Maraviroc in treatment-experienced patients with HIV-1 infection - experience from routine clinical practice.
OBJECTIVE
Few data are available about the efficacy of maraviroc (MVC) during routine use. We characterized indications for MVC use and the efficacy of MVC in clinical practice.


METHODS
Thirty-two patients treated with MVC at our institution between 2006 and 2009 were included. Genotypic (n +/- 31) and phenotypic (n +/- 13) tropism analysis was performed. We determined indications for MVC use, characteristics of antiretroviral combination partners and treatment outcome.


RESULTS
Complete suppression of viral replication was achieved in 78% after 6 months. A median increase of 124 CD4+ cells/microl after 6 months was observed. Concordance between phenotypic and genotypic tropism was found in 75%. Indications for MVC treatment included treatment failure (n +/- 15), intolerance to previous antiretrovirals (n +/- 6) and add-on MVC for intensification without changing the current regimen (n +/- 11). The add-on strategy was used in patients with a relatively low viremia in order to achieve complete viral load suppression or in situations with suppressed viral load but judged as unstable due to an extensive resistance pattern. Salvage drugs most frequently combined with MVC were darunavir (n +/- 14) and raltegravir (n +/- 14). - The genotypic assay had predicted CXCR4 tropism in 5 patients, using a false positive rate (FPR) of 20%. Lowering the FPR to 5% predicted CCR5 tropism in 4 cases, still resulting in sustained complete viral response under MVC use.


CONCLUSIONS
MVC containing salvage regimens achieve relevant CD4 cell increases and high viral response rates. In patients with few remaining treatment options it may be justified to lower the FPR-cutoff to 5% when predicting the coreceptor usage. Hereby, MVC could still be applied in selected patients with otherwise limited treatment options.
Reuter
S
S
Clinic for Gastroenterology, Hepatology and Infectious, University Hospital, Düsseldorf, Germany. Stefan.reuter@med.uni-duesseldorf.de
Braken
P
P
Jensen
B
B
Sierra-Aragon
S
S
Oette
M
M
Balduin
M
M
Kaiser
R
R
Häussinger
D
D
D000998:Antiviral Agents / Q000627:therapeutic use*; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D011446:Prospective Studies; D016879:Salvage Therapy; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D056189:Viral Tropism / Q000187:drug effects / Q000235:genetics; D053586:Virus Internalization; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D014230:Triazoles; D000077592:Maraviroc