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Marc Rubin - One of the best experts on this subject based on the ideXlab platform.
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Emergence of dual resistance to Zidovudine and Lamivudine in HIV-1-infected patients treated with Zidovudine Plus Lamivudine as initial therapy.
Journal of acquired immune deficiency syndromes (1999), 2000Co-Authors: Daniel R Kuritzkes, Marc Rubin, David Shugarts, Minoo Bakhtiari, David Poticha, Judy Johnson, Thomas R. Gingeras, Mitchell A. Kennedy, Joseph J. EronAbstract:Presence of mutations associated with resistance to Zidovudine or Lamivudine was determined in isolates of HIV-1 obtained after long-term follow-up of 64 infected individuals who received Zidovudine, Lamivudine, or both drugs as initial antiretroviral therapy. Zidovudine resistance mutations were less frequent in isolates from patients treated with combination Lamivudine Plus Zidovudine compared with Zidovudine alone, but these mutations accumulated over time. Phenotypic resistance to both drugs was found in isolates from 3 of 23 patients. In 3 other patients, Lamivudine- resistant virus detected at week 12 was replaced by wild-type virus after longer follow-up, which correlated with a return to baseline levels of plasma HIV-1 RNA. These results show that dual resistance to Zidovudine and Lamivudine develops over time despite the delayed emergence of Zidovudine- resistant mutations. These results also suggest a selective advantage in vivo for HIV-1 species that are wild-type at RT codon 184.
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Lamivudine Plus Zidovudine compared with zalcitabine Plus Zidovudine in patients with hiv infection a randomized double blind placebo controlled trial
Annals of Internal Medicine, 1996Co-Authors: John Bartlett, Chris Tsoukas, Sharon L Benoit, Victoria A Johnson, Joseph B Quinn, Gladys E Sepulveda, Christopher W Ehmann, Mary Ann Fallon, Pamela L Self, Marc RubinAbstract:Objective : To compare the safety and activity of Lamivudine Plus Zidovudine with the safety and activity of zalcitabine Plus Zidovudine in patients with moderately advanced human immunodeficiency virus (HIV) infection who had received Zidovudine. Design : A multicenter, randomized, double-blind, three-arm, 24-week study with a blinded extension through at least 52 weeks. Setting : 21 sites in the United States, Canada, and Puerto Rico. Patients : 254 patients who had received Zidovudine (median duration of previous therapy, 20 months) and had absolute CD4+ cell counts of 100 to 300 cells/mm 3 . Interventions : Patients were randomly assigned to receive one of three regimens : 150 mg of Lamivudine twice daily Plus 200 mg of Zidovudine three times daily (low-dose Lamivudine group) ; 300 mg of Lamivudine twice daily Plus 200 mg of Zidovudine three times daily (high-dose Lamivudine group) ; or 0.75 mg of zalcitabine Plus 200 mg of Zidovudine three times daily (zalcitabine group). Measurements : Immunologic activity was assessed primarily by changes in absolute CD4+ cell counts ; virologic activity was assessed by changes in plasma HIV RNA levels as measured by reverse transcriptase polymerase chain reaction. Safety of the treatment regimens was assessed through the reporting of adverse events. Results : 78% of patients completed 24 weeks of study treatment, and 63% of patients completed 52 weeks of study treatment. Changes in absolute CD4 + cell counts were significantly better for the low-dose and the high-dose Lamivudine groups than for the zalcitabine group (median changes at 52 weeks were +42.5 cells/mm 3 in the low-dose Lamivudine group, +23.33 cells/mm 3 in the high-dose Lamivudine group, and -29.58 cells/mm 3 in the zalcitabine group). Suppression of plasma HIV RNA levels was similar for all groups (median changes at 52 weeks were -0.48 log 10 copies/mL in the low-dose Lamivudine group, -0.51 log 10 copies/mL in the high-dose Lamivudine group, and -0.39 log 10 copies/mL in the zalcitabine group). No significant differences in safety were seen among the three regimens, although the low-dose Lamivudine regimen appeared to be better tolerated than the others. Conclusions : In patients with HIV infection who had previously received Zidovudine, 150 mg of Lamivudine Plus Zidovudine resulted in greater immunologic evidence of benefit than did 0.75 mg of zalcitabine Plus Zidovudine and was better tolerated than 300 mg of Lamivudine Plus Zidovudine.
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Lamivudine Plus Zidovudine Compared with Zalcitabine Plus Zidovudine in Patients with HIV Infection
Annals of Internal Medicine, 1996Co-Authors: John Bartlett, Chris Tsoukas, Sharon L Benoit, Victoria A Johnson, Joseph B Quinn, Gladys E Sepulveda, Mary Ann Fallon, Pamela L Self, W. Christopher Ehmann, Marc RubinAbstract:Objective: To compare the safety and activity of Lamivudine Plus Zidovudine with the safety and activity of zalcitabine Plus Zidovudine in patients with moderately advanced human immunodeficiency v...
