Kaasuvate infektsioonide ja inimese geneetilise faktori mõju HIV-iga nakatumisele süstivate narkomaanide hulgas

Väitekirja elektrooniline versioon ei sisalda publikatsiooneParenteraalne ülekanne on kõige efektiivsem HIV-i ülekandetee. Sellest lähtuvalt peetakse süstivaid narkomaane (SN) üheks kõige haavatavamaks grupiks. SN-de seas läbi viidud uuringud on paljastanud mitmeid isikuid, kes riskikäitumisele vaatamata ei nakatu HIV-ga. Lisaks geneetilistele polümorfismidele võivad HIV-i nakatumist mõjutada ka kaasuvad infektsioonid, mis suurendavad immuunsüsteemi koormust ja võivad seeläbi mõjutada organismi vastuvõtlikkust. Mõned viirused, nt inimese T-lümfotroopne viirus (HTLV) ja inimese pegiviirus (HPgV), avaldavad HIV-le inimese seisukohast kasulikku mõju. Käesoleva uurimustöö eesmärgiks oli HIV-ga kaasuvate infektsioonide (HTLV-1/2, HPgV) ja interferoon-lambda-4 (IFNλ4) geenis paikneva polümorfismi kirjeldamine ning nende mõju hindamine HIV-i nakatumisele. Selleks kaasati 345 SN-i, kontrollgruppidena kasutati terveid vabatahtlikke ja veredoonoreid. HTLV-1/2 määramisel tuvastasime ühe HTLV-2 positiivse SN-i, teised olid HTLV-1/2 negatiivsed. Kõik terved vabatahtlikud olid HTLV-1/2 negatiivsed. HPgV vireemiat esines kolmandikul SN-del, kuid antikehade esinemine oli oluliselt harvem. Tervete vabatahtlike seas oli HPgV vireemia viis korda madalama sagedusega, kuid antikehade sagedus oli sarnane SN-dega (vastavalt 1,7% ja 2,3%). Kõrge HPgV vireemia SN-de seas võib osaliselt tuleneda nende riskikäitumisest, aga ka HIV-i ja teiste infektsioonide poolt tekitatud immuunsüsteemi kahjustustest, mille tulemusena ei suudeta HPgV-st vabaneda ning infektsioon muutub krooniliseks. Madal HPgV antikehade tase võib tuleneda HPgV iseärasustest – vireemiale ei järgne alati antikehade teke ja tekkinud antikehad võivad kaduda. IFNλ4 rs12979860 puhul ei leidnud me seoseid rs12979860 genotüüpide ja HCV-ga nakatumise vahel. Samas, rs12979860 TT genotüübi kandjatel olid ligi kaks korda suuremad šansid olla HIV positiivne. Interaktsioonanalüüs näitas, et TT genotüübi avaldatud mõju vähenes süstimisaja kasvades. Kokkuvõttes on HTLV-1/2 väga harva esinev, mistõttu pole rutiinne testimine HTLV-1/2 suhtes tõenäoliselt kulutõhus. Samas on HPgV SN-de seas sage ning võib mõjutada HIV-i kulgu siin piirkonnas. IFNλ4 rs12979860 mõjutab küll HIV-i nakatumist, kuid jätkuv riskikäitumine vähendab antud polümorfismi mõju suurust.Parenteral modes are the most efficient routes of HIV transmission and thus, people who inject drugs (PWID) are considered to be one of the most vulnerable groups. However, PWID populations often reveal a number of individuals who despite being highly exposed do not get infected. In addition to genetic polymorphisms, coinfections may also play a role in HIV acquisition. Although most coinfections have adverse effects on HIV some (e.g. Human T-lymphotropic virus [HTLV] and Human Pegivirus [HPgV]) have beneficial. The aim of this thesis was to describe the prevalence of HIV coinfections (HTLV-1/2, HPgV) and a polymorphism in the interferon-lambda-4 gene (IFNλ4) and to evaluate their association with HIV acquisition. The study was conducted among 345 PWID. Healthy volunteers and blood donors were used as control groups. We found one of the PWID to be HTLV-2 positive and the rest were HTLV-1/2 negative. As expected, all healthy volunteers were negative for HTLV-1/2. HPgV viremia was present in third of PWID but the prevalence of HPgV seropositivity was significantly lower. The rate of HPgV viremia was five times lower among healthy volunteers but the rate of seropositivity was similar to PWID (1,7% and 2,3%, respectively). High rate of HPgV viremia among PWID might at least partially be due to their risk behaviour but it may also suggest that they are unable to clear HPgV viremia due to the immunocompromising effect of HIV and other infections. The low HPgV seropositivity detected in our study could be due to characteristics inherent to HPgV infection – the clearance of viremia is not always followed by the production of antibodies and produced antibodies might disappear over time. The IFNλ4 rs12979860 study revealed no associations between rs12979860 genotypes and HCV acquisition. However, we found the TT genotype to increase the susceptibility to HIV. According to the interaction analysis the scale of the influence of TT genotype decreased with increasing duration of intravenous drug use. In conclusion, HLTV-1/2 is rare in Estonia suggesting that there is no need for routine testing for these viruses. HPgV is common among PWID and could affect HIV acquisition and disease progression in this area. IFNλ4 rs12979860 TT genotype increases susceptibility to HIV but continuing risk behaviour diminishes the impact of this polymorphism.https://www.ester.ee/record=b522841

