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.

Prevalence of R5 strains in multi-treated HIV subjects and impact of new regimens including maraviroc in a selected group of patients with CCR5-tropic HIV-1 infection

“…Interestingly six viral strains from HIV-1 patients with a low viral load could only be characterized by genotyping test due to a limitation of the Trofile assay, which can only be applied to samples with a viral load !1000 HIV RNA copies/ml; V3 sequencing is characterized by a high rate of efficiency even when viremia is low. 27,[43][44][45] Our data emphasize the peculiarity of genotype testing that is also able to characterize viral strains from HIV subjects with low but detectable levels of HIV replication despite previous longlasting antiretroviral therapy. In addition, among the six patients not evaluable by Trofile, three were further included in the maraviroc protocol, showing a clear-cut drop in viral replication maintained throughout the observation period (from 12 to 36 months).…”

Increased CXCR4 Use of HIV-1 Subtype C Identified by Population Sequencing in Patients Failing Antiretroviral Treatment Compared with Treatment-Naive Patients in Botswana

“…An increase in CXCR4 use in treatment failure patients has previously been ascribed to factors such as suboptimal treatment [234], specific drug resistance mutations [234,276], or low CD4 counts [234,236,237]. However, in Botswana the treatment adherence rates have been good [257], and no statistically significant correlation could be observed in paper III between coreceptor use and specific drug resistance mutations or drug classes, although it should be noted that drug resistance profiles were available for only half of the patients.…”

Efficacy and safety of nucleoside‐sparing regimen based on raltegravir and ritonavir‐boosted darunavir in HIV‐1‐infected treatment‐experienced patients

“…However, a switch to nucleos(t)ide sparing regimens is also warranted. This mutation was previously shown to be the most common among patients with HIV‐1 resistance in northern Poland …”

“…This mutation was previously shown to be the most common among patients with HIV-1 resistance in northern Poland. 40 Overall, the therapy containing RAL and DRV/r can be described as safe and well-tolerated. In 7 out of 81 patients the therapy was discontinued due to side effects and laboratory results abnormalities.…”