Cellular HIV-1 DNA levels in drug sensitive strains are equivalent to those in drug resistant strains in newly-diagnosed patients in Europe

Demetriou, V.L.; van de Vijver, D.A.M.C.; Kousiappa, I.; Vercauteren, J.; e.a.

doi:10.1371/JOURNAL.PONE.0010976

Title

Cellular HIV-1 DNA levels in drug sensitive strains are equivalent to those in drug resistant strains in newly-diagnosed patients in Europe

Author

Demetriou, V.L.

van de Vijver, D.A.M.C.

Kousiappa, I.

Vercauteren, J.

e.a.

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 log10 HIV-1 copies/106 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.

Language

English

Source (journal)

PLoS ONE

Publication

2010

ISSN

1932-6203

DOI

10.1371/JOURNAL.PONE.0010976

Volume/pages

5 :6 (2010) , p. e10976,1-e10976,11