Back to Search
Start Over
Evolution of proviral DNA HIV-1 tropism under selective pressure of maraviroc-based therapy.
- Source :
-
The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2012 Jun; Vol. 67 (6), pp. 1479-85. Date of Electronic Publication: 2012 Feb 23. - Publication Year :
- 2012
-
Abstract
- Objectives: To evaluate the evolution of HIV-1 coreceptor tropism in proviral DNA of patients during maraviroc-based therapy.<br />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%].<br />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.<br />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.
- Subjects :
- Adult
Anti-HIV Agents pharmacology
Cyclohexanes pharmacology
DNA, Viral genetics
Female
HIV Envelope Protein gp120 genetics
HIV Infections virology
HIV-1 genetics
Humans
Male
Maraviroc
Middle Aged
Proviruses genetics
Selection, Genetic
Triazoles pharmacology
Anti-HIV Agents administration & dosage
Cyclohexanes administration & dosage
Evolution, Molecular
HIV Infections drug therapy
HIV-1 physiology
Proviruses physiology
Triazoles administration & dosage
Viral Tropism
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2091
- Volume :
- 67
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of antimicrobial chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 22361986
- Full Text :
- https://doi.org/10.1093/jac/dks055