 |
|
|
| |
Maraviroc Levels in Cerebrospinal Fluid
(CSF) and Seminal Plasma from HIV-Infected Patients
|
| |
| |
Reported by Jules Levin
17th CROI Feb 16-19 2010 SF
JM. Tiraboschi1*, J. Curto1, J. Niubo2 and D. Podzamczer1. 1Infectious Disease and 2Microbiology Services.
Hospital Universitari de Bellvitge, L’Hospitalet, Barcelona, Spain
AUTHOR CONCLUSIONS
MVC achieves levels in CSF within the range of IC50 or higher. Thus, MVC may be of benefit in patients with HIV neurological disorders. In semen, MVC exceeds several times the IC50. However, viral replication in semen may be observed despite virological suppression in plasma, suggesting semen may act as a distinct compartment. Most patients with undetectable plasma viral load while receiving nucleoside-sparing regimens including new drugs had viral suppression in reservoirs.
BACKGROUND
Replication of HIV-1 in viral sanctuaries such as lymphoid tissue, central nervous system or genital fluids may play an important role in HIV-1 pathogenesis, neurocognitive impairment or virus transmission. Penetration in human fluids differs between antiretroviral drugs.
OBJECTIVE
The aim of our study was determine Maraviroc levels in CSF and semen of a group of HIV-infected patients.
ABSTRACT
Background: Several studies have shown that penetration of ARV drugs into reservoirs may be associated with a decreased viral replication and clinical benefit. The aim of our study was determine Maraviroc levels in CSF and semen of a group of HIV-infected patients
Methods: Twelve CCR5+ HIV-1 adult antiretroviral-experienced patients receiving MVC-containing regimens for at least 1 month were enrolled. Both CSF and semen plus a blood sample were taken around 12 hours after the last MVC dose. Liquid chromatography tandem mass spectrometry (Tandem Labs, NJ, US) was used to determine MVC levels. HIV-1 viral load was determined by real time PCR, Abbott (detection limit 40 copies/mL).
Results: A total of 12 plasma samples, 12 CSF samples, and 9 semen samples were collected. Median CD4 count was 281 cells/uL (120 to 759) and the median HIV-1 viral load at the screening was <40 copies/mL. The median time on Maraviroc was 13.5 (4 to 60) weeks. Raltegravir was part of the background regimen in 92%, darunavir in 62% and etravirine in 42% of the patients. Nucleoside analogues were given in only one case.
Conclusions: MVC achieves levels in CSF within the range of IC50 or higher. Thus, MVC may be of benefit in patients with HIV neurological disorders. In semen, MVC exceeds several times the IC50. However, viral replication in semen may be observed despite virological suppression in plasma, suggesting semen may act as a dinstinct compartment. Most patients with undetectable plasma viral load while receiving nucleoside-sparing regimens, including new drugs, had viral suppression in reservoirs.
*: Patient 8 brought the semen sample for virological determinations several weeks later, he had stopped ARV and a new blood sample was obtained.
**: patient 5 had been on MVC-regimen for 4 weeks, and patient 10, for 58 weeks.
Three patients had detectable viral load (VL); 1777, 202 and 99 respectively and 1.9-2.8 log VL reduction after 4, 4 and 5 weeks of MVC-including regimens.
|
| |
|
|
|
|
|
