title: Genotypic tropism of antiretroviral-treated patients with drug resistant HIV-1.
abstract: CCR5 inhibitors remain an attractive antiretroviral treatment option for HIV-infected patients; however, tropism testing should be utilized prior their introduction. This study analyzed genotypic HIV-1 tropisms in patients with evidence of genotypic drug resistance to antiretroviral therapies in Northwest Poland. V3 loop sequences were analyzed from plasma samples obtained from patients presenting with virologic treatment failure while on combined antiretroviral treatment and with evidence of genotypic drug resistance. Genotypic X4 and R5 tropisms were identified using the geno2pheno algorithm with a false positive rate threshold set at 10%. Clinical data for all patients examined was collected, in addition to determining the CCR5 Δ32 genotype and calculating the genotypic susceptibility score (GSS). Virologic treatment failure and the presence of drug resistant mutations were observed in 37/450 (8.4%) patients on cART (combination antiretroviral therapy) with successful tropism analysis carried out on 35 (95%) cases. In 22 (62.9%) and 13 (37.1%) cases the R5 and X4 tropisms were predicted, respectively. An association between viral X4 tropism and the M41L (P = 0.04) resistance mutation and R5 tropism and the K103N (P = 0.07) resistance mutation were observed. GSS values were lower in the group with NRTI (P = 0.01) and NNRTI resistance (P = 0.048). In the majority of the drug resistant patients, R5 tropic viruses were found. As genotypic tropism testing is easy to carry out and interpret, its use in clinical practice would be highly useful in determining the use of appropriate drug therapies.
authors.affiliation: Department of Infectious Diseases and Hepatology, Pomeranian Medical University, Szczecin, Poland. mparczewski@yahoo.co.uk
authors.forename: Milosz
authors.initials: M
authors.lastname: Parczewski
authors.forename: Magdalena
authors.initials: M
authors.lastname: Leszczyszyn-Pynka
authors.forename: Anna
authors.initials: A
authors.lastname: Urbanska
authors.forename: Dorota
authors.initials: D
authors.lastname: Bander
authors.forename: Anna
authors.initials: A
authors.lastname: Boron-Kaczmarska
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology*; D006801:Humans; D008297:Male; D011044:Poland; D012367:RNA, Viral / Q000235:genetics; D015728:Receptors, HIV / Q000378:metabolism; D017211:Treatment Failure; D056189:Viral Tropism
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D015728:Receptors, HIV