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 |