Prediction of HIV-1 Coreceptor Usage (Tropism) by Sequence Analysis using a Genotypic Approach

Abstract

Maraviroc (MVC) is the first licensed antiretroviral drug from the class of coreceptor antagonists. It binds to the host coreceptor CCR5, which is used by the majority of HIV strains in order to infect the human immune cells (Fig. 1). Other HIV isolates use a different coreceptor, the CXCR4. Which receptor is used, is determined in the virus by the Env protein (Fig. 2). Depending on the coreceptor used, the viruses are classified as R5 or X4, respectively. MVC binds to the CCR5 receptor inhibiting the entry of R5 viruses into the target cell. During the course of disease, X4 viruses may emerge and outgrow the R5 viruses. Determination of coreceptor usage (also called tropism) is therefore mandatory prior to administration of MVC, as demanded by EMA and FDA.

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

“…In this regard, genotypic testing has the major advantage of offering results graded as FPR, that can be adapted to the patient's needs, whereas Trofile results are simply R5 or X4 or DM reports, without access to the raw data. 55,56 A correct reading of genotyping results focused on FPR could offer several advantages for clinical use.…”

HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia

“…Viral RNA isolation and RT-PCR amplification for protease-reverse transcriptase (PRRT), reverse transcriptase (RT), and integrase (IN) were completed as previously described [20] with subtype-optimized primers. Next-Generation-Sequencing (MiSeq, Illumina) with a 15% cut-off was performed.…”

HIV-1 subtypes and drug resistance profiles in a cohort of heterosexual patients in Istanbul, Turkey

“…The 1.5-kb PCR product was purified by Exo-SAP and sequenced as described [24,29]. Each PRRT sequence was screened for mutations in comparison with the reference strain HXB2 and subtyped by the COMET HIV-1 subtyping tool (http://comet.retrovirology.lu/).…”