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

Autori
Demetriou, VL ; van de Vijver, DA ; Kousiappa, I ; Balotta, C ; Clotet ; B ; Grossman, Z ; Jørgensen, LB ; Židovec-Lepej, Snježana ; Levy, I ; Nielsen, C ; Paraskevis, D ; Poljak, M ; Roman, F ; Ruiz, L ; Schmidt, JC ; Vandamme, AM ; Van Laethem, K ; Vercauteren, J ; Kostrikis, LG

Izvornik
PLoS One (1932-6203) 5 (2011), 6; E10976-e10976

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Cellular HIV-1 DNA levels; drug resistance strains; Europe

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA