Abstract
BackgroundDetermination of HIV-1 co-receptor use is a necessity before initiation of a CCR5 antagonist but the longevity of a CCR5-use prediction remains unknown.MethodsGenotypic co-receptor tropism determination was performed in 225 newly diagnosed individuals consulting an AIDS Reference Centre. Samples were collected at diagnosis and at initiation of antiretroviral therapy or just before closure of the study for patients who did not initiate therapy. For individuals with a discordant tropism prediction on the two longitudinal samples, analysis of intermediate samples and single genome sequencing of proviral DNA was performed to confirm the tropism switch. Deep sequencing was done to identify minor CXCR4 or CCR5-using populations in the initial sample.ResultsOverall, tropism switches were rare (7.6%). Only a geno2pheno false positive rate of <50% at baseline was retained as predictive for a subsequent switch from CCR5-use only to predicted CXCR4-use. Minor CXCR4-using virus populations were detected in the first sample of 9 of the 14 R5-to-X4 switchers but the subsequent outgrowth of these minor populations was documented in only 3.ConclusionsWith the current guidelines for treatment initiation at CD4+ T cell counts of <500 cells/mm3, co-receptor switch between diagnosis and starting antiretroviral therapy is rare. Patients with R5 viruses and a geno2pheno FPR of <50% are more prone to subsequent co-receptor switch than patients with an FPR of >50% and will need repeat tropism testing if initiation of maraviroc is considered and previous testing dates from more than a year before.
Highlights
The human immunodeficiency virus type 1 (HIV-1) is dependent on binding to the CD4 receptor and a co-receptor, either CCR5 or CXCR4, for entry into target cells
The results showed that pre-antiretroviral therapy (ART) coreceptor tropism switch is rare
Centre (ARC) of Ghent University Hospital (Belgium) between January 2001 and December 2009, 244 patients were retrospectively selected based on the criteria that the patient had to be newly diagnosed and that a blood sample, collected within 1 year of diagnosis, as well as a blood sample collected at the start of ART or by the end of the study period (August 2011) if no ART was initiated, had to be available
Summary
The human immunodeficiency virus type 1 (HIV-1) is dependent on binding to the CD4 receptor and a co-receptor, either CCR5 or CXCR4, for entry into target cells. The only entry inhibitor currently FDA/EMA approved is the CCR5 antagonist maraviroc. This drug can be initiated only after excluding the presence of virus able to use CXCR4. Phenotypic as well as genotypic assays have been developed for co-receptor tropism analysis and both can be used to screen for maraviroc sensitivity [1,2]. Determination of HIV-1 co-receptor use is a necessity before initiation of a CCR5 antagonist but the longevity of a CCR5-use prediction remains unknown. Methods: Genotypic co-receptor tropism determination was performed in 225 newly diagnosed individuals consulting an AIDS Reference Centre. Conclusions: With the current guidelines for treatment initiation at CD4+ T cell counts of
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