GBV-C esinemine, genotüübid ja mõju HIV-1 nakatumisele Eesti süstivate narkomaanide populatsioonis

Ligipääs piiratud kuni 01.06.20162016-06-0

Noroviiruse tüved Eestis 2015–2016 ägeda gastroenteriidiga hospitaliseeritud lastel vanuses 0–18 aastat

Eesti Arst 2022; 101(9):50

Acute gastroenteritis hospitalizations after implementation of universal mass vaccination against rotavirus

Eesti Arst 2020; 99(7):44

Dynamics of hepatitis C epidemic among people living with HIV in Estonia based on Estonian HIV cohort study

Materials to Dynamics of hepatitis C epidemic among people living with HIV in Estonia based on Estonian HIV cohort stud

No transmitted drug resistance to HIV integrase strand-transfer inhibitors after their scale-up in Estonia in 2017

ABSTRACT: Objectives: In Eastern Europe, HIV-1 transmitted drug resistance (TDR) data, especially in the integrase (IN) region, are limited. In Estonia, INSTI (integrase strand transfer inhibitors) TDR has been studied only prior to the INSTI scale-up in late 2010s. The current study aimed to determine the levels of protease (PR), reverse transcriptase (RT) and IN surveillance drug resistance mutations (SDRMs) among newly diagnosed patients in Estonia in 2017. Methods: The study included 216 newly diagnosed HIV-1 individuals from 1 January until 31 December 2017 in Estonia. Demographic and clinical data were obtained from the Estonian Health Board, the Estonian HIV Cohort Study (E-HIV) and clinical laboratories’ databases. The PR-RT and IN regions were sequenced and analysed for SDRMs and subtype determination. Results: Seventy-one percent (151/213) of available HIV-positive samples were successfully sequenced. The overall level of TDR was 7.9% (12/151; 95% CI 4.4%–13.8%); no dual or triple class resistance was detected. No major INSTI mutations were found. The distribution of SDRMs for NNRTI, NRTI and PI was 5.9% (9/151), 1.3% (2/151) and 0.7% (1/151), respectively. The predominant NNRTI mutation was K103N. CRF06_cpx was the predominant variant (59%) in the Estonian HIV-1 population, followed by subtype A (9%) and subtype B (8%). Conclusion: Although no major INSTI mutations were found, close monitoring of INSTI SDRMs is needed considering the extensive use of the first- and second-generation INSTIs. PR-RT TDR is slowly rising in Estonia, indicating the need for continuous surveillance in the future. Low genetic barrier NNRTIs should be avoided in the treatment regimens

A CCL5 Haplotype Is Associated with Low Seropositivity Rate of HCV Infection in People Who Inject Drugs.

The role of CC chemokine receptor 5 (CCR5) and its ligand CCL5 on the pathogenesis of HIV infection has been well studied but not for HCV infection. Here, we investigated whether CCL5 haplotypes influence HIV and HCV seropositivity among 373 Caucasian people who inject drugs (PWID) from Estonia.Study included 373 PWID; 56% were HIV seropositive, 44% HCV seropositive and 47% co-infected. Four CCL5 haplotypes (A-D) were derived from three CCL5 polymorphisms (rs2107538/rs2280788/rs2280789) typed by Taqman allelic discrimination assays. The data of CCR5 haplotypes were used from our previous study. The association between CCL5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis.Possessing CCL5 haplotype D (defined by rs2107538A/rs2280788G/rs2280789C) decreased the odds of HCV seropositivity compared to those not possessing it (OR = 0.19; 95% CI 0.09-0.40), which remained significant after adjustment to co-variates (OR = 0.08; 95% CI 0.02-0.29). An association of this haplotype with HIV seropositivity was not found. In step-wise logistic regression with backward elimination CCL5 haplotype D and CCR5 HHG*1 had reduced odds for HCV seropositivity (OR = 0.28 95% CI 0.09-0.92; OR = 0.23 95% CI 0.08-0.68, respectively) compared to those who did not possess these haplotypes, respectively.Our results suggest that among PWID CCL5 haplotype D and CCR5 HHG*1 independently protects against HCV. Our findings highlight the importance of CCL5 genetic variability and CCL5-CCR5 axis on the susceptibility to HCV