Cellular HIV-1 DNA Levels in Drug Sensitive Strains Are Equivalent to Those in Drug Resistant Strains in Newly-Diagnosed Patients in Europe

作者：Demetriou Victoria L^*; van de Vijver David A M C; Kousiappa Ioanna; Balotta Claudia; Clotet Bonaventura; Grossman Zehava; Jorgensen Louise B; Lepej Snjezana Z; Levy Itzchak; Nielsen Claus; Paraskevis Dimitrios; Poljak Mario; Roman Francois; Ruiz Lidia; Schmidt Jean Claude; Vandamme Anne Mieke; Van Laethem Kristel; Vercauteren Jurgen; Kostrikis Leondios G

来源：PLos One, 2010, 5(6): e10976.

DOI：10.1371/journal.pone.0010976

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. The CCR5 co-receptor tropism predominance implies that both resistant and non-resistant strains behave similarly in early infection. Furthermore, a correlation found between RNA-and DNA-derived sequences in the pol region suggests that genotypic drug-resistance testing could be carried out on either template.

• 出版日期2010-6-8
• 单位河北医科大学