Cerebrospinal fluid HIV-1 RNA, intrathecal immunoactivation, and drug concentrations after treatment with a combination of saquinavir, nelfinavir, and two nucleoside analogues: the M61022 study.

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Cerebrospinal fluid HIV-1 RNA, intrathecal immunoactivation, and drug concentrations after treatment with a combination of saquinavir, nelfinavir, and two nucleoside analogues: the M61022 study.

Yilmaz, Aylin, 1974 (författare): Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine

Fuchs, Dietmar (författare)

Hagberg, Lars, 1951 (författare): Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine

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Nillroth, Ulrika (författare)

Ståhle, Lars (författare)

Svensson, Jan-Olof (författare)

Gisslén, Magnus, 1962 (författare): Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine

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2006-03-27
2006
Engelska.
Ingår i: BMC infectious diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 6

Relaterad länk:: https://bmcinfectdis...; visa fler...; https://gup.ub.gu.se...; https://doi.org/10.1...; visa färre...

Tidskriftsartikel (refereegranskat)

Abstract Ämnesord

Stäng

BACKGROUND: The way various antiretroviral drugs and drug combinations affect HIV-1 infection in the central nervous system is still largely unknown. The aim of this study was to determine the cerebrospinal fluid (CSF) steady-state concentrations of saquinavir and nelfinavir in relation to plasma concentrations, and to study their effect in combination with two nucleoside reverse transcriptase inhibitors (NRTIs) on CSF viral loads, intrathecal immunoactivation, and blood-brain barrier integrity. METHODS: Paired CSF and plasma samples from 8 antiretroviral-naïve HIV-1 infected patients starting combination therapy with saquinavir, nelfinavir, and two nucleoside analogues were collected prior to treatment, and again after approximately 12 and 48 weeks of antiretroviral therapy. Additional plasma samples were taken at weeks 2, 4, 8, 24, and 36. The concentrations of protease inhibitors were analysed, as were levels of HIV-1 RNA, CD4+ T-cell count, beta2-microglobulin, neopterin, albumin ratio, IgG index, and monocytic cell count. RESULTS: None of the patients in the study presented with HIV-1 RNA < 50 copies/mL in CSF or plasma prior to treatment, compared to 5/7 at the end of the study. Signs of cell-mediated intrathecal immunoactivation, measured by neopterin and beta2-microglobulin, decreased significantly in both CSF and serum, although only 1/7 reached normal CSF neopterin levels after 48 weeks of treatment. There was no significant reduction of albumin ratio, IgG index or CSF monocytic cell count. Saquinavir median (range) concentrations were < 2.5 (< 2.5-96.0) nM unbound in plasma, and < 2.5 (< 2.5-9.0) nM total in CSF. Nelfinavir median (range) concentrations were 10.0 (< 2.0-31.0) nM unbound in plasma, and < 2.0 (< 2.0-23.0) nM total in CSF. Saquinavir and nelfinavir were detectable in 7/15 and 9/15 CSF samples, respectively. CONCLUSION: Saquinavir and nelfinavir, in combination with two NRTIs, decrease the CSF viral load and, to a lesser extent, intrathecal immunoactivation. We found reasonably high CSF concentrations of nelfinavir, but suboptimal concentrations of saquinavir.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

Adult
Anti-HIV Agents
blood
cerebrospinal fluid
therapeutic use
CD4 Lymphocyte Count
Drug Therapy
Combination
Female
HIV Infections
drug therapy
HIV-1
metabolism
Humans
Immunoglobulin G
blood
cerebrospinal fluid
Male
Middle Aged
Nelfinavir
blood
cerebrospinal fluid
therapeutic use
Neopterin
cerebrospinal fluid
RNA
Viral
blood
cerebrospinal fluid
Saquinavir
blood
cerebrospinal fluid
therapeutic use
beta 2-Microglobulin
blood
cerebrospinal fluid

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Av författaren/redakt...: Yilmaz, Aylin, 1 ...; Fuchs, Dietmar; Hagberg, Lars, 1 ...; Nillroth, Ulrika; Ståhle, Lars; Svensson, Jan-Ol ...; visa fler...; Gisslén, Magnus, ...; visa färre...

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