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Multicenter Study
. 2012 Jun;67(6):1479-85.
doi: 10.1093/jac/dks055. Epub 2012 Feb 23.

Evolution of proviral DNA HIV-1 tropism under selective pressure of maraviroc-based therapy

Silvia Baroncelli  1 , Clementina Maria Galluzzo, Liliana Elena Weimer, Maria Franca Pirillo, Anna Volpe, Alessandra Mercuri, Albertina Cavalli, Vincenzo Fragola, Laura Monno, Anna Degli Antoni, Nicoletta Ladisa, Daniela Francisci, Raffaella Bucciardini, Marco Floridia
Affiliations
Multicenter Study

Evolution of proviral DNA HIV-1 tropism under selective pressure of maraviroc-based therapy

Silvia Baroncelli et al. J Antimicrob Chemother. 2012 Jun.

Abstract

Objectives: To evaluate the evolution of HIV-1 coreceptor tropism in proviral DNA of patients during maraviroc-based therapy.

Methods: Fourteen heavily high active antiretroviral therapy (HAART)-treated patients with a CCR5 Trofile profile were monitored over a 24 month period from the start of maraviroc therapy. Whole-blood samples were obtained at different timepoints, and coreceptor tropism was determined for proviral DNA from the V3-loop region sequence using the Geno2Pheno algorithm [false positive rate (FPR): 20%].

Results: At the start of maraviroc treatment, 13/14 patients were viraemic (median: 4.33 log copies/mL). Concordance in R5 tropism (R5/R5) was observed between circulating HIV-RNA (Trofile) and HIV-DNA provirus in 10/14 patients (median FPR = 54.0%), while 4 patients showed a CXCR4-tropic R5/X4 variant in their provirus (FPR: 5.8%, 5.7%, 16.6% and 1.1%, respectively). All R5/R5 patients showed a stable HIV-1 DNA coreceptor usage. Two out of four R5/X4 patients showed a tropism shift in their archived provirus and, after 6 months a prevalence of R5-tropic virus was detected in DNA. The other two R5/X4 patients harboured the 11/25 genotype, and maintained X4 tropism in provirus during the study. Virological response did not reveal differences in RNA decay and CD4+ cell recovery in patients with discordant tropism.

Conclusions: A relatively good correlation between RNA and DNA tropism was observed at baseline. Proviral DNA tropism remained stable over 24 months of maraviroc-based therapy, indicating that determination of proviral DNA V3 sequence could be used in tropism prediction in clinical practice. The data also confirm the importance of the 11/25 rule in predicting viral tropism.

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Figures

Figure 1.
Figure 1.
Fluctuations in percentage FPR during the 24 months of maraviroc-based therapy.
Figure 2.
Figure 2.
Decay of HIV-RNA during the 24 months of maraviroc-based therapy. Black circles indicate patients harbouring a prevalence of X4-tropic variants at baseline.
Figure 3.
Figure 3.
CD4 cell recovery during 24 months of maraviroc-based therapy. Black circles indicate patients harbouring a prevalence of X4-tropic variants at baseline.
See this image and copyright information in PMC

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