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treatment with Lamivudine Zidovudine or both in hiv positive patients with 200 to 500 cd4 cells per cubic millimeter
The New England Journal of Medicine, 1995Co-Authors: Joseph J. Eron, Sharon L Benoit, Joseph B Quinn, Mary Ann Fallon, Joseph Jemsek, Rodger David Macarthur, Jorge Santana, Daniel R Kuritzkes, Marc RubinAbstract:Background The reverse-transcriptase inhibitor Lamivudine has in vitro synergy with Zidovudine against the human immunodeficiency virus (HIV). We studied the activity and safety of Lamivudine Plus Zidovudine as compared with either drug alone as treatment for patients with HIV infection, most of whom had not previously received Zidovudine. Methods Three hundred sixty-six patients with 200 to 500 CD4+ cells per cubic millimeter who had received Zidovudine for four weeks or less were randomly assigned to treatment with one of four regimens: 300 mg of Lamivudine every 12 hours; 200 mg of Zidovudine every 8 hours; 150 mg of Lamivudine every 12 hours Plus Zidovudine; or 300 mg of Lamivudine every 12 hours Plus Zidovudine. The study was double-blind and lasted 24 weeks, with an extension phase for another 28 weeks. Results Over the 24-week period, the low-dose and high-dose regimens combining Lamivudine and Zidovudine were associated with greater increases in the CD4+ cell count (P = 0.002 and P = 0.015, respec...
Peter Portegies - One of the best experts on this subject based on the ideXlab platform.
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cerebrospinal fluid β2 microglobulin monocyte chemotactic protein 1 and soluble tumour necrosis factor α receptors before and after treatment with Lamivudine Plus Zidovudine or stavudine
Journal of Neuroimmunology, 2000Co-Authors: Roelien H Enting, N.a. Foudraine, Joep M. A. Lange, Suzanne Jurriaans, Tom Van Der Poll, G J Weverling, Peter PortegiesAbstract:CSF levels of beta2-microglobulin (b2m), monocyte chemotactic protein-1 (MCP-1), soluble tumor necrosis factor receptors (sTNFRs), and HIV-1 RNA were determined in 16 neurologically asymptomatic HIV-1 infected patients before and 12 weeks after treatment with Lamivudine Plus Zidovudine or stavudine. b2m levels were significantly higher in patients (1.7 mg/l) compared with controls (0.8 mg/l) (P < 0.001), and decreased to 1.1 mg/l during treatment (P = 0.001). MCP-1 levels were low, and did not change during treatment. Levels of sTNFR type I were elevated in patients (0.92 ng/ml) compared to controls (0.30 ng/ml) (P = 0.03), but did not change during treatment. Levels of sTNFR type II were below the limit of detection in most patients and controls. In conclusion, CSF levels of b2m and HIV-I RNA, but not sTNFRs or MCP-1, are candidate surrogate markers of treatment efficacy in early CNS infection.
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Cerebrospinal-fluid HIV-1 RNA and drug concentrations after treatment with Lamivudine Plus Zidovudine or stavudine.
Lancet (London England), 1998Co-Authors: N.a. Foudraine, Richard M. W. Hoetelmans, Joep M. A. Lange, Frank De Wolf, Birgit H. B. Van Benthem, Jaap J Maas, I. P. M. Keet, Peter PortegiesAbstract:Summary Background Treatment and prevention of HIV-1-related central-nervous-system disease may be dependent on penetration of antiretroviral drugs into the central nervous system. Few data are available about cerebrospinal-fluid penetration and concomitant changes of HIV-1-RNA concentrations during treatment with antiretroviral agents. We investigated these effects in HIV-1-infected people. Methods 28 antiretroviral-naive individuals with CD4 cell counts of 200μL or more and plasma HIV-1-RNA concentrations of 10 000 or more copies/mL who were free of neurological symptoms were randomly assigned Lamivudine Plus either stavudine (n=17) or Zidovudine (n=11). We did lumbar punctures on 28 individuals before and 22 individuals after 12 weeks of treatment to assess HIV-1-RNA and drug concentrations in cerebrospinal fluid. Findings All 28 individuals had detectable HIV-1-RNA concentrations in the cerebrospinal fluid (median 4·64 log 10 copies/mL and 4·20 log 10 copies/mL in the Lamivudine Plus Zidovudine and Lamivudine Plus stavudine groups, respectively). There was no correlation between plasma and cerebrospinal-fluid HIV-1-RNA concentrations (r=0·18, p=0·35). After 12 weeks of treatment none of the individuals had detectable HIV-1-RNA concentrations in the cerebrospinal fluid. The highest drug concentration in the cerebrospinal fluid was for Lamivudine followed by stavudine and Zidovudine. Concentrations were consistent over time, unlike plasma concentrations. Therefore, we found time-dependent cerebrospinal-fluid to plasma drug-penetration ratios, which were highest for Zidovudine followed by stavudine and Lamivudine. Interpretation The two drug combinations were equally effective in the decrease of cerebrospinal fluid HIV-1-RNA concentrations. All drugs penetrated the cerebrospinal fluid. Antiretroviral drugs other than Zidovudine might be useful in the prevention of AIDS dementia complex.
