological tests and comparative evaluation of electrophoretic mobility of heteroduplexes (HMA) revealed that all 74 samples under study belonged to subtype A. Genetic differences between these viruses did not exceed 2%. Thus, it was the variant of subtype A prevalent in CIS countries which caused the outbreak of HIV infection among drug addicts in the Irkutsk region, but not viruses of subtypes B, C or A/E typical for this risk group in relatively nearby China.

[Analysis of gag gene subtypes of HIV-1 variants isolated in Russia by comparative assessment of heteroduplex electrophoretic mobility]. / Analiz subtipov gena gag variantov VICh-1, vydelennykh v Rossii, metodom sravnitel'noi otsenki élektroforeticheskoi podvizhnosti geterodupleksov.

Using heteroduplex mobility assay modified for gag gene analysis (HMA-gag), 37 HIV-1 samples previously genotyped by gag and env nucleotide sequencing were studied. It has been demonstrated that both sensitivity and specificity of HMA-gag were 100%. The gag gene region derived from 20 env subtype A HIV-1 isolates was analyzed by this method. AG recombinant, representing a circulating recombinant form of HIV-1 (AGlbNG) was found among five HIV-1 strains isolated from patients infected through heterosexual contacts in Russia. No novel recombinant forms were found among fifteen HIV-1 variants infected from drug users in 7 cities of Russia. The proposed HMA-gag method extends the potentialities of investigating the genetic variability of HIV-1 and in combination with the previously proposed method for env gene is a convenient approach to search for recombinant forms of this virus.

[A genetic analysis of variants of the human immunodeficiency virus type 1 (HIV-1) circulating among drug abusers in Moscow and Moscow Province]. / Geneticheskii analiz variantov virusa immunodefitsita cheloveka tipa 1 (VICh-1), tsirkuliruiushchikh sredi narkomanov v Moskve i Moskovskoi oblasti.

The genetic analysis of the variants of human immunodeficiency virus of type 1 (HIV-1), circulating among drug addicts in Moscow and Moscow Province, has been carried out. The serological analysis of 122 blood specimens taken from HIV-infected drug addicts, residing in Moscow and 22 settlements of the Moscow region, has shown that in this region HIV-1 variant of subtype A spreads among drug addicts. These data have been confirmed by the results of the analysis of 44 specimens, made with the use of the method of the heteroduplex mobility assay for gene env. As revealed in this study, HIV-1 variants spreading at present among drug addicts in Moscow and the Moscow region are genetically related to viruses of subtype A, detected earlier in this group of risk in other regions of Russia, the Ukraine, Belarus and other countries of Eastern Europe.

[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.

[Nucleotide sequence of gag and env genes of human immunodeficiency virus type 1, found in Russia: detection of new recombinant variants]. / Nukleotidnye posledovatelnosti genov gag i env izoliatov virusa immunodefitsita cheloveka tipa 1, vyisvlennykh v Rossii: obnaruzhenie novykh rekombinantnykh variantov.

Phylogenetic analysis of nucleotide sequences of gag and env genes of type 1 human immunodeficiency virus (HIV-1) variants isolated from individuals infected through sexual intercourse or nosocomially (by injections with nonsterile syringes) showed that 5 of 27 (18.5%) isolated strains were recombinants. Two viruses found in the Russian Far East had gagAenvE genotype, three other recombinants had envG genotype; gag gene of one isolate belonged to subtype A and gag genes of two others belonged to subtype D. Detection of new recombinant variants in addition to the A/B recombinant described previously shows that these viruses can contribute to the HIV-1 genetic variability in 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.

[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.