Frequency and predictors of HIV-1 co-receptor switch in treatment naive patients.
BACKGROUND
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. 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.


RESULTS
Overall, 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.


CONCLUSIONS
With the current guidelines for treatment initiation at CD4(+) T cell counts of <500 cells/mm(3), 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.
Aids Reference Laboratory, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Gent, Belgium.
Virginie
V
Mortier
Kenny
K
Dauwe
Leen
L
Vancoillie
Delfien
D
Staelens
Filip
F
Van Wanzeele
Dirk
D
Vogelaers
Linos
L
Vandekerckhove
Kristen
K
Chalmet
Chris
C
Verhofstede
D044966:Anti-Retroviral Agents / Q000494:pharmacology; D065100:CCR5 Receptor Antagonists / Q000494:pharmacology; D003510:Cyclohexanes / Q000494:pharmacology; D005838:Genotype; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D000077592:Maraviroc; D010802:Phylogeny; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology
D044966:Anti-Retroviral Agents; D065100:CCR5 Receptor Antagonists; C584933:CCR5 protein, human; C527276:CXCR4 protein, human; D003510:Cyclohexanes; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014230:Triazoles; D000077592:Maraviroc