Roelien H Enting - One of the best experts on this subject based on the ideXlab platform.
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cerebrospinal fluid β2 microglobulin monocyte chemotactic protein 1 and soluble tumour necrosis factor α receptors before and after treatment with Lamivudine Plus Zidovudine or stavudine
Journal of Neuroimmunology, 2000Co-Authors: Roelien H Enting, N.a. Foudraine, Joep M. A. Lange, Suzanne Jurriaans, Tom Van Der Poll, G J Weverling, Peter PortegiesAbstract:CSF levels of beta2-microglobulin (b2m), monocyte chemotactic protein-1 (MCP-1), soluble tumor necrosis factor receptors (sTNFRs), and HIV-1 RNA were determined in 16 neurologically asymptomatic HIV-1 infected patients before and 12 weeks after treatment with Lamivudine Plus Zidovudine or stavudine. b2m levels were significantly higher in patients (1.7 mg/l) compared with controls (0.8 mg/l) (P < 0.001), and decreased to 1.1 mg/l during treatment (P = 0.001). MCP-1 levels were low, and did not change during treatment. Levels of sTNFR type I were elevated in patients (0.92 ng/ml) compared to controls (0.30 ng/ml) (P = 0.03), but did not change during treatment. Levels of sTNFR type II were below the limit of detection in most patients and controls. In conclusion, CSF levels of b2m and HIV-I RNA, but not sTNFRs or MCP-1, are candidate surrogate markers of treatment efficacy in early CNS infection.
Joep M. A. Lange - One of the best experts on this subject based on the ideXlab platform.
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cerebrospinal fluid β2 microglobulin monocyte chemotactic protein 1 and soluble tumour necrosis factor α receptors before and after treatment with Lamivudine Plus Zidovudine or stavudine
Journal of Neuroimmunology, 2000Co-Authors: Roelien H Enting, N.a. Foudraine, Joep M. A. Lange, Suzanne Jurriaans, Tom Van Der Poll, G J Weverling, Peter PortegiesAbstract:CSF levels of beta2-microglobulin (b2m), monocyte chemotactic protein-1 (MCP-1), soluble tumor necrosis factor receptors (sTNFRs), and HIV-1 RNA were determined in 16 neurologically asymptomatic HIV-1 infected patients before and 12 weeks after treatment with Lamivudine Plus Zidovudine or stavudine. b2m levels were significantly higher in patients (1.7 mg/l) compared with controls (0.8 mg/l) (P < 0.001), and decreased to 1.1 mg/l during treatment (P = 0.001). MCP-1 levels were low, and did not change during treatment. Levels of sTNFR type I were elevated in patients (0.92 ng/ml) compared to controls (0.30 ng/ml) (P = 0.03), but did not change during treatment. Levels of sTNFR type II were below the limit of detection in most patients and controls. In conclusion, CSF levels of b2m and HIV-I RNA, but not sTNFRs or MCP-1, are candidate surrogate markers of treatment efficacy in early CNS infection.
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Cerebrospinal-fluid HIV-1 RNA and drug concentrations after treatment with Lamivudine Plus Zidovudine or stavudine.
Lancet (London England), 1998Co-Authors: N.a. Foudraine, Richard M. W. Hoetelmans, Joep M. A. Lange, Frank De Wolf, Birgit H. B. Van Benthem, Jaap J Maas, I. P. M. Keet, Peter PortegiesAbstract:Summary Background Treatment and prevention of HIV-1-related central-nervous-system disease may be dependent on penetration of antiretroviral drugs into the central nervous system. Few data are available about cerebrospinal-fluid penetration and concomitant changes of HIV-1-RNA concentrations during treatment with antiretroviral agents. We investigated these effects in HIV-1-infected people. Methods 28 antiretroviral-naive individuals with CD4 cell counts of 200μL or more and plasma HIV-1-RNA concentrations of 10 000 or more copies/mL who were free of neurological symptoms were randomly assigned Lamivudine Plus either stavudine (n=17) or Zidovudine (n=11). We did lumbar punctures on 28 individuals before and 22 individuals after 12 weeks of treatment to assess HIV-1-RNA and drug concentrations in cerebrospinal fluid. Findings All 28 individuals had detectable HIV-1-RNA concentrations in the cerebrospinal fluid (median 4·64 log 10 copies/mL and 4·20 log 10 copies/mL in the Lamivudine Plus Zidovudine and Lamivudine Plus stavudine groups, respectively). There was no correlation between plasma and cerebrospinal-fluid HIV-1-RNA concentrations (r=0·18, p=0·35). After 12 weeks of treatment none of the individuals had detectable HIV-1-RNA concentrations in the cerebrospinal fluid. The highest drug concentration in the cerebrospinal fluid was for Lamivudine followed by stavudine and Zidovudine. Concentrations were consistent over time, unlike plasma concentrations. Therefore, we found time-dependent cerebrospinal-fluid to plasma drug-penetration ratios, which were highest for Zidovudine followed by stavudine and Lamivudine. Interpretation The two drug combinations were equally effective in the decrease of cerebrospinal fluid HIV-1-RNA concentrations. All drugs penetrated the cerebrospinal fluid. Antiretroviral drugs other than Zidovudine might be useful in the prevention of AIDS dementia complex.
