Background: The aim of the study was to detect whether in experimental Salmonella enterica Typhimurium infection the probiotic Lactobacillus fermentum ME-3 in combination with fluoroquinolone therapy would eradicate S. Typhimurium, prevent the development of liver and spleen granulomas and improve the indices of oxidative stress in the ileum mucosa.

BACKGROUND A high copy number of CCL3L1, the most potent HIV-suppressive chemokine, associates with reduced HIV susceptibility. Whether CCL3L1 influences acquisition of multiple blood-borne infections (HCV, HIV-1, HBV) that occurs commonly among intravenous drug users (IDUs) is unknown. METHODS We determined CCL3L1 copy number by real-time PCR among 374 Caucasian IDUs from Estonia of whom 285 were HCV-positive, 208 HIV+, 177 HCV+/HIV+, and 57 HCV−/HIV−. RESULTS In univariate and multivariate analyses, HCV and HBV seropositivity, and duration of IDU each strongly predicted HIV seropositivity. A high CCL3L1 copy number (>2) associated with a 80% reduced risk of acquiring HIV, after adjusting for age, gender, HCV/HBV status, CCR5-Δ32 polymorphism and IDU duration (OR=0.20; 95% CI=0.09–0.45). By contrast, CCL3L1 gene dose did not influence HCV seropositivity. Among HCV+ IDUs, there was a 3.5-fold over- and 65% under-representation of a high CCL3L1 copy number among HCV+/HIV− and HCV+/HIV+ subjects, respectively. CONCLUSION Among IDUs exposed heavily to HCV/HIV, CCL3L1 copy number is a major determinant of HIV seropositivity, but not HCV seropositivity. The contrasting distribution of a protective high CCL3L1 copy number among HCV+/HIV− vs HCV+/HIV+ IDUs may reflect that HIV preferentially selects for subjects with a low CCL3L1 gene dose.

Background TLR3 recognizes dsRNA and triggers immune responses against RNA and DNA viruses. A polymorphism in TLR3, rs3775291 (Leu412Phe), has been associated with the increased susceptibility to enteroviral myocarditis, protection against tick-borne encephalitis virus and HIV-1 infection. We investigated Caucasian intravenous drug users (IDUs) and blood donors in order to evaluate the associations between TLR3 genotypes and susceptibility to HIV infection. Materials and methods A total of 345 Caucasian IDUs were recruited, 50% of them were HIV positive, 89% HCV and 77% HBV positive. Based on their history of needle sharing, 20 of the HIV negative IDUs were classified as highly exposed HIV seronegatives (HESNs), 68 as non-HESNs and 85 as unexposed. The control group consisting of 497 blood donors tested negative for all three viruses. TLR3 rs3775291 were determined by using TaqMan Allelic Discrimination Assay. Results The TLR3 rs3775291 T allele frequency was similar among the HIV negative and HIV positive IDUs and blood donors – 36%, 31% and 34%, respectively. The frequency of persons possessing at least one TLR3 rs3775291 T allele was significantly higher in HESNs compared with blood donors and HIV positive IDUs (80% vs. 55%; p = 0.037 and 80% vs. 53%; p = 0.031, respectively). In the univariate analysis, persons who possessed at least one T allele had reduced odds of being HIV seropositive (OR = 0.29, 95% CI = 0.09–0.90). This association remained significant (OR = 0.25, 95% CI = 0.07–0.87) after the adjustment for other co-variates (HCV, HBV serostatus and duration of intravenous drug use). Conclusions The TLR3 rs3775291 T allele has a protective effect against HIV infection among HESNs IDUs.

Human immunodeficiency virus (HIV)-1 transmitted drug resistance in the drug-naïve population is of growing relevance in Estonia, where the number of antiretroviral (ARV) treatment-experienced subjects has been exponentially increasing during the last 10 y. The aim of this study was to estimate the rate of transmitted drug resistance among newly diagnosed subjects in Estonia in 2008. Genotypic resistance testing for viral genomic RNA was conducted for 201 subjects tested HIV-positive between 1 April and 30 November 2008. Of 145 genotyped viral strains in newly diagnosed patients, 123 were CRF06_cpx, 2 were subtype A1 and 3 were subtype B; in 17 cases viral sequences revealed recombinant structures similar to CRF06_cpx, subtype A1 and CRF02_AG. Resistance mutations were found in 8 (5.5%) virus strains, and 3 strains were resistant to at least 2 ARV classes. A total of 2.8% of sequences harboured mutations indicating nucleoside/nucleotide reverse transcriptase inhibitor resistance (M41L, M184V, M184I, T215C and T215D), 2.1% non-nucleoside reverse transcriptase inhibitor resistance (K103N, P225H) and 2.8% protease inhibitor resistance (M46I, L90M). These data suggest the need to extend genotypic HIV-1 drug resistance testing to newly diagnosed HIV-positive subjects to prevent potential ARV treatment failure.

All non-B HIV-1 subtypes and circulating recombinant forms (CRFs) are characterized by several polymorphisms in protease (PR) region. In addition, in recent years the increasing use of antiretroviral treatment (ART) has rapidly raised the spread of transmitted drug resistance. We aimed to determine the presence of naturally occurring polymorphisms and transmitted drug resistance mutations (DRMs) in ART naïve HIV-1-positive subjects in Estonia. A total of 115 drug-naive HIV-1-infected subjects (mean age 27 years; 70% male; 65% infected via intravenous drug use and 34% by heterosexual contact) were enrolled. Viral genomic RNA from plasma was directly sequenced in PR, revertase (RT), and envelope (env) regions. Phylogenetic analysis of RT and env regions revealed that 89% and 3% of sequenced viruses belonged to CRF06_cpx and subtype A1, respectively, and 6% were described as unique recombinants (signed A1-06) between CRF06_cpx and subtype A1 viruses. No primary DRMs were found in PR or RT regions indicating the absence of transmitted drug resistance. The most common polymorphisms in the PR region were K14R, M36I, H69K, and L89M seen in 96%, 100%, 99%, and 100%, respectively. The clinical relevance of these polymorphisms in terms of success of ART has to be monitored in future clinical studies.