Natural polymorphisms and transmitted drug resistance in Estonian HIV-1 CRF06_cpx and its recombinant viruses
Failid
Kuupäev
2011-10-05
Autorid
Ajakirja pealkiri
Ajakirja ISSN
Köite pealkiri
Kirjastaja
Abstrakt
Viimastel kümnenditel on HIV-1 infektsioon muutunud maailma üheks olulisemaks nakkushaiguseks. HIV-1 on väga mitmekesine jagunedes nelja gruppi (M, N, O ja P), millest grupp M on jaotatud 9 subtüübiks ja kümneteks rekombinantseteks vormideks. Põhimõtteline murrang HIV vastases ravis saavutati 1990ndate keskel, mil kasutusele võeti HAART – kombinatsioon kolmest või enamast antiretroviirus (ARV) ravimist, mis on suunatud vähemalt kahe erineva sihtmärgi vastu. Siiani on jäänud ARV ravi üheks olulisemaks probleemiks kiiresti kujunev ravimresistentsus (RR), mille tagajärjel on tõusnud ka ülekanduv RR. Lisaks on teadmata HIV-1 subtüüpide mõju RR tekkele.
Eestis sai kontsentreeritud HIV epideemia alguse 2000. aastal kui hakkas kiirelt levima siiani Euroopas haruldane HIV-1 CRF06_cpx tüvi. Demograafiliselt on Eesti HIV epideemia sarnane Ida-Euroopa omale, kus nakatunuteks olid põhiliselt noored meessoost süstivad narkomaanid.
Käesoleva töö eesmärk oli määrata: (i) Eestis levinud HIV-1 CRF06_cpx viiruse looduslikult levinud RR mutatsioonid peamiste ARV ravimite märklaud piirkondades (proteaas, revertaas ja integraas); (ii) ülekanduva RR määr vahetult peale intensiivse ARV alustamist; (iii) CRF06_cpx viirustüve mõju RR mutatsioonide kujunemisele.
Töö käigus selgus, et:
1. Eesti HIV-1 CRF06_cpx viirustel ei esine loodulikke RR mutatsioone ei PR, RT ega IN piirkondades, mis näitab, et need viirused on tundlikud kõigile laialtlevinud ARV ravimitele. Samas leiti, et Eesti HIV-1 CRF06_cpx viirusel esinevad mitmed looduslikud polümorfismis PR ja IN piirkonnas.
2. Ülekandunud RR oli 2008. aastaks tõusnud 5,5%. Nimetatud tase on piiriks, kust alates rahvusvahelised ravijuhised soovitavad HIV-1 genotüüpilist RR testi.
3. RR mutatsioonid Eesti CRF06_cpx ravikogemusega viirustel sarnanevad subtüüp B viirustega, viidates nimetatud viiruste sarnasele ravivastusele laiemalt kasutaud ARV ravirežiimide korral.
During the last decades HIV-1 infection has emerged as one of the most important infection diseases. Based on HIV-1 diversity these viruses can be divided into four groups (M, N, O and P) from which group M contains 9 subtypes and tens of recombinant forms. Breakthrough in HIV treatment took place in mid-1990s when HAART was introduced. It contains the combination of three or more antiretroviral (ARV) agents against at least two different targets. The major problem in HIV treatment is emerging drug resistance (DR) and due to that also the increasing number of transmitted DR. Additionally, the influence of HIV-1 subtypes on DR is unknown. In Estonia the concentrated HIV epidemic burst in year 2000 when rare recombinant CRF06_cpx was introduced into the population of mainly young male intravenous drug users. The aim of current study was to determine: (i) natural DR mutations of HIV-1 CRF06_cpx in main ARV agents target regions (protease, revertase and integrase); (ii) the level of transmitted DR; (iii) the influence of CRF06_cpx on the development of DR mutations. Current study revealed that: 1. Estonian CRF06_cpx viruses do not possess natural DR mutations in PR, RT and IN regions indicating that these viruses are susceptible to all main ARV classes. However, Estonian HIV-1 CRF06_cpx viruses possess several naturally occurring polymorphisms in PR and IN region. 2. In 2008 the level of transmitted DR has been raised to 5.5% which is the threshold for the pretreatment HIV genotypic DR testing by the international HIV treatment guidelines. 3. The pattern of treatment experienced HIV-1 CRF06_cpx viruses are comparable to that seen in subtype B viruses suggesting their similar response to the most widely used ARV therapies.
During the last decades HIV-1 infection has emerged as one of the most important infection diseases. Based on HIV-1 diversity these viruses can be divided into four groups (M, N, O and P) from which group M contains 9 subtypes and tens of recombinant forms. Breakthrough in HIV treatment took place in mid-1990s when HAART was introduced. It contains the combination of three or more antiretroviral (ARV) agents against at least two different targets. The major problem in HIV treatment is emerging drug resistance (DR) and due to that also the increasing number of transmitted DR. Additionally, the influence of HIV-1 subtypes on DR is unknown. In Estonia the concentrated HIV epidemic burst in year 2000 when rare recombinant CRF06_cpx was introduced into the population of mainly young male intravenous drug users. The aim of current study was to determine: (i) natural DR mutations of HIV-1 CRF06_cpx in main ARV agents target regions (protease, revertase and integrase); (ii) the level of transmitted DR; (iii) the influence of CRF06_cpx on the development of DR mutations. Current study revealed that: 1. Estonian CRF06_cpx viruses do not possess natural DR mutations in PR, RT and IN regions indicating that these viruses are susceptible to all main ARV classes. However, Estonian HIV-1 CRF06_cpx viruses possess several naturally occurring polymorphisms in PR and IN region. 2. In 2008 the level of transmitted DR has been raised to 5.5% which is the threshold for the pretreatment HIV genotypic DR testing by the international HIV treatment guidelines. 3. The pattern of treatment experienced HIV-1 CRF06_cpx viruses are comparable to that seen in subtype B viruses suggesting their similar response to the most widely used ARV therapies.
Kirjeldus
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Märksõnad
HIV-1, mutatsioonid, polümorfism, ravimiresistentsus, mutations, polymorphism, drug resistance