Author/Editor     Demetriou, Victoria L; van de Vijver, David AMC; Kousiappa, Ioanna; Balotta, Claudia; Clotet, Nonaventura; Grossman, Zehava; Jorgensen, B; Lepej, Z Snježana; Levy, Itzchak; Poljak, Mario
Title     Cellular HIV-1 DNA levels in drug sensitive strains are equivalent to those in drug resistant strains in newly-diagnosed patients in Europe
Type     članek
Source     PloS One
Vol. and No.     Letnik 5, št. 6
Publication year     2010
Volume     str. e10976
Language     eng
Abstract     Background: HIV-1 genotypic drug resistance is an important threat to the success of antiretroviral therapy and transmitted resistance has reached 9% prevalence in Europe. Studies have demonstrated that HIV-1 DNA load in peripheral blood mononuclear cells (PBMC) have a predictive value for disease progression, independently of CD4 counts and plasma viral load. Methodology/principal findings: Molecular-beacon-based real-time PCR was used to measure HIV-1 second template switch (STS) DNA in PBMC in newly-diagnosed HIV-1 patients across Europe. These patients were representative for the HIV-1 epidemic in the participating countries and were carrying either drug-resistant or sensitive viral strains. The assay design was improved from a previous version to specifically detect M-group HIV-1 and human CCR5 alleles. The findings resulted in a median of 3.32 log(10) HIV-1 copies/10(6) PBMC and demonstrated for the first time no correlation between cellular HIV-1 DNA load and transmitted drug-resistance. A weak association between cellular HIV-1 DNA levels with plasma viral RNA load and CD4(+) T-cell counts was also reconfirmed. Co-receptor tropism for 91% of samples, whether or not they conferred resistance, was CCR5. A comparison of pol sequences derived from RNA and DNA, resulted in a high similarity between the two. Conclusions/significance: An improved molecular-beacon-based real-time PCR assay is reported for the measurement of HIV-1 DNA in PBMC and has investigated the association between cellular HIV-1 DNA levels and transmitted resistance to antiretroviral therapy in newly-diagnosed patients from across Europe. The findings show no correlation between these two parameters, suggesting that transmitted resistance does not impact disease progression in HIV-1 infected individuals. (Abstract truncated at 2000 characters)
Descriptors     HIV-1
DRUG RESISTANCE, MICROBIAL
DNA, VIRAL
GENOTYPE
VIRAL LOAD
POLYMERASE CHAIN REACTION
LEUKOCYTES, MONONUCLEAR
HIV INFECTIONS
DISEASE PROGRESSION
PHYLOGENY