N.a. Foudraine - One of the best experts on this subject based on the ideXlab platform.
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cerebrospinal fluid β2 microglobulin monocyte chemotactic protein 1 and soluble tumour necrosis factor α receptors before and after treatment with Lamivudine Plus Zidovudine or stavudine
Journal of Neuroimmunology, 2000Co-Authors: Roelien H Enting, N.a. Foudraine, Joep M. A. Lange, Suzanne Jurriaans, Tom Van Der Poll, G J Weverling, Peter PortegiesAbstract:CSF levels of beta2-microglobulin (b2m), monocyte chemotactic protein-1 (MCP-1), soluble tumor necrosis factor receptors (sTNFRs), and HIV-1 RNA were determined in 16 neurologically asymptomatic HIV-1 infected patients before and 12 weeks after treatment with Lamivudine Plus Zidovudine or stavudine. b2m levels were significantly higher in patients (1.7 mg/l) compared with controls (0.8 mg/l) (P < 0.001), and decreased to 1.1 mg/l during treatment (P = 0.001). MCP-1 levels were low, and did not change during treatment. Levels of sTNFR type I were elevated in patients (0.92 ng/ml) compared to controls (0.30 ng/ml) (P = 0.03), but did not change during treatment. Levels of sTNFR type II were below the limit of detection in most patients and controls. In conclusion, CSF levels of b2m and HIV-I RNA, but not sTNFRs or MCP-1, are candidate surrogate markers of treatment efficacy in early CNS infection.
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Cerebrospinal-fluid HIV-1 RNA and drug concentrations after treatment with Lamivudine Plus Zidovudine or stavudine.
Lancet (London England), 1998Co-Authors: N.a. Foudraine, Richard M. W. Hoetelmans, Joep M. A. Lange, Frank De Wolf, Birgit H. B. Van Benthem, Jaap J Maas, I. P. M. Keet, Peter PortegiesAbstract:Summary Background Treatment and prevention of HIV-1-related central-nervous-system disease may be dependent on penetration of antiretroviral drugs into the central nervous system. Few data are available about cerebrospinal-fluid penetration and concomitant changes of HIV-1-RNA concentrations during treatment with antiretroviral agents. We investigated these effects in HIV-1-infected people. Methods 28 antiretroviral-naive individuals with CD4 cell counts of 200μL or more and plasma HIV-1-RNA concentrations of 10 000 or more copies/mL who were free of neurological symptoms were randomly assigned Lamivudine Plus either stavudine (n=17) or Zidovudine (n=11). We did lumbar punctures on 28 individuals before and 22 individuals after 12 weeks of treatment to assess HIV-1-RNA and drug concentrations in cerebrospinal fluid. Findings All 28 individuals had detectable HIV-1-RNA concentrations in the cerebrospinal fluid (median 4·64 log 10 copies/mL and 4·20 log 10 copies/mL in the Lamivudine Plus Zidovudine and Lamivudine Plus stavudine groups, respectively). There was no correlation between plasma and cerebrospinal-fluid HIV-1-RNA concentrations (r=0·18, p=0·35). After 12 weeks of treatment none of the individuals had detectable HIV-1-RNA concentrations in the cerebrospinal fluid. The highest drug concentration in the cerebrospinal fluid was for Lamivudine followed by stavudine and Zidovudine. Concentrations were consistent over time, unlike plasma concentrations. Therefore, we found time-dependent cerebrospinal-fluid to plasma drug-penetration ratios, which were highest for Zidovudine followed by stavudine and Lamivudine. Interpretation The two drug combinations were equally effective in the decrease of cerebrospinal fluid HIV-1-RNA concentrations. All drugs penetrated the cerebrospinal fluid. Antiretroviral drugs other than Zidovudine might be useful in the prevention of AIDS dementia complex.
